Publications by authors named "Marc Klein"

63 Publications

Immunoglobulin Preparations Can Mislead Clinical Decision-Making in Follow-Up of Differentiated Thyroid Cancer.

Endocr Pract 2020 Sep;26(9):1031-1038

Université de Lorraine, CHRU-Nancy, Department of Endocrinology, Diabetology and Nutrition, Nancy, France; Université de Lorraine, Inserm UMR_S 1116 - DCAC, Nancy, France.. Electronic address:

Objective: Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient's plasma and potentially trigger an immune response in the recipient's immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing.

Methods: To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins.

Results: In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations.

Conclusion: Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures.

Abbreviations: CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody.
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http://dx.doi.org/10.4158/EP-2020-0053DOI Listing
September 2020

Adherence to growth hormone therapy guidelines in a real-world French cohort of adult patients with growth hormone deficiency.

Ann Endocrinol (Paris) 2021 Feb 5;82(1):59-68. Epub 2020 Dec 5.

Novo Nordisk, 100 Esplanade du Général de Gaulle, 92400 Paris, France.

Objective: Using real-world data from patients with growth hormone deficiency (GHD), we evaluated whether clinical practice in France adheres to international guidelines regarding somatropin dose adjustment, and assessed the long-term effectiveness and safety of somatropin.

Methods: Data were obtained from a national prospective systematic longitudinal routine follow-up programme of naive/non-naive adults with childhood-onset (CO) or adult-onset (AO) GHD treated with Norditropin® (Novo Nordisk A/S).

Results: Between 2003 and 2006, 331 treatment-naive and non-naive adults with severe GHD were enrolled and followed for a median duration of approximately 5 years; 328 patients were available for analysis. At baseline, mean patient age was 39.2 years; median standard deviation score (SDS) for insulin-like growth factor-1 (IGF-1) level was -2.2 in naive patients, subsequently fluctuating between -0.1 and +0.3 SDS during the study period. Mean GH doses ranged between 0.25 and 0.51mg/day (naive patients) and 0.39 and 0.46mg/day (non-naive patients). Despite generally receiving a higher somatropin dose, women (naive/non-naive) tended to have lower IGF-1 levels than men. Median somatropin dose was consistently higher in patients with CO-GHD than patients with AO-GHD. Extreme IGF-1 values (<-2 or >+2 SDS) were not systematically accompanied by somatropin dose adjustments. Waist circumference improved in approximately one third of patients, at a mean 3.5 years. Somatropin was well tolerated; there were no cardiovascular or cerebrovascular events during the 5-year analysis period.

Conclusion: Current clinical practice of physicians in France follows international guidelines regarding somatropin dose adjustment in adults with GHD. However, dose adjustments are not always sufficient, notably in women, and treatment effects may have been delayed due to low somatropin dose (Clinical trial registration NCT01580605).
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http://dx.doi.org/10.1016/j.ando.2020.11.007DOI Listing
February 2021

Robotic adrenalectomy in patients with pheochromocytoma: a systematic review.

Gland Surg 2020 Jun;9(3):844-848

Département de Chirurgie Viscérale, Métabolique et Cancérologique (CVMC), Unité multidisciplinaire de chirurgie métabolique, endocrinienne et thyroïdienne (UMET), CHRU Brabois, Université de Lorraine, Nancy, France.

Pheochromocytomas (PHEOs) are neural crest cell tumors producing catecholamines. PHEOS need to be early diagnosed and adequately managed. Adrenalectomy is the gold standard treatment of these type of tumors. There has been major improvement of surgical technologies with the development of laparoscopic and robotic systems these past several years. We conducted a review of the literature to evaluate the robotic approach for adrenalectomy for patients with PHEO.
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http://dx.doi.org/10.21037/gs-2019-ra-05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347808PMC
June 2020

IMMUNOGLOBULIN PREPARATIONS CAN MISLEAD CLINICAL DECISION-MAKING IN FOLLOW-UP OF DIFFERENTIATED THYROID CANCER.

Endocr Pract 2020 Jun 23. Epub 2020 Jun 23.

Université de Lorraine, CHRU-Nancy, Department of Endocrinology, Diabetology and Nutrition, Nancy, F-54000, France.

Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid specific thyroglobulin antibodies present in the donor plasma may interfere with the interpretation of measurements of autoantibodies to thyroglobulin in the recipient's plasma and potentially trigger immune response in recipient's immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient-outcomes are not known. Thyroglobulin is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer, following total thyroidectomy and radioactive iodine ablation. However, presence of autoantibodies to thyroglobulin in the circulation interferes with thyroglobulin measurements. Assessment of levels of autoantibodies to thyroglobulin is thus recommended as a part of standard follow-up of differentiated thyroid cancer together with thyroglobulin testing. To understand the potential mechanisms and pathophysiological significance of possible interferences associated with administration immunoglobulin preparations and thyroglobulin measurement, we overview here the current knowledge on interactions between thyroglobulin autoimmunity and immunoglobulin preparations, and illustrate diagnostic challenges and the perspectives for follow-up of patients with differentiated thyroid cancer treated with exogenous immunoglobulins from the point of view of an endocrinologist, a biologist, and a pharmacologist.
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http://dx.doi.org/10.4158/EP-2020-0053DOI Listing
June 2020

Management of thyroid dysfunctions in the elderly. French Endocrine Society consensus 2019 guidelines. Short version.

