ESES Review of Recently Published Literature

Collection: T. Clerici1, F. Triponez2 
Compilation and design: U. Beutner1
1: Department of Surgery, Cantonal Hospital St. Gallen, St Gallen, Switzerland
2: Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland
Ulrich.beutner@kssg.ch

May - August 2009
Data retrieval from Pubmed: 29. September 2009

Contents
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	Page
Thyroid
Parathyroid
Adrenals
NET
ENETS Consensus Guidelines

Pubmed-ID: 	PubMed-Identifier (unique number for each Pubmed entry)

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Thyroid
Meta-Analyses
Treatment Modalities for Graves' Ophthalmopathy: Systematic Review and Metaanalysis.
J Clin Endocrinol Metab, 94(8):2708-16.
Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, Ezrachi D, Shimon I, Leibovici L. 2009.
BACKGROUND: Graves' ophthalmopathy (GO) is a common cause of morbidity in patients with Graves' disease. Optimal treatment of GO remains unclear, and an evidence-based approach may improve patients' outcome. METHODS: A systematic review and metaanalysis of randomized, controlled trials comparing treatment modalities for GO vs. placebo, no intervention, or other treatments. Primary outcome was the clinical activity score (CAS). RESULTS: Thirty-three trials evaluating 1367 patients fulfilled inclusion criteria. In patients with moderate to severe GO, iv pulse corticosteroids were significantly better than oral corticosteroids in reducing CAS [standardized mean difference -0.64, 95% confidence interval (CI) -1.11 to -0.17, chi(2) 7.91, I(2) 62%, random effect], with lower rate of adverse events. Somatostatin analogs showed a minor but statistically significant advantage over placebo (mean difference -0.63, 95% CI -0.98 to -0.28). There was no advantage of orbital radiotherapy over sham radiation in CAS, but radiotherapy was superior for response rates of diplopia (odds ratio 4.88, 95% CI 1.93-12.34, two trials). Treatment with combination of orbital radiotherapy and corticosteroids was significantly better than with either treatment alone (standardized mean difference -1.05, 95% CI -1.62 to -0.48). CONCLUSIONS: Current evidence demonstrates the efficacy of iv corticosteroids in decreasing CAS in patients with moderate to severe GO. Intravenous pulse corticosteroids therapy has a small but statistically significant advantage oral therapy and causes significantly fewer adverse events. Somatostatin analogs have marginal clinical efficacy. The efficacy of orbital radiotherapy as single therapy remains unclear, whereas the combination of radiotherapy with corticosteroids has better efficacy than either radiotherapy or oral corticosteroids alone.
PubMed-ID: 19491222
http://dx.doi.org/10.1210/jc.2009-0376
Value of 18F-FDG-PET/PET-CT in Differentiated Thyroid Carcinoma With Radioiodine-Negative Whole-Body Scan: a Meta-Analysis.
Nucl Med Commun, 30(8):639-50.
Dong MJ, Liu ZF, Zhao K, Ruan LX, Wang GL, Yang SY, Sun F, Luo XG. 2009.
AIM: The aim of this study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose-PET (FDG-PET) and FDG-PET/computed tomography (CT) in the detection of recurrent or metastatic differentiated thyroid carcinoma (DTC) that was not identified by radioiodine whole-body scintigraphy (WBS). PATIENTS AND METHODS: A total of 25 studies (comprising 789 patients) that were published from January 1990 to September 2008 were reviewed. These studies evaluated the role of FDG-PET and FDG-PET/CT in the detection of recurrent or metastatic DTC that radioiodine WBS failed to detect. Systematic methods were used to identify, select, and evaluate the methodological quality of the studies and to summarize the overall findings of sensitivity and specificity. RESULTS: In total, 17 studies with 571 patients who had recurrent or metastatic DTC and a radioiodine-negative whole-body scan were collected, and the overall patient-based sensitivity and specificity of FDG-PET were 0.835 [95% confidence interval (CI): 0.791-0.873] and 0.843 (95% CI: 0.791-0.886), respectively. Of these studies, six included lesion-based data, totaling 237 lesions, and the pooled lesion-based sensitivity and specificity were 0.916 (95% CI: 0.863-0.953) and 0.775 (95% CI: 0.660-0.865), respectively. The pooled sensitivity and specificity in the DTC patients who presented with elevated serum thyroglobulin and negative 131I scan were 0.885 (95% CI: 0.828-0.929) and 0.847 (95% CI: 0.715-0.934), respectively. In the six studies where the 165 patients were diagnosed by using FDG-PET/CT, pooled sensitivity and specificity were 0.935 (95% CI: 0.870-0.973) and 0.839 (95% CI: 0.723-0.920), respectively. CONCLUSION: FDG-PET is especially effective in detecting patients with elevated thyroglobulin levels and normal radioiodine WBS; FDG-PET/CT is a more sensitive method in the follow-up of thyroid cancer recurrence or metastases, particularly in those with negative WBS.
PubMed-ID: 19512954
http://dx.doi.org/10.1097/MNM.0b013e32832dcfa7

Randomized controlled trials
Clinical Outcomes of Adjuvant External-Beam Radiotherapy for Differentiated Thyroid Cancer - Results After 874 Patient-Years of Follow-Up in the MSDS-Trial.
Nuklearmedizin, 48(3):89-98.
Biermann M, Pixberg M, Riemann B, Schuck A, Heinecke A, Schmid KW, Willich N, Dralle H, Schober O. 2009.
AIM: Evaluate the clinical benefit of external beam radiotherapy (RTx) for locally invasive thyroid carcinoma with follicular cell differentiation (DTC). PATIENTS, METHODS: The Multicentre Study on Differentiated Thyroid Cancer (MSDS) was planned as a prospective multicenter trial on the benefit of adjuvant RTx in locally invasive DTC (pT4; UICC 1997) with or without lymph node metastases and no known distant metastases. All patients were treated with thyroidectomy, 131I-therapy, and TSH-suppression and were randomized to receive additional RTx or not. In 4/2003 the trial became a prospective cohort study after only 45 of then 311 patients had consented to randomization. 351 of 422 patients met the trial's inclusion criteria. Age was 48 +/- 12 years (mean +/- SD). 25% were men. Tumours were papillary in 90% and follicular in 10%. Of 47 patients randomized or allocated to RTx, 26 actually received RTx. RESULTS: Mean follow-up was 930 days. In an actual treatment analysis, 96% (25/26) of the RTx-patients reached complete remission (CR) vs. 86% in the non-RTx patients. Recurrences occurred in 0 vs. 3 % of patients: 6 reoperated for regional lymph node metastases, 1 tracheal invasion treated with tracheoplasty, 1 local invasion necessitating laryngectomy, 2 distant metastases (1 lung, 1 lung + bone). Serious chronic RTx toxicity occurred in 1/26 patients. CONCLUSION: The MSDS trial showed low mortality and recurrence rates and a weak benefit of RTx in terms of local control that did however not reach statistical significance. Routine RTx in locally invasive DTC can no longer be recommended.
PubMed-ID: 19322503
http://dx.doi.org/10.3413/nukmed-0221
The Effectiveness of FloSeal Matrix Hemostatic Agent in Thyroid Surgery: a Prospective, Randomized, Control Study.
Langenbecks Arch Surg, 394(5):837-42.
Testini M, Marzaioli R, Lissidini G, Lippolis A, Logoluso F, Gurrado A, Lardo D, Poli E, Piccinni G. 2009.
BACKGROUND: The objective of this study was to compare the effectiveness of FloSeal matrix hemostatic agent with hemostatic surgical procedures and Tabotamp in thyroid surgery. METHODS: One hundred fifty-five consecutive total thyroidectomy patients were recruited at our institution between January 2005 and December 2007. Exclusion criteria were applied. Patients were randomized to one of three hemostatic approaches: 49 received surgical procedures only, and 52 received oxidized regenerated cellulose patch (Tabotamp Fibrillar 2.5 x 5 cm) and 54 FloSeal (5,000 U/5 mL). The same surgeon performed all operations. RESULTS: Mean operating time was reduced in the FloSeal group (105 min) vs. surgical (133 min, p = 0.02) and vs. Tabotamp (122 min, p = 0.0003). Also, wound drain removal occurred earlier with FloSeal (p = 0.006 vs. surgical; p = 0.008 vs. Tabotamp) resulting in shorter postoperative hospital stay in the FloSeal group (p = 0.02 vs. surgical; p = 0.002 vs. Tabotamp). CONCLUSIONS: FloSeal matrix is an effective additional agent to conventional haemostatic procedures in thyroid surgery.
PubMed-ID: 19421770
http://dx.doi.org/10.1007/s00423-009-0497-5
Surgery and Radio Ablation Therapy Combined: Introducing a 1-Week-Condensed MHH-Procedure Bonding Total Thyroidectomy and Radio Ablation Therapy With Recombinant Human Thyrotropin.
Eur J Endocrinol, 
Emmanouilidis N, Muller J, Jager M, Kaaden S, Helfritz F, Guner Z, Kespohl H, Knitsch W, Knapp W, Klempnauer J, Scheumann G. 2009.
Objective. The objective of this study was to determine if the use of recombinant human thyrotropin (rhTSH) to stimulate radio-iodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay. Design. Our aim was to compare the standard procedure of DTC-treatment, which consists of thyroidectomy followed by four weeks of hypothyroidism and a conclusive ablative activity of 131Iodine, with a new shortened treatment in which L-T4 medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction of sick-leave days overall without any reduction in safety or the efficacy. Methods. N=25 patients were randomized either for surgery and rhTSH stimulation or surgery and L-T4-abstinence before the first application of radio-iodine. Ablation success was determined by neck ultra-sound and serum Tg during follow-up. RhTSH-receivers were monitored for an average of 635days (SD+/-289) and patients in L-T4-abstinence for an average of 624days (SD+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick-leave. Results/Conclusions. Our shortened treatment proved to be equally efficacious and safe in comparison to the conventional therapy. At the same time it facilitated the reduction of average sick-leave time from ~29days (L-T4-abstinence) down to ~6days (rhTSH- stimulation) as well as sustaining the patient's quality-of-life by the complete avoidance of hypothyroidism.
PubMed-ID: 19687168
http://dx.doi.org/10.1530/EJE-08-0641

Other Articles
Evaluation of Gene Expression Profiles in Thyroid Nodule Biopsy Material to Diagnose Thyroid Cancer.
J Clin Endocrinol Metab, 93(4):1195-202.
Durand S, Ferraro-Peyret C, Selmi-Ruby S, Paulin C, El AM, Berger F, Berger-Dutrieux N, Decaussin M, Peix JL, Bournaud C, Orgiazzi J, Borson-Chazot F, Rousset B. 2008.
CONTEXT: Detection of thyroid cancer among benign nodules on fine-needle aspiration biopsies (FNAB), which presently relies on cytological examination, is expected to be improved by new diagnostic tests set up from genomic data. OBJECTIVE: The aim of the study was to use a set of genes discriminating benign from malignant tumors, on the basis of their expression levels, to build tumor classifiers and evaluate their capacity to predict malignancy on FNAB. DESIGN: We analyzed the level of expression of 200 potentially informative genes in 56 thyroid tissue samples (benign or malignant tumors and paired normal tissue) using nylon macroarrays. Gene expression data were subjected to a weighted voting algorithm to generate tumor classifiers. The performances of the classifiers were evaluated on a series of 26 sham FNAB, i.e. FNAB carried out on thyroid nodules after surgical resection. RESULTS: A series of 19 genes with a similar expression in follicular adenomas and normal tissue and discriminating follicular adenomas+normal tissue from the following: 1) follicular thyroid carcinomas (FTCs), 2) papillary thyroid carcinomas (PTCs), or 3) both FTCs and PTCs. These were used to generate four classifiers, the FTCs, PTCs, common (FTC+PTCs), and global classifiers. In 23 of the 26 sham FNAB, the four classifiers yielded a diagnosis in agreement with the diagnosis of the pathologist used as reference; in the three other cases, the correct diagnosis was given by three of four classifiers. CONCLUSIONS: We developed a procedure of molecular diagnosis of benign vs. malignant tumors applicable to the material collected by FNAB. The molecular test complied with a preclinical validation stage; it must be now evaluated on ultrasound-guided FNAB in a large-scale prospective study.
PubMed-ID: 18211972
http://dx.doi.org/10.1210/jc.2007-1571
Primary Malignant Fibrous Histiocytoma of the Thyroid.
Eur J Surg Oncol, 35(6):649-53.
Zeng Q, Tang PZ, Xu ZG, Qi YF, Wu XX, Liu WS. 2009.
AIMS AND METHODS: To study the clinical features, diagnosis, and treatment of primary malignant fibrous histiocytoma of the thyroid (MFH-T). Treatment and outcome were analyzed retrospectively in a consecutive series of 12 patients with primary MFH-T treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from 1987 to 2007. RESULTS: All 12 patients underwent surgery; surgery alone was used in four patients. Five patients were given post-operative radiotherapy, and one patient was given pre-operative radiotherapy. Two patients were given post-operative chemotherapy. Five patients had locoregional recurrence, and five had distant metastases in follow-up. Median survival was 9 months. One patient is alive, and has no evidence of disease. Six patients died six months after treatment, and the other four patients died in 10, 14, 18, and 24 months after treatment, respectively. Nine patients died of the disease, and one patient died of cerebral hemorrhage after treatment. CONCLUSION: Primary MFH-T is very rare and has a poor prognosis. Although surgical resection of MFH-T is the treatment of choice in MFH-T, the results are unsatisfactory.
PubMed-ID: 18922667
http://dx.doi.org/10.1016/j.ejso.2008.09.001
Excellent Prognosis of Patients With Nonhereditary Medullary Thyroid Carcinoma With Ultrasonographic Findings of Follicular Tumor or Benign Nodule.
World J Surg, 33(5):963-8.
Fukushima M, Ito Y, Hirokawa M, Miya A, Kobayashi K, Akasu H, Shimizu K, Miyauchi A. 2009.
BACKGROUND: Medullary thyroid carcinoma (MTC) accounts for only 1.4% of all thyroid malignancies in Japan. Generally, MTC shows ultrasonographic findings typical of thyroid carcinoma. However, in our experience, some MTC may be diagnosed as a follicular tumor or a benign nodule on ultrasonography because ultrasonographic findings of malignancy are lacking. In this study we investigated differences in biological behavior between these two types of MTC. METHODS: Seventy-seven patients with nonhereditary MTC who underwent surgery in our department between 1988 and 2007 were enrolled in this study. Of these patients, 54 were diagnosed as having thyroid carcinoma (malignant, or M-type) but the remaining 23 were diagnosed as having follicular tumor or benign nodule (benign, or B-type) on ultrasonography. RESULTS: Clinically apparent lateral node metastasis, extrathyroid extension, and extranodal tumor extension were observed in 37%, 17%, and 11% of M-type patients, respectively, but none of the B-type patients showed any of these features. All B-type patients but only 59% of M-type patients were biochemically cured. Lymph node metastasis was pathologically confirmed in 38 and 65% of B-type and M-type patients, respectively. Eight patients showed recurrence and three have died of carcinoma to date; all of these patients were M-type patients. CONCLUSIONS: B-type MTC is highly indolent and shows an excellent prognosis. However, thyroidectomy and lymph node dissection for B-type MTC should be the same as for M-type MTC because 38% of B-type MTC showed pathologic node metastasis.
PubMed-ID: 19198929
http://dx.doi.org/10.1007/s00268-009-9939-z
Molecular Characteristics of Papillary Thyroid Carcinomas Without BRAF Mutation or RET/PTC Rearrangement: Relationship With Clinico-Pathological Features.
Endocr Relat Cancer, 16(2):467-81.
Durand S, Ferraro-Peyret C, Joufre M, Chave A, Borson-Chazot F, Selmi-Ruby S, Rousset B. 2009.
About 60-70% of papillary thyroid carcinomas (PTC) present a BRAF(T1799A) gene mutation or a rearrangement of RET gene (RET/PTC). In this study, we examined whether PTC without BRAF(T1799A) mutation and without RET/PTC rearrangement named PTC-ga(-) were distinguishable from PTC-ga(+) (with one or the other gene alteration) on the basis of gene expression characteristics. We analyzed the mutational state of 116 PTC and we compared gene expression profiles of PTC-ga(+) and PTC-ga(-) from data of a 200 gene macroarray and quantitative PCR. Seventy five PTC were PTC-ga(+) and 41 were PTC-ga(-). Unsupervised analyses of macroarray data by hierarchical clustering led to a complete segregation of PTC-ga(+) and PTC-ga(-). In a series of 42 genes previously recognized as PTC 'marker' genes, 22 were found to be expressed at a comparable level in PTC-ga(-) and normal tissue. Thyroid-specific genes, TPO, TG, DIO1, and DIO2 were under-expressed in PTC-ga(+) but expressed at a normal level in PTC-ga(-). A few genes including DUOX1 and DUOX2 were selectively dys-regulated in PTC-ga(-). Tumor grade of PTC-ga(-) was lower than that of PTC-ga(+). There was a strong association between the mutational state and histiotype of PTC; 81% of PTC follicular variants were corresponded to PTC-ga(-), whereas 84% of PTC of classical form were PTC-ga(+). In conclusion, we show that PTC without BRAF(T1799A) mutation or RET/PTC rearrangement, mainly corresponding to follicular variants, maintain a thyroid differentiation expression level close to that of normal tissue and should be of better prognosis than PTC with one or the other gene alteration.
PubMed-ID: 19208736
http://dx.doi.org/10.1677/ERC-08-0081
Surgical Treatment of Low- and Intermediate-Risk Papillary Thyroid Cancer With Minimally Invasive Video-Assisted Thyroidectomy.
J Clin Endocrinol Metab, 94(5):1618-22.
Miccoli P, Pinchera A, Materazzi G, Biagini A, Berti P, Faviana P, Molinaro E, Viola D, Elisei R. 2009.
BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) was introduced in the clinical practice to treat small benign thyroid nodules. This method has recently been demonstrated to produce the same completeness as a conventional thyroidectomy in patients with papillary thyroid cancer (PTC). The low number of treated cases and the limited follow-up of these patients represent the major limitations of these studies. OBJECTIVE: The aim of the study was to compare the outcome of two groups of PTC patients, one treated with MIVAT and the other with conventional thyroidectomy, after a median follow-up of 5 yr. STUDY GROUP: A total of 221 PTC patients were enrolled in this study according to the following criteria: 171 were treated with MIVAT (group A), and 50 were treated with conventional thyroidectomy (group B). RESULTS: The outcome and the cumulative (131)I activity administered to achieve curative status were compared. After a mean follow-up of 3.6 +/- 1.5 yr (range, 1-8 yr; median, 5 yr), no differences were found between group A and group B. A similar rate of permanent hypoparathyroidism and/or nerve cord palsy was found in both groups. CONCLUSION: We demonstrated that PTC patients operated on with MIVAT had a good outcome after 5 yr. This was similar to the outcome of patients treated with conventional thyroidectomy and the same degree of exposure to (131)I. These results, together with the evidence of a similar degree of completeness and rate of complications between the two surgical techniques, show that MIVAT is a valid option to treat low- and intermediate-risk PTC patients.
PubMed-ID: 19223525
http://dx.doi.org/10.1210/jc.2008-1418
Natural Orifice Surgery on Thyroid Gland: Totally Transoral Video-Assisted Thyroidectomy (TOVAT): Report of First Experimental Results of a New Surgical Method.
Surg Endosc, 23(5):1119-20.
Benhidjeb T, Wilhelm T, Harlaar J, Kleinrensink GJ, Schneider TA, Stark M. 2009.
BACKGROUND: Neck surgery is one of the newest fields of application of minimally invasive surgery. The technique of minimally invasive video-assisted thyroidectomy (MIVAT) developed by Miccoli [1] is the method that has so far become most widespread. Limiting factors of this method include the bothersome 20-mm cervical incision and consequently the specimen size to remove. Several papers describing an access outside the front neck region have been published. Such approaches are via the chest, axillary, a combined axillary bilateral breast, or a bilateral axillary breast approach [2-5]. The development of cervical scarless thyroid surgery is a great step toward better cosmetic outcomes. However, these techniques just moved the scars from the front neck region to the axilla or the chest where they are still visible. And the mentioned minimally invasive accesses as well as the conventional approaches to the thyroid gland do not respect the anatomically given surgical planes. This may result in complaints by the patients, e.g., scar development and swallowing disorders. Furthermore, the extracervical approaches do not comply with the use of the term "minimally invasive," because they are associated with an extensive dissection of the chest and neck region, thus being rather maximally invasive for the patients. The main goal of this project was the introduction of a technique of thyroid resection that fulfills the following criteria: (i. Respecting surgical planes and minimizing surgical trauma in thyroidectomy, ii. The access itself should be close to the thyroid gland to achieve a minimally invasive procedure, iii. Achieving an optimal cosmetic result may only be obtained by performing a scarless operation, iv. This optimal cosmetic result with scarless surgery should be achieved with minimal trauma, v. The minimally invasive character of this approach and the optimal cosmetic result may not be reached at the expense of patient's safety.). The technique that meets all of these criteria is the transoral access because the distance between the sublingual place and the thyroid gland is short, thus avoiding extensive dissection maneuvers. Furthermore, the mouth mucosa can be sutured without difficulties and repairs itself without leaving any visible scars. Feasibility of the transoral access has been recently demonstrated by a member of our group in a porcine model by using a modified axilloscope [6]. However, the described technique is a hybrid one because an additional medial access (3.5-mm incision) 15-mm below the larynx was necessary for the insertion of a fixation forceps through a trocar. The main goal of our project was the investigation and introduction of a technique of totally endoscopic thyroid resection that is minimally invasive and safe for the patient and at the same time cosmetically optimal (scarless). METHODS: For this purpose, a total of five human cadavers were used. In three cadavers, safety and reproducibility to reach and resect the thyroid gland was assessed according to a defined road map. At the end of the procedure, the cadavers were dissected to evaluate all defined anatomical key structures regarding possible injuries and also allow an evaluation of the surgery performed. The TOVAT itself was performed on two more human cadavers with the help of one 5-mm and two 3-mm trocars that were introduced through the mouth floor and the vestibulum of the mouth subplatysmal. A working space was created by insufflating CO(2) at a pressure of 4-6 mmHg ("air dissection"). Surgical dissection of the further working space was realized with 3-mm bipolar scissors. The procedure consists of the following steps: (i. Patient in supine position and nasotracheal intubation, ii. 5-mm small incision between the carunculae sublinguales, iii. Penetration through the mouth floor along the superficial fascia colli with a blunt instrument, iv. Insertion of a 5-mm trocar, v. Blunt dissection subplatysmal by CO(2) insufflation ("air dissection"), vi. CO(2) insufflation (4-6 mmHg) and creation of a working space, vii. Insertion of two 3-mm trocars in the vestibulum oris on the right and left side, viii. Separation of the platysma from the strap muscles approximately at level of the larynx, extending up to the suprasternal notch. Laterally, this dissection can be continued up to the medial border of the sternocleidomastoid muscles, ix. Division of the linea alba coli and exposure of the strap muscles, x. Separation of the strap muscles from the thyroid gland, xi. Isthmus transection and blunt dissection of the thyroid gland from the trachea, xii. Dissection and division of the upper pole arteries and medial thyroid vein closely to the gland, xiii. Division of branches of the inferior thyroid artery closely to the gland, xiv. If necessary, preparation of the retro-thyroidal area, including visualization of the recurrent laryngeal nerve, xv. Thyroid resection from cranial to caudal and transoral removal of the specimen through the 5-mm midline incision. If the gland is too large, the midline incision can be extended longitudinally, xvi. All three incisions are closed with absorbable sutures.) RESULTS: Description of landmarks of surgical steps and dissection of defined anatomic structures could be achieved. The subplatysmal space could be reached without any major problems within a short time. Anatomical dissection showed intact muscles and vascular structures. One-side subtotal thyroid resection could be successfully performed without any additional skin incision in 60 minutes. CONCLUSIONS: The minimally invasive aspect and the scarless character of TOVAT form the rationale for the preclinical investigation of this method in human cadavers. We could succeed in defining objective parameters, which describe the procedure in details and also allow an evaluation of the surgery performed. Access and feasibility of TOVAT could be demonstrated. The next step will be its application in living pigs before it may be applied in humans. To our knowledge of the literature, this is the first report on NOS application in thyroid surgery and also the first totally and scarless performed video-assisted thyroidectomy.
