P. Thieblot

The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.

CONTEXT Germline mutations in SDHx genes cause hereditary paraganglioma. OBJECTIVE The aim of the study was to assess the indications for succinate dehydrogenase (SDH) genetic testing in a prospective study. DESIGN A total of 445 patients with head and neck and/or thoracic-abdominal or pelvic paragangliomas were recruited over 5 yr in 20 referral centers. In addition to classical direct sequencing of the SDHB, SDHC, and SDHD genes, two methods for detecting large genomic deletions or duplications were used, quantitative multiplex PCR of short fluorescent fragments (QMPSF) and multiplex ligation-dependent probe amplification (MLPA). RESULTS A large variety of SDH germline mutations were found by direct sequencing in 220 patients and by QMPSF and MLPA in 22 patients (9.1%): 130 in SDHD, 96 in SDHB, and 16 in SDHC. Mutation carriers were younger and more frequently had multiple or malignant paraganglioma than patients without mutations. A head and neck paraganglioma was present in 97.7% of the SDHD and 87.5% of the SDHC mutation carriers, but in only 42.7% of the SDHB carriers. A thoracic-abdominal or pelvic location was present in 63.5% of the SDHB, 16.1% of the SDHD, and in 12.5% of the SDHC mutation carriers. Multiple paragangliomas were diagnosed in 66.9% of the SDHD mutation carriers. A malignant paraganglioma was documented in 37.5% of the SDHB, 3.1% of the SDHD, and none of the SDHC mutation carriers. CONCLUSIONS SDH genetic testing, including tests for large genomic deletions, is indicated in all patients with head and neck and/or thoracic-abdominal or pelvic paraganglioma and can be targeted according to clinical criteria.

Epidemiology, clinical presentation, treatment and prognosis of a regional series of 26 anaplastic thyroid carcinomas (ATC). Comparison with the literature.

OBJECTIVE The aim of this study is to retrospectively describe the epidemiological and clinical features, therapeutic modalities, prognostic factors and survival figures in a population of patients with anaplastic thyroid carcinoma (ATC) observed in Auvergne, France. We compared these data with those in the literature. MATERIAL AND METHODS The analysis was conducted based on a computer database containing a regional register recorded by health professionals treating ATC. RESULTS Of the 1500 cancers observed over 16 years, 26 were identified as ATC. The male/female ratio was 1/2.7 and the average age: 72.1; 76.9% of the cases had thyroid medical history, average tumor size at diagnosis was 7.35 cm with N1 in the course of illness in 61.5% of cases, M1 in 34.6% of cases. Surgery was performed in 84.6% of cases, radiotherapy in 53.8% and chemotherapy in 19.2%. The average survival was 9 months, the survival median: 4 months. CONCLUSION Our results show that, in univariate analysis, age above 75, capsular invasion, lymph nodes metastasis, tumor residue after surgery and lack of multimodal treatment (particularly radiotherapy in patients without tumor residue) are factors of poor prognosis. In a multivariate analysis only age above 75, followed by node invasion, capsular invasion, and finally female gender are factors of poor prognosis.

Amiodarone-Induced Thyrotoxicosis Recurrence After Amiodarone Reintroduction.

Reintroduction of amiodarone in patients with a history of amiodarone-induced thyrotoxicosis (AIT) is rarely used. To date, the risk of AIT recurrence after amiodarone reintroduction is unpredicted. The aim of the study was to evaluate the risk of AIT recurrence. Retrospectively, from 2000 to 2011, all euthyroid patients with a history of AIT with amiodarone reintroduction were included. Type and severity of the first AIT, amiodarone chronology, and thyroid function evolution after reintroduction of amiodarone were investigated: 46 of 172 patients with AIT history needed amiodarone reintroduction. At first AIT episode, the mean age was 62.2 ± 16 years with male gender predominance; 65% of patients were classified as type 1 AIT. AIT recurred in 14 patients (30%), 12 patients developed hypothyroidism (26%), and 20 patients remained euthyroid (44%). Characteristics of type 1 AIT during the first episode, namely briefer exposure period to amiodarone and longer duration of treatment to normalize thyroid hormones, were predictive of AIT recurrence; 73% of patients (8 of 11) with previous episode of type 1 AIT, who did not receive a preventive thioamide treatment, developed a second episode of AIT. Thioamide preventive treatment could be useful to prevent type 1 AIT recurrence. In conclusion, AIT recurrence after amiodarone reintroduction is 4 times more frequent in patients with type 1 AIT history. Thyroid ablation before amiodarone reintroduction in patients with a history of type 1 AIT is preferred. Preventive thioamide treatment could be suggested in patients with type 1 AIT history pending for surgery.

The Clinical Spectrum of RET proto-oncogene mutations in codon 790

OBJECTIVE Due to a strong genotype-phenotype correlation, the timing of prophylactic thyroidectomy in rearranged during transfection (RET) gene mutation carriers is usually dictated by genetic analysis. SUBJECTS AND METHODS We report a nationwide retrospective study of the clinical data of 77 French patients from 19 families with a mutation in codon 790 of the RET proto-oncogene. RESULTS The average age at diagnosis was 35.6 years ± 20.5. Thirty-nine patients were women. Fifty-five patients underwent operations for the treatment of medullary thyroid carcinoma (MTC) at the mean age of 38 years (4-82 years). The mean follow-up duration was 89 months. TNM staging was as follows: T0NxMx in 19, TxNxMx in 1, T1NxMx in 22, T1N1Mx in 8, T2N1Mx in 1 and T3N1Mx in four patients. In the T1/x-Nx group, 96% were considered cured after surgery. In the N1 group (n=13), six patients had multifocal disease and five patients were cured. Age and gender were not significant predictors of remission. Twenty-two patients did not undergo an operation (age 1.5-78 years); among them, 11 patients had a mean basal calcitonin (CT) level of 9.8 pg/ml (2-24) after 53 months of follow-up. One patient had been operated on for phaeochromocytoma (PHEO), and their CT level remained normal for 262 months. CONCLUSIONS This study confirms that RET 790 mutation is associated with a non-aggressive form of multiple endocrine neoplasia type 2, as 28% of the patients were followed up without thyroidectomy, 25% had been thyroidectomised with no tumour being detected and even patients with MTC had slow-evolving disease. Moreover, only one patient had PHEO, and no-one had primary hyperparathyroidism.