Ann Endocrinol (Paris) 2020 10 21;81(5):511-515. Epub 2020 May 21.

Service d'endocrinologie et maladies métaboliques, CHU de Larrey, 31059 Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/j.ando.2020.05.002DOI Listing
October 2020

Robotic adrenalectomy: when and how?

Gland Surg 2020 Feb;9(Suppl 2):S166-S172

Unit of Metabolic, Endocrine, and Thyroid Surgery (UMET), Department of Visceral and Metabolic Surgery, Hospital Brabois Adultes, CHRU Nancy, University of Lorraine, Nancy, France.

Currently, laparoscopic adrenalectomy is considered as the preferred technique to manage adrenal tumors. However, there are no prospective randomized studies evaluating this strategy. With the recent advances in surgical equipment and the widespread of robotic technology, a robotic approach is considered as an interesting option in some medical centers. This approach seems to be feasible and safe but high-level evidence of its benefits is still lacking. This review summarizes indications, advantages and drawbacks of robotic adrenalectomy and describes its surgical technique.
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http://dx.doi.org/10.21037/gs.2019.12.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044087PMC
February 2020

Ultrasound and cytological characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features compared to papillary carcinomas.

Ann Endocrinol (Paris) 2020 Feb 25;81(1):28-33. Epub 2020 Jan 25.

Service d'endocrinologie diabétologie et nutrition, CHRU Nancy, 54511 Vandœuvre-lès-Nancy, France. Electronic address:

Introduction: NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features, formerly non-invasive encapsulated follicular variant of papillary thyroid carcinoma) has been removed from the carcinoma category because of its indolent character and good prognosis. This change impacts clinical and surgical management, since these tumors no longer require total thyroidectomy, or complementary radioactive iodine therapy for <4cm tumor. The aim of the present study was to identify preoperative ultrasound and cytological differences between NIFTP and papillary thyroid carcinoma (PTC).

Materials And Methods: A retrospective study included 81 patients who underwent total thyroidectomy or thyroid lobectomy with histologic diagnosis of PTC, NIFTP or invasive follicular variant of PTC (IFVPTC) between January 1st, 2016 and May 31st, 2018. Ultrasound and cytological data were analyzed and compared between NIFTP and non-NIFTP (PTC and invasive follicular variant of PTC).

Results: Fourteen NIFTPs, 67 PTCs, including 20 IFVPTCs, were included. In comparison with non-NIFTP PTC, nodules in NIFTP were more often isoechoic (69.2% vs. 17.4%; P=0.0007), with smooth borders (92.3% vs. 31.1%; P=0.0001) and TI-RADS score 2, 3 or 4a. Cytologically, NIFTPs were mainly in categories AUS/FLUS, FN and SusM of the Bethesda System for Reporting Thyroid Cytopathology. Only nuclear pseudo-inclusions were significantly associated with non-NIFTP (P=0.0031).

Conclusion: NIFTP appears non-suspect on preoperative ultrasound and indeterminate on cytology. These differences with respect to PTC can guide diagnosis and surgical treatment.
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http://dx.doi.org/10.1016/j.ando.2019.10.004DOI Listing
February 2020

Immune check point inhibitors-induced hypophysitis: a retrospective analysis of the French Pharmacovigilance database.

Sci Rep 2019 12 19;9(1):19419. Epub 2019 Dec 19.

Department of Clinical Pharmacology and Pharmacovigilance, University Hospital of Nancy Brabois, Biologie Médicale & Biopathologie, Rue du Morvan, 54511, Vandoeuvre Lès Nancy, France.

Immune control point (ICI) inhibitors represent a significant advance in the management and survival of cancers such as melanoma or non-small cell bronchial carcinoma. However, they induce unusual side effects, such as hypophysitis, which are rarely described elsewhere. This nationwide retrospective study describes the characteristics of hypophysitis reported in the French pharmacovigilance database (FPVD). We requested for all cases of ICI-related hypophysitis registered in the FPVD before May 2018. An endocrinologist and a pharmacologist reviewed all cases. About 94 pituitary cases were selected, involving 49 females and 45 men. Ipilimumab alone or in combination was the most represented ICI (56%). Most cases (61%) were grade 3 severity and the majority (90%) were corticotropic deficiency cases. Cases with thyroid and/or gonadotropic involvement were 21% and 1% respectively. Five patients (8%) had panhypopituitarism. Pituitary MRI, when performed, was in favor of hypophysitis in 50%. No patient recovered his previous hormonal function. The mean time of onset was significantly shorter with ipilimumab than other ICIs. ICI-related hypophysitis generate deficits that do not spontaneously recover, even at a distance from the event, unlike thyroiditis. Patients must then benefit from long-term coordinated onco-endocrinological management, adapted to their own specific deficits.
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http://dx.doi.org/10.1038/s41598-019-56026-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923385PMC
December 2019

Conversion During Laparoscopic Adrenalectomy for Pheochromocytoma: A Cohort Study in 244 Patients.