PubMed-ID: 19263151
http://dx.doi.org/10.1007/s00464-009-0347-0
Clinical Relevance of Single-Photon Emission Computed Tomography/Computed Tomography of the Neck and Thorax in Postablation (131)I Scintigraphy for Thyroid Cancer.
J Clin Endocrinol Metab, 94(6):2075-84.
Aide N, Heutte N, Rame JP, Rousseau E, Loiseau C, Henry-Amar M, Bardet S. 2009.
CONTEXT: In patients with differentiated thyroid carcinoma, postablation (131)I scintigraphy aims to detect residual neck disease and distant metastases, usually found in lungs and bones. New hybrid single-photon emission computed tomography/computed tomography (SPECT-CT) cameras that permit functional and anatomical image fusion may improve its clinical relevance. OBJECTIVE: Our objective was to test the added value of neck and thorax SPECT-spiral CT to whole-body scan (WBS) in postablation (131)I scintigraphy. DESIGN AND SETTING: This was a single-referral-center prospective study with a median follow-up of 21 months. PATIENTS AND METHODS: Postablation (131)I WBS and neck and thorax SPECT-CT were performed in 55 consecutive patients treated in 2006. WBS and SPECT-CT data were blindly reviewed, scored negative (benign), positive (malignant), or indeterminate and were correlated to the patient outcome. RESULTS: At patient level, WBS and SPECT-CT were negative in 67 and 78% of patients, positive in 4 and 15%, and indeterminate in 29 and 7%, respectively. Overall, nine patients (16%) presented treatment failure (persistent or recurrent disease) 1-16 months after radioiodine ablation. In the 16 patients with indeterminate WBS, negative SPECT-CT ruled out suspicion of disease in nine of nine patients, and positive SPECT-CT confirmed malignant lesions in four of five patients. Positive SPECT-CT predicted treatment failure better than positive WBS (McNemar's test, P = 0.03). CONCLUSIONS: This study demonstrates the complementary role of neck and thorax SPECT-CT to WBS in postablation (131)I scintigraphy. Because SPECT-CT allows one to confirm or to rule out residual disease in most cases where WBS remains indeterminate, we recommend its use when available.
PubMed-ID: 19276233
http://dx.doi.org/10.1210/jc.2008-2313
Sentinel Lymph Node Biopsy in Papillary Thyroid Cancer: Comparison Study of Blue Dye Method and Combined Radioisotope and Blue Dye Method in Papillary Thyroid Cancer.
Eur J Surg Oncol, 35(9):974-9.
Lee SK, Choi JH, Lim HI, Kim WW, Kim SM, Choe JH, Lee JE, Shin JH, Choi JY, Kim JH, Kim JS, Nam SJ, Yang JH. 2009.
AIM: Occult lymph node metastasis is common in differentiated thyroid cancer (DTC). However, the role of lymph node dissection in the treatment of DTC remains controversial. The authors investigated the usefulness of methylene blue dye only method and combined radioisotope and methylene blue dye method for detecting SLN and compared the values of these two methods in patients with DTC. METHODS: From February to May 2008, 97 patients with DTC underwent sentinel lymph node biopsy (SLNB). The methylene blue dye method (dye only method) was used in 54 of the 97 patients, and radioisotope and methylene blue dye method (combined method) in 43 patients. RESULTS: The SLNs were identified in 89 patients, and the sensitivity and specificity of SLNB in the 97 patients were 85% and 100% respectively. For the dye only method, sensitivity, specificity, and the false negative rate (FNR) were 79%, 100%, and 21%; and for the combined method (43 patients) the corresponding figures were, 91%, 100%, and 9%, respectively. Six patients with SLN metastasis in the lateral neck underwent additional modified radical neck dissection (MRND). CONCLUSIONS: SLNB was found to be feasible, repeatable, and accurate in evaluating the lymph node status in patient with DTC. The present study indicates that the combined method could reduce false negative rate and increase detection rates of sentinel lymph node metastases, especially in lateral neck, compared to the dye only method.
PubMed-ID: 19285827
http://dx.doi.org/10.1016/j.ejso.2009.02.008
Inhibition of Src With AZD0530 Reveals the Src-Focal Adhesion Kinase Complex As a Novel Therapeutic Target in Papillary and Anaplastic Thyroid Cancer.
J Clin Endocrinol Metab, 94(6):2199-203.
Schweppe RE, Kerege AA, French JD, Sharma V, Grzywa RL, Haugen BR. 2009.
CONTEXT: Focal adhesion kinase (FAK) and Src are overexpressed and activated in many cancers and have been associated with tumor progression. The role of the Src-FAK complex has not been characterized in papillary and anaplastic thyroid cancer (PTC and ATC). OBJECTIVE: The goal of this study was to determine the role of Src and FAK in the growth and invasion of PTC and ATC. DESIGN: PTC and ATC cells were treated with the oral Src inhibitor, AZD0530, to determine the consequences of Src inhibition using growth and invasion assays. FAK and phospho-FAK levels were analyzed in cell lines as well as in PTC tumor samples. RESULTS: AZD0530 treatment inhibited the growth and invasion in four of five thyroid cancer cell lines, and inhibition did not correlate with basal levels of phospho-Src. Instead, we show for the first time that FAK, a critical substrate and effector of Src, is phosphorylated at tyrosine residue 861 (pY861) in PTC and ATC cells, and high levels of phospho-FAK correlate with AZD0530 sensitivity. We further showed that pY861-FAK phosphorylation is Src-dependent. Sensitivity to AZD0530 was confirmed using a preclinical three-dimensional culture model. Phospho-ERK1/2 was not affected by AZD0530, indicating that Src signaling does not require MAPK. Finally, FAK and pY861-FAK were expressed in 10 of 10 and five of 10 PTC tumors, respectively. CONCLUSIONS: Inhibition of the Src-FAK complex represents a promising therapeutic strategy for patients with advanced thyroid cancer, and phospho-FAK represents a potential biomarker for response.
PubMed-ID: 19293266
http://dx.doi.org/10.1210/jc.2008-2511
Molecular Testing for Mutations in Improving the Fine-Needle Aspiration Diagnosis of Thyroid Nodules.
J Clin Endocrinol Metab, 94(6):2092-8.
Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, Fagin JA, Falciglia M, Weber K, Nikiforova MN. 2009.
CONTEXT: Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diagnosis in thyroid nodules. However, 10-40% of nodules are diagnosed as indeterminate by cytology, making it difficult to optimally manage these patients. OBJECTIVE: The aim of this study was to establish the feasibility and role of testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules. DESIGN: The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPARgamma mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months). RESULTS: A sufficient amount of nucleic acids were isolated in 98% of samples. Thirty-two mutations were found, including 18 BRAF, eight RAS, five RET/PTC, and one PAX8/PPARgamma. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed significant improvement in the diagnostic accuracy and allowed better prediction of malignancy in the nodules with indeterminate cytology. CONCLUSIONS: These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology.
PubMed-ID: 19318445
http://dx.doi.org/10.1210/jc.2009-0247
Endoscopic Thyroidectomy in China.
Surg Endosc, 23(7):1675-7.
Ng WT. 2009.
PubMed-ID: 19343423
http://dx.doi.org/10.1007/s00464-009-0455-x
Glutathione Peroxidase 3 Gene Polymorphisms and Risk of Differentiated Thyroid Cancer.
Surgery, 145(5):508-13.
Lin JC, Kuo WR, Chiang FY, Hsiao PJ, Lee KW, Wu CW, Juo SH. 2009.
BACKGROUND: The antioxidant enzyme glutathione peroxidase 3 (GPX3) can lessen the oxidative stress in the thyroid gland. We tested for the association between tagging single nucleotide polymorphisms (tSNPs) of the GPX3 gene and the risk of differentiated thyroid cancer (DTC). METHODS: A total of 6 tSNPs (rs3763013, rs8177412, rs3805435, rs3828599, rs3792796, and rs2070593) of GPX3 were genotyped in Chinese DTC cases (n = 268) and controls (n = 378). Multivariate logistic regression was performed to estimate the genetic effect with adjustment for age and sex. RESULTS: There was no significant finding of genotype analysis in each tSNP associated with DTC, papillary thyroid carcinoma, or patients with regional lymph node metastasis. In the older group (age > or =45 years), subjects who carried at least 1 G allele of rs3805435 had a decreased risk of DTC compared with patients of AA homozygote (sex- and age-adjusted odds ratio [OR] = 0.50, P = .009). An individual with at least 1 T allele of rs3828599 had a decreased risk of DTC compared with an individual of the CC homozygote (sex- and age-adjusted OR = 0.53, P = .018). An individual carrying the TC genotype of rs8177412 in the older group had an increased risk of DTC than controls (sex- and age-adjusted OR = 1.73, P = .037). CONCLUSION: We found that the G allele of rs3805435 or the T allele of rs3828599 may exert a protective effect for DTC in the older population, whereas the C allele of rs8177412 confers an increased risk effect for DTC.
PubMed-ID: 19375609
http://dx.doi.org/10.1016/j.surg.2008.12.008
Central Lymph Node Dissection As a Secondary Procedure for Papillary Thyroid Cancer: Is There Added Morbidity?
Surgery, 145(5):514-8.
Alvarado R, Sywak MS, Delbridge L, Sidhu SB. 2009.
BACKGROUND: Routine central lymph node dissection (CLND) for papillary thyroid cancer (PTC) at the time of initial thyroidectomy has been advocated with a demonstrated decrease in post-ablation serum thyroglobulin compared to total thyroidectomy alone. Patients now present with central compartment metastatic disease after initial thyroid cancer surgery, or with a diagnosis of PTC after diagnostic lobectomy requiring completion thyroidectomy, and an undissected central compartment. Our aim was to compare the clinical outcomes in patients with PTC who underwent CLND as a secondary event with those having initial CLND. METHODS: A retrospective cohort study of 193 patients who underwent CLND for PTC between June 2002 and November 2007 was undertaken. Data gathered included patient demographics, number of lymph nodes excised, lymph node involvement, and incidence of postoperative complications. RESULTS: One-hundred and seventy (M/F: 28/142) patients (Grp A) had a CLND as part of their primary surgical procedure while 23 (M/F: 10/13) patients (Grp B) underwent CLND as a secondary procedure (12 therapeutic/11 prophylactic procedures). The mean number of lymph nodes sampled and the % involved in the 2 groups A and B were 9.2 vs 10.2 and 64% vs 61%, respectively. Similarly, the incidence of temporary hypocalcemia (12% vs 9%), permanent hypoparathyroidism (1.8% vs 0%), temporary recurrent laryngeal nerve (RLN) paresis (3% vs 4%), permanent RLN paresis (0.6% vs 0%), and wound infection (0.6% vs 4.3%) was comparable in groups A and B. CONCLUSION: This study demonstrates that there is no additional morbidity when CLND is performed as a secondary procedure for patients with PTC. Secondary CLND should be performed in patients with proven central compartment metastatic disease after previous thyroidectomy and can be offered safely as a prophylactic procedure to patients at high risk for central lymph node metastasis when CLND has not been performed at initial primary operation for PTC.
PubMed-ID: 19375610
http://dx.doi.org/10.1016/j.surg.2009.01.013
The Usefulness of Sonographic Features in Selection of Thyroid Nodules for Biopsy in Relation to the Nodule's Size.
Eur J Endocrinol, 161(1):103-11.
Popowicz B, Klencki M, Lewinski A, Slowinska-Klencka D. 2009.
OBJECTIVE: To evaluate the efficacy of selected ultrasound (US) features of thyroid focal lesions useful for establishing indications for fine-needle aspiration biopsy (FNAB) with regard to the lesion's size. METHODS: US imaging features of 1141 thyroid nodules (shape, echogenicity, pattern of blood flow, presence of microcalcifications and the presence of other nodules in the thyroid) and their palpability were compared with the post-operative histopathological outcomes. The efficacy of the selected sets of the features was assessed for small nodules (SN)< or =15 mm and large nodules (LN)>15 mm, as well as separately for nodules< or =10 mm. RESULTS: Logistic regression analysis showed that in SN hypoechogenicity (odds ratios, OR: 3.18), microcalcifications (OR: 19.12), solitary occurrence (OR: 3.29) and height-to-width ratio> or =1 (OR: 8.57) were independent risk factors for malignancy. The optimal set of small lesions that should be biopsied includes all lesions presenting at least one of the above-mentioned features (sensitivity 98%, specificity 44%). In the LN group, the selection criteria based on the shape of lesions and hypoechogenicity were less sensitive than in the SN group, but they allowed further reduction in the number of performed FNABs. Large nodules primarily selected for FNAB should be hypoechoic, more tall then wide or contain microcalcifications (sensitivity 84%, specificity 72%). CONCLUSIONS: The obtained results provide rationale for using features from the US examination in selecting both small and large nodules for FNAB. In the case of LN, the usefulness of sonographic features is less sensitive, but more specific than in the case of SN.
PubMed-ID: 19376834
http://dx.doi.org/10.1530/EJE-09-0022
Predictive Factors for Ipsilateral or Contralateral Central Lymph Node Metastasis in Unilateral Papillary Thyroid Carcinoma.
Ann Surg, 249(5):840-4.
Koo BS, Choi EC, Yoon YH, Kim DH, Kim EH, Lim YC. 2009.
OBJECTIVES: To investigate the incidence and the risk factors for occult ipsilateral or contralateral central neck lymph node (LN)metastasis in patients with unilateral papillary thyroid carcinoma (PTC) and a clinically negative neck. SUMMARY BACKGROUND DATA: Elective central lymph node dissection (CLND) in patients with PTC remains controversial. There have been few prospective studies assessing accurate histopathologic information and predictive factors for the presence of metastasis to the ipsilateral or contralateral central compartment of the neck in patients with PTC and clinically negative neck nodes. METHODS: We reviewed a prospective protocol of 111 unilateral PTC patients with clinically node-negative necks who have received total thyroidectomy and elective bilateral CLND from 2005 to 2007. The relationships between LN metastasis to the ipsilateral or contralateral central neck compartment and clinico-pathologic factors such as age, sex, size of primary tumor, perithyroidal invasion, lymphovascular invasion, and capsular invasion were analyzed. RESULTS: Occult central neck LN metastasis was present in 54.1% (60/111). Of these patients, bilateral central LN metastases were present in 50% (30/60), unilateral ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of ipsilateral central LN metastasis was significantly higher in male patients, high risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and carcinoma with lymphovascular invasion (P < 0.05). The rate of contralateral central LN metastasis was significantly higher in cases of carcinoma with a maximal diameter of greater than 1 cm, lymphovascular invasion or histologically proven metastasis to the ipsilateral central LN (P < 0.05). Multivariate analysis showed that the tumor size was an independent risk factor for the presence of ipsilateral central LN metastasis, and the presence of ipsilateral central LN metastasis was the only independent predictor for the presence of contralateral central LN metastasis. CONCLUSIONS: Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.
PubMed-ID: 19387316
http://dx.doi.org/10.1097/SLA.0b013e3181a40919
Intact Parathyroid Hormone Measurement 1 Hour After Thyroid Surgery Identifies Individuals at High Risk for the Development of Symptomatic Hypocalcemia.
Am J Surg, 197(5):648-53.
Lim JP, Irvine R, Bugis S, Holmes D, Wiseman SM. 2009.
BACKGROUND: There is currently no consensus regarding the utilization of intact parathyroid hormone (iPTH) for predicting postthyroid surgery hypocalcemia. The objective of this study was to determine a threshold value for the 1-hour postoperative iPTH level that can identify those patients at significantly increased risk for the development of symptomatic hypocalcemia. METHODS: A prospective study of 21 individuals undergoing either total or completion thyroid operations was performed. One-hour postoperative iPTH levels were drawn along with ionized calcium at 6 hours postoperatively and at 7 am the following morning. Symptoms of hypocalcemia were recorded. RESULTS: Of the 21 patients recruited into the study cohort, there were 18 individuals that developed hypocalcemia (4 symptomatic and 14 asymptomatic) and 3 that remained normocalcemic. The mean iPTH level 1 hour postoperatively was significantly different when comparing the normocalcemic, asymptomatic hypocalcemic, and symptomatic hypocalcemic patient groups (6.50 pmol/L versus 3.76 pmol/L versus 0.7 pmol/L, respectively; P = .007). An iPTH level <or=2.5 pmol/L was 100% sensitive for predicting which individuals would go on to develop symptomatic hypocalcemia. CONCLUSIONS: This study suggests that a 1-hour postoperative iPTH level <or=2.5 pmol/L can identify those individuals at risk for developing symptomatic hypocalcemia. Therefore, we recommend early calcium supplementation for these patients to decrease their postoperative morbidity from symptomatic hypocalcemia.
PubMed-ID: 19393358
http://dx.doi.org/10.1016/j.amjsurg.2008.12.012
A New Anchor Electrode Design for Continuous Neuromonitoring of the Recurrent Laryngeal Nerve by Vagal Nerve Stimulations.
Langenbecks Arch Surg, 394(5):903-10.
Schneider R, Przybyl J, Hermann M, Hauss J, Jonas S, Leinung S. 2009.
PURPOSE: Intraoperative neuromonitoring has the limitation that the recurrent laryngeal nerve (RLN) is still at risk for damage between two stimulations with a handheld bipolar stimulation electrode. The purpose of this study was to establish the vagal anchor electrode for real-time monitoring of the RLN in surgical routine and to be alerted to imminent nerve failure by electromyography (EMG) signal analysis whereby the nerve damage becomes reversible. PATIENTS AND METHODS: This fully implantable electrode has been used in addition to a conventional handheld bipolar stimulation electrode during thyroid surgery on 45 consecutive patients (78 nerves at risk) stratified to low- and high-risk groups. The signal analysis was performed as real-time audio/video feedback by the use of a new multichannel EMG system. RESULTS: No complications were attributable to the use of the anchor electrode. The mean delay to place the anchor electrode was 1.45 min, whereas the mean stimulation time of the vagus nerve was 38 min. Stable and repeatable signals were evocable in all cases with one exception. No permanent RLN paralyses occurred in this study. CONCLUSIONS: The vagal anchor electrode is safe and easy to use. It allows continuous neuromonitoring without any threats. The new technique will provide more security, especially during preparation steps on the RLN that are difficult for the surgeon.
PubMed-ID: 19430809
http://dx.doi.org/10.1007/s00423-009-0503-y
Feasibility of Intraoperative Neuromonitoring During Thyroid Surgery After Administration of Nondepolarizing Neuromuscular Blocking Agents.
World J Surg, 33(7):1408-13.
Chu KS, Wu SH, Lu IC, Tsai CJ, Wu CW, Kuo WR, Lee KW, Chiang FY. 2009.
BACKGROUND: A short-acting depolarizing neuromuscular blocking agent (NMBA), succinylcholine, has been utilized for thyroid operations with intraoperative neuromonitoring (IONM). Because of its potential to cause serious side effects, this prospective study tried to determine the feasibility of IONM after administration of a nondepolarizing NMBA during thyroid operations. METHODS: Complete IONM data for 179 patients who had normal cord mobility were investigated: 90 patients received an induction dose of rocuronium (group R) and 89 received atracurium (group A). Electromyography signals were obtained from the vagus nerve before and after resection of the thyroid lobe and were defined as V(1) and V(2) signals, respectively. Accelerometry (percent twitch) was used to monitor the quantitative degree of neuromuscular blockade. RESULTS: V(1) and V(2) signals were obtained successfully in all patients. The percent twitch at the V(1) signal was significantly lower than that at the V(2) signal in both groups (39% +/- 20% vs. 69% +/- 26% in group R; 35% +/- 28% vs. 56% +/- 35 % in group A; both p < 0.01). However, the magnitude of the V(1) and V(2) signals did not differ significantly in either in group (473.8 +/- 290.8 microV vs. 528 +/- 316.2 microV in group R; 584.8 +/- 394.3 microV vs. 637.8 +/- 458.2 microV in group A; both p > 0.05). CONCLUSIONS: A single dose of either rocuronium or atracurium was feasible for IONM during thyroid surgery and provided adequate muscle relaxation for tracheal intubation.
PubMed-ID: 19430831
http://dx.doi.org/10.1007/s00268-009-0049-8
Differentiated Thyroid Cancer: ESMO Clinical Recommendations for Diagnosis, Treatment and Follow-Up.
Ann Oncol, 20 Suppl 4:143-6.
Pacini F, Castagna MG, Brilli L, Pentheroudakis G. 2009.
PubMed-ID: 19454437
http://dx.doi.org/10.1093/annonc/mdp156
Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association.
Thyroid, 19(6):565-612.
Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA, Jr. 2009.
