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05/2019 | eur j nucl med mol imaging
Functional imaging of concomitant lingual thyroid and parathyroid adenoma.
Ferriere A, Schwartz P, Haissaguerre M, Hindie E, Tabarin A


01/04/2019 | J Clin Endocrinol Metab   IF 5.8
Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma.
Buffet A, Ben Aim L, Leboulleux S, Drui D, Vezzosi D, Libe R, Ajzenberg C, Bernardeschi D, Cariou B, Chabolle F, Chabre O, Darrouzet V, Delemer B, Desailloud R, Goichot B, Esvant A, Offredo L, Herman P, Laboureau S, Lefebvre H, Pierre P, Raingeard I, Reznik Y, Sadoul JL, Hadoux J, Tabarin A, Tauveron I, Zenaty D, Favier J, Bertherat J, Baudin E, Amar L, Gimenez-Roqueplo AP

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. OBJECTIVE: Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. DESIGN: We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. Patients were divided into two groups: genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and historic patients, who only benefited from the genetic test several years after initial PPGL diagnosis. RESULTS: Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). CONCLUSION: Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.

03/2019 | lancet diabetes endocrinol
Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.
Castinetti F, Waguespack SG, Machens A, Uchino S, Hasse-Lazar K, Sanso G, Else T, Dvorakova S, Qi XP, Elisei R, Maia AL, Glod J, Lourenco DM Jr, Valdes N, Mathiesen J, Wohllk N, Bandgar TR, Drui D, Korbonits M, Druce MR, Brain C, Kurzawinski T, Patocs A, Bugalho MJ, Lacroix A, Caron P, Fainstein-Day P, Borson Chazot F, Klein M, Links TP, Letizia C, Fugazzola L, Chabre O, Canu L, Cohen R, Tabarin A, Spehar Uroic A, Maiter D, Laboureau S, Mian C, Peczkowska M, Sebag F, Brue T, Mirebeau-Prunier D, Leclerc L, Bausch B, Berdelou A, Sukurai A, Vlcek P, Krajewska J, Barontini M, Vaz Ferreira Vargas C, Valerio L, Ceolin L, Akshintala S, Hoff A, Godballe C, Jarzab B, Jimenez C, Eng C, Imai T, Schlumberger M, Grubbs E, Dralle H, Neumann HP, Baudin E

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.

03/2019 | bull cancer
[Update of the recommendations of good clinical practice for the use of PET in oncology].
Salaun PY, Abgral R, Malard O, Querellou-Lefranc S, Quere G, Wartski M, Coriat R, Hindie E, Taieb D, Tabarin A, Girard A, Grellier JF, Brenot-Rossi I, Groheux D, Rousseau C, Deandreis D, Alberini JL, Bodet-Milin C, Itti E, Casasnovas O, Kraeber-Bodere F, Moreau P, Philip A, Balleyguier C, Lucian A, Cachin F

Positron Emission Tomography (PET) is a functional nuclear medicine imaging technique which clinical value in oncology has been demonstrated. PET indications are constantly evolving, thanks to the contribution of research. The use of PET in oncology has been the subject of recommendations according to the Standard-Options-Recommendations methodology from the Federation Nationale des Centres de Lutte Contre le Cancer in 2002, updated in 2003. However, many scientific works have been published since 2003 and new tracers have also obtained a marketing authorization in France. The objective of this work was therefore to update the recommendations established in 2003. In this context, in collaboration with the Societe francaise de medecine nucleaire, a working group was set up for the development of good clinical practice recommendations under the HAS-INCA methodological label. The present document is issued from a comprehensive review of the literature and rigorous appraisal by a panel of national experts, organ specialists, clinical oncologists, surgeons, and imaging specialists. It is intended to be used as a guide to decision-making for those oncology teams that are able to manage patients in various situations in which the AMM label is not sufficiently precise.