J Surg Res 2019 11 26;243:309-315. Epub 2019 Jun 26.

University of Lorraine, CHU Nancy - Hospital Brabois Adultes, Department of Digestive, Hepato-Biliary and Endocrine Surgery, Nancy, France; INSERM U954, University of Lorraine, Faculty of Medicine, Nancy, France. Electronic address:

Background: Recent advances in anesthetic and laparoscopic surgical management have improved perioperative outcomes in patients with pheochromocytoma. However, patients converted to laparotomy during laparoscopic adrenalectomy for pheochromocytoma have never been evaluated specifically in terms of intraoperative hemodynamic instability and postoperative complications.

Methods: Retrospective analysis of prospectively maintained databases in five medical centers from 2002 to 2013. Inclusion criteria were consecutive patients who underwent laparoscopic unilateral total adrenalectomy for pheochromocytoma.

Results: Two hundred forty-four patients were included. Mean tumor size was 43.9 ± 20 mm with 92 patients (38%) having a tumor diameter > 50 mm. During adrenalectomy, 19 of 244 patients (7.7%) had to be converted to laparotomy. In multivariable analysis, the need for preoperative hospitalization (3.379, 1.209-9.445; P = 0.020), tumor size > 6 cm (2.97, 0.996-8.868; P = 0.050), and ratio of intraoperative systolic blood pressure >200 mmHg duration to anesthesia duration (1.060, 1.007-1.117; P = 0.027) remained significantly associated with conversion. Conversion was significantly associated with postoperative grade II-V Clavien morbidity rate (4.259, 1.471-12.326; P = 0.007) and duration of hospitalization (12.92, 2.90-58.82; P < 0.001).

Conclusions: This study shows that preoperative hospitalization and larger tumor were more frequent in patients undergoing conversion to laparotomy during laparoscopic adrenalectomy for pheochromocytoma. Conversion is associated with increased intraoperative hypertensive episodes and postoperative complications rate. Clinicians should be cognizant of these risks and prepare patients appropriately for conversion when deemed necessary.
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http://dx.doi.org/10.1016/j.jss.2019.05.042DOI Listing
November 2019

Fertility desires and reproductive needs of transgender people: Challenges and considerations for clinical practice.

Clin Endocrinol (Oxf) 2019 07 17;91(1):10-21. Epub 2019 Apr 17.

Department of Endocrinology, Diabetology and Nutrition, University Hospital Centre Nancy, Vandoeuvre-lès-Nancy, France.

The majority of transgender and gender nonconforming persons seeking medical care are of reproductive age. Hormonal treatment and sex reassignment surgery, which are used in the management of gender dysphoria, compromise fertility potential. Children and adolescents with gender dysphoria have specific treatment regimens starting with puberty-blocking medications. According to international guidelines, fertility preservation should be discussed before any hormonal treatment, although our knowledge on the reproductive needs of transgender and gender nonconforming persons is limited. Recently, some data have emerged on fertility management in some centres for the adult population with gender dysphoria. The goal of this review was to summarize the available evidence on the fertility desires and parental roles of transgender and gender nonconforming people. In light of newly emerging societal challenges, we aim to provide some considerations for clinical practice and suggest further areas of research.
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http://dx.doi.org/10.1111/cen.13982DOI Listing
July 2019

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.

Lancet Diabetes Endocrinol 2019 03 16;7(3):213-220. Epub 2019 Jan 16.

Endocrine Oncology, Institut Gustave Roussy Ecole Doctorale de Cancerologie, Villejuif, France.

Background: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection.

Methods: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features.

Findings: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs.

Interpretation: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.

Funding: None.
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http://dx.doi.org/10.1016/S2213-8587(18)30336-XDOI Listing
March 2019

Early F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma.

Eur J Nucl Med Mol Imaging 2019 03 7;46(3):686-695. Epub 2019 Jan 7.

Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, Strasbourg, France.

Purpose: Data on the diagnostic value of F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated.

Methods: Of 34 patients with suspicion of insulinoma-related HH examined by dual time-point carbidopa-assisted F-FDOPA PET/CT, 24 with histologically proven insulinoma were retrospectively included. One patient underwent two PET/CT examinations for relapsing insulinoma after surgical excision. Thus, 25 preoperative F-FDOPA PET/CT studies were finally retained and analysed. All studies were performed under carbidopa premedication (200 mg orally, 1-2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after F-FDOPA injection) over the upper abdomen and a delayed whole-body acquisition starting 20-30 min later. The cytological and/or histopathological diagnosis of insulinoma was the diagnostic standard of truth.