BACKGROUND: Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and challenging malignancy. The American Thyroid association (ATA) chose to create specific MTC Clinical Guidelines that would bring together and update the diverse MTC literature and combine it with evidence-based medicine and the knowledge and experience of a panel of expert clinicians. METHODS: Relevant articles were identified using a systematic PubMed search and supplemented with additional published materials. Evidence-based recommendations were created and then categorized using criteria adapted from the United States Preventive Services Task Force, Agency for Healthcare Research and Quality. RESULTS: Clinical topics addressed in this scholarly dialog included: initial diagnosis and therapy of preclinical disease (including RET oncogene testing and the timing of prophylactic thyroidectomy), initial diagnosis and therapy of clinically apparent disease (including preoperative testing and imaging, extent of surgery, and handling of devascularized parathyroid glands), initial evaluation and treatment of postoperative patients (including the role of completion thyroidectomy), management of persistent or recurrent MTC (including the role of tumor marker doubling times, and treatment of patients with distant metastases and hormonally active metastases), long-term follow-up and management (including the frequency of follow-up and imaging), and directions for future research. CONCLUSIONS: One hundred twenty-two evidence-based recommendations were created to assist in the clinical care of MTC patients and to share what we believe is current, rational, and optimal medical practice.
PubMed-ID: 19469690
http://dx.doi.org/10.1089/thy.2008.0403
Follicular Thyroid Carcinoma in an Iodine-Replete Endemic Goiter Region: a Prospectively Collected, Retrospectively Analyzed Clinical Trial.
Ann Surg, 249(6):1023-31.
Asari R, Koperek O, Scheuba C, Riss P, Kaserer K, Hoffmann M, Niederle B. 2009.
OBJECTIVE: To determine risk factors for presence of lymph node or distant metastases in patients with follicular thyroid cancer (FTC) at the time of diagnosis and whether there is a relationship between the type of tumor invasion and metastases. SUMMARY BACKGROUND DATA: FTC often presents distant metastases at the initial diagnosis. As distant metastases are independent prognostic factors in a patient's survival, determination of clinicopathologic characteristics for patients who are at higher risk for developing metastases is of greater clinical importance. METHODS: The prognostic significance of gender (male vs. female), age (<or=40 years vs. <40 years), tumor size (<or=40 mm vs. >40 mm), number of lesions (uni- vs. multifocality), type of invasion (minimally invasive vs. widely invasive), and oncocytic changes (with vs. without) were analyzed in 207 patients, according to presence of lymph node and distant metastases at the time of initial surgery. According to the type of invasion, the carcinoma-specific survival and the disease-free survival of minimally invasive (MI) and widely invasive (WI) FTC were estimated and compared. RESULTS: None of the 127 patients with MI growth presented with lymph node metastases but 9.4% distant metastases. Overall risk factors for the presence of lymph node metastases at the initial diagnosis were multifocality (P = 0.02) and widely invasion (P = 0.0001) and for distant metastases age >45 years (P = 0.007), tumor size larger than 40 mm (P = 0.03) and widely invasion (P = 0.0001).WI-FTC patients show larger tumors (P = 0.0001), older age (P = 0.0001), and are presented more frequently in recurrent goiter disease (P = 0.0001). The estimated 10 years carcinoma-specific survival and disease-free survival for MI-tumors were significantly better than for WI-tumors (P = 0.0001). CONCLUSIONS: Total thyroidectomy is recommended in all patients with FTC because of early distant metastases. Patients with WI-FTC need a more aggressive surgical treatment because of higher tendency for lymph node metastases. MI-FTC has an excellent prognosis with no sign of lymph node metastases, which emphasizes a limited need for nodal surgery.
PubMed-ID: 19474675
http://dx.doi.org/10.1097/SLA.0b013e3181a77b7b
Thyroid Fine-Needle Aspiration Biopsy: Variability in Reporting.
Thyroid, 19(7):717-23.
Lewis CM, Chang KP, Pitman M, Faquin WC, Randolph GW. 2009.
BACKGROUND: The low incidence of thyroid cancer despite the high prevalence of thyroid nodules necessitates a screening tool to determine which patients require surgical management. The utility of fine-needle aspiration biopsy (FNAB) for this purpose requires a low false-negative (FN) rate and an acceptable sensitivity and specificity for the detection of malignancy. While reviewing our institution's experience with thyroid FNAB, we found significant discrepancies in how statistics of thyroid FNAB were tabulated and reported in the literature. Here we examine the sources of these discrepancies by evaluating large series of thyroid FNAB with regard to cytopathologic reporting and statistical calculation. METHODS: Published series of thyroid FNAB with >200 FNAB and available histological data with sufficient raw data to recalculate statistics were analyzed. Considering indeterminate and malignant results to be positive FNAB results, since, in a four-tier system, both lead to surgical management, specificity, sensitivity, accuracy, positive predictive value, negative predictive value, FN, and false-positive (FP) rates were recalculated. Differences between reported and recalculated statistics were then evaluated for significance. RESULTS: Nineteen studies and 20 series were identified. The following are reported and recalculated means, respectively: for sensitivity, 81% and 86%; for specificity, 81% and 62%; for accuracy, 77% and 71%; for positive predictive value, 65% and 50%; for negative predictive value, 84% and 93%; for FN rates, 13% and 14%; for FP rates, 10% and 38%. FP rates had a mean of 1.4% when recalculated considering only malignant FNAB as positive tests. Specificity and FP rates had statistically significant differences between the means of reported and recalculated values. CONCLUSIONS: Thyroid FNAB remains the screening tool of choice in the evaluation of thyroid nodules. However, the variability in the calculation of reported thyroid FNAB statistics highlights the need for uniformity in statistical reporting for accurate understanding of thyroid FNAB's clinical utility.
PubMed-ID: 19485775
http://dx.doi.org/10.1089/thy.2008.0425
Vocal Fold Palsy After Surgery in Elderly Thyroid Cancer Patients With Versus Without Comorbid Diabetes.
Surgery, 145(6):685-6.
Polednak AP. 2009.
PubMed-ID: 19486774
http://dx.doi.org/10.1016/j.surg.2009.01.009
A Pathologic Re-Review of Follicular Thyroid Neoplasms: the Impact of Changing the Threshold for the Diagnosis of the Follicular Variant of Papillary Thyroid Carcinoma.
Surgery, 145(6):687-8.
Duggan MA, Di FL, Alakija P, Falk V. 2009.
PubMed-ID: 19486776
http://dx.doi.org/10.1016/j.surg.2009.03.011
Potency and Tolerance of Calcitonin Stimulation With High-Dose Calcium Versus Pentagastrin in Normal Adults.
J Clin Endocrinol Metab, 94(8):2970-4.
Doyle P, Duren C, Nerlich K, Verburg FA, Grelle I, Jahn H, Fassnacht M, Mader U, Reiners C, Luster M. 2009.
OBJECTIVE: The objectives of the study was to compare pentagastrin- and calcium-stimulated serum human calcitonin (hCT) levels for nonsmoking healthy adults without evidence of thyroid disorders and determine reference ranges of basal and pentagastrin- and calcium-stimulated serum hCT levels. DESIGN: This was a healthy volunteer study including within-group and intergroup comparisons. SETTING: The study was conducted at a tertiary referral center. SUBJECTS: Subjects included 50 healthy, nonsmoking volunteers (25 female; aged 22-57 yr) without evidence of thyroid abnormality. Interventions: hCT was measured using a calcitonin two-site automated chemiluminescent immunometric assay (the most common hCT assay in clinical practice) in serum samples obtained before and 2, 5, and 15 min after iv stimulation using pentagastrin, 0.5 microg/kg body weight, or calcium gluconate, 2.5 mg/kg. MAIN OUTCOME MEASURES: Reference ranges for basal, unstimulated, and pentagastrin- or calcium-stimulated hCT and pentagastrin and calcium tolerability in healthy adults were measured. RESULTS: The 95th percentile basal hCT values did not differ between males and females (5.0 vs. 5.7 pg/ml). The 95th percentile maximal stimulated hCT values rose distinctly after pentagastrin (peak men, 37.8 pg/ml; women, 26.2 pg/ml) and even more so after calcium (peak men, 131.1 pg/ml, women, 90.2 pg/ml). No hCT increase was detected in four of 25 men and 12 of 25 women after pentagastrin vs. none of 24 men and two of 18 women after calcium. Calcium was associated with fewer and less intense adverse effects than was pentagastrin. CONCLUSION: High-dose calcium is a more potent and better-tolerated hCT stimulator than is pentagastrin. The reference ranges for basal and stimulated hCT established via automated chemiluminescent assay were lower than those reported for other assays.
PubMed-ID: 19491231
http://dx.doi.org/10.1210/jc.2008-2403
Prophylactic Thyroidectomy in RET Carriers at Risk for Hereditary Medullary Thyroid Cancer.
Thyroid, 19(6):551-4.
Machens A, Dralle H. 2009.
PubMed-ID: 19499987
http://dx.doi.org/10.1089/thy.2009.0144
Is Routine Dissection of Level II-B and V-A Necessary in Patients With Papillary Thyroid Cancer Undergoing Lateral Neck Dissection for FNA-Confirmed Metastases in Other Levels.
World J Surg , 33(8):1680-3.
Farrag T, Lin F, Brownlee N, Kim M, Sheth S, Tufano RP. 2009.
BACKGROUND: The purpose of the present study was to determine the utility of routine dissection of level II-B and level V-A in patients with papillary thyroid cancer (PTC) undergoing lateral neck dissection for ultrasound-guided fine-needle aspiration (FNA)-confirmed lateral nodal metastasis in at least one neck nodal level. METHODS: In a retrospective review, we studied the charts of 53 consecutive patients (February 2002-December 2007) with PTC who had undergone therapeutic lateral neck dissection that included at least level II-(A and B) and/or level V-(A and B). The levels were designated as such in situ prior to surgical pathology specimen processing. Reports of the preoperative FNA cytopathologic findings, the extent of lateral neck dissection by levels, and the postoperative final histopathologic examination were reviewed. RESULTS: A total of 53 patients underwent therapeutic lateral neck dissection for FNA-confirmed nodal metastasis of PTC at a minimum of one lateral neck level. All 53 patients had preoperative ultrasonography and FNA confirmation of lateral neck disease: 46 patients had PTC, 5 had the tall cell variant of PTC, and 2 had the follicular variant of PTC on final surgical pathology. Ten patients underwent neck dissection at the time of thyroidectomy, and 43 patients underwent neck dissection for lateral neck recurrence/persistence of PTC following a previous thyroidectomy and radioactive iodine +/- previous neck dissection. A total of 46 patients underwent unilateral neck dissection and 7 patients underwent bilateral neck dissection; thus 60 neck dissection specimens were evaluated. Level II (A and B) was excised in 59/60 neck dissections, with 33 of 59 specimens (33/59 = 60%) positive for metastasis. Level II-B was positive 5 times (5/59; 8.5-95% CI: 2.4, 20.4), and each time level II-B was positive, level II-A was also grossly (and histopathologically--seen at the time of surgery) positive for metastasis. Level III was excised 58 times and was positive in 38 specimens (38/58 = 66%). Level IV was excised 58 times and was positive in 29 specimens (29/58 = 50%). Level V (A and B) was excised 40 times and was positive in 16 specimens (16-40 = 40%). Level V-A did not account for any of the positive level V results (0%). CONCLUSIONS: Cervical lateral neck metastases in PTC occur in a predictable pattern, with levels III, II-A, and IV most commonly involved. Patients with PTC who undergo lateral neck dissection for FNA-confirmed nodal metastases might harbor disease in level II-B, especially if level II-A is involved. We recommend elective dissection of level II-B only when level II-A is involved, based on FNA confirmation, or when it is grossly involved on intraoperative evaluation. Routine dissection of level V-B is recommended in this patient population, while elective dissection of level V-A is not necessary.
PubMed-ID: 19506945
http://dx.doi.org/10.1007/s00268-009-0071-x
Images in Clinical Medicine. Graves' Hyperthyroidism.
N Engl J Med, 360(24):e31.
Iraci GS, Fux-Otta C. 2009.
PubMed-ID: 19516029
http://dx.doi.org/10.1056/NEJMicm0707562
Unexpected Effect of Furosemide on Radioiodine Urinary Excretion in Patients With Differentiated Thyroid Carcinomas Treated With Iodine 131.
Thyroid, 19(8):843-8.
Matovic MD, Jankovic SM, Jeremic M, Tasic Z, Vlajkovic M. 2009.
BACKGROUND: In patients receiving (131)I for therapeutic purposes, diuretics are frequently used in an attempt to accelerate elimination of unbound radioiodine, reduce its adverse effects, and shorten the hospital stay. The aims of our study were to investigate the influence of furosemide therapy on urinary excretion of (131)I in patients with differentiated thyroid cancer (DTC), referred to radioiodine ablation after thyroidectomy, and to investigate whether diuretics are useful in daily practice in patients with DTC. METHODS: Forty-three patients with DTC who had normal renal function and low (131)I uptake in cervical region (3.55 +/- 3.45%) were included in this study. The furosemide (20 mg) and potassium chloride (250 mg) were given orally to 23 patients 3 hours after the (131)I administration, and then q8h for 3 days. Twenty patients did not receive either furosemide or potassium chloride. After (131)I administration, the patients collected their urine for 3 days, and radioactivity of urine sample from each micturition was expressed as percentage of the administered dose. Radioactivity of blood samples was measured after 72 hours, and the values were corrected for decay of (131)I and expressed in relation to the administered dose. Initial whole-body measurement (immediately after (131)I administration) and the whole-body measurement after 72 hours were recorded for all patients. The 72-hour whole-body measurement was corrected for decay of (131)I, and expressed as a percentage of the initial whole-body measurement. RESULTS: Urinary excretion of (131)I was significantly lower in the patients who were taking furosemide and potassium chloride compared with the control group. The whole-body measurements after 72 hours (13.22 +/- 6.55% vs. 8.24 +/- 3.39% of the initial; p < 0.01, respectively) and the blood radioactivity (34.66 +/- 24.84 vs. 11.64 +/- 8.32 cpm/mL per 1 MBq of administered (131)I, p < 0.01) were found to be unexpectedly higher in the patients who were taking furosemide and potassium chloride compared with the control group. CONCLUSION: Our results demonstrated that furosemide given as an adjuvant medication in patients with DTC causes a significant decrease in urinary excretion of radioiodine and its higher blood concentration. Therefore, furosemide should not be recommended as an adjuvant therapy to radioiodine ablation in patients with DTC previously iodine depleted by low-iodine diet.
PubMed-ID: 19519221
http://dx.doi.org/10.1089/thy.2008.0400
BRAF V600E Mutation Analysis Increases Diagnostic Accuracy for Papillary Thyroid Carcinoma in Fine-Needle Aspiration Biopsies.
Eur J Endocrinol, 161(3):467-73.
Zatelli MC, Trasforini G, Leoni S, Frigato G, Buratto M, Tagliati F, Rossi R, Cavazzini L, Roti E, gli Uberti EC. 2009.
OBJECTIVE: Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid cancers, presenting the V600E activating BRAF mutation in 29-83% of cases. The aim of our study is to analyze the influence of BRAF mutation analysis on the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) in patients with suspected PTC. DESIGN AND METHODS: Thyroid cytoaspirates from 469 nodules (size: 1.1+/-0.8 cm) with ultrasonographic features suspicious of malignant lesion, performed in 374 patients, were submitted to cytological evaluation and to biomolecular analysis, carried out after somatic DNA isolation, specific PCR amplification, and subsequent automated direct sequencing. All PCR fragments were also processed by specific enzyme restriction analysis. RESULTS: BRAF V600E mutation was found in 48 samples, 41 of which were also cytologically diagnosed as PTC, with histologic confirmation after thyroidectomy. Total thyroidectomy was perfomed also in seven patients with negative cytology but positive BRAF mutation, with histological confirmation of PTC in all. Among the 429 BRAF-negative samples, 407 had negative cytology for PTC, while 22 were diagnosed as suspected PTC and underwent total thyroidectomy with histological diagnosis of PTC in 17 and benign lesion in five. The prevalence of BRAF V600E mutation among histologically diagnosed PTC patients was 64%. Biomolecular analysis significantly increased cytology sensitivity for PTC from 77.3 to 86.7% (P<0.01). CONCLUSIONS: These data indicate that BRAF V600E mutation analysis can significantly improve FNAB diagnostic accuracy. However, biomolecular analysis is complementary to cytology, which should always be performed.
PubMed-ID: 19574281
http://dx.doi.org/10.1530/EJE-09-0353
How to Perform a Thyroidectomy in an Outpatient Setting.
Langenbecks Arch Surg, 394(5):897-902.
Champault A, Vons C, Zilberman S, Labaille T, Brosseau S, Franco D. 2009.
PURPOSE: In France, the current practice for postoperative care of thyroidectomy is still inpatient care. No series of outpatient thyroidectomy has been reported. The aim of this work was to assess the acceptability, feasibility, and safety of outpatient unilateral thyroid lobectomy in a university hospital. MATERIALS AND METHODS: The procedure was proposed to patients presenting with nodule(s) in one lobe of the thyroid and fulfilling predetermined inclusion criteria. The surgical protocol included no drainage and, progressively, no dressing. Standard anesthetic, analgesic, and antiemetic protocols were used. Unplanned admission, complication, and re-operation rates were evaluated. RESULTS: Among 153 unilateral thyroid lobectomies performed, 95 (62%) were planned for outpatient surgery. The proportion of outpatient unilateral thyroid lobectomies increased during an 8-year period from 36% to 90%. One patient was re-operated because local hemorrhage was diagnosed in the recovery room. He was discharge the next day. Eighteen patients (13.7%) were admitted because of nausea (n = 6), dizziness, and physical discomfort mostly due to anxiety (n = 5). Seventy-seven patients were discharged as planned 6 to 8 h after the operation. No patient was readmitted. CONCLUSIONS: Outpatient unilateral thyroid lobectomy is feasible and safe in the setting of appropriate facilities and management protocol. Strict control of postoperative nausea is essential, and a preoperative education for ambulatory surgery is useful to minimize patient anxiety and increase acceptability.
PubMed-ID: 19575215
http://dx.doi.org/10.1007/s00423-009-0527-3
The Pros and Cons of Prophylactic Central Compartment Lymph Node Dissection for Papillary Thyroid Carcinoma.
Thyroid, 19(7):683-9.
Mazzaferri EL, Doherty GM, Steward DL. 2009.
PubMed-ID: 19583485
http://dx.doi.org/10.1089/thy.2009.1578
Treatment Options for Graves Disease: a Cost-Effectiveness Analysis.
J Am Coll Surg, 209(2):170-9.
In H, Pearce EN, Wong AK, Burgess JF, McAneny DB, Rosen JE. 2009.
BACKGROUND: First-line treatment for Graves disease is frequently 18 months of antithyroid medication (ATM). Controversy exists concerning the next best line of treatment for patients who have failed to achieve euthyroidism; options include lifelong ATM, radioactive iodine (RAI), or total thyroidectomy (TT). We aim to determine the most cost-effective option. STUDY DESIGN: We performed a cost-effectiveness analysis comparing these different strategies. Treatment efficacy and complication data were derived from a literature review. Costs were examined from a health-care system perspective using actual Medicare reimbursement rates to an urban university hospital. Outcomes were measured in quality-adjusted life-years (QALY). Costs and effectiveness were converted to present values; all key variables were subjected to sensitivity analysis. RESULTS: TT was the most cost-effective strategy, resulting in a gain of 1.32 QALYs compared with RAI (at an additional cost of 9,594 US dollars) and an incremental cost-effectiveness ratio of 7,240 US dollars/QALY. RAI was the least costly option at 23,600 US dollars but also provided the least QALY (25.08 QALY). Once the cost of TT exceeds 19,300 US dollars, the incremental cost-effectiveness ratio of lifelong ATM and TT reverse and lifelong ATM becomes the more cost-effective strategy at 15,000US dollars/QALY. CONCLUSIONS: This is the first formal cost-effectiveness study in the US of the optimal treatment for patients with Graves disease who fail to achieve euthyroidism after 18 months of ATM. Our findings demonstrate that TT is more cost effective than RAI or lifelong ATM in these patients; this continues until the cost of TT becomes > 19,300 US dollars.
PubMed-ID: 19632593
http://dx.doi.org/10.1016/j.jamcollsurg.2009.03.025
Levothyroxine Therapy in Preventing Nodular Recurrence After Hemithyroidectomy: a Retrospective Study.
J Endocrinol Invest, 32(4):330-4.
Alba M, Fintini D, Lovicu RM, Paragliola RM, Papi G, Rota CA, Pontecorvi A, Corsello SM. 2009.
AIM: To determine the effect of levothyroxine (L-T4) therapy on the recurrence rate of nodular disease in patients previously treated with lobectomy for benign nodular goiter. METHODS: Two hundred and thirty-tree patients (38 males, 195 females; age 49.9+/-13.1 yr) with no post-surgical evidence of nodular disease in the remnant, were followed- up yearly with serum TSH and ultrasound (US). Nodular recurrence was defined as a lesion of at least 5 mm at US. Patients were divided in 2 groups based on whether or not they had been treated with L-T4 after surgery: Group 1 (45 patients) who did not receive any L-T4, and Group 2 (188 patients) treated with L-T4. Group 2 was further subdivided in Group 2a (123 patients) receiving L-T4 substitutive therapy (TSH>or=0.5 and <or=3 mUI/l) and Group 2b (65 patients) receiving L-T4 at TSH-suppressive dose (TSH<0.5 mUI/l). RESULTS: Mean observation period was 5.8+/-4.7 yr. Overall, 71 out of 233 (30.5%) patients experienced recurrence of thyroid nodular disease: 29 patients (64.4%) in Group 1, 24 (19.5%) patients in Group 2a, and 18 (27.7%) patients in Group 2b. The recurrence rate was significantly lower (p<0.001) in Group 2 compared with Group 1, but no significant difference was observed between Groups 2a and 2b. CONCLUSION: In patients who have undergone hemithyroidectomy for benign monolobar nodular disease, L-T4 therapy may prevent recurrence of nodular disease. TSH suppression may not be required for prevention of recurrence in the remnant thyroid tissue.
PubMed-ID: 19636201 
Mapping the Compound Muscle Action Potentials of Cricothyroid Muscle Using Electromyography in Thyroid Operations: a Novel Method to Clinically Type the External Branch of the Superior Laryngeal Nerve.
Ann Surg, 250(2):293-300.
Selvan B, Babu S, Paul MJ, Abraham D, Samuel P, Nair A. 2009.
OBJECTIVE: Variations of the external branch of the superior laryngeal nerve (EBSLN) are well represented in literature but with conflicting reports about the types and variations. Using EMG, the cricothyroid compound muscle action potential (CMAP) was recorded, to identify the EBSLN and classified them according to clinical variation during routine thyroid operations. SUMMARY BACKGROUND DATA: There is increasing awareness among patients and physicians of the consequences of injury to the external laryngeal nerve in thyroid surgeries. There are at least 4 types, which are described in the literature. The gold standard of nerve identification is EMG, which we used during operations in this study to identify all the EBSLN by demonstrating CMAP and reclassify them. Based on this principle, to avoid injury during thyroidectomy, we propose a new classification. METHODS: This study was a prospective, descriptive study of the EBSLN done during elective thyroidectomy operations. CMAP was demonstrated and EMG was plotted to identify and type them according to clinical variations. The distance between the entry of superior thyroid vessels (STVs) to the lobe and the EBSLN, relationship with the cricothyroid muscle and inferior constrictor muscle were taken into consideration. Based on the possible risk to this during thyroidectomy, we divided them into 4 types. RESULTS:: A total of 70 external laryngeal nerves were dissected and confirmed by the CMAPs in 35 total thyroidectomy patients. Using CMAPs, all the nerves were identified. CONCLUSION: New clinical typing of the EBSLN will give a better understanding of the EBSLN in the intraoperative period. EBSLN need not be identified in routine thyroidectomy operations. Even in large goiters, the incidence of nerve at risk does not increase significantly. Injury to EBSLN can be avoided if the principle of ligating the STVs individually away from the CT muscle and close to the capsule of the gland is followed.
