L’hypersécrétion de catécholamines est dans 10 à 20 % des cas, secondaire à un paragangliome (PGL). Les phéochromocytomes et les PGLs présentent un risque de récidive métastatique ou de nouvelle tumeur de 16 % à 10 ans [1]. Mr B, âgé de 51 ans, présente comme principal antécédent un PGL de 6 cm rétropéritonéale latéro-aortique gauche opéré en 2005 (Ki à 13,5 %), avec initialement une hyperfixation isolé en TEP-FDG. En 2013, le patient présente une récidive symptomatique due à 3 lésions supracentimétriques hypermétaboliques en TEP-FDG, à proximité du pédicule rénal gauche. La chirurgie permettra l’exérèse de 4 lésions (Ki 67 à 15 %, score PASS à 8). Un an plus tard, les normétanéphrines (NMN) sont augmentées de façon isolées à 2,5 fois la normale et le bilan morphologique montre une lésion de 17 mm en regard du pédicule vasculaire rénal gauche, hyper métabolique en TEP-FDG. L’enquête génétique n’a pas retrouvé d’anomalie pour les gènes SDHx et VHL. Après avis auprès de la RCP Comète, devant les risques chirurgicaux et la localisation rétro péritonéale un traitement par peginterféron alfa est proposé. À 3 mois de l’instauration, les NMN sont quasi normalisées, et la réévaluation morphologique retrouve une régression de la lésion de plus de 50 %. Comme décrit dans la littérature [2], un traitement par interféron-alpha pourrait être une alternative thérapeutique en cas de récidive de PGL, qui doit être évaluée sur de plus grand échantillon.

Il existe de nombreuses recommandations recentes sur le traitement des dyslipidemies (SFC-EAS/AHA-ACC/IAS), parfois contradictoires. Certaines situations cliniques se situant a la frontiere du champ traite par les recommandations, nous avons souhaite evaluer le comportement des endocrinologues francais face a ces situations. Cinq cent seize endocrinologues (289 femmes et 212 hommes) ont repondu a 6 cas cliniques soumis en ligne via un sondage effectue en juillet et septembre 2015. Selon la methode Delphi, 10 experts ont attribue une note sur 10 a chaque item de chaque cas clinique appreciant la conformite escomptee par rapport aux recommandations therapeutiques et l’agressivite therapeutique. Les variables explicatives prises en compte en analyse univariee puis multivariee ont ete : sexe, âge, inter-region d’exercice, lieu d’exercice, mode d’exercice et lecture reguliere d’au moins une revue internationale. La conformite est en moyenne de 6,2 (± 2,0) et l’agressivite de 5,1 (± 1,7), proches des valeurs moyennes etablies par les experts. Le score de conformite et celui de l’agressivite sont etroitement correles (r = 0,669, p Les tranches d’âges extremes et l’exercice liberal sont des facteurs associes avec une moindre conformite aux recommandations, toutefois cette enquete suggere que de nombreux facteurs additionnels non explores sont susceptibles d’intervenir.

Context Multiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed. Objective The aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1. Design Data regarding a study of 734 cases of MEN1 from the multicenter ‘Groupe d'étude des Tumeurs Endocrines’ were analyzed. Results There were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females ( P =0.06, P =0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females ( P <0.001, P <0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis ( P =0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%). Conclusion The phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d’étude des Tumeurs Endocrines P Goudet, C Bonithon-Kopp, A Murat, P Ruszniewski, P Niccoli, F Ménégaux, G Chabrier, F Borson-Chazot, A Tabarin, P Bouchard, G Cadiot, A Beckers, I Guilhem, O Chabre, P Caron, H Du Boullay, B Verges and C Cardot-Bauters Centre Hospitalier Universitaire de Dijon, Service de Chirurgie Endocrinienne, Dijon, France, INSERM CIE1; Centre Hospitalier Universitaire de Dijon, Centre d’Investigation clinique-Epidémiologie clinique, Dijon, France, Clinique d’Endocrinologie, Centre Hospitalier Universitaire, Nantes, France, Service de Gastro-entérologie, Groupement Hospitalier Universitaire Nord, Hôpital Beaujon, Clichy, France, Service d’Endocrinologie, Diabète et Maladies métaboliques, Centre Hospitalier Universitaire La Timone, Marseille, France, Service de Chirurgie Générale, Viscérale et Endocrinienne, Groupement Hospitalier Universitaire Est, Hôpital de la Pitié, Paris, France, Service de Médecine interne et Nutrition, Centre Hospitalier Universitaire, Hôpital de Hautepierre, Strasbourg, France, Service d’Endocrinologie, Centre Hospitalier Universitaire Est, Hôpital Wertheimer, Lyon, France, Service d’Endocrinologie, Centre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, France, Service d’Endocrinologie, Groupement Hospitalier Universitaire Est, Hôpital Saint Antoine, Paris, France, Service d’Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire, Hôpital Robert Debré, Reims, France, Service d’Endocrinologie Clinique, Centre Hospitalier Universitaire de Liège, Liège, Belgium, Service d’Endocrinologie, Diabète et Maladies métaboliques, Centre Hospitalier Universitaire de Rennes, Hôpital Sud, Rennes, France, Service d’Endocrinologie, Diabète et Maladies métaboliques, Centre Hospitalier Universitaire de Grenoble, Hôpital Michalon, Grenoble, France, Service d’Endocrinologie, Diabète et Maladies métaboliques, Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey, Toulouse, France, Service d’Endocrinolgie, Centre Hospitalier de Chambéry, Chambéry, France, Service d’Endocrinologie, Diabète et Maladies métaboliques, Centre Hospitalier Universitaire de Dijon, Hôpital du Bocage, Dijon, France and Service de Médecine interne et Endocrinologie, Clinique Marc Linquette, Centre Hospitalier Régional et Universitaire, Lille, France