Results: F-FDOPA PET/CT localized insulinoma in 21 of the 25 studies, leading to a primary lesion detection rate of 84%. Four lesions (19%) were detected only on early acquisitions. The false-negative tumour detection rates were, respectively, 22% and 12.5% in patients receiving and not receiving treatment for hypoglycaemic symptoms at the time of PET/CT. In benign insulinomas, the early maximum standardized uptake value (SUVmax) was significantly higher than the delayed SUVmax. Compared to the 21 benign lesions, four malignant insulinomas showed significantly higher F-FDOPA uptake. Lesion size, fasting-end insulin and C-peptide levels correlated with tumour F-FDOPA uptake, dopaminergic tumour volume and metabolic burden.

Conclusion: The present study showed that F-FDOPA PET/CT combined with carbidopa premedication and early pancreatic acquisitions is a valuable diagnostic option in patients with insulinoma when GLP1R-based imaging is not available. The results also provide new insights into the relationships between tumour secretion and imaging phenotype in insulinomas.
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http://dx.doi.org/10.1007/s00259-018-4245-3DOI Listing
March 2019

Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1: A GTE and AFCE Cohort Study (Groupe d'étude des Tumeurs Endocrines and Association Francophone de Chirurgie Endocrinienne).

Ann Surg 2020 12;272(6):1094-1101

INSERM, U1231, Epidemiology and Clinical Research in Digestive Cancers Team, Dijon, France.

Objective: To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size.

Summary Background Data: DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known.

Methods: The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d'étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases.

Results: Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared.

Conclusions: DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.
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http://dx.doi.org/10.1097/SLA.0000000000003162DOI Listing
December 2020

Graves' disease: Introduction, epidemiology, endogenous and environmental pathogenic factors.

Ann Endocrinol (Paris) 2018 Dec 11;79(6):599-607. Epub 2018 Sep 11.

Service d'endocrinologie-diabétologie-nutrition, CHU de Pointe-à-Pitre, route de Chauvel, 97159 Pointe-à-Pitre, France. Electronic address:

Graves' disease is the most frequent cause of hyperthyroidism. Many questions remain about the choice of diagnostic evaluations and treatment strategy according to clinical context (age, gender, pregnancy, etc.) and about the best management of the main extrathyroidal complication that is Graves orbitopathy. The exact pathogenic mechanisms are not fully clear. They associate genetic factors, interactions between endogenous and environmental factors, and immune system dysregulation. Graves' orbitopathy is one of the consequences of this partial understanding. Iatrogenic Graves' disease induced by the new targeted therapies are described and could help to better understand the molecular pathways involved in the disease and to develop new therapeutic approaches.
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http://dx.doi.org/10.1016/j.ando.2018.09.002DOI Listing
December 2018

Thyroiditis and immune check point inhibitors: the post-marketing experience using the French National Pharmacovigilance database.

Fundam Clin Pharmacol 2019 Apr 14;33(2):241-249. Epub 2018 Nov 14.

Department of Clinical Pharmacology and Pharmacovigilance, University Hospital of Nancy, 29 avenue du Maréchal de Lattre de Tassigny, Nancy, 54035, France.

Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, is seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database. This database was queried for nivolumab, pembrolizumab, and ipilimumab-induced adverse drug reactions reported before April 30, 2017. Both a pharmacologist and an endocrinologist have reviewed each case to select only those of peripheral thyroiditis (thyrotoxicosis and hypothyroidism). During this period, 110 thyroiditis following ICI therapy were reported. Sex/ratio was around one. Most of the cases (47.2%) were asymptomatic. Although some thyrotoxicosis cases were severe, no orbitopathy was reported. Hypothyroidism and thyrotoxicosis were equally described. Antithyroid antibodies were positive in only 16% patients. The ultrasonography was informative in 19% patients. Levothyroxine supplementation was necessary in 57% patients, leading to 19% recovery. With a dedicated optimized management, most of the cases did not require immunotherapy discontinuation. Finally, immune-mediated related thyroiditis is increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.
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http://dx.doi.org/10.1111/fcp.12423DOI Listing
April 2019

Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer.

Thyroid 2018 09;28(9):1174-1179

8 Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave Roussy , Villejuif et Université Paris Saclay, France .

Background: Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is frequent in advanced follicular (FTC) and poorly differentiated thyroid (PDTC) carcinomas and has been implicated in oncogenesis and tumor progression. This study investigated the efficacy and safety of buparlisib, a pan-PI3K inhibitor in radioiodine refractory FTC and PDTC.

Methods: The primary endpoint of this open-label, multicenter, phase 2 pilot study was progression-free survival (PFS) at 6 months. The sample size was determined considering that a PFS ≤50% at 6 months would denote an absence of benefits (null hypothesis). Secondary endpoints were objective response rate, PFS at 12 months, overall survival at 6 and 12 months, and safety based on the frequency and severity of adverse events (AEs).