PubMed-ID: 19638904
http://dx.doi.org/10.1097/SLA.0b013e3181b17342
Individualization of Lymph Node Dissection in RET (Rearranged During Transfection) Carriers at Risk for Medullary Thyroid Cancer: Value of Pretherapeutic Calcitonin Levels.
Ann Surg, 250(2):305-10.
Machens A, Lorenz K, Dralle H. 2009.
OBJECTIVE: This study sought to define the need for lymph node dissection in Rearranged during Transfection (RET) carriers at risk for hereditary medullary thyroid cancer. SUMMARY BACKGROUND DATA: Controversy surrounds the need for lymph node dissection to complement thyroidectomy in RET carriers. METHODS: Integration of molecular, biochemical, histopathologic, and clinical information from 308 RET carriers referred for (re-)operation to a specialist surgical center. RESULTS: The carriers differed significantly in age at thyroidectomy when stratified by histopathology (tumor-free thyroid, node-negative, and node-positive medullary thyroid cancer) and mutated codon (611, 618, 620, 634, 768, 790, 804, 891, and 918). The wide overlap among the 3 histopathologic groups compromised individual predictions based on age alone. There was a significant relationship between the presence of lymph node metastases and increased pretherapeutic basal calcitonin levels. All 46 carriers with node-positive medullary thyroid cancer, who harbored 1 to 68 positive nodes, exhibited increased pretherapeutic basal calcitonin levels (91.4 pg/mL or higher). Conversely, 74 (44%) of 168 carriers with normal thyroids, C-cell hyperplasia, or node-negative medullary thyroid cancer displayed normal pretherapeutic basal calcitonin levels (negative predictive value 100%). Prediction of lymph node metastasis was better in carriers of codon 918 mutations (positive predictive value, PPV, 80%-100%) and those older than 20 years of age (PPV, 50%). DISCUSSION: In the absence of clinical evidence to the contrary, RET carriers with normal pretherapeutic basal calcitonin levels may forgo lymph node dissection. The usefulness of calcitonin thresholds to break down the block of carriers with increased calcitonin levels should be explored further.
PubMed-ID: 19638924
http://dx.doi.org/10.1097/SLA.0b013e3181ae333f
Results of Rosiglitazone Therapy in Patients With Thyroglobulin-Positive and Radioiodine-Negative Advanced Differentiated Thyroid Cancer.
Thyroid, 19(9):953-6.
Kebebew E, Lindsay S, Clark OH, Woeber KA, Hawkins R, Greenspan FS. 2009.
BACKGROUND: Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR) gamma agonist that has shown promise as both an antiproliferative and redifferentiating agent for the treatment of thyroid cancer in preclinical studies. We investigated the efficacy and side effects of rosiglitazone therapy in patients with differentiated thyroid cancer of follicular cell origin that fails to take up radioiodine or is unresectable. METHODS: Twenty patients with differentiated thyroid cancer were enrolled in an open-label, phase II trial of oral rosiglitazone treatment (4 mg daily for 1 week, then 8 mg daily for 7 weeks). RESULTS: Five of 20 patients had a positive radioiodine scan after rosiglitazone treatment. Four patients had radioiodine uptake in the neck and one patient had uptake in the pelvis. Unstimulated thyroglobulin levels after rosiglitazone treatment increased in five patients, remained stable in 12 patients, and decreased in three patients. Seven patients had progressive disease on follow-up cross-sectional imaging; six patients in the size and number of lung metastasis and two patients in the size of the neck tumors. Overall, five patients had a partial response (decreased thyroglobulin or positive radioiodine uptake), three patients had stable disease (no change in thyroglobulin and radioiodine uptake status), and 12 patients had disease progression (increased thyroglobulin). By RECIST criteria, no patient had a complete or partial response to rosiglitazone treatment at 3 months follow-up. The mean follow-up time after protocol treatment was 12 months (median 12 months). CONCLUSIONS: Our findings suggest that rosiglitazone therapy may induce radioiodine uptake and reduce serum thyroglobulin levels in some patients with differentiated thyroid cancer but this did not result in clinically significant response on long-term follow-up. Moreover, no patients had response to rosiglitazone therapy by anatomic imaging studies.
PubMed-ID: 19678746
http://dx.doi.org/10.1089/thy.2008.0371

Parathyroid
Meta-Analyses
- None -
Randomized controlled trials
Effect of Surgery on Cardiovascular Risk Factors in Mild Primary Hyperparathyroidism.
J Clin Endocrinol Metab , 94(7):2255-61.
Bollerslev J, Rosen T, Mollerup CL, Nordenstrom J, Baranowski M, Franco C, Pernow Y, Isaksen GA, Godang K, Ueland T, Jansson S. 2009.
CONTEXT: Mild primary hyperparathyroidism (pHPT) seems to have a good prognosis, and indications for active treatment (surgery) are widely discussed. The extraskeletal effects of PTH, such as insulin resistance, arterial hypertension, and cardiovascular (CV) risk, may however be reversible by operation. OBJECTIVE: Our aim was to study biochemical markers of bone turnover, indices of the metabolic syndrome, and various risk markers for CV disease in patients with mild pHPT randomized to observation without surgery or operative treatment and followed for 2 yr. DESIGN/SETTING/PATIENTS: A total of 116 patients (mean age, 63 +/- 8 yr; 19 men and 97 women) who on May 1, 2008, had performed the 2-yr visit in a randomized study on mild pHPT (serum calcium at baseline, 2.69 +/- 0.11 mmol/liter) and where frozen samples were available from baseline and follow-up participated in the study. RESULTS: Calcium and PTH levels were normalized after surgery, and biochemical markers of bone turnover decreased by 35%, followed by a significant increase in BMD in the spine (2.7%; P < 0.01) and femoral neck (1.1%; P < 0.02) compared with the observation group. No significant differences were observed between the groups for blood pressure, markers of insulin resistance, detailed cholesterol metabolism, adipokines, or parameters of inflammation and CV surrogate markers. CONCLUSIONS: We observed expected effects on biochemical markers of bone turnover and bone mass after surgical treatment of mild pHPT, with stable values in the group randomized to observation. For a variety of measures of the metabolic syndrome, adipokines, and CV risk factors, no benefit of operative treatment could be demonstrated. Neither did we observe any deleterious effects of conservative management in the 2-yr perspective.
PubMed-ID: 19351725
http://dx.doi.org/10.1210/jc.2008-2742
Utility of Intraoperative Bilateral Internal Jugular Venous Sampling With Rapid Parathyroid Hormone Testing in Guiding Patients With a Negative Sestamibi Scan for Minimally Invasive Parathyroidectomy--a Randomized Controlled Trial.
Langenbecks Arch Surg, 394(5):827-35.
Barczynski M, Konturek A, Hubalewska-Dydejczyk A, Cichon S, Nowak W. 2009.
BACKGROUND AND AIMS: The purpose of this study was to determine the utility of bilateral internal jugular venous sampling with rapid parathyroid hormone assay (BIJV-IOPTH) in comparison to endocrine surgeon-performed ultrasonography of the neck as an alternative localizing modality in guiding patients with primary hyperparathyroidism (pHPT) and negative sestamibi scans for minimally invasive parathyroidectomy (MIP). PATIENTS AND METHODS: Seventy eight consenting patients with a negative subtraction sestamibi scan planned for parathyroidectomy underwent additional ultrasound parathyroid imaging and were randomized to undergo surgery without vs. with additional BIJV-IOPTH; n = 39 in each group. The patients with a positive alternative imaging test were qualified for video-assisted MIP, whereas the others underwent open neck explorations. The primary outcome measure was the number of patients with true-positive results of alternative imaging tests. RESULTS: Of the 78 patients, 50 (64%) had a single adenoma, eight (10.3%) had double adenomas, and 20 (25.7%) demonstrated four-gland hyperplasia. Ultrasonography alone vs. combined with BIJV-IOPTH was true positive in detecting a solitary parathyroid adenoma in 8/24 (33.3%) vs. 17/26 (65.4%) patients, respectively (p = 0.023). Curative video-assisted MIP was successfully performed in all the patients with true-positive results. The remaining individuals were cured by more extensive open neck explorations (unilateral-4/39 vs. 4/39, respectively; p = 1.0 or bilateral-27/39 vs. 18/39, respectively; p = 0.039). CONCLUSIONS: Most patients with pHPT and a negative subtraction sestamibi scan (64%) have a single adenoma. BIJV-IOPTH as an addition to a surgeon-performed ultrasound of the neck allows for more accurate guiding for MIP in patients with a solitary parathyroid adenoma and negative subtraction sestamibi scans.
PubMed-ID: 19529955
http://dx.doi.org/10.1007/s00423-009-0516-6

Other Articles
Total Parathyroidectomy Without Autotransplantation in Dialysis Patients and Renal Transplant Recipients, Long-Term Follow-Up Evaluation.
Am J Surg, 198(2):178-83.
Drakopoulos S, Koukoulaki M, Apostolou T, Pistolas D, Balaska K, Gavriil S, Hadjiconstantinou V. 2009.
BACKGROUND: Persistent secondary hyperparathyroidism not responding to medication is treated successfully with surgical excision of parathyroid glands (total parathyroidectomy [PTX]). PTX without autotransplantation of parathyroid glands excludes the risk for recurrence of hyperparathyroidism. METHODS: During the years 2002 to 2005, 36 total parathyroidectomies were performed in 33 patients: 21 dialysis patients because of end-stage renal disease and 12 renal transplant recipients. RESULTS: PTX without autotransplantation was performed successfully in 33 patients, whereas 3 patients were reoperated for remaining parathyroid glands. Immediate improvement of clinical symptoms and a decrease of serum calcium and parathormone levels were observed after surgical procedures. Oral replacement treatment with vitamin D (1a-calcidiol) and calcium was commenced and long-term follow-up evaluation (23.5 +/- 7.6 mo) showed that calcium homeostasis was controlled adequately. CONCLUSIONS: PTX without autotransplantation is a safe and effective surgical procedure for the treatment of resistant secondary hyperparathyroidism with immediate response of clinical symptoms. Replacement treatment with vitamin D and calcium provides satisfactory coverage of individual needs.
PubMed-ID: 19217601
http://dx.doi.org/10.1016/j.amjsurg.2008.08.017
Negative Preoperative Localization Leads to Greater Resource Use in the Era of Minimally Invasive Parathyroidectomy.
Am J Surg, 197(6):769-73.
Harari A, Allendorf J, Shifrin A, DiGorgi M, Inabnet WB. 2009.
BACKGROUND: Successful preoperative localization plays an important role in patient selection for focused parathyroidectomy. METHODS: The case records of 499 consecutive patients with presumed hyperparathyroidism who underwent neck exploration were reviewed. Positive imaging patients (n = 373) had a localizing study that clearly showed a single abnormal parathyroid gland whereas negative imaging patients (n = 44) failed to localize or had discordant imaging results. RESULTS: Positive imaging patients were more likely to have a single adenoma (93.0% vs 72.1%; P < .001), and were less likely to require a bilateral exploration (8.1% vs 70.4%; P < .001). Negative imaging patients required more frozen sections (.9 +/- 1.3 vs .2 +/- .7; P < .001), and longer surgical time (77.3 +/- 52.5 min vs 48.4 +/- 34.6 min; P < .001). The cure rate was significantly higher in the positive imaging group (96.0% vs 87.1%; P < .03), with no difference in the incidence of complications (3.2% vs 2.3%; P value was not significant). CONCLUSIONS: Patients with unsuccessful or discordant preoperative localization have a higher incidence of multigland disease, lower cure rate, and consume more institutional resources than patients with successful preoperative localization.
PubMed-ID: 19249736
http://dx.doi.org/10.1016/j.amjsurg.2008.04.023
Do Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism in San Francisco, CA, and Bursa, Turkey, Differ?
Am J Surg, 198(2):188-92.
Kirdak T, Duh QY, Kebebew E, Clark OH. 2009.
BACKGROUND: To compare the preoperative clinical symptoms and associated conditions and findings in operations in age- and sex-matched patients with primary hyperparathyroidism (PHPT) living in the two different regions of the world to determine whether PHPT differs in various countries. METHODS: Fifty-two patients from Bursa, Turkey were matched with 52 age and sex matched patients from San Francisco, USA. Patients' preoperative symptoms, biochemical and radiologic findings and surgical procedures were documented. RESULTS: More patients in the American Group (15%) had preoperatively persistant or recurrent hyperparathyroidism, P = 0.016. Serum parathyroid hormone levels were higher in Turkish group (546 +/- 75.33 pg/mL) than in American group (146 +/- 75.33 pg/mL). More Turkish patients had osteoporosis (P < 0.05). The size of parathyroid adenomas was significantly greater in Turkish patients (25.2 +/- 1.18 mm) than in American patients (17.5 +/- 1.18 mm), P < 0.001. CONCLUSIONS: Patients with PHPT from Bursa, Turkey have higher plasma parathyroid hormone levels, larger parathyroid adenomas and more severe bone disease than in age and sex matched patients with PHPT in San Francisco.
PubMed-ID: 19306981
http://dx.doi.org/10.1016/j.amjsurg.2008.09.031
Acute Pancreatitis in Primary Hyperparathyroidism: a Population-Based Study.
J Clin Endocrinol Metab, 94(6):2115-8.
Khoo TK, Vege SS, bu-Lebdeh HS, Ryu E, Nadeem S, Wermers RA. 2009.
CONTEXT: The association between acute pancreatitis and primary hyperparathyroidism (PHPT) is controversial. OBJECTIVE: The aim of the study was to address the incidence and disease characteristics of acute pancreatitis in PHPT from a large inception cohort of community residents. DESIGN AND SETTING: Patients with acute pancreatitis were identified in an Olmsted County, Minnesota, cohort of PHPT subjects diagnosed from 1965-2001 and compared to matched control subjects. MAIN OUTCOME MEASURES: The estimated rate of developing acute pancreatitis was calculated by person-years method. Cox models assessed the effect of PHPT disease status on the development of acute pancreatitis. RESULTS: Of 684 patients with PHPT, 10 patients (1.5%) developed acute pancreatitis, compared to 32 of 1364 control patients (2.3%). The estimated rate of development of acute pancreatitis in PHPT was 114 per 100,000 person-years, compared to 140 per 100,000 person-years in control subjects (P = 0.56). The estimated hazard ratio of acute pancreatitis for PHPT relative to the control subjects was 0.84 (P = 0.89). The majority of subjects with PHPT and acute pancreatitis were women (n = 7), and the mean age was 70.6 yr at the time of acute pancreatitis. PHPT was present an average of 137 months before the development of acute pancreatitis, and contributing causes for acute pancreatitis were in identified in four patients. Maximal serum calcium levels in PHPT were not significantly associated with the development of acute pancreatitis. CONCLUSIONS: Acute pancreatitis was not increased in community patients with PHPT, and therefore, there does not appear to be a causal relationship between PHPT and acute pancreatitis.
PubMed-ID: 19318456
http://dx.doi.org/10.1210/jc.2008-1965
Neuropsychological Features in Primary Hyperparathyroidism: a Prospective Study.
J Clin Endocrinol Metab, 94(6):1951-8.
Walker MD, McMahon DJ, Inabnet WB, Lazar RM, Brown I, Vardy S, Cosman F, Silverberg SJ. 2009.
CONTEXT: Data regarding the presence, extent, and reversibility of psychological and cognitive features of primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: This study evaluated psychological symptoms and cognitive function in PHPT. DESIGN: This is a case-control study in which symptoms and their improvement 6 months after surgical cure of PHPT were assessed. SETTINGS: The study was conducted in a university hospital metabolic bone disease unit and endocrine surgery practice. PARTICIPANTS: Thirty-nine postmenopausal women with PHPT and 89 postmenopausal controls without PHPT participated in the study. INTERVENTION: Participants with PHPT underwent parathyroidectomy. OUTCOME MEASURES: Measurements used in the study were: Beck Depression Inventory (BDI); State-Trait Anxiety Inventory, Form Y (STAI-Y); North American Adult Reading Test (NAART); Wechsler Memory Scale Logical Memory Test, Russell revision (LM); Buschke Selective Reminding Test (SRT); Rey Visual Design Learning Test (RVDLT); Booklet Category Test, Victoria revision (BCT); Rosen Target Detection Test (RTD); Wechsler Adult Intelligence Scale-Revised Digit Symbol Subtest (DSy); Wechsler Adult Intelligence Scale Digit Span Subtest (DSpan). RESULTS: At baseline, women with PHPT had significantly higher symptom scores for depression and anxiety than controls and worse performance on tests of verbal memory (LM and SRT) and nonverbal abstraction (BCT). Depressive symptoms, nonverbal abstraction, and some aspects of verbal memory (LM) improved after parathyroidectomy to the extent that scores in these domains were no longer different from controls. Baseline differences and postoperative improvement in cognitive measures were independent of anxiety and depressive symptoms and were not linearly associated with serum levels of calcium or PTH. CONCLUSIONS: Mild PHPT is associated with cognitive features affecting verbal memory and nonverbal abstraction that improve after parathyroidectomy.
PubMed-ID: 19336505
http://dx.doi.org/10.1210/jc.2008-2574
Significance of Biochemical Parameters in Differentiating Uniglandular From Multiglandular Disease and Limiting Use of Intraoperative Parathormone Assay.
World J Surg, 33(6):1219-23.
Thakur A, Sebag F, Slotema E, Ippolito G, Taieb D, Henry JF. 2009.
BACKGROUND: We studied whether serum calcium and parathormone (PTH) levels are significantly different for uniglandular disease (UGD) and multiglandular disease (MGD) and whether intraoperative rapid intact parathormone (IOPTH) monitoring can be avoided in some cases of minimally invasive parathyroidectomy (MIP) without affecting cure rates, substantiating various previous published studies. METHOD: This is a single-referral-center retrospective review of prospectively collected data for 281 patients with sporadic primary hyperparathyroidism (sPHPT) from January 1999 to February 2005. The calcium and PTH values were categorized using the following parameters: calcium > or = 3 mmol/l = 1, < 3 mmol/l = 0, PTH > or = 100 pg/ml = 1, PTH < 100 = 1. RESULTS: P values for serum calcium and PTH by ANOVA were 0.0547 and 0.3936, respectively, and by the Mann-Whitney test were 0.1606 and 0.6208, respectively. We had 118 patients with concordant technetium 99 m sestamibi scintigraphy (MIBI) and neck ultrasonography (US) and UGD was confirmed in 118 (100%) cases. CONCLUSIONS: No significant difference between serum calcium and PTH for UGD and MGD was found. IOPTH monitoring could be avoided when there is concordant positive MIBI and neck US for single, unilateral, hyperfunctioning gland without affecting cure rates.
PubMed-ID: 19363691
http://dx.doi.org/10.1007/s00268-009-0029-z
Vitamin D Therapy in Patients With Primary Hyperparathyroidism and Hypovitaminosis D.
Eur J Endocrinol, 161(1):189-93.
Tucci JR. 2009.
OBJECTIVE: To determine whether vitamin D repletion of patients with primary hyperparathyroidism (PHPT) and vitamin D deficiency or insufficiency (hypovitaminosis D) has deleterious clinical and/or biochemical effects. DESIGN: Prospective audit of the effect of vitamin D repletion on biochemical data in 56 patients with PHPT. Patients were treated with 50,000 units of vitamin D2 weekly for 8 weeks with biochemical measurements at 5 and 10 weeks, and subsequently after 12 weeks on 800 units of vitamin D3 daily, and in those with hypovitaminosis D after 12 weeks of up to 100 000 units of vitamin D(2) monthly. METHODS: Serum calcium, albumin, phosphorus, 25-OHD, intact parathyroid hormone (PTH) and urine calcium/creatinine (Ca/Cr) ratios were measured before and during vitamin D therapy. RESULTS: Patients treated with 50,000 units of vitamin D2 weekly for 8 weeks resulted in a significant increase in serum 25-OHD levels from 36.4 to 89.4 nmol/l at 5 weeks (P<0.0001) and 88.6 nmol/l at 10 weeks (P<0.0001). There were no significant changes in serum calcium. At 10 weeks, there was a non-significant decrease in serum PTH and in urine Ca/Cr ratios. None of the patients developed any calcium-related adverse events. Subsequently, patients with subnormal 25-OHD levels on 800 units of vitamin D daily were treated for the next 12 weeks with up to 100,000 units of vitamin D2 monthly with normalization of serum 25-OHD in all but 4 patients. CONCLUSION: These data fail to demonstrate any adverse effects of vitamin D repletion in PHPT.
PubMed-ID: 19383807
http://dx.doi.org/10.1530/EJE-08-0901
PTH Secretion of "Manipulated" Parathyroid Adenomas.
Langenbecks Arch Surg, 394(5):891-5.
Riss P, Asari R, Scheuba C, Bieglmayer C, Niederle B. 2009.
PURPOSE: Increased secretion of parathyroid hormone (PTH) and its fragments intraoperatively may influence PTH monitoring. The purpose of this study was to investigate whether "intended intraoperative manipulation" of parathyroid adenomas through mechanical stimulation (through squeezing or manual rubbing) would lead to increased PTH excretion. The different PTH fragments that result from this kind of manipulation were correlated and analyzed. METHODS: The enlarged glands of six consecutive patients who underwent open minimally invasive parathyroid exploration were "manipulated" for 30 s as soon as they had been identified. Blood samples were drawn before skin incision, at the beginning of the manipulation, 30 s, and at 2-, 5-, 10-, and 15-min intervals. Serum levels of (1-84)PTH were measured and (7-84)PTH was calculated. RESULTS: An increased PTH secretion was documented in four of six "manipulated" single adenomas (mean PTH +/- SD 312 +/- 497 pg/ml). The PTH of one patient rose from 343 to 1,747 pg/ml. The ratio of (1-84)PTH to (7-84)PTH was 1.3 +/- 0.6 (median +/- SD):1 at "baseline" and 1.4 +/- 0.2:1 after manipulation. The coefficient of determination (R(2)) for the "baseline values" and for the values after manipulation is R(2) = 0.9816 and R(2) = 0.9985, respectively. CONCLUSIONS: First, secretion of PTH varies widely after manual manipulation of adenomas. Second, PTH fragments circulate in the same ratio before and after "manipulation.".