Multinodular goiter is a common disorder, found in 5% of the general population. If only one thyroid lobe is affected, hemithyroidectomy may be preferred to total thyroidectomy, to limit the risk of complications and avoid hormone replacement therapy, but incurs a risk of subsequent completion thyroidectomy. The aim of the present study is to determine whether the arguments in favor of hemithyroidectomy are justified and whether it still provides real benefit.A retrospective observational study based on prospective data included all patients who underwent surgery for goiter or nodule in our center between September 2010 and September 2014. Rates of hormone replacement 6 months after hemithyroidectomy, postoperative complications and completion thyroidectomy during the postoperative year due to the discovery of carcinoma were analyzed.Four hundred and ninety-three patients were studied: 335 with total thyroidectomy and158 with hemithyroidey. The rate of hormone replacement 6 months after hemithyroidectomy was 84.4%. The rate of definitive hypocalcemia was 6.3% in total thyroidectomy and zero in hemithyroidectomy (P < 0.05). There was no significant difference between groups in terms of recurrent laryngeal nerve palsy (1.8% versus 1.9%; P = 1) or hematoma (1.2% versus 3.5%; P = 0.15). A total of 11.3% of hemithyroidectomies required completion due to discovery of carcinoma (mean interval between surgeries 3.58 ± 2.5 months).This study suggests that hemithyroidectomy does not in fact avoid the risk of hormone replacement and places the patient at risk of completion thyroidectomy. However, it does avoid a 6% rate of hypocalcemia. We would recommend hemithyroidectomy only in case of single toxic or euthyroid nodule with healthy contralateral lobe and/or refusal of hormone replacement by the patient.Le goitre multinodulaire est une pathologie fréquente, de l’ordre de 5 % de la population générale. Si un seul lobe thyroïdien est atteint, l’isthmolobectomie peut être préférée à une thyroïdectomie totale pour diminuer les risques de complications et éviter la supplémentation hormonale, mais expose le patient à un risque de totalisation. Le but de cette étude est de savoir si ces arguments sont justifiés et s’il reste vraiment un intérêt à l’isthmolobectomie.Nous avons réalisé une étude observationnelle rétrospective basée sur des données recueillies de façon prospective. Nous avons étudié tous les patients opérés d’un goitre ou nodule thyroïdien dans notre centre entre septembre 2010 et septembre 2014. Nous avons analysé le taux de supplémentation hormonale à 6 mois après isthmolobectomie, les complications postopératoires et le taux de totalisation dans l’année du fait de la découverte d’un carcinome thyroïdien.Nous avons étudié 493 patients (335 thyroïdectomies totales et 158 isthmolobectomies). Le taux de supplémentation hormonale était de 84,4 % à 6 mois de l’isthmolobectomie. Nous avons trouvé un taux d’hypocalcémie définitive de 6,3 % parmi les cas de thyroïdectomies totales et aucun parmi les isthmolobectomies (p < 0,05). Il n’y avait pas de différence significative en terme de paralysie récurrentielle (1,8 % versus 1,9 %; p = 1) ou d’hématome (1,2 % contre 3,5 %; p = 0,15). Au total, 11,3 % des isthmolobectomies ont été totalisées en raison de la découverte d’un carcinome, avec un intervalle moyen de 3,58 ± 2,5 mois après la première opération.Cette étude suggère que l’isthmolobectomie ne réduit pas le risque de supplémentation hormonale et expose le patient au risque d’une totalisation secondaire. Néanmoins, l'isthmolobectomie prévient le risque de 6 % d’hypocalcémie associée à la thyroïdectomie totale. Nous recommandons une isthmolobectomie en cas de nodule unique (toxique ou euthyroïdien) avec un lobe controlatéral sain et/ou en cas de refus de supplémentation hormonale du patient après chirurgie.