Results: Forty-three patients (19M/24 F; median age: 67 years) with metastatic, radioiodine refractory, progressive disease received buparlisib, 100 mg, daily. Histology was PDTC in 25 (58%), FTC in 17 (40%), and Hürthle cell carcinoma in 1 (2%). RAS mutation was found in 44% (12/27) and activation of the PI3K pathway in 35% (8/23) of tested tumors. The probability of PFS was 41.7% [95% confidence interval (CI) 7.7-55.5] at 6 months and 20.9% [CI 0-35.7] at 12 months, lower than the 50% expected PFS. At 6 months, 25.6% patients had stable disease, 48.8% were progressive and 25.6% had stopped treatment due to AE. The response to therapy was not influenced by age, sex, histology, or genetic alterations. The overall survivals at 6 and 12 months were 85.9% [CI 76-97] and 78.7 % [CI 67-92], respectively. The mean tumor growth rate decreased from 3.78 mm/month [CI 2.61-4.95] before treatment to 0.8 mm/month [CI -0.2-1.88] during treatment (p < 0.02). Severe grade 3-4 AEs occurred in 27 patients (63%), including hepatitis (25%), hyperglycemia (21%), mood disorders (12%), and skin toxicity (12%), with favorable outcome after temporary or permanent treatment discontinuation or dose reduction.

Conclusions: Buparlisib did not result in significant efficacy in advanced FTC and PDTC. However, the decrease in tumor growth rate may suggest incomplete inhibition of oncogenic pathways and/or escape mechanisms. This should lead to evaluate combined therapy associating inhibitors of both the PI3K and mitogen-activated protein kinase pathways.
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http://dx.doi.org/10.1089/thy.2017.0663DOI Listing
September 2018

18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas.

Neuroendocrinology 2018 27;107(3):228-236. Epub 2018 Jun 27.

Aix-Marseille Université, INSERM, U1251, Marseille Medical Genetics and AP-HM, Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares Hypophysaires HYPO, Marseille,

Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas (PHEO). However, its utility in determining predictive factors for the secretion of catecholamines remains poorly studied.

Methods: Thirty-nine histologically confirmed PHEO were included in this retrospective single-center study. Patients underwent 18F-FDOPA PET/CT before surgery, with an evaluation of several uptake parameters (standardized uptake values [SUVmax and SUVmean] and the metabolic burden [MB] calculated as follows: MB = SUVmean × tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and chromogranin A. Thirty-five patients were screened for germline mutations in the RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for real-time measurement of catecholamine release by carbon fiber amperometry.

Results: The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r = 0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006). In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar correlation was observed between MB and 24-h urinary combined MN and NM (r = 0.86, p = 0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p = 0.01).

Conclusion: While the 18F-FDOPA PET/CT MB of PHEO strongly correlates with the concentration of MN, amperometric recordings suggest that 18F-FDOPA uptake could be enhanced by overactivity of catecholamine exocytosis.
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http://dx.doi.org/10.1159/000491578DOI Listing
January 2019

The computed tomography adrenal wash-out analysis properly classifies cortisol secreting adrenocortical adenomas.

Endocrine 2018 03 13;59(3):529-537. Epub 2018 Jan 13.

Department of Endocrinology, University Hospital of Nancy, Nancy, France.

Purpose: Adrenocortical lesions are characterized through imaging, hormonal and histopathological analysis. Our aim was to compare the radiological features of adrenocortical lesions with their cortisol-secreting status and histopathological Weiss score.

Methods: Seventy five patients operated between 2004 and 2016 in the University Hospital of Nancy for either adrenocortical carcinomas (ACC) or adrenocortical adenomas (ACA) were enrolled in this study. We collected cortisol parameters, Computed Tomography (CT) scans (unenhanced density, wash-out (WO) analysis) and F-Fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) datas. The histopathological Weiss score ultimately differentiates ACA (score ≤ 2) from ACC (score ≥ 3). One-way ANOVA, Fisher's exact and unpaired t tests were used for statistical analysis with significancy reached at p < 0.05.

Results: There were 23 ACC and 52 ACA with 40 patients (53%) who had an autonomous secretion of cortisol. On CT scan, ACC were larger compared to ACA (108 vs. 37 mm, p < 0.0001). A roughly similar proportion of cortisol-secreting (22/25) and non-secreting (15/19) ACA were atypical (i.e., unenhanced density value ≥ 10 Hounsfield Units [HU]), however 85% of cortisol-secreting vs. 40% of non-secreting ACA were classified as benigns by the relative WO analysis (p = 0.08). Likewise, there was a trend for a higher F-FDG uptake in cortisol-secreting ACA compared to non-secreting ACA (p = 0.053).

Conclusions: The relative adrenal WO analysis consolidates the benign nature of an ACA, especially in case of cortisol oversecretion, a condition known to compromise the diagnostic accuracy of the 10 HU unenhanced CT attenuation threshold.
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http://dx.doi.org/10.1007/s12020-018-1522-7DOI Listing
March 2018

A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study.

Eur J Cancer 2017 05 20;76:110-117. Epub 2017 Mar 20.