PubMed-ID: 19396458
http://dx.doi.org/10.1007/s00423-009-0495-7
Morphometric Vertebral Fractures in Postmenopausal Women With Primary Hyperparathyroidism.
J Clin Endocrinol Metab, 94(7):2306-12.
Vignali E, Viccica G, Diacinti D, Cetani F, Cianferotti L, Ambrogini E, Banti C, Del FR, Bilezikian JP, Pinchera A, Marcocci C. 2009.
CONTEXT: An increased risk of fracture in patients with primary hyperparathyroidism (PHPT) compared to the general population has been reported, but available data are controversial. OBJECTIVE: The aim of the study was to evaluate the rate of vertebral fractures (VFs) by dual-energy x-ray absorptiometry in postmenopausal women with sporadic PHPT and compare the results with a control group. DESIGN AND SETTING: A case-control study was performed at a referral center. PARTICIPANTS: A total of 150 consecutive patients and 300 healthy women matched for age and menopausal age participated in the study. RESULTS: VFs were detected in 37 of 150 (24.6%) patients and 12 of 300 (4.0%) controls (P < 0.0001). The majority of VFs were mild. Stepwise multiple logistic regression analysis showed that in PHPT patients lumbar spine bone mineral density was the only variable independently associated with the prevalence of VFs (P = 0.003). The rate of fracture was higher in symptomatic (34.1%) than asymptomatic (21.1%) patients, but this difference was not statistically significant (P = 0.15). Among asymptomatic patients, fracture rate was significantly higher in those who met the criteria for parathyroidectomy (28.1%) than in those who did not (11.1%) (P = 0.03). Compared to controls, the fracture rate was significantly higher in patients with symptomatic and asymptomatic PHPT who met the criteria for surgery (P < 0.0001), but not in those who did not meet the criteria (P = 0.06). CONCLUSIONS: VF rate is increased in postmenopausal women with PHPT compared to controls, independently of whether they are classified as symptomatic or asymptomatic. The question of whether the finding of mild morphometric VFs in the latter represents an indication for parathyroid surgery remains to be established.
PubMed-ID: 19401378
http://dx.doi.org/10.1210/jc.2008-2006
Dynamics of Parathyroid Hormone Secretion After Total Parathyroidectomy and Autotransplantation.
World J Surg , 33(7):1403-7.
Conti-Freitas LC, Foss-Freitas MC, Lucca LJ, da Costa JA, Mamede RC, Foss MC. 2009.
BACKGROUND: Secondary hyperparathyroidism is a common complication in uremic patients. Total parathyroidectomy combined with partial autotransplantation into brachioradialis muscle has been the preference among the options for surgical treatment. This study was designed to evaluate the reserve and ability of suppression of autotransplanted parathyroid tissue using dynamics tests. METHODS: We studied, prospectively, 12 patients in recent (RP) and late (LP) postoperative of total parathyroidectomy with autotransplantation. For analysis of the secretory reserve capacity, we induced hypocalcemia by ethylenediaminetetraacetic acid (EDTA) infusion. Furthermore, for analysis of the ability for parathyroid hormone (PTH) suppression, the hypercalcemia test was used, by intravenous administration of calcium in LP. RESULTS: In RP, there was a decrease in the average serum levels of PTH, phosphorus, and alkaline phosphatase, which ranged from 13 to 231 (87 +/- 65) pg/ml, 2.3 to 6.2 (3.3 +/- 1.1) mg/dl, and 77 to 504 (250 +/- 135) U/L, respectively, similar to that observed in LP. The analysis of the average curve of variations in PTH during testing of the stimulus with EDTA showed lack of secretion in RP and partial response in LP. Impaired suppression ability of the graft in LP was observed in the test with intravenous calcium. CONCLUSIONS: Total parathyroidectomy followed by partial autotransplantation was effective in reducing PTH serum levels in patients with terminal kidney disease. The elevation of serum calcium during the suppression test was not able to inhibit the autograft gland secretion of PTH. The assessment of parathyroid graft function demonstrated an inability to respond to the stimulus of hypocalcemia induced by EDTA, although there was a partial recovery, in late postoperative period.
PubMed-ID: 19404704
http://dx.doi.org/10.1007/s00268-009-0057-8
Is Minimally Invasive Parathyroidectomy Without QPTH Monitoring Justified?
Langenbecks Arch Surg, 394(5):875-80.
Riss P, Scheuba C, Asari R, Bieglmayer C, Niederle B. 2009.
BACKGROUND: It is matter of discussion if quick parathyroid hormone (QPTH) monitoring is helpful in patients with primary hyperparathyroidism (PHPT) and "localized single-gland disease" (SGD; concordant sestamibi and ultrasound results) to further increase the rate of success (permanent normocalcemia) of performing selective parathyroidectomy by minimally invasive parathyroid exploration (MIP). The aim of this study was to evaluate if a randomized controlled trial was justified in order to clarify this discussion. MATERIALS AND METHODS: The prospective database of patients with sporadic PHPT, SGD, MIP, and QPTH monitoring (1999-2005) was evaluated regarding the "conversion rate" to bilateral exploration and permanent normocalcemia ("QPTH" group). Retrospectively, the patients were analyzed a second time "without" applying QPTH monitoring ("non-QPTH" group). Statistical differences between both groups were calculated (McNemar's test). RESULTS: By definition, 338 patients with "localized SGD" underwent MIP. MIP was finished in 308 (91.1%) patients. Five of 308 patients (1.6%) showed persisting (n = 1) or recurrent disease (n = 4). In 30 of 338 patients (8.9%), a conversion to bilateral exploration was necessary (false preoperative localization 15 patients--one patient not cured; multiple-gland disease correctly indicated by QPTH monitoring 15 patients--one patient not cured). Analyzing the "non-QPTH" group, 14 additional patients showed persisting disease. Thus, without using QPTH monitoring, the rate of persisting PHPT would increase from 0.9% (three patients) to 5.0% (17 patients; p = 0.0005). CONCLUSION: Intraoperative QPTH assay seems necessary even in patients with "localized SGD" by two techniques in an endemic goiter region. Abandoning QPTH monitoring would more than double the rate of persisting disease. A randomized trial seems not to be justified.
PubMed-ID: 19440730
http://dx.doi.org/10.1007/s00423-009-0505-9
Cinacalcet Reduces Serum Calcium Concentrations in Patients With Intractable Primary Hyperparathyroidism.
J Clin Endocrinol Metab, 94(8):2766-72.
Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR, Lu J, Peacock M. 2009.
CONTEXT: Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia. OBJECTIVE: The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT. DESIGN: This was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk. SETTING: The study was conducted at 23 centers in Europe, the United States, and Canada. PATIENTS: The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter). INTERVENTION: During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted. MAIN OUTCOME MEASURE: The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase. RESULTS: Mean +/- sd baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias. CONCLUSIONS: In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need.
PubMed-ID: 19470620
http://dx.doi.org/10.1210/jc.2008-2640
The Fallen One: the Inferior Parathyroid Gland That Descends into the Mediastinum.
J Am Coll Surg, 208(5):887-93.
Callender GG, Grubbs EG, Vu T, Hofstetter WL, Fleming JB, Woodburn KL, Lee JE, Evans DB, Perrier ND. 2009.
BACKGROUND: Inferior parathyroid glands are located along the embryologic migration path of the thymus and can rest in the thyrothymic ligament or anterior mediastinum. Our nomenclature system designates these glands as "fallen" (type F) glands. This study reviews our experience with type F parathyroid glands to determine which can be retrieved successfully through a cervical incision. STUDY DESIGN: A retrospective review of patients who underwent parathyroidectomy between June 1998 and May 2008 was performed. Patient demographics, localization studies, and operative and pathologic reports were analyzed. Distance from the superior aspect of the clavicle to the target parathyroid gland was measured. RESULTS: Sixty (9.2%) patients had a type F parathyroid gland. Parathyroidectomy was performed through cervical incision in 54 (90%) patients and 6 (10%) required a thoracic approach. Preoperative imaging identified parathyroid glands located >or=6 cm below the superior aspect of the clavicle in eight patients. Of these, six (75%) required a thoracic approach and two (25%) were resected through a cervical incision with concomitant thymectomy. Parathyroidectomy was successfully performed through a cervical incision in all 52 (100%) patients in whom the target parathyroid gland was <6 cm below the superior aspect of the clavicle (Fisher's exact test, p < 0.001). CONCLUSIONS: A cervical approach allows successful retrieval of type F parathyroid glands located <6 cm below the superior aspect of the head of the clavicle in the anterior mediastinum. Parathyroidectomy for glands located >or=6 cm below the superior aspect of the clavicle can be attempted from the neck with concomitant thymectomy, but the majority will require a thoracic approach.
PubMed-ID: 19476855
http://dx.doi.org/10.1016/j.jamcollsurg.2009.01.032
Outpatient Minimally Invasive Parathyroidectomy Is Safe for Elderly Patients.
J Am Coll Surg, 208(6):1071-6.
Shin SH, Holmes H, Bao R, Jimenez C, Kee SS, Potylchansky E, Lee JE, Evans DB, Perrier ND. 2009.
BACKGROUND: Elderly patients with primary hyperparathyroidism (PHPT) are often not referred for surgical intervention because of concern of comorbid conditions that may increase perioperative complications. Because PHPT is more common in the elderly, we sought to compare indications and complications of minimally invasive parathyroidectomy in patients 70 years of age and older (elderly) with their younger counterparts. STUDY DESIGN: A review was conducted of a prospectively collected database of all patients undergoing parathyroidectomy on our endocrine surgery service. Data collected included patient demographic, biochemical pathologic, and operative findings. Wilcoxon rank sum and chi-square tests were used for comparisons. RESULTS: Three hundred eighty-eight patients with PHPT recently underwent parathyroidectomy over a 3-year period (elderly, n=101; younger, n=287). The elderly cohort had significantly higher median preoperative creatinine (elderly, 2.0 mg/dL; younger,1.0 mg/dL; p=0.002) and parathyroid hormone (elderly, 145 pg/mL; younger, 123 pg/mL; p=0.026) levels. The elderly cohort also had more severe osteoporosis, with a significantly worse median bone mineral density T-score (elderly, -2.5; younger, -1.8; p<0.001). The rate of postoperative complications was similarly low in both groups (elderly, 5.9%; younger, 3.5%; p=0.38). CONCLUSIONS: Minimally invasive parathyroidectomy for PHPT can be performed as safely in elderly patients as in their younger counterparts. Elderly patients with PHPT are more likely to have osteoporosis and higher creatinine levels at the time of surgical referral. Additional study of the role of earlier intervention is warranted.
PubMed-ID: 19476894
http://dx.doi.org/10.1016/j.jamcollsurg.2009.01.048
When Initial Postexcision PTH Level Does Not Fall Appropriately During Parathyroidectomy: What to Do Next?
World J Surg, 33(8):1665-73.
O'Neal PB, Poylin V, Mowschenson P, Parangi S, Horowitz G, Pant P, Hasselgren PO. 2009.
BACKGROUND: Inadequate fall in the intraoperative parathyroid hormone (PTH) level after removing enlarged parathyroid gland(s) typically signifies additional hyperfunctioning gland(s), prompting further neck dissection, but it may also be a false negative result. We analyzed intraoperative management of patients with an inadequate fall on PTH after excision of enlarged parathyroid gland(s). METHODS: Analysis involved a prospective database of 189 patients undergoing 193 procedures for primary hyperparathyroidism. The PTH level was determined before neck incision and 10-15 min after excision of enlarged parathyroid gland(s). A PTH decrease > 50% and into normal range was used as the criterion of successful parathyroidectomy. RESULTS: In 48 of 193 operations, initial postexcision PTH level did not fall appropriately. That inadequate fall in PTH level was a false negative result in 16 patients (33%) and cure was achieved without additional neck exploration in all but one patient, who had additional (negative) neck exploration after excision of a parathyroid adenoma. In all patients with false negative postexcision PTH assay, operative findings concurred with preoperative imaging tests. CONCLUSIONS: Inadequate fall in intraoperative PTH may be false negative, particularly after removal of an adenoma found in the location determined by preoperative imaging. Repeat PTH may confirm the initial assay as false negative, obviating the need for additional neck dissection. Importantly, if repeat PTH does not fall appropriately, additional neck exploration needs to be performed.
PubMed-ID: 19495864
http://dx.doi.org/10.1007/s00268-009-0084-5
Reoperative Surgery for Primary Hyperparathyroidism.
Br J Surg, 96(7):699-701.
Bartsch DK, Rothmund M. 2009.
PubMed-ID: 19526608
http://dx.doi.org/10.1002/bjs.6701
Hyperparathyroidism-Jaw Tumor Syndrome: a Report of Three Large Kindred.
Langenbecks Arch Surg, 394(5):817-25.
Iacobone M, Masi G, Barzon L, Porzionato A, Macchi V, Ciarleglio FA, Palu G, De CR, Viel G, Favia G. 2009.
BACKGROUND: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal disease caused by inactivating germ-line mutations of HRPT2 gene, with subsequent loss of Parafibromin expression. It is characterized by familial HPT, ossifying jaw tumors, and other associated neoplasms. METHODS: Clinical, histopathological, and genetic features of three large Italian unrelated HPT-JT kindred were assessed. RESULTS: Three different germ-line HRPT2 inactivating mutations were identified. Seventeen affected members and six healthy mutation carriers were found. HPT was diagnosed in virtually all affected patients, at a median age of 36.3 years (range 11-71). In all cases, a single parathyroid involvement was found at surgery, although a metachronous multiglandular involvement causing recurrence after selective parathyroidectomy occurred in 17.6% of cases, after a mean disease-free interval of 13.7 years (range 5-27). Parathyroid carcinoma, atypical parathyroid adenoma, and jaw tumor occurred in one case; uterine involvement in 61.5% of women; other associated neoplasms were thyroid carcinoma (two cases) and renal and colon carcinoma (one case). Immunohistochemistry confirmed the loss of Parafibromin as the distinctive feature of the disease both in parathyroid and uterine tumors. CONCLUSIONS: HPT-JT has a frequent single-gland parathyroid involvement and a relatively increased risk of parathyroid carcinoma. The penetrance of the disease is high but incomplete. Regardless of the denomination of the syndrome, jaw tumors occur rarely, while uterine involvement is frequently present. Selective parathyroidectomy may be an effective strategy, but a prolonged follow-up is required because of the risk of recurrences and malignancies. A systematic investigation is also required because of associated malignancies.
PubMed-ID: 19529956
http://dx.doi.org/10.1007/s00423-009-0511-y
Evaluation of Halle, Miami, Rome, and Vienna Intraoperative IPTH Assay Criteria in Guiding Minimally Invasive Parathyroidectomy.
Langenbecks Arch Surg, 394(5):843-9.
Barczynski M, Konturek A, Hubalewska-Dydejczyk A, Cichon S, Nowak W. 2009.
BACKGROUND AND AIMS: Intraoperative parathyroid hormone assay (IOPTH) has been used during minimally invasive parathyroidectomy (MIP) to predict operative success. However, the applied criteria are not equivalent in detection of multiglandular disease (MGD) and predicting cure. The purpose of this study was to evaluate the most commonly applied criteria of IOPTH in patients undergoing MIP in a tertiary referral center. MATERIALS AND METHODS: A retrospective review of 260 patients with sporadic primary hyperparathyroidism and concordant results of sestamibi scanning and ultrasound of the neck undergoing MIP (135 video-assisted and 125 open) between Dec 2002 and May 2008, with a 6-month postoperative follow-up of intact parathyroid hormone and serum calcium levels, was performed. The main outcome measures included evaluation of predictive values of Halle, Miami, Rome, and Vienna IOPTH interpretation criteria. RESULTS: The following overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive values were found, respectively: 65%, 62.9%, 100%, 100%, and 14.2% for Halle criterion; 97.3%, 97.6%, 93.3%, 99.6%, and 70% for Miami criterion; 83.8%, 82,9%, 100%, 100%, and 26.3% for Rome criterion; and 92.3%, 92.2%, 93.3%, 99.6%, and 60.9% for Vienna criterion. CONCLUSIONS: Miami criterion followed by Vienna criterion was found to be the best balanced among other criteria, with the highest accuracy in intraoperative prediction of cure. However, Rome criterion followed by Halle criterion was found to be the most useful in intraoperative detection of MGD. Nevertheless, their application in patients qualified for MIP with concordant results of sestamibi scanning and ultrasound of the neck would result in a significantly higher number of negative conversions to bilateral neck explorations and only a marginal improvement in the success rate of primary operations.
PubMed-ID: 19529957
http://dx.doi.org/10.1007/s00423-009-0510-z
Does Multiple Gland Disease in Primary Hyperparathyroidism Correlate With Age or Sex?
Langenbecks Arch Surg, 394(5):885-90.
Wirowski D, Lammers BJ, Pohl P, Schwarz K, Goretzki PE. 2009.
PURPOSE: Paediatric primary hyperparathyroidism (PHPT) patients suffer more often from multiple gland disease (MGD) than adults. The question occurs whether MGD in adult PHPT patients also correlates with age or sex and whether familial PHPT plays a decisive role. This is significant, as it would influence our decision for a focused approach or the bilateral cervical exploration. MATERIALS AND METHODS: We retrospectively analysed 465 consecutive PHPT patients who underwent surgery in our department between September 2001 and December 2008. RESULTS: PHPT patients aged 40 years or younger suffered significantly more often from MGD than older patients (22.9% versus 11.0%). If familial PHPT disorders, which were more common in young patients, were excluded, the divergence between these two groups vanished (12.5% versus 10.0%). There was no statistical significant difference in the frequency of MGD between men (12.2%) and women (12.3%). CONCLUSIONS: If familial PHPT can be ruled out, the frequency of MGD in adult PHPT patients does not correlate with age or with sex. Therefore, age and sex do not imply specific surgical approaches in adult PHPT patients.
PubMed-ID: 19533167
http://dx.doi.org/10.1007/s00423-009-0521-9
Endoscopic Total Parathyroidectomy and Partial Parathyroid Tissue Autotransplantation for Patients With Secondary Hyperparathyroidism: a New Surgical Approach.
World J Surg, 33(8):1674-9.
Sun Y, Cai H, Bai J, Zhao H, Miao Y. 2009.
BACKGROUND: Secondary hyperparathyroidism (SHPT) (i.e., renal hyperparathyroidism) is one of the most serious complications in long-term hemodialysis patients. The purpose of this retrospective study was to explore the feasibility of a new surgical approach--endoscopic total parathyroidectomy with autotransplantation (ETP+AT)--and evaluate its practical application for patients with SHPT. METHODS: The study included 34 SHPT patients who underwent ETP+AT from among 67 cases at the Department of Minimally Invasive Surgery, the First Affiliated Hospital of Nanjing Medical University over a 3-year period. The other 33 patients underwent traditional total parathyroidectomy with autotransplantation (TP+AT). Two criteria were used as indications to perform ETP+AT in SHPT patients. The first was a high serum parathyroid hormone level (PTH >800 pg/ml) associated with hypercalcemia and/or hyperphosphatemia that which were refractory to medical treatment. The second criterion was the presence of clinical symptoms including pruritus, bone and joint pain, muscle weakness, progression of soft tissue calcification, and spontaneous fractures. Ultrasonography, (99m)Tc sestamibi scans, and computed tomography were used to evaluate the thyroid and parathyroid glands. RESULTS: There was no surgery-related mortality among any of the patients with ETP+AT. One patient underwent conventional neck exploration because of bleeding and injury of a unilateral recurrent laryngeal nerve after the operation. Preoperative symptoms were alleviated, and the serum PTH and alkaline phosphatase levels, hyperphosphatemia, and hypercalcemia were improved or normalized in most patients. Recurrence was observed in one patient with a sixth parathyroid gland behind his thyroid, and the patient required a second operation. Hypoparathyroidism was not found after the operation. The clinical data were compared between ETP+AT and TP+AT. CONCLUSIONS: ETP+AT is a safe option for the treatment of SHPT with low morbidity and mortality, shorter hospital stay and low recurrence rate. It is important to avoid intraoperative bleeding, identify all parathyroid glands during the surgery, and choose adequate parathyroid tissues for autografting.
PubMed-ID: 19533223
http://dx.doi.org/10.1007/s00268-009-0086-3
Surgery for Patients With Primary Hyperparathyroidism and Negative Sestamibi Scintigraphy--a Feasibility Study.
Langenbecks Arch Surg, 394(5):881-4.
Thier M, Nordenstrom E, Bergenfelz A, Westerdahl J. 2009.
BACKGROUND: We report the surgical treatment of a consecutive series of scan negative patients with the intention of unilateral parathyroid exploration with the aid of intraoperative quick PTH (qPTH). MATERIALS AND METHODS: The study included 35 consecutive sestamibi scan negative patients (27 women, eight men) with sporadic pHPT subjected to first time surgery. Median age was 70 years and median preoperative calcium level 2.8 mmol/L. RESULTS: Thirty-three patients had a histological diagnosis of a parathyroid adenoma (median weight 0.48 g [range 0.12 g-2.5 g]). Nineteen patients were explored bilaterally and 16 patients (46%) were operated unilaterally. The median operation time was 40 min in the unilateral group and 95 min in the bilateral group (p < 0.001). Three patients were treated for postoperative hypocalcemia after bilateral exploration versus none in the unilateral group (p = 0.23). With a minimum of 12 months of follow-up, 33 patients (94.3%) were cured. One case of recurrent HPT presented after bilateral exploration with visualization of four glands. One case of persistent HPT was observed after unilateral exploration. qPTH was predictive of operative failure in both patients. CONCLUSION: Forty-six percent of the patients in our study could be operated unilaterally with a total cure rate of 94%. Patients in the unilateral group had a significant shorter operation time and a lower incidence of postoperative hypocalcemia. In conclusion our investigation shows that limited parathyroid exploration can safely be performed on patients with negative sestamibi scintigraphy by the aid of qPTH.
PubMed-ID: 19547996
http://dx.doi.org/10.1007/s00423-009-0524-6
Benefits of Surgeon-Performed Ultrasound for Primary Hyperparathyroidism.
Langenbecks Arch Surg, 394(5):861-7.
Arora S, Balash PR, Yoo J, Smith GS, Prinz RA. 2009.