01/02/2019 | Eur J Endocrinol   IF 4.3
Diagnosis of mosaic mutations in the MEN1 gene by next generation sequencing.
Coppin L, Ferriere A, Crepin M, Haissaguerre M, Ladsous M, Tabarin A, Odou MF


01/02/2019 | J Clin Endocrinol Metab   IF 5.8
CT Characteristics of Pheochromocytoma: Relevance for the Evaluation of Adrenal Incidentaloma.
Canu L, Van Hemert JAW, Kerstens MN, Hartman RP, Khanna A, Kraljevic I, Kastelan D, Badiu C, Ambroziak U, Tabarin A, Haissaguerre M, Buitenwerf E, Visser A, Mannelli M, Arlt W, Chortis V, Bourdeau I, Gagnon N, Buchy M, Borson-Chazot F, Deutschbein T, Fassnacht M, Hubalewska-Dydejczyk A, Motyka M, Rzepka E, Casey RT, Challis BG, Quinkler M, Vroonen L, Spyroglou A, Beuschlein F, Lamas C, Young WF, Bancos I, Timmers HJLM

Background: Up to 7% of all adrenal incidentalomas (AIs) are pheochromocytomas (PCCs). In the evaluation of AI, it is generally recommended that PCC be excluded by measurement of plasma-free or 24-hour urinary fractionated metanephrines. However, recent studies suggest that biochemical exclusion of PCC not be performed for lesions with CT characteristics of an adrenocortical adenoma (ACA). Aim: To determine the proportion of PCCs with ACA-like attenuation or contrast washout on CT. Methods: For this multicenter retrospective study, two central investigators independently analyzed the CT reports of 533 patients with 548 histologically confirmed PCCs. Data on tumor size, unenhanced Hounsfield units (HU), absolute percentage washout (APW), and relative percentage washout (RPW) were collected in addition to clinical parameters. Results: Among the 376 PCCs for which unenhanced attenuation data were available, 374 had an attenuation of >10 HU (99.5%). In the two exceptions (0.5%), unenhanced attenuation was exactly 10 HU, which lies just within the range of 10 and available washout data, 22 (28.9%) had a high APW and/or RPW, suggestive of ACA. Conclusion: Based on the lack of PCCs with an unenhanced attenuation of <10 HU and the low proportion (0.5%) of PCCs with an attenuation of 10 HU, it seems reasonable to abstain from biochemical testing for PCC in AIs with an unenhanced attenuation of

01/02/2019 | J Clin Endocrinol Metab   IF 5.8
Prognosis of malignant pheochromocytoma and paraganglioma (MAPP-Prono study): an ENS@T retrospective study.
Hescot S, Curras-Freixes M, Deutschbein T, van Berkel A, Vezzosi D, Amar L, de la Fouchardiere C, Valdes N, Riccardi N, Do Cao C, Bertherat J, Goichot B, Beuschlein F, Drui D, Canu L, Niccoli P, Laboureau S, Tabarin A, Leboulleux S, Calsina B, Libe R, Faggiano A, Schlumberger M, Borson-Chazot F, Mannelli M, Gimenez-Roqueplo AP, Caron P, Timmers HJLM, Fassnacht M, Robledo M, Borget I, Baudin E

Background: Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival in MPP patients. Patients and Methods: Retrospective multicentric study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010. Results: We included 169 patients from 18 European centers. Main characteristics of MPP patients were: primary pheochromocytoma in 53% of patients, tumor or hormone-related symptoms in 57% or 58% of cases, positive plasma or urine hormones in 81% of patients, identification of a mutation in SDHB in 42 % of cases. Metastatic sites included the bone (64%), lymph node (40%), lung (29%) and liver (26%); mean time between initial and malignancy diagnosis was 43 months (0-614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age <40 years, metanephrines <5-fold the upper limits of the normal range and low proliferative index. In multivariate analysis, hypersecretion (Hazard Ratio 3.02[1.65-5.55]; p:0.0004) was identified as independent significant prognostic factors of worst overall survival. Conclusions: Our results do not confirm SDHB mutations as a major prognostic parameter in MPP and suggest additional key molecular events involved in MPP tumor progression. Aside from SDHB mutation, the biology of aggressive MPP remains to be understood.