Department of Medical Oncology, Institut Claudius Régaud, IUCT, Toulouse, France.

Purpose: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting.

Patients And Methods: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point. Secondary end-points were progression-free survival, overall survival and safety.

Results: Seventy-one patients were enrolled from August 2007 to October 2009, 41 MDTC/4 MATC patients and 26 MMTC patients. Patients received a median of 8 and 9 cycles, respectively. In the MDTC/MATC group, 13% of patients and 43% of cycles and in the MMTC group, 23% of the patients and 48.8% of cycles remained at 50 mg/d, respectively. The primary end-point was reached with an objective response rate of 22% (95% CI: 10.6-37.6) in MDTC patients and in 38.5% (95% CI: 22.6-56.4) in MMTC patients. No objective response was seen in MATC patients. Median progression-free survival and overall survival were 13.1 and 26.4 months in MDTC patients, 16.5 and 29.4 months in MMTC patients. The most frequent side effects were asthenia/fatigue (27.8% ≥ grade 3), mucosal (9.9% ≥ grade 3), cutaneous toxicities, hand-foot syndrome (18.3% ≥ grade 3). Of all, 14.1% had a cardiac event. Nine unexpected side effects were reported, out of which, five induced deaths.

Conclusion: Sunitinib is active in MDTC and MMTC patients. Side effects were more severe than with previous reports. If using sunitinib, alternative schedule/dosage should be considered.
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http://dx.doi.org/10.1016/j.ejca.2017.01.029DOI Listing
May 2017

Black and white autoimmunity: early warning colours of adrenal crisis.

Lancet Diabetes Endocrinol 2017 06 11;5(6):482. Epub 2016 Oct 11.

Endocrinology, University Hospital of Nancy, Vandœuvre-lès-Nancy, France.

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http://dx.doi.org/10.1016/S2213-8587(16)30117-6DOI Listing
June 2017

Long-Term Quality of Life and Pregnancy Outcomes of Differentiated Thyroid Cancer Survivors Treated by Total Thyroidectomy and I(131) during Adolescence and Young Adulthood.

Int J Endocrinol 2016 8;2016:7586482. Epub 2016 Feb 8.

Department of Endocrinology, University Hospital Center of Nancy, 54000 Nancy, France; Department of Endocrinology, University Hospital Center of Poitiers, 86000 Poitiers, France.

Introduction. Differentiated thyroid cancer (DTC) is rare and confers good prognosis. Long-term health related quality of life (HRQoL) and pregnancy outcomes are not well known in subjects treated during adolescence and young adulthood. Methods. Cross-sectional analysis of HRQoL and global self-esteem, using SF-36 and ISP-25 surveys, and of pregnancy outcomes in female survivors of DTC treated by total thyroidectomy and I(131) before age of 25 years. Results. Forty-five of 61 patients (74%) responded to the survey. Cumulative I(131) activity was ≤3.85 GBq in 18 subjects and >3.85 GBq in 27 subjects. Mean time from diagnosis was 7.6 ± 5.2 years for the group ≤ 3.85 GBq versus 16.9 ± 11.6 years for the group > 3.85 GBq (P < 0.05). No significant alteration in long-term HRQoL and global self-esteem was observed. Thirty pregnancies after I(131) were noted in patients from the group > 3.85 GBq and 10 in patients from the group ≤ 3.85 GBq. Frequency of miscarriages was of 17% (group > 3.85 GBq) and 10% (group ≤ 3.85 GBq) with 9 and 24 live births, respectively. No congenital malformations or first year mortality was noted. Conclusion. Long-term HRQoL, global self-esteem, and pregnancy outcomes are not affected in young female survivors of DTC.
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http://dx.doi.org/10.1155/2016/7586482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761673PMC
March 2016

Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.

Endocr Relat Cancer 2016 04 2;23(4):221-33. Epub 2016 Mar 2.

Department of Endocrinology, Centre Hospitalier Universitaire de Liege, University of Liege, Liege, Belgium

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes.
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http://dx.doi.org/10.1530/ERC-16-0082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877443PMC
April 2016

Thyroid side effects prophylaxis in front of nuclear power plant accidents.

Ann Endocrinol (Paris) 2016 Feb 29;77(1):1-6. Epub 2016 Jan 29.

University of Lorraine, Department of Endocrinology and Medical Gynecology, University Hospital of Nancy, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.

The better knowledge of the mechanisms of nuclear incidents and lessons learned from accidents in the recent past to improve the effectiveness of measures taken following a nuclear accident exposure to fallout of radioactive iodine isotopes. Thus, immediate, passive measures, such as containment, and stopping consumption of contaminated products are paramount. The earliest possible administration of stable iodine as potassium iodide (KI) reduces significantly (up to 90% if taken at the same time of the accident) thyroid radioactive contamination. These tablets should be given in priority to children and pregnant women. The side effects are minor. KI is not recommended for persons aged over 60 years, or for adults suffering from cardiovascular disorders.
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http://dx.doi.org/10.1016/j.ando.2015.12.003DOI Listing
February 2016

Efficacy and safety of denosumab for the treatment of osteoporosis: A systematic review.