BACKGROUND: Focused, minimally invasive parathyroidectomy (MIP) is widely accepted when preoperative imaging localizes a single parathyroid adenoma. Many surgeons use (99m)Tc-sestamibi scintigraphy (MIBI) +/-, a cervical ultrasound for preoperative localization. We propose that surgeon-performed ultrasound (SUS) is the only imaging modality required in most patients with primary hyperparathyroidism (pHPT), resulting in patient convenience and reduced cost. MATERIALS AND METHODS: Since July 2006, patients with pHPT underwent MIP based solely on a positive SUS. Intraoperative parathyroid hormone assay was used to determine the extent of operation. A retrospective review from July 2006 through December 2008 identified 160 patients who underwent parathyroidectomy after SUS on their initial office visit. RESULTS: SUS correctly identified an enlarged parathyroid gland in 119/160 (74%) patients. In 41 patients, SUS was the only localizing study. MIBI was done in 119 patients. In 54 patients, SUS confirmed the MIBI, and in 28 patients with a negative MIBI, SUS was positive. In the 41 patients with a negative SUS, an MIBI was positive in ten. Ninety-eight patients had MIP. Theoretically, 85 MIBIs were unnecessary because of a positive SUS corresponding to a potential cost savings of at least $90,000. CONCLUSION: SUS to localize parathyroid adenomas is accurate and facilitates MIP. It provides substantial cost savings and patient convenience and should be the first diagnostic procedure performed for patients suspected to have pHPT. MIBI can be reserved for those patients in whom ultrasound has failed to localize a parathyroid gland.
PubMed-ID: 19547997
http://dx.doi.org/10.1007/s00423-009-0522-8
Bone Metabolism After Cinacalcet Administration in Patients With Secondary Hyperparathyroidism.
J Bone Miner Metab, 
Yano S, Suzuki K, Sumi M, Tokumoto A, Shigeno K, Himeno Y, Sugimoto T. 2009.
Cinacalcet, an allosteric modulator of a calcium (Ca)-sensing receptor, significantly suppresses parathyroid hormone (PTH) secretion and bone turnover rate in chronic hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). In this study, bone metabolism after cinacalcet treatment was examined, because hungry bone syndrome is sometimes experienced after parathyroidectomy in severe SHPT. We conducted a prospective observational study in 17 HD patients with SHPT. Cinacalcet was started at 25 mg/day, and the dose was increased step by step based on serum calcium level. A significant decrease in serum Ca and intact PTH concentration was found within 2 weeks. Tartrate-resistant acid phosphatase 5b, a good bone resorption marker, was significantly decreased at week 2 of the study. Serum bone alkaline phosphatase, a marker of bone formation, was increased at week 2 compared with the basal level. It became, however, gradually decreased until week 14. Only one patient whose bone turnover was considerably high had a mild numbness feeling. These results suggest that cinacalcet treatment might transiently accelerate bone formation with rapid suppression of bone resorption. This uncoupling could be involved in a mechanism by which cinacalcet decreases serum Ca level.
PubMed-ID: 19548062
http://dx.doi.org/10.1007/s00774-009-0102-6
Surgical Strategy for Sporadic Primary Hyperparathyroidism an Evidence-Based Approach to Surgical Strategy, Patient Selection, Surgical Access, and Reoperations.
Langenbecks Arch Surg, 394(5):785-98.
Mihai R, Barczynski M, Iacobone M, Sitges-Serra A. 2009.
PURPOSE: Progress in parathyroid imaging has brought substantial changes in the surgical strategy to approach patients with sporadic primary hyperparathyroidism (pHPT). The present review is focused on the safety and efficacy of limited parathyroid exploration. MATERIALS AND METHODS: Review of the literature focused on studies dealing with unilateral (two-gland exploration) or selective parathyroidectomy (one-gland exploration) in selected patients with pHPT and on the classification of published reports according to the degree of evidence. RESULTS: Parathyroid exploration limited to a solitary parathyroid adenoma can be considered a minimally invasive procedure that can be performed by the minicervicotomy, video-assisted, or endoscopic approaches. In properly selected patients, it affords results comparable to those of four-gland bilateral exploration in terms of cure and recurrence. It causes less postoperative hypocalcemia. CONCLUSIONS: Selective parathyroidectomy is an option for patients with positive preoperative localization tests undergoing first-time surgery who have no family history of pHPT, no goiter for which surgical therapy is proposed, and are not on lithium therapy.
PubMed-ID: 19554347
http://dx.doi.org/10.1007/s00423-009-0529-1
Intraoperative Real-Time (99m)Tc-Sestamibi Scintigraphy With Miniature Gamma Camera Allows Minimally Invasive Parathyroidectomy Without IoPTH Determination in Primary Hyperparathyroidism.
Langenbecks Arch Surg, 394(5):869-74.
Cassinello N, Ortega J, Lledo S. 2009.
BACKGROUND: Minimally invasive parathyroidectomy (MIP) is being widely accepted as the procedure of choice for the treatment of primary hyperparathyroidism (PHPT), which is caused by a parathyroid single adenoma in more than 80% of cases in some series. Preoperative location studies, like sestamibi scans, allow the proper identification of pathologic gland and intraoperative parathormone (ioPTH) assay is used to confirm the removal of the adenoma. We have studied the feasibility of a new miniature gamma camera (MGC) used intraoperatively to locate parathyroid adenomas and confirm its correct excision. MATERIALS AND METHODS: Twenty patients with PHPT positively diagnosed by preoperative sestamibi scans underwent a MIP. In the first five patients, both ioPTH assay and the new hand-held MGC were used consecutively to locate and confirm the excision of the pathologic gland. For the next 15 cases, PTH was measured but not used intraoperatively for diagnosis and the MGC was the only diagnostic tool employed to perform the operation. Concordance between preoperative and intraoperative scintigraphy, surgical time, success rate, and complications are analyzed. RESULTS: All cases were operated on successfully by a MIP. After 1 year follow-up, the drop of PTH and the normalization of calcium levels confirmed the excision of all pathologic tissue. The MGC proved its usefulness in all patients offering accurate real-time intraoperative images for location and confirming the success of the procedure. CONCLUSIONS: The MGC is a useful instrument in MIP for PHPT. It may be used as complementary to the standard tools used to date, or even replace them, at least in selected cases of single adenomas.
PubMed-ID: 19562365
http://dx.doi.org/10.1007/s00423-009-0523-7
Outcome of Parathyroidectomy for Patients With Renal Disease and Hyperparathyroidism: Predictors for Recurrent Hyperparathyroidism.
ANZ J Surg, 79(5):378-82.
Low TH, Clark J, Gao K, Eris J, Shannon K, O'Brien C. 2009.
BACKGROUND: A small group of patients with renal disease-related secondary or tertiary hyperparathyroidism require surgical parathyroidectomy. Among them, 5-20% require further re-exploration and excision of parathyroid tissue because of recurrent disease. The aims of the present study were to review the characteristics and outcomes of patients undergoing parathyroidectomy for renal disease related hyperparathyroidism and to identify the risk factors for recurrent hyperparathyroidism. METHODS: Review of data from a dedicated head and neck database at Royal Prince Alfred Hospital between 1988 and 2004. RESULTS: There were 115 patients of whom 68 (59%) patients were treated with subtotal parathyroidectomy (STP), 43 (37%) were treated with total parathyroidectomy (TP) and 4 (3%) were treated with TP with autotransplant. Of those, 11 (9.6%) patients developed recurrent hyperparathyroidism (9 had STP, 1 had TP and 1 had TP with autotransplant). On re-exploration, persistent hyperplastic parathyroid tissue was located at the site of partially excised parathyroid gland (64%), autotransplanted parathyroid tissue (9%), anterior mediastinum (18%) and intrathyroidal parathyroid (9%). Predictors for recurrent hyperparathyroidism are STP (P= 0.049), preoperative symptom of calciphylaxis or calcinosis (P= 0.024), elevated preoperative calcium level (P= 0.007) and elevated post-operative PTH levels (P= 0.014). Post-operative PTH levels less than 10 pmol/L has a positive predictive value of 97.5% for cure (P= 0.02). CONCLUSION: More aggressive surgical approach could be indicated in patients with preoperative hypercalcaemia and calcinosis/calciphylaxis. Post-operative PTH can be utilized as a marker for cure after parathyroidectomy in hyperparathyroidism of renal disease.
PubMed-ID: 19566521
http://dx.doi.org/10.1111/j.1445-2197.2009.04893.x
Positional Statement of the European Society of Endocrine Surgeons (ESES) on Modern Techniques in PHPT Surgery.
Langenbecks Arch Surg, 394(5):761-4.
Bergenfelz AO, Hellman P, Harrison B, Sitges-Serra A, Dralle H. 2009.
PubMed-ID: 19575214
http://dx.doi.org/10.1007/s00423-009-0533-5
Preoperative 99Tc(m)-Sestamibi Scintigraphy With SPECT Localizes Most Pathologic Parathyroid Glands.
Langenbecks Arch Surg, 394(5):811-5.
Lindqvist V, Jacobsson H, Chandanos E, Backdahl M, Kjellman M, Wallin G. 2009.
BACKGROUND AND AIMS: Surgery is the only curative treatment for primary hyperparathyroidism. Focused surgical techniques are being practiced with increasing frequency. Preoperative imaging, such as scintigraphy, is a prerequisite for focused surgery. There is controversy about which preoperative imaging method should be used. The sensitivity reported for parathyroid scintigraphy varies considerably. This study was designed to determine the accuracy of the preoperative imaging routinely used at our institution. MATERIAL AND METHODS: This retrospective study included consecutive patients who underwent a routine dual-phase sestamibi-SPECT (single photon emission computed tomography) scintigraphy and subsequent operation with follow-up. Scintigraphy results were evaluated by comparing the results to surgical findings and histopathology. RESULTS: Two hundred and sixty-four individuals entered the study. Sensitivity for scintigraphy was 84%, specificity 91%, positive predictive value 91%, and negative predictive value 84%. CONCLUSIONS: Sestamibi-SPECT scintigraphy is a sensitive preoperative modality with high positive predictive value. Scintigraphy is a good indicator for when to perform a focused surgical approach and could often correctly guide the actual operation.
PubMed-ID: 19578871
http://dx.doi.org/10.1007/s00423-009-0536-2
Imaging for Primary Hyperparathyroidism--an Evidence-Based Analysis.
Langenbecks Arch Surg, 394(5):765-84.
Mihai R, Simon D, Hellman P. 2009.
OBJECTIVE: Imaging in patients with primary hyperparathyroidism has been proven difficult. During the last decade, sestamibi scintigraphy and ultrasound (US) have been used with various success. The importance of these procedures has risen since minimal invasive parathyroid (MIP) surgery also has developed, and it is claimed that preoperative localization usually is needed before embarking on such a procedure. METHODS: We have scanned the most recent literature in this matter in order to identify evidence, using commonly accepted grading, and also concluded a number of recommendations. RESULTS AND CONCLUSIONS: We found evidence at level III leading to recommendations at grade B, that sestamibi scintigraphy is a recommended first test, but that US by an experienced investigator may be an alternative. MIP may be performed when both tests are concordant, and in case of only one test being positive, unilateral exploration and use of intraoperative PTH measurements are recommended. Bilateral neck exploration is used when both tests are negative. For reoperative procedures, repeat investigations are recommended, but also to use US-guided fine needle aspiration and PTH measurements as well as venous sampling. However, for reoperative procedures, the level of evidence is weaker-level IV, but recommendations still at grade B.
PubMed-ID: 19590890
http://dx.doi.org/10.1007/s00423-009-0534-4
Intraoperative Adjuncts in Surgery for Primary Hyperparathyroidism.
Langenbecks Arch Surg, 394(5):799-809.
Harrison BJ, Triponez F. 2009.
PURPOSE: This paper is a review of the evidence base to produce recommendations for the use of intraoperative parathyroid hormone (PTH), radioguided parathyroidectomy (RGP), methylene blue (MB), frozen section, and intraoperative neuromonitoring during surgery for primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: A Medline keyword search of English-language articles led to the production of a draft document, subsequently revised by committee, containing levels of evidence and the grading of recommendations as proposed by the Agency for Healthcare Research and Quality. RESULTS: Literature review provides the basis for clear recommendations on the use of intraoperative PTH at surgery for PHPT. There is little evidence to support the use of RGP, MB, routine frozen section, and intraoperative neuromonitoring.
PubMed-ID: 19590891
http://dx.doi.org/10.1007/s00423-009-0532-6
Hyperparathyroidism.
Lancet, 374(9684):145-58.
Fraser WD. 2009.
Hyperparathyroidism is due to increased activity of the parathyroid glands, either from an intrinsic abnormal change altering excretion of parathyroid hormone (primary or tertiary hyperparathyroidism) or from an extrinsic abnormal change affecting calcium homoeostasis stimulating production of parathyroid hormone (secondary hyperparathyroidism). Primary hyperparathyroidism is the third most common endocrine disorder, with the highest incidence in postmenopausal women. Asymptomatic disease is common, and severe disease with renal stones and metabolic bone disease arises less frequently now than it did 20-30 years ago. Primary hyperparathyroidism can be cured by surgical removal of an adenoma, increasingly by minimally invasive parathyroidectomy. Medical management of mild disease is possible with bisphosphonates, hormone replacement therapy, and calcimimetics. Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. However, the biochemical definition of vitamin D deficiency and its treatment are subject to much debate. Secondary hyperparathyroidism as the result of chronic kidney disease is important in the genesis of renal bone disease, and several new treatments could help achieve the guidelines set out by the kidney disease outcomes quality initiative.
PubMed-ID: 19595349
http://dx.doi.org/10.1016/S0140-6736(09)60507-9
Impact of Modern Techniques on Short-Term Outcome After Surgery for Primary Hyperparathyroidism: a Multicenter Study Comprising 2,708 Patients.
Langenbecks Arch Surg, 394(5):851-60.
Bergenfelz AO, Jansson SK, Wallin GK, Martensson HG, Rasmussen L, Eriksson HL, Reihner EI. 2009.
PURPOSE: Preoperative localization procedures and the use of intraoperative parathyroidism (iOPTH) have led to a shift of paradigm from bilateral neck exploration to focused parathyroidectomy in primary hyperparathyroidism (pHPT). However, only a small number of randomized trials from specialized centers have been published. The main purpose of the study was to analyze the impact of localization procedures and iOPTH on short-term outcome after pHPT surgery in a multi-institutional setting. METHODS: An audit for quality assurance in pHPT surgery was performed in 23 Scandinavian departments in 2004-2008. Data were gathered prospectively in a database. Two thousand seven hundred and eight patients were registered and 78% were females. The median serum calcium level was 2.79 mmol/l. RESULTS: Localization procedures were performed in 1,831 patients (68%), (sestamibi in 54% and ultrasound in 41%) and iOPTH in 792 operations (29%). Bilateral exploration was performed in 61%, focused parathyroidectomy in 17%, and unilateral exploration in 22%. Histology showed parathyroid adenoma in 82%, with the median weight of 0.6 g. The alleviation of hypercalcemia at the first follow-up was 93% (94% for primary operation). In the multivariate logistic regression analysis, iOPTH increased cure rate (OR 1.70, 95% CI 1.14-2.53, p = 0.0092). The risk for postoperative medically treated hypocalcemia decreased with the use of localization procedures (OR 0.56, 95% CI 0.43-0.78, p = 0.0004) and iOPTH (OR 0.56, 95% CI 0.39-0.90, p = 0.0015). CONCLUSIONS: Localization procedures and iOPTH decreased the risk for hypocalcemia after pHPT surgery. Additionally, iOPTH influenced short-term cure rate favorably.
PubMed-ID: 19618204
http://dx.doi.org/10.1007/s00423-009-0540-6
Two Hundred and Two Consecutive Operations for Secondary Hyperparathyroidism: Has Medical Management Changed the Profiles of Patients Requiring Parathyroidectomy?
Surgery, 146(2):296-9.
Shen WT, Kebebew E, Suh I, Duh QY, Clark OH. 2009.
BACKGROUND: Because of improvements in the medical management of end-stage renal disease, some surgeons perceive that they now perform fewer operations for secondary hyperparathyroidism, and that current patients have more advanced disease. METHODS: One hundred and seventy-two patients undergoing 202 operations for secondary hyperparathyroidism between 1988 and 2007 were reviewed. Patients operated on in the past decade (1998-2007) were compared with those from the previous decade (1988-1997). The main outcome measures were pre- and post-operative biochemical and symptom profiles, operation performed, and recurrence. RESULTS: One hundred and thirty first-time operations and 72 reoperations were performed. From 1988 to 1997, 106 operations were performed, compared with 96 from 1998 to 2007. There were no demographic differences between decades. There were no differences in preoperative serum calcium (10.0 mg/dL vs 10.2 mg/dL), PTH (1622 ng/L vs 1424 ng/L), phosphate (6.9 mg/dL vs 7.0 dL), and alkaline phosphatase (339 U/L vs 347 U/L). Symptom profiles were similar. Patients in the past decade were less likely to require reoperation (6% vs 22%) (P < .05). CONCLUSION: Despite improvements in medical management, the population of patients requiring parathyroidectomy for secondary hyperparathyroidism has remained constant in number and preoperative biochemical and symptom profiles over the past 2 decades. However, fewer patients have required reoperation in the past decade.
PubMed-ID: 19628088
http://dx.doi.org/10.1016/j.surg.2009.03.032
Age and Gender Distribution of Primary Hyperparathyroidism and Incidence of Surgical Treatment in a European Country With a Particularly High Life Expectancy.
Swiss Med Wkly, 139(27-28):400-4.
Richert L, Trombetti A, Herrmann FR, Triponez F, Meier C, Robert JH, Rizzoli R. 2009.
OBJECTIVE: Primary hyperparathyroidism (PHPT) is a frequently encountered endocrine disease in the elderly, but little is known about ist epidemiology in the aging European population. This study investigates the age- and sex-dependence of PHPT and the incidence of parathyroidectomy (PTX) in Switzerland, a country with a particularly high life expectancy. DESIGN: A population-based study was performed using data from the Swiss Federal Statistical Office covering years 2000 to 2004. Anonymised hospital discharge codes for PHPT and PTX were analysed, and the hospitalisation rate for PHPT and incidence of PTX were calculated. RESULTS: The mean annual hospitalisation rate of patients with PHPT was 8.3/100,000 inhabitants. The rate was approximately three times higher in women than in men, with the highest estimate found in women > or = 80 years (63.7/ 100,000). The population-adjusted annual incidence of PTX was 3.8/100,000 inhabitants. PTX incidence was higher in individuals > or = 50 years than in younger persons (8.7/100,000 vs 1.3/100,000), with a peak in patients aged 70-74 years. CONCLUSIONS: In a European population with high life expectancy, the hospitalisation rate of PHPT is higher in women and increases continuously with age. Incidence of PTX is highest in patients aged 70-74 years. These findings underscore the need for further research on the impact of population aging on the treatment patterns of PHPT.
PubMed-ID: 19629768
http://dx.doi.org/smw-12635
Bone Mineral Density Analysis in Patients With Primary Hyperparathyroidism Associated With Multiple Endocrine Neoplasia Type 1 After Total Parathyroidectomy.
Clin Endocrinol (Oxf), 
Coutinho FL, Lourenco Jr DM, Toledo RA, Montenegro FL, Correia-Deur JE, Toledo SP. 2009.
Objective: Limited data have been reported on the effect of parathyroidectomy (PTx) on bone mineral density (BMD) in the setting of patients with hyperparathyroidism (HPT) associated with multiple endocrine neoplasia type 1 (MEN1). This study investigates the impact of total PTx on BMD in patients with HPT/MEN1. Design and patients: A case series study was performed in a tertiary academic hospital. Sixteen HPT/MEN1 cases from six families harbouring MEN1 germline mutations were subjected to total PTx followed by parathyroid auto-implant in the forearm. Measurements: BMD values were assessed using DXA. Results: Before PTx, reduced BMD (Z-score <-2.0) was highly prevalent in the proximal one third of the distal radius (1/3 DR) (50%), lumbar spine (LS) (43.7%), ultradistal radius (UDR) (43.7%), femoral neck (FN) (25%) and total femur (TF) (18.7%) in the cases. Fifteen months after PTx, we observed a BMD improvement in the LS (from 0.843 to 0.909 g/cm(2); +8.4%, p=0.001), FN (from 0.745 to 0.798 g/cm(2); +7.7%, p=0.0001) and TF (from 0.818 to 0.874 g/cm(2); +6.9%, p<0.0001). No significant change was noticed in the 1/3 DR and UDR after PTx. Conclusions: The present data confirmed BMD recovery in the LS and FN after PTx in HPT/MEN1 cases. We also documented a significant BMD increase in the TF and no change in both the 1/3 DR and UDR BMD after PTx. Our data suggest that lumbar spine and proximal femur are the most informative sites to evaluate the short-term BMD outcome after PTx in HPT/MEN1 subjects.
PubMed-ID: 19650788
http://dx.doi.org/10.1111/j.1365-2265.2009.03672.x
Surgical Therapy for Familial Hyperparathyroidism.
Am Surg, 75(7):579-82.
Sharma J, Weber CJ. 2009.
Isolated familial hyperparathyroidism (FHPT) not associated with multiple endocrine neoplasia is a rare and aggressive form of primary hyperparathyroidism. The traditional management of FHPT is a bilateral neck exploration with an increased rate of multigland hyperplasia, supernumerary glands, and recurrence. A prospective database was queried, which included 1383 consecutive parathyroidectomies between 1992 and 2008, and 28 patients with FHPT were identified. Patient demographics, pathology, intraoperative parathyroid hormone (IOPTH) kinetics, recurrence patterns, and accuracy of localization studies were analyzed. Twenty-one patients underwent bilateral neck explorations as an initial surgery, and seven patients had nine unilateral neck explorations for recurrent hyperparathyroidism. Overall cure rate was 89.2 per cent with a mean follow-up of 2.9 years (range: 6 months to 9.2 years); 64.3 per cent of patients had multigland disease. IOPTH helped identify supernumerary glands in three (12.5%) patients and accurately lateralized recurrent disease in eight of nine surgeries (88.8%). Tc-99m-Sestamibi failed to identify multigland disease in 11 patients (52.3%). FHPT has a greater prevalence of multigland disease, decreased utility of sestamibi scanning, and a higher recurrence rate than sporadic primary hyperparathyroidism. In FHPT, IOPTH is a useful adjunct in identifying additional tumors and in select cases may play a role in tumor localization.
PubMed-ID: 19655601
Evaluation of Preoperative and Postoperative Thyroid Pathologies in Patients Operated for Primary Hyperparathyroidism.
Endocr Pract, 1-18.
Gul K, Ozdemir D, Korukluoglu B, Ersoy PE, Aydin R, Ugras SN, Ersoy R, Cakir B. 2009.