01/01/2019 | j endocr soc
Unilateral Adrenalectomy Could Be a Valid Option for Primary Nodular Adrenal Disease: Evidence From Twins.
Kyrilli A, Lytrivi M, Bouquegneau MS, Demetter P, Lucidi V, Garcia C, Moreno-Reyes R, Tabarin A, Corvilain B, Driessens N

Primary pigmented nodular adrenal disease (PPNAD) accounts for <1% of ACTH-independent Cushing syndrome. We describe the case of twin female patients with PPNAD who both had sustainable disease control after unilateral adrenalectomy, which corroborates current evidence in favor of unilateral adrenalectomy for a subset of patients with PPNAD. Patient A presented with a 10-kg weight gain over the past year and facial plethora. Diagnostic evaluation revealed abolition of normal cortisol rhythm with suppressed ACTH levels, normal adrenal CT and MRI imaging and a slightly left-predominant adrenal uptake on (131)I iodomethyl norcholesterol scintigraphy coupled with single-photon emission CT/CT. PPNAD was confirmed after genetic testing revealed a known pathogenic PRKA1A mutation (c.709 (-7-2) del6). At that time, her twin sister (patient B) was asymptomatic. Patient A underwent successful unilateral adrenalectomy and histology confirmed PPNAD. Two years after initial onset of symptoms in patient A, patient B was seen for the same subtle symptoms of progressive weight gain. Diagnostic test results were identical, revealing the same clinical features and mutational status as patient A. Patient B also underwent unilateral adrenalectomy with a favorable outcome. Follow-up 3 years after surgery for patient A and 18 months for patient B showed sustained disease control without recurrence and uncompromised quality of life, with no adrenal insufficiency having occurred. Unilateral adrenalectomy can be a successful therapeutic approach for patients with PPNAD with a mild phenotype without the risk and the inconvenience of subsequent adrenal insufficiency, which alters quality of life.

01/2019 | endocrine   IF 3.2
Signs and symptoms of acromegaly at diagnosis: the physician's and the patient's perspectives in the ACRO-POLIS study.
Caron P, Brue T, Raverot G, Tabarin A, Cailleux A, Delemer B, Renoult PP, Houchard A, Elaraki F, Chanson P

PURPOSE: Acromegaly is characterized by a broad range of manifestations. Early diagnosis is key to treatment success, but is often delayed as symptomatology overlaps with common disorders. We investigated sign-and-symptom associations, demographics, and clinical characteristics at acromegaly diagnosis. METHODS: Observational, cross-sectional, multicenter non-interventional study conducted at 25 hospital departments in France that treat acromegaly ( NCT02012127). Adults diagnosed with acromegaly < 5 years were enrolled. Demographic and clinical data were obtained from medical reports and patient questionnaires. Sign-and-symptom associations were assessed by multiple correspondence analysis (MCA). RESULTS: Overall, 472 patients were included in the analyses. MCA was unsuccessful in identifying sign-and-symptom associations at diagnosis. Endocrinologists (29.5% patients) and other clinical specialists (37.2% patients) were commonly first to suspect acromegaly. Morphologic manifestations (83.7-87.9% patients), snoring syndrome (81.4% patients), and asthenia (79.2% patients) were frequently present at diagnosis; differences were found between sexes for specific manifestations. Rates of discrepancy between patient- and physician-reported manifestations were highest for functional signs. Earliest manifestations prior to diagnosis, according to how they were detected, were enlarged hands and feet (6.4 +/- 6.8 and 6.2 +/- 6.9 years, functional signs), hypertension (6.6 +/- 7.5 years, complementary examination) and carpal/cubital tunnel syndrome (5.7 +/- 6.7 years, functional signs with complementary examination). CONCLUSIONS: Results confirm the broad range of manifestations at diagnosis and delay in recognizing the disease. We identified early manifestations and sex differences that may aid physicians in diagnosing acromegaly. Discrepancy rates suggest physicians should obtain the patient's perspective and seek functional signs during diagnosis.

01/2019 | endocrine   IF 3.2
Correction to: Signs and symptoms of acromegaly at diagnosis: the physician's and the patient's perspectives in the ACRO-POLIS study.
Caron P, Brue T, Raverot G, Tabarin A, Cailleux A, Delemer B, Renoult PP, Houchard A, Elaraki F, Chanson P

The original version of this article unfortunately contained a mistake in corresponding author name as Philippe Chanson in the affiliation section.