Background. Once familial medullary thyroid carcinoma gene carrier status is established, thyroidectomy must be performed in infancy for mutations in exon 10, but in familial medullary thyroid carcinoma with non-cysteine RET mutations, which is characterized by a late onset of C-cell disease, the appropriate timing of thyroidectomy is unclear.Methods. We analyzed the rases of 76 patients who underwent thyroidectomy (mean age, 35.2 years); 66 patients underwent concomitant lymphadenectomy.Results. Before the operation, 35 patients had abnormal basal calcitonin levels. Nine and 30 patients had negative or positive pentagastrin test results, respectively. We found normal thyroid in 4% of the patients, C-cell hyperplasia in 29% of the patients, medullary thyroid carcinoma in 67% of the patients (microscopic in 82.4%), and nodal metastases in 19.6% of the patients. The aggressiveness of the disease varied significantly between those Patients with preoperative positive pentagastrin test results and those patients with high basal calcitonin levels, with a surgical cure rate of 60% and 34.3%, respectively. All patient who did not achieve cure had high basal preoperative calcitonin levels, which were related to macroscopic medullary thyroid carcinoma and nodal metastases in 5 of 9 patients.Conclusion. Thyroidectomy should not be delayed until basal calcitonin level becomes abnormal, at which time advanced disease may be present. As soon as the pentagastrin stimulation test becomes abnormal, operation should be undertaken on early staged disease to achieve cure for the patient. When performed while pentagastrin stimulation test is still negative, thyroidectomy may be truly prophylactic and should be recommended at 5 to 6 years.

Familial medullary thyroid carcinoma only is related to germ. line mutations in the protooncogene RET, mainly in exons 10, whereas noncysteine mutations (exons 13-15) are considered infrequent. We analyzed 148 patients from 47 familial medullary thyroid carcinoma only families, and we found noncysteine RET mutations in 59.5% of these families. Of the index cases with noncysteine mutations, 43.4% presented with a multinodular goiter and high basal calcitonin; they were older at diagnosis than those with mutation in exon 10 and had more multifocal medullary thyroid carcinoma, but no difference in size, bilaterality, presence of C cell hyperplasia, or nodal metastases was found. Gene carriers with noncysteine RET mutations had a lower incidence of medullary thyroid carcinoma (78.2% vs. 94.1%) than those with mutation in exon 10; 20.2% had C cell hyperplasia only, although thyroidectomized at an older age. In conclusion, familial medullary thyroid carcinoma with noncysteine RET mutations are not infrequent and are overrepresented in presumed sporadic medullary thyroid carcinoma, suggesting that RET analysis should routinely be extended to exons 13,14, and 15. The phenotype is characterized by a late onset of the disease, suggesting a delayed appearance of C cell disease rather than a less aggressive form. In familial medullary thyroid carcinoma gene carriers, the optimal timing for thyroidectomy remains controversial. Based on these data, we propose that surgery should be performed before elevation of the basal calcitonin level, potentially as soon as the pentagastrin test becomes abnormal.

OBJECTIVE:The aim of this prospective study is to update our knowledge of the chronology of pheochromocytoma occurrence in multiple endocrine neoplasia type 2 (MEN 2), and to better manage MEN 2 patients after the genetic diagnosis.DESIGN:Eighty-seven non-index gene carrier MEN 2 patients were included in this prospective study: 84 patients with MEN 2A (from 52 families) and 3 with MEN 2B (from 3 families).METHODS:Medullary thyroid carcinoma (MTC) was diagnosed by measuring plasma calcitonin in basal conditions or after pentagastrin stimulation. The search for pheochromocytoma consisted of clinical evaluation, 24 h determination of urinary catecholamines and adrenal imaging. The mean age at genetic diagnosis of MEN 2 was 14.0+/-7.0 years, the mean duration for the follow-up was 7.6+/-2.8 years.RESULTS:All 87 patients had a MTC detected at the same time as the genetic diagnosis was made. Urinary catecholamine measurements led to the diagnosis of pheochromocytoma and a combination of imaging techniques enabled the correct localization of both unilateral or bilateral adrenal involvement. Pheochromocytoma was detected simultaneously with MTC in only seven patients, and seven others were detected throughout the follow-up. Of the 14 patients with pheochromocytoma, 11 had bilateral involvement: nine were initially bilateral and two became so during follow-up.CONCLUSION:This study demonstrates that in MEN 2, MTC is the lesion which appears earliest. Pheochromocytoma develops later during the evolution of the disease, and necessitates regular clinical and biological monitoring throughout follow-up. Determination of urinary and/or plasma catecholamines and metanephrines should be performed to detect pheochromocytoma. Imaging techniques lead to the detection of both unilateral and bilateral pheochromocytoma, thus making video-assisted laparoscopic adrenalectomy possible.