Objective: The coexistence of thyroid diseases in patients with primary hyperparathyroidism (PHPT) can present a challenge in the clinical decision making and management of these patients. In this study, we aimed to evaluate rates of different thyroid pathologies in patients undergoing parathyroidectomy for PHPT.Methods: Sixty patients with PHPT were included. All patients were evaluated with ultrasonography (US) and parathyroid scintigraphy and where needed fine needle aspiration biopsy (FNAB). Standard neck exploration was the surgical procedure in all patients.Results: In preoperative thyroid US evaluation, diffuse thyroiditis (without nodule) was detected in 13 patients, solitary nodule in 9 patients (7 with coexistent thyroiditis), multiple nodules in 24 patients (5 coexistent with thyroiditis) and normal in 14 patients. As a result, rates of thyroiditis and nodular goiter in patients with PHPT were found to be 41.7% and 55%, respectively. Collectively, prevalence of thyroid pathology was observed as 76.7%. Thyroidectomy was performed with parathyroidectomy in 42 patients. Indications for thyroid surgery were cytologically nondiagnostic or suspicious nodules in 5 patients and hyperthyroidism in 4 patients, while 33 patients were operated depending on ultrasonographic or intraoperative findings. Postoperatively 9 (15%) patients were diagnosed as thyroid carcinoma. 4 of these were operated due to cytologic results, whereas 5 were operated for other reasons.Conclusion: Thyroid pathologies, particularly thyroid carcinomas are common in PHPT patients. This coexistence should be considered while deciding surgical procedure. We think intraoperative evaluation of thyroid is as important as preoperative evaluation with US and FNAB in patients with thyroid pathologies accompanying PHPT.
PubMed-ID: 19703812
http://dx.doi.org/10.4158/EP09138.OR
National Trends in Parathyroid Surgery From 1998 to 2008: a Decade of Change.
J Am Coll Surg, 209(3):332-43.
Greene AB, Butler RS, McIntyre S, Barbosa GF, Mitchell J, Berber E, Siperstein A, Milas M. 2009.
BACKGROUND: The introduction of limited explorations (LE) for parathyroidectomy broadened the management possibilities for hyperparathyroidism. We sought to document this evolution of change in parathyroid surgery. STUDY DESIGN: Members of the American Association of Endocrine Surgeons and the American College of Surgeons were sent a 49-question survey, and 256 surgeons, accounting for 46% of parathyroid operations nationwide, responded. Associations derived from questionnaire data were tested for significance using chi-square and Kruskal-Wallis methods. RESULTS: Currently, 10% of surgeons practice bilateral neck exploration, 68% practice LE, and 22% have a mixed practice. Five years ago, these percentages were, respectively, 26%, 43%, and 31%; and 10 years ago they were 74%, 11%, and 15%. Shift to LE was greatest among endocrine surgeons, high-volume surgeons, and surgeons trained by mentors who practiced LE. A focal, single-gland examination under general anesthesia and 23-hour observation are preferred by most surgeons. Half of all general surgeons, in contrast to fewer than 10% of endocrine surgeons, never monitor parathyroid hormone intraoperatively, even with LE. Dramatic differences were apparent among subsets of surgeons in operative volumes, indications for bilateral neck exploration, followup care, expertise with ultrasound and sestamibi, and perceptions of cure and complication rates. Evidence-based literature and guidance from surgical societies had the greatest influence on the decision to practice LE. CONCLUSIONS: This survey formally documents the evolution of practice patterns in parathyroid surgery over the last decade. Although LE has achieved wide acceptance, surgical management of hyperparathyroidism has become increasingly disparate. This trend may highlight a need to define best-practice guidelines.
PubMed-ID: 19717037
http://dx.doi.org/10.1016/j.jamcollsurg.2009.05.029

Adrenals
Meta-Analyses
- None -
Randomized controlled trials
- None -
Other Articles
Laparoscopic Adrenalectomy for Pheochromocytoma: Take the Vein Last?
Surg Endosc, 23(5):965-8.
Vassiliou MC, Laycock WS. 2009.
BACKGROUND: Traditionally, the adrenal vein has been ligated early during excision of a pheochromocytoma. Patient anatomy or size of the lesion can sometimes make early vein dissection difficult or unsafe. This study aimed to demonstrate the safety and efficacy of delayed adrenal vein ligation during laparoscopic adrenalectomy for pheochromocytoma. METHODS: A retrospective review of all laparoscopic adrenalectomies for pheochromocytoma from 1997 to 2007 was conducted. All the patients had confirmed histologic evidence of pheochromocytoma. The procedures were performed using the same technique, which involved division of the adrenal vein late in the procedure after the gland had been dissected free. Patient records were reviewed for evidence of intraoperative hemodynamic variations, blood loss, length of stay, and postoperative morbidity. RESULTS: The review examined 27 adrenalectomies performed for 25 patients. Intraoperative hypertension exceeding 170 mmHg was observed in seven patients (26.9%). The overall morbidity was 7.7%, and the mean length of hospital stay was 1.7 days. No deaths occurred. CONCLUSIONS: Delayed adrenal vein ligation during laparoscopic adrenalectomy for pheochromocytoma is safe and effective. The intraoperative hemodynamic parameters are comparable with those reported in the literature for the "vein first" technique. Dividing the vein late is an alternative approach to laparoscopic excision of adrenal pheochromocytoma and should be considered in appropriate situations.
PubMed-ID: 19116738
http://dx.doi.org/10.1007/s00464-008-0264-7
Clinical Aspects of SDHx-Related Pheochromocytoma and Paraganglioma.
Endocr Relat Cancer, 16(2):391-400.
Timmers HJ, Gimenez-Roqueplo AP, Mannelli M, Pacak K. 2009.
Paragangliomas (PGLs) derive from either sympathetic chromaffin tissue in adrenal and extra-adrenal abdominal or thoracic locations, or from parasympathetic tissue of the head and neck. Mutations of nuclear genes encoding subunits B, C, and D of the mitochondrial enzyme succinate dehydrogenase (SDHB 1p35-p36.1, SDHC 1q21, SDHD 11q23) give rise to hereditary PGL syndromes PGL4, PGL3, and PGL1 respectively. The susceptibility gene for PGL2 on 11q13.1 remains unidentified. Mitochondrial dysfunction due to SDHx mutations have been linked to tumorigenesis by upregulation of hypoxic and angiogenesis pathways, apoptosis resistance and developmental culling of neuronal precursor cells. SDHB-, SDHC-, and SDHD-associated PGLs give rise to more or less distinct clinical phenotypes. SDHB mutations mainly predispose to extra-adrenal, and to a lesser extent, adrenal PGLs, with a high malignant potential, but also head and neck paragangliomas (HNPGL). SDHD mutations are typically associated with multifocal HNPGL and usually benign adrenal and extra-adrenal PGLs. SDHC mutations are a rare cause of mainly HNPGL. Most abdominal and thoracic SDHB-PGLs hypersecrete either norepinephrine or norepinephrine and dopamine. However, only some hypersecrete dopamine, are biochemically silent. The biochemical phenotype of SDHD-PGL has not been systematically studied. For the localization of PGL, several positron emission tomography (PET) tracers are available. Metastatic SDHB-PGL is the best localized by [(18)F]-fluorodeoxyglucose PET. The identification of SDHx mutations in patients with PGL is warranted for a tailor-made approach to the biochemical diagnosis, imaging, treatment, follow-up, and family screening.
PubMed-ID: 19190077
http://dx.doi.org/10.1677/ERC-08-0284
18F-Fluorodeoxyglucose Positron Emission Tomography for the Diagnosis of Adrenocortical Tumors: a Prospective Study in 77 Operated Patients.
J Clin Endocrinol Metab, 94(5):1713-22.
Groussin L, Bonardel G, Silvera S, Tissier F, Coste J, Abiven G, Libe R, Bienvenu M, Alberini JL, Salenave S, Bouchard P, Bertherat J, Dousset B, Legmann P, Richard B, Foehrenbach H, Bertagna X, Tenenbaum F. 2009.
CONTEXT: Most adrenal incidentalomas are nonfunctioning adrenocortical adenomas (ACAs). Adrenocortical carcinomas (ACCs) are rare but should be recognized at an early stage. OBJECTIVE: The objective of the study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) to predict malignancy in patients without a previous history of cancer. DESIGN: This was a prospective, multicenter study from 2001 to 2006. SETTING: The study was conducted at a network of seven university hospitals in Paris. PATIENTS: Seventy-seven patients were included. All underwent surgery because of hypersecretory and/or growing benign lesions (n = 18), obvious ACCs (n = 21), or radiologically indeterminate lesions (n = 38). MAIN OUTCOME MEASURE: The degree of (18)F-FDG PET uptake [maximum standardized uptake value (maxSUV)] was related to the pathological findings serving as a reference, and its diagnostic value was compared with that of computerized tomography (CT) scan. RESULTS: Pathology eventually diagnosed 43 ACAs, 22 ACCs, and 12 nonadrenocortical lesions. Using a cutoff value above 1.45 for adrenal to liver maxSUV ratio, the sensitivity and specificity to distinguish ACAs from ACCs were, respectively, 1.00 (95% confidence interval 0.85-1.00) and 0.88 (95% confidence interval 0.75-0.96). Among the 38 indeterminate lesions at CT scan, we could analyze a subgroup of 16 adrenocortical tumors with high unenhanced density (>10 HU) and an inappropriate washout: (18)F-FDG PET correctly predicted the benignity in 13 of 15 ACAs. CONCLUSIONS: In a multidisciplinary team approach, (18)F-FDG PET helps to manage suspicious CT scan lesions. An adrenal to liver maxSUV ratio less than 1.45 is highly predictive of a benign lesion.
PubMed-ID: 19190108
http://dx.doi.org/10.1210/jc.2008-2302
Contrasting Clinical Manifestations of SDHB and VHL Associated Chromaffin Tumours.
Endocr Relat Cancer, 16(2):515-25.
Srirangalingam U, Khoo B, Walker L, MacDonald F, Skelly RH, George E, Spooner D, Johnston LB, Monson JP, Grossman AB, Drake WM, Akker SA, Pollard PJ, Plowman N, Avril N, Berney DM, Burrin JM, Reznek RH, Kumar VK, Maher ER, Chew SL. 2009.
Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.
PubMed-ID: 19208735
http://dx.doi.org/10.1677/ERC-08-0239
Pheochromocytomas and Extra-Adrenal Paragangliomas Detected by Screening in Patients With SDHD-Associated Head-and-Neck Paragangliomas.
Endocr Relat Cancer, 16(2):527-36.
Havekes B, van der Klaauw AA, Weiss MM, Jansen JC, van der Mey AG, Vriends AH, Bonsing BA, Romijn JA, Corssmit EP. 2009.
Patients with SDHD-associated head-and-neck paragangliomas (HNP) are at risk for developing pheochromocytomas for which screening has been advised. To assess clinical, biochemical, and radiological outcomes of screening in a large single-center cohort of SDHD-positive patients with HNP and to address the necessity for repetitive follow-up, we evaluated 93 patients with SDHD-associated HNP (p.Asp92Tyr, p.Leu139Pro). Screening consisted of measurement of 24 h urinary excretion of catecholamines and/or their metabolites in duplicate, which was repeated with intervals of 2 years if initial biochemical screening was negative. In patients, in whom urinary excretion was above the reference limit, imaging studies with (123)I-MIBG (metaiodobenzylguanidine) scintigraphy and magnetic resonance imaging (MRI) and/or computed tomography (CT) were performed. Pheochromocytomas and extra-adrenal paragangliomas were treated surgically after appropriate blockade. Median follow-up was 4.5 years (range 0.5-19.5 years). Twenty-eight out of the 93 patients were included in our study and underwent additional imaging for pheochromocytomas/extra-adrenal paragangliomas. In 11 out of the 28 patients intra-adrenal pheochromocytomas were found. Extra-adrenal paragangliomas were discovered in eight patients. These tumors were detected during initial screening in 63% of cases, whereas 37% were detected after repeated biochemical screening. One patient was diagnosed with a biochemically silent pheochromocytoma. The high prevalence of pheochromocytomas/extra-adrenal paragangliomas in patients with SDHD-associated HNP warrants regular screening for tumors in these patients. Paragangliomas that do not secrete catecholamines might be more prevalent than previously reported. Future studies will have to establish whether routine imaging studies should be included in the screening of SDHD mutation carriers, irrespective of biochemical screening.
PubMed-ID: 19289533
http://dx.doi.org/10.1677/ERC-09-0024
Role of Unilateral Adrenalectomy in Bilateral Primary Aldosteronism: a 22-Year Single Center Experience.
J Clin Endocrinol Metab, 94(7):2437-45.
Sukor N, Gordon RD, Ku YK, Jones M, Stowasser M. 2009.
OBJECTIVE: The aim of the study was to examine blood pressure and biochemical responses to unilateral adrenalectomy in patients with bilateral primary aldosteronism (PA) and identify predictive parameters. CONTEXT: PA considered due to bilateral autonomous production of aldosterone is usually treated medically. Unilateral adrenalectomy has been considered ineffective. Because quality outcome data are lacking and medical treatment may cause adverse effects or fail to control hypertension, defining the role for unilateral adrenalectomy in bilateral PA is an important clinical issue. DESIGN AND SETTING: Between 1984 and 2004, 51 of 684 patients diagnosed with bilateral PA underwent unilateral adrenalectomy. This report is based on the records of the 40 considered suitable for inclusion, who were followed for at least 12 (median, 56.4) months. RESULTS: Hypertension was cured in 15% of patients and improved in 20%, usually within 1 yr of unilateral adrenalectomy. The proportion with controlled hypertension was significantly (P < 0.001) higher after adrenalectomy (65%) than before (25%). Mean systolic (P < 0.001) and diastolic (P < 0.001) blood pressure, left ventricular mass index (P < 0.05), plasma upright aldosterone (P < 0.05), and aldosterone/renin ratio (P < 0.001) fell. Serum creatinine independently predicted hypertension cure. CONCLUSION: Although this retrospective analysis of patients from a single center does not permit prediction of response rates among patients diagnosed elsewhere, it suggests that unilateral adrenalectomy can be beneficial in some patients with apparent bilateral PA and should not be dismissed as a treatment option.
PubMed-ID: 19401369
http://dx.doi.org/10.1210/jc.2008-2803
Should We Use Laparoscopic Adrenalectomy for Metastases? Scandinavian Multicenter Study.
J Surg Oncol, 100(1):43-7.
Marangos IP, Kazaryan AM, Rosseland AR, Rosok BI, Carlsen HS, Kromann-Andersen B, Brennhovd B, Hauss HJ, Giercksky KE, Mathisen O, Edwin B. 2009.
INTRODUCTION: Laparoscopic adrenalectomy for metastases is considered controversial. Multicenter retrospective study was performed to gain new knowledge in this issue. MATERIALS AND METHODS: From January 1997 till November 2008, 41 adrenalectomies were performed during follow-up of the patients operated for malignant tumors. The median age was 64 (52-77) years. Metastases were confirmed in 31/41 cases. Metastatic lesions were further studied and to define factors influencing on survival, patients were divided to sub-groups of metachronous/synchronous, tumor origin and tumor size. RESULTS: The median operative time was 104 (50-230) min, the median blood loss was 100 (0-500) ml. One procedure (3.2%) was converted. There were 3 (10.7%) intraoperative and 2 (7.4%) postoperative complications. The median tumor size was 6 (1.5-16) cm. Pathohistological analysis revealed 12 colorectal, 9 renal cell carcinoma, 5 lung carcinoma, 4 melanoma, and 1 hepatocellular metastases. The resection margin was not free in one case (3.7%). The median hospital stay was 2 (1-21) days. The median length of survival was 29 +/- 2.1 months for all patients. CONCLUSION: Laparoscopic adrenalectomy for metastases is feasible regardless of their sizes. However these procedures should be performed by highly skilled laparoscopic surgeon in a fully equipped operating room and with a coordinated operation team.
PubMed-ID: 19431158
http://dx.doi.org/10.1002/jso.21293
The Succinate Dehydrogenase Genetic Testing in a Large Prospective Series of Patients With Paragangliomas.
J Clin Endocrinol Metab, 94(8):2817-27.
Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP. 2009.
CONTEXT: Germline mutations in SDHx genes cause hereditary paraganglioma. OBJECTIVE: The aim of the study was to assess the indications for succinate dehydrogenase (SDH) genetic testing in a prospective study. DESIGN: A total of 445 patients with head and neck and/or thoracic-abdominal or pelvic paragangliomas were recruited over 5 yr in 20 referral centers. In addition to classical direct sequencing of the SDHB, SDHC, and SDHD genes, two methods for detecting large genomic deletions or duplications were used, quantitative multiplex PCR of short fluorescent fragments (QMPSF) and multiplex ligation-dependent probe amplification (MLPA). RESULTS: A large variety of SDH germline mutations were found by direct sequencing in 220 patients and by QMPSF and MLPA in 22 patients (9.1%): 130 in SDHD, 96 in SDHB, and 16 in SDHC. Mutation carriers were younger and more frequently had multiple or malignant paraganglioma than patients without mutations. A head and neck paraganglioma was present in 97.7% of the SDHD and 87.5% of the SDHC mutation carriers, but in only 42.7% of the SDHB carriers. A thoracic-abdominal or pelvic location was present in 63.5% of the SDHB, 16.1% of the SDHD, and in 12.5% of the SDHC mutation carriers. Multiple paragangliomas were diagnosed in 66.9% of the SDHD mutation carriers. A malignant paraganglioma was documented in 37.5% of the SDHB, 3.1% of the SDHD, and none of the SDHC mutation carriers. CONCLUSIONS: SDH genetic testing, including tests for large genomic deletions, is indicated in all patients with head and neck and/or thoracic-abdominal or pelvic paraganglioma and can be targeted according to clinical criteria.
PubMed-ID: 19454582
http://dx.doi.org/10.1210/jc.2008-2504
Survival of Patients With Metastatic Malignant Pheochromocytoma and Efficacy of Combined Cyclophosphamide, Vincristine, and Dacarbazine Chemotherapy.
J Clin Endocrinol Metab, 94(8):2850-6.
Nomura K, Kimura H, Shimizu S, Kodama H, Okamoto T, Obara T, Takano K. 2009.
CONTEXT: About 10% of pheochromocytomas are malignant. Exact survival has not been reported, nor has an analysis of the efficacy of chemotherapy on survival time. OBJECTIVE: The aim of this study was to analyze the survival curves and survival times of patients with malignant pheochromocytoma and to determine the efficacy of chemotherapy on prolongation of life. DESIGN: An inception cohort and Kaplan-Meier survival analysis was conducted. PATIENTS AND OUTCOME MEASURES: Thirty-two patients with metastasized malignant pheochromocytoma were analyzed for survival. Twenty-five patients had undergone excision of their primary tumors. Survival curves were compared among the 16 patients in this group treated with combined chemotherapy using cyclophosphamide, vincristine and dacarbazine (CVD) and the nine patients not treated with chemotherapy. RESULTS: The survival curve of the 32 patients declined continuously and linearly to at least 20 yr after the diagnosis of pheochromocytoma. The 50% survival rate was estimated to be 14.7 yr. In the 25 patients whose primary tumor was excised, patients who already had metastases at the time of pheochromocytoma diagnosis had better survival than those whose metastases were found later. The survival rate after diagnosis of metastasis was worse in the CVD group than in controls. When the effects of CVD were examined after stratifying several factors, female gender and adrenal origin of tumor were found to be negative prognostic factors for CVD chemotherapy. CONCLUSION: The present study revealed a long survival time. CVD chemotherapy was not shown to extend survival, especially for women and patients with adrenal gland-derived primary tumors.
PubMed-ID: 19470630
http://dx.doi.org/10.1210/jc.2008-2697
Bilateral Adrenalectomy for Refractory Cushing Disease: a Safe and Definitive Therapy.
J Am Coll Surg, 208(6):1059-64.
Smith PW, Turza KC, Carter CO, Vance ML, Laws ER, Hanks JB. 2009.
BACKGROUND: Refractory Cushing disease (CD) is associated with considerable morbidity and mortality. Bilateral adrenalectomy (BA) offers effective permanent treatment. Both open and laparoscopic approaches have been used, but longterm comparisons are few. STUDY DESIGN: We reviewed 40 consecutive BA for refractory CD from 1995 through 2007. Surgical results were evaluated. A Short Form-36 Quality-of-Life (QOL) survey was performed. RESULTS: Eighty-five percent (34 of 40) of patients were women, and median age was 41.9 years (range, 22.2 to 78.3 years). All had persistent CD after transsphenoidal operation (mean, 1.7; range, 1 to 3). Median followup was 5.0 years. Thirty-eight percent (15 of 40) of procedures were performed laparoscopically; 1 was converted to open. There were no operative or 30-day mortalities, and there was 1 90-day mortality. Morbidities occurred in 7 of 40 (18%) patients. Median length of stay was shorter in the laparoscopic group (4 versus 6 days; p < 0.001). All patients achieved clinical reversal of hypercortisolism, including the 5 (13%) with ectopic adrenal tissue. Elevated serum ACTH (> 200 ng/mL) was present during followup in 33% (13 of 40). A QOL survey demonstrated 86% of patients felt good to excellent compared with 1 year pre-BA. Chronic fatigue was present most or all of the time in 46%, and patients were below population norms on 7 of 8 Short Form-36 scales. No difference was evident in QOL between laparoscopic and open adrenalectomy. CONCLUSIONS: Our experience demonstrates excellent survival and clinical results, despite the inherent risk in patients with CD. There are persistent fatigue and QOL deficits that are not ameliorated by laparoscopic compared with open resection.
PubMed-ID: 19476892
http://dx.doi.org/10.1016/j.jamcollsurg.2009.02.054
Adjuvant Mitotane for Adrenocortical Cancer--Working Through Uncertainty.
J Clin Endocrinol Metab, 94(6):1879-80.
Terzolo M, Fassnacht M, Ciccone G, Allolio B, Berruti A. 2009.
PubMed-ID: 19494162
http://dx.doi.org/10.1210/jc.2009-0120
The Approach to the Patient With Paraganglioma.
J Clin Endocrinol Metab, 94(8):2677-83.
Neumann HP, Eng C. 2009.
The multidisciplinary management of patients with paragangliomas and pheochromocytomas remains challenging. The cornerstone of excellent multidisciplinary management of such patients is genetic classification and management in a tertiary care referral center. Up to one third of all symptomatic presentations of pheochromocytoma or paraganglioma are due to germline mutations in one of six genes defining multiple endocrine neoplasia type 2, von Hippel-Lindau disease, neurofibromatosis type 1, and the paraganglioma syndromes types 1, 3, and 4. This genetic classification forms the basis early diagnosis and follow-up including management of relatives. Easily available clinical information such as tumor location and number, age, gender, and family history must be used to prioritize which gene should be tested. Mutation carriers should undergo regular check-up to detect and treat metachronous paraganglial and extraparaganglial tumors, and depending on syndrome, other extraparaganglial neoplasias such as medullary thyroid cancer and renal clear cell carcinomas in time. Adrenal and extraadrenal retroperitoneal tumors should be operated by surgeons highly experienced in minimal invasive, endoscopic techniques.