Spontaneous rupture of Achilles tendon and Cushing's disease. Case report

Spontaneous rupture of Achilles tendon is observed in patients with tumors, metabolic disorders, infections and systemic diseases. Fluoroquinolones may cause tendinopathies. In addition, spontaneous rupture uncommonly occurs in Cushings syndrome. We report a case of Cushings disease revealed by recurrent rupture of Achilles tendon. Tendon tears are described in patients receiving long-term steroid treatment, probably via a mechanism similar to that one occurring in Cushings syndrome. Although exceptional, this diagnosis should be discussed in patients with spontaneous rupture of Achilles tendon.

Risque de récidive d’hyperthyroïdie après la réintroduction d’amiodarone

∗Auteur correspondant. Introduction.– L’hyperthyroïdie induite par l’amiodarone (HIA) augmente la morbidité/mortalité chez des patients présentant des antécédents cardiovasculaires. Certaines situations nécessitent la reprise de l’amiodarone malgré des antécédents d’HIA. Le risque de dysthyroïdie à la réintroduction n’est pas documenté. L’objectif est de déterminer le risque de récidive d’hyperthyroïdie après réintroduction d’amiodarone chez des patients avec antécédent d’HIA. Méthodes.– Les patients avec antécédents d’HIA nécessitants une reprise d’amiodarone entre 2000 et 2011 ont été inclus. Les données concernant le type et la sévérité de l’HIA (1er épisode), la durée d’exposition à l’amiodarone, et l’évolution du bilan thyroïdien après reprise de l’amiodarone ont été recueillis de manière rétrospective. Résultats.– Cinquante-deux patients ont été inclus. L’âge moyen au diagnostic du premier épisode d’HIA était de 62,2 ± 16 ans. 65,8 % des cas était HIA de type 1. Avant la réintroduction d’amiodarone, 6 patients ont bénéficié d’un traitement radical. L’amiodarone a été repris sans traitement prophylactique chez 22 patients et un traitement préventif par les antithyroïdiens de synthèse (ATS) a été prescrit en parallèle à l’amiodarone pour 24 patients. 14 (30,4 %) patients ont présenté une récidive d’hyperthyroïdie 34,9 ± 39,1 mois après la réintroduction de l’amiodarone ; 12 (26 %) ont développé une hypothyroïdie et 20 (43,6 %) sont restés en euthyroïdie. Un traitement prophylactique de récidive par les ATS pourrait prévenir la récidive (p = 0,06). Conclusion.– Après une durée moyenne de suivi de 3 ans, le risque de récidive d’HIA n’est pas négligeable (30,4 % des cas). Un traitement prophylactique par les thionamides pourrait diminuer ce risque.

P100 Complications diabétiques : intérêt du dépistage des populations précaires par le score EPICES

Introduction Dans l’hypothese ou la situation de precarite serait liee a des formes de diabete plus compliquees, le reperage des patients diabetiques en situation de precarite permettrait une action de prevention plus ciblee et d’intensifier leur suivi. Le score EPICES (Evaluation de la Precarite, Indice des Centres d’Examen de Sante), valide comme score de precarite pourrait permettre de reperer ces patients a risque. Patients et methodes Il s’agit d’une etude monocentrique descriptive realisee en CHU de novembre 2006 a juillet 2007. Les patients diabetiques ont ete repartis en 2 groupes selon leur statut de precarite (score EPICES > 30,17) ou non. L’equilibre du diabete ainsi que les differentes complications ont ete ensuite comparees dans les 2 groupes. La qualite de vie de ces 2 groupes de patients a egalement ete etudiee grâce au questionnaire SF-36. Resultats Cent deux patients ont rempli le questionnaire. 97 patients ont ete inclus : 18 porteurs d’un diabete de type 1 et 79 d’un diabete de type 2. Aucun lien statistique n’a pu etre mis en evidence entre score EPICES et valeur de l’HbA1c. Concernant les complications, la nephropathie est statistiquement reliee au seuil de precarite (p = 0,0489) tandis que la neuropathie tend a l’etre sans etre significative (p = 0,0624). Aucun lien n’apparait avec les autres complications. Les patients diabetiques precaires presentent par contre plus de comorbidites : surpoids (p = 0,001) et hypoHDLemie (p = 0,0424), cette derniere relation disparaissant apres ajustement sur l’âge, le delai d’evolution du diabete et le sexe. La qualite de vie des patients diabetiques precaires est bien moindre dans tous les aspects de la vie quotidienne etudies. Conclusion Alors que precarite et equilibre glycemique ne sont pas correles, les sujets diabetiques precaires depistes grâce au score EPICES sont exposes a un plus haut risque renal et cardio-vasculaire. La qualite de vie de ces patients est correlee a leur score EPICES de precarite.