RET is a receptor tyrosine kinase gene which is responsible for three different inherited cancer syndromes namely multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as for Hirschsprung disease (HSCR), a congenital disorder affecting the intestinal motility. Germ-line mutations in the RET exons 10 and 11 were demonstrated in the majority of the MEN 2A and FMTC patients. On the other hand, one codon of RET exon 16 is preferentially changed in MEN 2B patients. Recently, a germ-line mutation in the exon 13 was described in one FMTC family as well as in four sporadic MTCs. In the present study, we observed the same exon 13 mutation in two FMTC families. In addition, we identified a previously unreported substitution of RET exon 14 in two unrelated FMTC families. Both mutations segregate with the disease in these four FMTC families and involve the tyrosine kinase domain of RET. Haplotype analysis using polymorphic markers tightly linked to the RET gene indicates that in each pedigree the mutation arose as an independent event.

Antibodies were of the IgG type and non-specific at elution. A search for other causes of haemolytic anaemia with positive Coombs' test gave negative results. Antiamiodarone antibodies have recently been discovered; they reflect an immunological disturbance due to this drug and might be responsible for some of the undesirable effects of amiodarone. In our patients, hyperthyroidism and haemolytic anaemia were induced by a dual mechanism: accumulation of amiodarone and induction of an effect of this drug on the immune system.

Nous rapportons les observations de deux malades qui ont développé à la suite d'un traitement prolongé par amiodarone, une hyperthyroïdie et une anémie hémolytique immune. Les anticorps étaient de type IgG sans spécificité à l'élution. La recherche des autres étiologies d'anémie hémolytique à test de Coombs positif est restée négative. Il a été récemment mis en évidence des anticorps antiamiodarone témoignant d'un dérèglement immunologique dû à la molécule et pouvant être responsable de certains effets indésirables. Dans nos deux observations il est vraisemblable que l'hyperthyroïdie et l'anémie hémolytique relèvent d'un double mécanisme: accumulation de l'amiodarone et induction d'un mécanisme immunologique par cette molécule.

The influence of glycaemic control and diabetes characteristics on plasma concentrations of magnesium, zinc, copper, selenium, rubidium and bromine has been evaluated in 44 diabetics (30 insulin-dependent, 14 non insulin-dependent), and the results obtained were compared to those of 309 control subjects of the same mean age. Diabetics had reduced plasma magnesium concentrations (P less than 0.01) but normal erythrocyte magnesium levels. Plasma zinc and selenium concentrations were reduced, whereas those of copper were increased and those of bromine and rubidium were normal. Correlation between glycaemic control, evaluated by measurement of glycosylated haemoglobin levels, and each of the parameters studied was only demonstrated with magnesium in insulin-dependent diabetics (r = -0.561; P less than 0.02). No correlation was found with the other clinical or anthropometric characteristics of the diabetic patients studied. Diabetes seems to be associated with numerous abnormalities of plasma trace elements and magnesium, but the mechanism of these abnormalities has not yet been elucidated. A decrease in zinc and selenium concentrations and an increase in copper concentrations might be additional factors of atherogenicity.

The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.

The characteristics of an ultrasensitive thyrotropin (TSH) assay method using monoclonal antibodies (TSH-U) were determined in euthyroid subjects, either healthy or with extra-thyroid disease, in treated and untreated hyper-and hypothyroid subjects and in subjects under amiodarone. The thyroid function was evaluated by free thyroxine (FT4) and free triiodothyronine (FT3) assays and by TSH tests and TSH response to TRH. With a sensitivity of 1 and a specificity of 0.94, the TSH-U assay proved highly reliable to evaluate the thyroid function. Dysthyroidism can be excluded when TSH-U levels are normal (0.15 to 4.5 microU/ml). In case of low TSH-U level, measurements of FT4 and FT3 and, if required, thyroid gland scintigraphy are necessary to confirm a diagnosis of hyperthyroidism. In contrast, a high TSH-U level is sufficient for affirm diagnosis of hypothyroidism. The TSH-U assay makes the TRH test redundant and can differentiate between hyperthyroxinaemia with euthyroidism and with hyperthyroidism. It is an effective method to detect disorders in thyroid function and it calls for a re-evaluation of thyroid diagnostic strategy.