Ann Endocrinol (Paris) 2015 Dec 27;76(6):650-7. Epub 2015 Nov 27.

Department of Endocrinology, Lorraine University, University Hospital Center of Nancy, Vandœuvre-lès-Nancy, France. Electronic address:

Denosumab is an anti-RANK ligand (RANKL) monoclonal antibody approved for the treatment of postmenopausal osteoporosis and prevention of skeletal metastasis complications. Administered subcutaneously every 6 months, it reduces the risk of vertebral fracture by 70% and of hip fracture by 40%. Its safety profile is acceptable. Denosumab may be used to treat patients with moderate to severe renal insufficiency. It has anti-fracture activity equivalent to that of zoledronic acid, but no residual effect, and no action at all beyond 6 months. In France, denosumab is reimbursed as a second-line treatment after a first attempt with bisphosphonate.
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http://dx.doi.org/10.1016/j.ando.2015.10.009DOI Listing
December 2015

Robotic lateral transabdominal adrenalectomy.

J Surg Oncol 2015 Sep 15;112(3):305-9. Epub 2015 Jul 15.

Department of Digestive, Université de Lorraine, CHU Nancy (Hopital Brabois Adultes), Hepato-Biliary, Endocrine Surgery, and Surgical Oncology, France.

Laparoscopic transabdominal adrenalectomy is considered to be the standard of care for adrnalectomy. Widespread adoption of robotic technology has positioned robotic adrenalectomy as an option in some medical centers. Many studies have compared laparoscopic versus robotic approaches to perform adrenalectomy and evaluated potential advantages to balance higher costs. This review summarizes current available data regarding the use of the robotic system to perform adrenalectomy (RA) and its comparison with laparoscopic adrenalectomy (LA).
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http://dx.doi.org/10.1002/jso.23960DOI Listing
September 2015

Systematic review on success of narrow-diameter dental implants.

Int J Oral Maxillofac Implants 2014 ;29 Suppl:43-54

Purpose: The aim of this systematic review was to determine the survival and success rates of narrow-diameter implants (NDI) in different clinical indications compared to standard diameter implants.

Materials And Methods: Implant diameters were categorized into categories 1 (< 3.0 mm), 2 (3.00 to 3.25 mm), and 3 (3.30 to 3.50 mm). Retro- and prospective studies with more than 10 patients and a follow-up time of 1 year or more were included.

Results: A literature search from 1995 to 2012 revealed 10 articles reporting on implant diameters < 3 mm (Category 1), 12 articles reporting on implant diameters 3 to 3.25 mm (Category 2), and 16 articles reporting on implant diameters 3.3 to 3.5 mm (Category 3). The quality of the studies was mostly low with a high risk of bias. Dental implants < 3.0 mm (mini-implants) were one-piece in the edentulous arch and non-loaded frontal region with survival rates between 90.9% and 100%. For dental implants with a diameter between 3.0 and 3.25 mm, most were two-piece implants inserted into narrow tooth gaps without loading and in the frontal region. Survival rates for these implants ranged between 93.8% and 100%. Implants of 3.3 to 3.5 mm were two-piece and were also used in the load-bearing posterior region. Survival rates were between 88.9% and 100%, and success rates ranged between 91.4% and 97.6%. A meta-analysis was conducted for NDI (3.3 to 3.5 mm), which showed no statistically significant difference in implant survival compared to conventional implants with an odds ratio of 1.16 (0.7 to 1.69).

Conclusions: Narrow-diameter implants of 3.3 to 3.5 mm are well documented in all indications including load-bearing posterior regions. Smaller implants of 3.0 to 3.25 mm in diameter are well documented only for single-tooth non-load-bearing regions. Mini-implants < 3.0 mm in diameter are only documented for the edentulous arch and single-tooth non-load-bearing regions, and success rates are not available. Long-term follow-up times > 1 year and information on patient specific risk factors (bruxism, restoration type) are also missing.
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http://dx.doi.org/10.11607/jomi.2014suppl.g1.3DOI Listing
June 2014

Characterization and plasma measurement of the WE-14 peptide in patients with pheochromocytoma.

PLoS One 2014 11;9(2):e88698. Epub 2014 Feb 11.

Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France.