PubMed-ID: 19657044
http://dx.doi.org/10.1210/jc.2009-0496

NET
Meta-Analyses
- None -
Randomized controlled trials
- None -

ENETS Consensus Guidelines
ENETS Consensus Guidelines for the Standard of Care in Neuroendocrine Tumors.
Neuroendocrinology, 90(2):159-61.
Plockinger U, Wiedenmann B, de Herder WW. 2009.
PubMed-ID: 19713708
http://dx.doi.org/10.1159/000225945
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Towards a Standardized Approach to the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors and Their Prognostic Stratification.
Neuroendocrinology, 90(2):162-6.
Kloppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M, Rindi G, Plockinger U. 2009.
PubMed-ID: 19060454
http://dx.doi.org/10.1159/000182196
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological Examinations.
Neuroendocrinology, 90(2):167-83.
Sundin A, Vullierme MP, Kaltsas G, Plockinger U. 2009.
PubMed-ID: 19077417
http://dx.doi.org/10.1159/000184855
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Echocardiography.
Neuroendocrinology, 90(2):190-3.
Plockinger U, Gustafsson B, Ivan D, Szpak W, Davar J. 2009.
PubMed-ID: 19713710
http://dx.doi.org/10.1159/000225947
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers.
Neuroendocrinology, 90(2):194-202.
O'Toole D, Grossman A, Gross D, Delle FG, Barkmanova J, O'Connor J, Pape UF, Plockinger U. 2009.
PubMed-ID: 19713711
http://dx.doi.org/10.1159/000225948
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Pre- and Perioperative Therapy in Patients With Neuroendocrine Tumors.
Neuroendocrinology, 90(2):203-8.
Akerstrom G, Falconi M, Kianmanesh R, Ruszniewski P, Plockinger U. 2009.
PubMed-ID: 19713712
http://dx.doi.org/10.1159/000225949
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biotherapy.
Neuroendocrinology , 90(2):209-13.
Oberg K, Ferone D, Kaltsas G, Knigge UP, Taal B, Plockinger U. 2009.
PubMed-ID: 19077379
http://dx.doi.org/10.1159/000183751
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Chemotherapy in Patients With Neuroendocrine Tumors.
Neuroendocrinology, 90(2):214-9.
Eriksson B, Annibale B, Bajetta E, Mitry E, Pavel M, Platania M, Salazar R, Plockinger U. 2009.
PubMed-ID: 19713713
http://dx.doi.org/10.1159/000225950
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Peptide Receptor Radionuclide Therapy With Radiolabeled Somatostatin Analogs.
Neuroendocrinology, 90(2):220-6.
Kwekkeboom DJ, Krenning EP, Lebtahi R, Komminoth P, Kos-Kudla B, de Herder WW, Plockinger U. 2009.
The purpose of this guideline is to assist physicians caring for patients with neuroendocrine tumors in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT), and in defining the minimum requirements for PRRT. This guideline also makes recommendations on what minimal patient, tumor, and treatment outcome characteristics should be reported for PRRT in order to make comparisons between studies possible. It is not this guideline's aim to give specific recommendations on the use of specific radiolabeled somatostatin analogs for PRRT because different analogs are being used, and their availability depends on national law and local permissions.
PubMed-ID: 19713714
http://dx.doi.org/10.1159/000225951
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Follow-Up and Documentation.
Neuroendocrinology, 90(2):227-33.
Arnold R, Chen YJ, Costa F, Falconi M, Gross D, Grossman AB, Hyrdel R, Kos-Kudla B, Salazar R, Plockinger U. 2009.
PubMed-ID: 19713715
http://dx.doi.org/10.1159/000225952

Other Articles
Survival and Prognostic Factor Analysis of 146 Metastatic Neuroendocrine Tumors of the Mid-Gut.
Neuroendocrinology, 89(4):471-6.
Strosberg J, Gardner N, Kvols L. 2009.
Background: Gastrointestinal neuroendocrine tumors (NETs) are heterogeneous neoplasms that vary in mortality according to location of primary tumor and stage of disease. Past analyses of survival suggest a trend towards improving longevity among patients with metastatic mid-gut NETs. Methods: We evaluated all cases of metastatic NETs of the mid-gut seen in our institution between 1999 and 2003, measuring survival from time of diagnosis of distant metastatic disease. Median and 5-year survival rates were estimated using Kaplan-Meier methodology. We assessed the impact of various prognostic factors including age, gender, hepatic cytoreductive surgery, and operative resection of the primary tumor. Results: 146 cases of metastatic mid-gut NETs were identified. The median overall survival was 103 months and the 5-year survival rate was 75%. Most patients (91%) received octreotide therapy. Other medical treatments included hepatic artery embolization, chemotherapy, and peptide receptor radiotherapy. Primary tumor resection was performed in 69% of cases, and hepatic cytoreductive surgery in 22% of cases. A median survival of 95 months was observed among patients who did not undergo cytoreductive surgery. Operative resection of the primary tumor was not associated with a significant survival advantage. Conclusions: Median overall survival is 103 months (8.5 years) in patients with metastatic mid-gut NETs. Among patients who are not candidates for hepatic cytoreductive surgery, median survival is 95 months (7.9 years). Resection of the primary tumor does not appear to be associated with a survival benefit in the metastatic setting.
PubMed-ID: 19174605
http://dx.doi.org/10.1159/000197899
Use of Intraoperative Insulin Assay for the Localisation of Insulinoma.
World J Surg, 33(5):969-71.
Scott-Coombes D, Eatock F, Henley R, Luzio SD. 2009.
BACKGROUND: The curative treatment for patients with insulinoma is the surgical removal of the tumour; however, these tumours are small and therefore their preoperative localisation using ultrasound and CT scans may be difficult. METHODS: Intraoperative serum insulin measurements were used as an aid to the surgical management of seven unselected and consecutive presentations of insulinoma. RESULTS: In six of the seven cases we were able to demonstrate an increase in the peripheral serum insulin concentration between 3 and 5 min after manual examination of the tumour. In addition, there was a 50% decrease in concentration 10 min after removal of the tumour. CONCLUSIONS: We believe that intraoperative insulin measurements are of use in demonstrating the functionality of tumours localised by intraoperative ultrasound and surgical examination. In addition, they act as an indicator of the completeness of surgery post tumour excision.
PubMed-ID: 19225834
http://dx.doi.org/10.1007/s00268-009-9946-0
Prognostic Factors Influencing Survival From Metastatic (Stage IV) Gastroenteropancreatic Well-Differentiated Endocrine Carcinoma.
Endocr Relat Cancer, 16(2):585-97.
Durante C, Boukheris H, Dromain C, Duvillard P, Leboulleux S, Elias D, de BT, Malka D, Lumbroso J, Guigay J, Schlumberger M, Ducreux M, Baudin E. 2009.
Survival of metastatic gastroenteropancreatic well-differentiated endocrine carcinoma (GEP WDEC) is not well characterized. We evaluated the long-term outcome and prognostic factors for survival in 118 patients with distant metastases from GEP WDEC. Inclusion criteria were 1) pathological review by a single pathologist according to the present WHO criteria, 2) absence of previous therapy apart from surgery, 3) complete morphological evaluation within 3 months including somatostatin receptor scintigraphy, and 4) follow-up at Gustave-Roussy Institute until death or study's end. Clinical, biological marker, and pathological parameters were analyzed in univariate and multivariate statistical models. Survival after the first complete imaging work-up of the metastatic disease was determined using Kaplan-Meier method. Overall, survival for 5 years after the diagnosis of metastatic disease was 54%. In multivariate analysis, age (hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.01-1.08, P = 0.01), the number of liver metastases (HR: 3.4, 95% CI: 1.4-8.3, P = 0.01), tumor slope (HR: 1.1, 95% CI: 1.0-1.1, P = 0.001), and initial surgery (HR: 0.3, 95% CI: 0.1-0.8, P = 0.01) were predictive of survival. Five-year survival was 100%, 91% (95% CI, 51-98%), 62% (95% CI, 37-83%), and 9% (95% CI, 6-32%) when patients had 0, 1, 2, 3 or more poor prognostic features respectively. This study enables the stratification of metastatic GEP WDEC patients into distinct risk groups. These risk categories can be used to tailor therapeutic approaches and also to design and interpret clinical trials.
PubMed-ID: 19240182
http://dx.doi.org/10.1677/ERC-08-0301
Thymic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1: a Comparative Study on 21 Cases Among a Series of 761 MEN1 From the GTE (Groupe Des Tumeurs Endocrines).
World J Surg, 33(6):1197-207.
Goudet P, Murat A, Cardot-Bauters C, Emy P, Baudin E, du Boullay CH, Chapuis Y, Kraimps JL, Sadoul JL, Tabarin A, Verges B, Carnaille B, Niccoli-Sire P, Costa A, Calender A. 2009.
BACKGROUND: Thymic neuroendocrine tumors (Th-NET) present a poor prognosis for patients with multiple endocrine neoplasia type 1 (MEN1). The purpose of this article was to study the clinical, biological, and pathological features of Th-NET in a large cohort of patients with MEN1. METHODS: The 761-patient MEN1 cohort from the GTE registry was used (Groupe des Tumeurs Endocrines). RESULTS: The actuarial probability of occurrence was 2.6% (range, 1.3-5.5%) at aged 40 years. All, except one, Th-NET patients were men. Four patients had no other associated lesions. The youngest patient was aged 16 years. Mean age at the time of diagnosis was 42.7 (range, 16.1-67.5) years. The 10-year probability of survival was 36.1% (range, 11.5-62%). Seven patients (33%) belonged to clustered MEN1 families. The spectrum of associated lesions in patients with Th-NET was not statistically different from the spectrum of the remainder of the cohort. Various endocrine markers were high, but none were sensitive or specific enough to be useful for Th-NET detection. CT-scan and MRI were always positive at the time of diagnosis. No particular mutation was found to be associated with Th-NET. Five cases underwent prophylactic thymectomy without success. CONCLUSIONS: Several end points may be helpful for future guidelines: (1) earlier detection of Th-NET in MEN1 patients is required; (2) screening of both sexes is necessary; (3) a prospective study comparing MRI vs. CT scan in yearly screening for Th-NET is needed; (4) a reinforced screening program must be established for patients who belong to clustered families; and (5) thymectomies must be performed in specialized centers.
PubMed-ID: 19294466
http://dx.doi.org/10.1007/s00268-009-9980-y
Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2.
J Clin Endocrinol Metab, 94(6):1938-44.
Boedeker CC, Erlic Z, Richard S, Kontny U, Gimenez-Roqueplo AP, Cascon A, Robledo M, de Campos JM, van Nederveen FH, de Krijger RR, Burnichon N, Gaal J, Walter MA, Reschke K, Wiech T, Weber J, Ruckauer K, Plouin PF, Darrouzet V, Giraud S, Eng C, Neumann HP. 2009.
BACKGROUND: Head and neck paragangliomas (HNPs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC, or SDHD (SDHx) genes. Heritable non-SDHx HNP might occur in von Hippel-Lindau disease (VHL, VHL gene), multiple endocrine neoplasia type 2 (MEN2, RET gene), and neurofibromatosis type 1 (NF1, NF1 gene). Reports of non-SDHx HNP presentations are scarce and guidance for genetic testing nonexistent. PATIENTS AND METHODS: An international consortium registered patients with HNPs and performed mutation analyses of the SDHx, VHL, and RET genes. Those with SDHx germline mutations were excluded for purposes of this study. Personal and family histories were evaluated for paraganglial tumors, for the major tumor manifestations, and for family history of VHL, MEN2, or NF1. RESULTS: Twelve patients were found to have hereditary non-SDHx HNPs of a total of 809 HNP and 2084 VHL registrants, 11 in the setting of germline VHL mutations and one of a RET mutation. The prevalence of hereditary HNP is five in 1000 VHL patients and nine in 1000 non-SDHx HNP patients. Comprehensive literature review revealed previous reports of HNPs in five VHL, two MEN2, and one NF1 patient. Overall, 11 here presented HNP cases, and four previously reported VHL-HNPs had lesions characteristic for VHL and/or a positive family history for VHL. CONCLUSIONS: Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes.
PubMed-ID: 19336503
http://dx.doi.org/10.1210/jc.2009-0354
Screening of Patients With Multiple Endocrine Neoplasia Type 1 (MEN-1): a Critical Analysis of Its Value.
World J Surg, 33(6):1208-18.
Waldmann J, Fendrich V, Habbe N, Bartsch DK, Slater EP, Kann PH, Rothmund M, Langer P. 2009.
BACKGROUND: Screening of multiple endocrine neoplasia type 1 (MEN-1) patients is widely recommended because one-fifth succumb to malignant neoplasms. However, recommendations for screening modalities and intervals are based mostly on nonprospective data. METHODS: Thirty-five of 48 MEN-1 patients were evaluated at least twice by an annual screening program in a single-center, prospective, nonrandomized study between 1997 and 2006. The screening program comprised anamnesis, clinical examination, imaging procedures, and extensive biochemical evaluations. Prospectively diagnosed lesions were evaluated separately from nonprospectively diagnosed lesions at first evaluation. RESULTS: The median age of the patients was 45 years (range = 15-70) at initial assessment. They were followed for a median of 72 months (range = 24-108) by a median of 6 (range = 2-10) evaluations. The vast majority of lesions were nonprospectively diagnosed at initial evaluation: 13 of 17 patients had primary hyperparathyroidism (pHPT), 24 of 29 had pancreatic endocrine tumors (PETs), and 4 of 4 had carcinoids. Vice versa adrenal lesions were mostly prospectively detected (18/23). Malignancy was observed in 10 patients (28%) in the initial assessment and without symptoms in 5 patients (9 PETs, 3 carcinoids). Endoscopic ultrasound (EUS) of 29 patients detected 88 PETs which were followed for 157 patient years. The mean annual growing rate was 13.28 +/- 28.23 mm with respect to the baseline tumor diameter of 9 mm. In 35 patients the mean incidence of newly diagnosed PETs was 0.52/year. Adrenal lesions were invariably nonfunctional. A mean change in diameter of 6.7 +/- 23.44% was monitored and malignant transformation was absent. CONCLUSIONS: Most lesions are detected at initial screening, particularly malignant tumors. Computed tomography of the abdomen and chest did not identify additional lesions. The interval between screenings could be extended to 3 years based on annually calculated growth rates and the incidence of MEN-1-associated lesions. The assessment of calcium, gastrin, and prolactin is sufficient for biochemical screening in MEN-1.
PubMed-ID: 19350320
http://dx.doi.org/10.1007/s00268-009-9983-8
Prolonged Survival After Hepatic Artery Embolization in Patients With Midgut Carcinoid Syndrome.
Br J Surg, 96(5):517-21.
Sward C, Johanson V, Nieveen van DE, Jansson S, Nilsson O, Wangberg B, Ahlman H, Kolby L. 2009.
BACKGROUND: Hepatic artery embolization (HAE) is a palliative treatment for patients with liver metastases from neuroendocrine tumours. HAE reduces hormonal symptoms, but its impact on survival has been questioned. METHODS: Biochemical responses and survival in consecutive patients with disseminated liver metastases from midgut carcinoid tumours were studied after HAE. Repeat HAE was performed in selected patients with radiological and biochemical signs of progression. RESULTS: Of 107 patients who had HAE, the median survival from the first procedure was 56 (range 1-204) months. Prolonged survival showed a strong correlation with reduction of urinary 5-hydroxyindoleacetic acid (P = 0.003) and plasma chromogranin A (P = 0.001) levels. The biochemical response to repeat HAE was similar to that for the first procedure (P = 0.002). The complication rate was low (7.5 per cent), as was the mortality rate (1.9 per cent) within 1 month of HAE. CONCLUSION: HAE is safe, provides good control of hormonal symptoms, and prolongs survival in biochemically responsive patients. It is a valuable palliative option for patients with midgut carcinoid syndrome due to liver metastases and can be repeated in patients with a favourable response to the first procedure.
PubMed-ID: 19358175
http://dx.doi.org/10.1002/bjs.6587
Multiple Endocrine Neoplasia Type I Variants and Phenocopies: More Than a Nosological Issue?
J Clin Endocrinol Metab, 94(5):1518-20.
Falchetti A, Brandi ML. 2009.
PubMed-ID: 19420274
http://dx.doi.org/10.1210/jc.2009-0494
Predictive Value of 18F-FDG PET and Somatostatin Receptor Scintigraphy in Patients With Metastatic Endocrine Tumors.
J Nucl Med, 50(6):858-64.
Garin E, Le JF, Devillers A, Cuggia M, de Lajarte-Thirouard AS, Bouriel C, Boucher E, Raoul JL. 2009.
The treatment of metastatic neuroendocrine tumors depends on the aggressiveness of the disease. We wanted to know whether (18)F-FDG PET and somatostatin receptor scintigraphy (SRS) can predict early disease progression and patient survival. METHODS: We undertook a prospective study of patients with metastatic neuroendocrine tumor diagnosed between September 2003 and January 2006. After obtaining signed informed consent from the patients, we performed CT, SRS, and (18)F-FDG PET and reviewed histologic data. CT was repeated every 3 mo to assess the risk of early progressive disease (first 6 mo), progression-free survival, and overall survival. RESULTS: Thirty-eight patients (mean age, 60 +/- 15 y) were included. Histologically, 4 patients had a high-grade and 34 a low-grade tumor. The results of (18)F-FDG PET and SRS were positive in 15 and 27 patients. The 2-y overall survival and progression-free survival were 73% and 45%; 16 patients had early progressive disease. Most (18)F-FDG PET-positive patients had early progressive disease (14/15, vs. 2/23 (18)F-FDG PET-negative patients), and most SRS-negative patients had early progressive disease (9/11, vs. 7/27 SRS-positive patients); (18)F-FDG PET gave excellent negative and positive predictive values of 91% and 93%; (18)F-FDG PET results correlated with progression-free survival (P < 0.001) and overall survival (P < 0.001) even when only low-grade tumors were considered. SRS was associated with progression-free survival (P < 0.001) and overall survival (P < 0.03). At multivariate analysis, only (18)F-FDG PET was predictive of progression-free survival. CONCLUSION: (18)F-FDG PET exhibits excellent predictive values for early tumor progression. (18)F-FDG PET and SRS results correlate with progression-free survival and overall survival even for histologically low-grade tumors. These explorations could be included in the initial work-up for metastatic neuroendocrine tumor.
PubMed-ID: 19443590
http://dx.doi.org/10.2967/jnumed.108.057505
Noninvasive Imaging of Pancreatic Beta Cells.
Nat Rev Endocrinol, 5(7):394-400.
Malaisse WJ, Louchami K, Sener A. 2009.
Noninvasive imaging and quantification of pancreatic, insulin-producing beta cells has been considered a high-priority field of investigation for the past decade. In the first review on this issue, attention was already paid to various agents for labeling beta cells, including 6-(125)I-D-glucose, (65)Zn, (3)H-glibenclamide, (3)H-mitiglinide, an (125)I-labeled mouse monoclonal antibody against beta-cell surface ganglioside(s), D-(U-(14)C)-glucose and 2-deoxy-2-(18)F-D-glucose to label glycogen accumulated in beta cells in response to sustained hyperglycemia, and, last but not least, an analog of D-mannoheptulose. This Review discusses these methods and further contributions. For instance, emphasis is placed on labeling beta cells with (11)C-dihydrotetrabenazine, which is the most advanced method at present. Attention is also drawn to the latest approaches for noninvasive imaging and functional characterization of pancreatic beta cells. None of these procedures is used in clinical practice yet.
PubMed-ID: 19468290
http://dx.doi.org/10.1038/nrendo.2009.103
Reoperative Surgery in Sporadic Zollinger-Ellison Syndrome: Longterm Results.
J Am Coll Surg, 208(5):718-22.
Grobmyer SR, Vogel SB, McGuigan JE, Copeland EM, Hochwald SN. 2009.
BACKGROUND: Most patients with Zollinger-Ellison Syndrome (ZES), even those in whom gastrinoma is found and resected at initial operation, will suffer from persistent or recurrent disease in longterm followup. There is currently no consensus about managing patients with recurrent or persistent ZES. Our unit has historically maintained an aggressive approach toward monitoring and reoperation for patients with sporadic ZES. STUDY DESIGN: We performed a review of a consecutive series of patients evaluated and managed at our institution between 1970 and 2007 for ZES. "Biochemical cure" was defined as normal serum gastrin assays and negative imaging studies. Reoperations were performed for elevations in serum gastrin assays and positive findings on imaging studies. RESULTS: Fifty-two patients with sporadic ZES were analyzed. Median followup was 14 years. Among patients with sporadic ZES, 37 patients underwent operative management. The most common operations were resection of duodenal gastrinoma (n=8) and total gastrectomy (n=7). Nine patients underwent 15 reoperations for recurrent or persistent disease. "Biochemical cure" was obtained in four patients (44%) undergoing reoperation for ZES. Three of these patients remained without evidence of recurrence at 4, 9, and 12 years after their curative re-resection. Only one of nine patients who underwent reoperation died of metastatic gastrinoma. CONCLUSIONS: Primary and reoperative surgery in patients with sporadic ZES results in a significant rate of "biochemical cure." In selected patients with recurrent or persistent disease, reoperation for resection of gastrinoma is associated with excellent longterm survival and is warranted.
PubMed-ID: 19476823
http://dx.doi.org/10.1016/j.jamcollsurg.2008.11.017
Peptide-Receptor Radionuclide Therapy for Endocrine Tumors.
Nat Rev Endocrinol, 5(7):382-93.
van EM, Krenning EP, Kam BL, de JM, Valkema R, Kwekkeboom DJ. 2009.
Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is a promising option for the treatment of somatostatin-receptor-positive endocrine tumors. Treatment with somatostatin analogs labeled with (111)In, (90)Y or (177)Lu can result in symptomatic improvement, although tumor remission is seldom achieved with (111)In-labeled analogs. In this Review, the findings of several studies on the use of PRRT for endocrine tumors are evaluated. Large variation in the antitumor effects of (90)Y-octreotide was reported between studies: an objective response (> or =50% tumor regression) was achieved in 9-33% of patients. After treatment with (177)Lu-octreotate, an objective response was achieved in 29% of patients and a minor response (25-50% tumor regression) was achieved in 16% of patients; stable disease was present in 35% of patients. Treatment with (177)Lu-octreotate resulted in a survival benefit of several years and markedly improved quality of life. Serious, delayed adverse effects were rare after PRRT. Although randomized, clinical trials have not yet been performed, data on the use of PRRT compare favorably with those from other treatment approaches, such as chemotherapy. If these results can be replicated in large, controlled trials, PRRT might become the preferred option in patients with metastatic or inoperable gastroenteropancreatic neuroendocrine tumors.
PubMed-ID: 19488074
http://dx.doi.org/10.1038/nrendo.2009.105