Granins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors. The aim of the present study was to investigate the tumoral chromogranin A (CgA)-derived peptide WE-14 and the potential advantage to combine plasma WE-14 detection with the EM66 assay and the existing current CgA assay for the diagnosis of pheochromocytoma. Compared to healthy volunteers, plasma WE-14 levels were 5.4-fold higher in patients with pheochromocytoma, but returned to normal values after surgical resection of the tumor. Determination of plasma CgA and EM66 concentrations in the same group of patients revealed that the test assays for these markers had an overall 84% diagnostic sensitivity, which is identical to that determined for WE-14. However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays. By combining the results of the three assays, the sensitivity for the diagnosis of pheochromocytoma was increased to 95%. In fact, the combination of WE-14 with either CgA or EM66 test assays achieved 100% sensitivity for the diagnosis of paragangliomas and sporadic or malignant pheochromocytomas if taken separately to account for the heterogeneity of the tumor. These data indicate that WE-14 is produced in pheochromocytoma and secreted into the general circulation, and that elevated plasma WE-14 levels are correlated with the occurrence of this chromaffin cell tumor. In addition, in association with other biological markers, such as CgA and/or EM66, WE-14 measurement systematically improves the diagnostic sensitivity for pheochromocytoma. These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088698PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921219PMC
October 2014

Secisbp2 is essential for embryonic development and enhances selenoprotein expression.

Antioxid Redox Signal 2014 Aug 4;21(6):835-49. Epub 2014 Feb 4.

1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .

Aims: The selenocysteine insertion sequence (SECIS)-binding protein 2 (Secisbp2) binds to SECIS elements located in the 3'-untranslated region of eukaryotic selenoprotein mRNAs. Selenoproteins contain the rare amino acid selenocysteine (Sec). Mutations in SECISBP2 in humans lead to reduced selenoprotein expression thereby affecting thyroid hormone-dependent growth and differentiation processes. The most severe cases also display myopathy, hearing impairment, male infertility, increased photosensitivity, mental retardation, and ataxia. Mouse models are needed to understand selenoprotein-dependent processes underlying the patients' pleiotropic phenotypes.

Results: Unlike tRNA[Ser]Sec-deficient embryos, homozygous Secisbp2-deleted embryos implant, but fail before gastrulation. Heterozygous inactivation of Secisbp2 reduced the amount of selenoprotein expressed, but did not affect the thyroid hormone axis or growth. Conditional deletion of Secisbp2 in hepatocytes significantly decreased selenoprotein expression. Unexpectedly, the loss of Secisbp2 reduced the abundance of many, but not all, selenoprotein mRNAs. Transcript-specific and gender-selective effects on selenoprotein mRNA abundance were greater in Secisbp2-deficient hepatocytes than in tRNA[Ser]Sec-deficient cells. Despite the massive reduction of Dio1 and Sepp1 mRNAs, significantly more corresponding protein was detected in primary hepatocytes lacking Secisbp2 than in cells lacking tRNA[Ser]Sec. Regarding selenoprotein expression, compensatory nuclear factor, erythroid-derived, like 2 (Nrf2)-dependent gene expression, or embryonic development, phenotypes were always milder in Secisbp2-deficient than in tRNA[Ser]Sec-deficient mice.

Innovation: We report the first Secisbp2 mutant mouse models. The conditional mutants provide a model for analyzing Secisbp2 function in organs not accessible in patients.

Conclusion: In hepatocyte-specific conditional mouse models, Secisbp2 gene inactivation is less detrimental than tRNA[Ser]Sec inactivation. A role of Secisbp2 in stabilizing selenoprotein mRNAs in vivo was uncovered.
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http://dx.doi.org/10.1089/ars.2013.5358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116110PMC
August 2014

Is thyroid cancer recurrence risk increased after transplantation?

J Clin Endocrinol Metab 2013 Oct 24;98(10):3981-8. Epub 2013 Jul 24.

Fédération d'Endocrinologie, Groupement Hospitalier Est, 59 Boulevard Pinel, 69677 Bron Cedex, France.

Context: An increased cancer mortality is reported in transplanted patients.

Objective: This multicentric study aimed to investigate the rate of thyroid cancer recurrence after transplantation.

Results: Sixty-eight patients (35 male/33 female) with a history of both thyroid cancer and organ transplantation were recruited via two nationwide French networks. Histological analysis identified 58 papillary (88%), 5 follicular (7.5%), and 3 poorly differentiated cancer cases (4.5 %). Thirty-one patients (52%) presented high recurrence risk tumors. In the 36 patients with thyroid cancer diagnosed after transplantation, the 5-year disease-free survival (DFS) was 74.7% (SE: 7.3%). One patient died after progression of a poorly differentiated cancer. Persistent disease was observed in six high-risk patients. One of them underwent a second transplantation and disease remained stable after 5 years of follow-up. Thyroid cancer had been diagnosed before transplantation in 32 patients. One patient with cystic fibrosis and thyroid lung metastases at the time of lung transplantation underwent a 4-year remission. For the 31 patients in remission at the time of transplantation, the 5-year DFS was 93.1% (SE: 4.8%). Two patients with local recurrence presented subsequent remission. For the entire study population, the 5-year and 9-year DFS were 81.9% (SE: 5.5%) and 75.6% (SE: 7.9%), respectively. Recurrence or persistent disease occurred in patients with high-risk tumors.

Conclusions: The prognosis of thyroid cancer does not seem to be altered by transplantation. This suggests that a history of thyroid cancer should not be considered a contraindication.
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http://dx.doi.org/10.1210/jc.2013-1357DOI Listing
October 2013