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203 publication(s) since Janvier 1986:

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12/10/2018 | Eur J Endocrinol   IF 4.3
Should we avoid using ketoconazole in patients with severe Cushing's syndrome and increased levels of liver enzymes?
Ollivier M, Haissaguerre M, Ferriere A, Tabarin A

We read with interest the paper of Young et al. in which the authors recommend avoiding ketoconazole in the treatment of Cushing's syndrome when patients display increased liver enzymes (>2-fold the upper limit of normal (ULN)). We found in a small series of patients that We read with interest the paper of Young et al. in which the authors recommend avoiding ketoconazole in the treatment of Cushing's syndrome when patients display increased liver enzymes (>2-fold the upper limit of normal (ULN)). Although limited, our experience suggests that liver function tests may improve during ketoconazole treatment and that, in a life-threatening situation such as severe Cushing's syndrome, increased liver enzymes should not preclude ketoconazole prescription.

09/2018 | Thyroid   IF 7.6
Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer.
Borson-Chazot F, Dantony E, Illouz F, Lopez J, Niccoli P, Wassermann J, Do Cao C, Leboulleux S, Klein M, Tabarin A, Eberle MC, Benisvy D, de la Fouchardiere C, Bournaud C, Lasolle H, Delahaye A, Rabilloud M, Lapras V, Decaussin-Petrucci M, Schlumberger M

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

The management of pheochromocytoma and paraganglioma has deeply evolved over the last years due to the discovery of novel genes of susceptibility, especially SDHx, MAX and TMEM127. While the modalities of diagnosis and management of patients presenting with hereditary pheochromocytoma and paraganglioma are now well defined, screening and follow-up strategies for asymptomatic mutation carriers remain a matter of debate. This raises major questions as these asymptomatic patients will require a lifelong follow-up. The aim of this review is an attempt to give insights on the optimal screening and follow-up strategies of asymptomatic carriers of SDHx, MAX and TMEM127 mutations, with additional thoughts on the forensic and psychological aspects of the management of such patients with rare diseases.

06/2018 | Clin Endocrinol (Oxf)   IF 3.1
Worse Health-Related Quality of Life at long-term follow-up in patients with Cushing's disease than patients with cortisol producing adenoma. Data from the ERCUSYN.
Valassi E, Feelders R, Maiter D, Chanson P, Yaneva M, Reincke M, Krsek M, Toth M, Webb SM, Santos A, Paiva I, Komerdus I, Droste M, Tabarin A, Strasburger CJ, Franz H, Trainer PJ, Newell-Price J, Wass JA, Papakokkinou E, Ragnarsson O

OBJECTIVE: Hypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS). METHODS: Data from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed. RESULTS: At baseline, HRQoL did not differ between PIT-CS (n = 293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 41 +/- 18 and 44 +/- 20, respectively (P = .7). At long-time follow-up (>1 year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 +/- 20 vs 62 +/- 23; P = .045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P < .001), and older age at diagnosis with worse total score (P = .01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P < .001). CONCLUSION: PIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.

06/2018 | Ann Endocrinol (Paris)   IF 1.4
Do the diagnostic criteria for subclinical hypercortisolism exist?
Tabarin A

'Subclinical hypercortisolism' (SH) refers to a condition associated with a mild chronic increase in cortisol secretion. By definition, patients with SH do not exhibit specific symptoms of overt Cushing's syndrome (such as purple striae, easy bruising, proximal muscle weakness), SH has been preferred to 'subclinical Cushing's syndrome', a semantic ambiguity since Cushing's syndrome is, by definition, a set of symptoms; and to the term 'preclinical Cushing syndrome' because the progression toward overt clinical hypercortisolism is very rare. However, SH still is misnomer as a number of studies suggest that this condition may induce long-term non-specific adverse conditions related to the mild cortisol excess (i.e. diabetes, hypertension, obesity, and osteoporosis). Various attempts have been made to define SH that remains a matter of controversies and uncertainties.

21/05/2018 | Clin Endocrinol (Oxf)   IF 3.1
Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score.
Vinolas H, Grouthier V, Mehsen-Cetre N, Boisson A, Winzenrieth R, Schaeverbeke T, Mesguich C, Bordenave L, Tabarin A

OBJECTIVE: Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid-treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. SETTING: University Hospital. DESIGN: Monocentric retrospective cross-sectional and longitudinal studies of consecutive patients. PATIENTS: A total of 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post-operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non-secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2 years after cure. RESULTS: Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (P < .03). As compared to patients with nonsecreting incidentalomas, patients with MACE had significantly decreased TBS (P < .04) but not BMD. Overt fragility fractures tended to be associated with low TBS (P = .07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its aetiology (P < .01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; P < .02). CONCLUSION: Trabecular bone score may be a promising, noninvasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice.

05/2018 | Eur J Endocrinol   IF 4.3
Diagnostic accuracy of computed tomography to identify adenomas among adrenal incidentalomas in an endocrinological population.
Marty M, Gaye D, Perez P, Auder C, Nunes ML, Ferriere A, Haissaguerre M, Tabarin A

CONTEXT: The recent recommendations of the European Endocrine Society states that the performance of computed tomography (CT) to characterize 'true' adrenal incidentalomas (AIs) remains debatable. OBJECTIVE: To determine relevant thresholds for usual CT parameters for the diagnosis of benign tumors using robust reference standard among a large series of 'true' AIs recruited in an endocrinological setting. DESIGN: Retrospective study of 253 AIs in 233 consecutive patients explored in a single university hospital: 183 adenomas, 33 pheochromocytomas, 23 adrenocortical carcinomas, 5 other malignant tumors and 9 other benign tumors. Reference standard was histopathology in 118 AIs, biological diagnosis of pheochromocytoma in 2 AIs and size stability after at least 1 year of follow-up in 133 AIs. METHODS: Sensitivity, specificity and positive and negative predictive values were estimated for various thresholds of size, unenhanced attenuation (UA), relative and absolute wash-out (RPW, APW) of contrast media. 197 scans were reviewed independently in a blinded fashion by two expert radiologists to assess inter-observer reproducibility of measurements. RESULTS: Criteria associated with a 100% positive predictive value for the diagnosis of benign AI were: a combination of size and UA: 30 mm and 20 HU or 40 mm and 15 HU, respectively; RPW >53%; and APW >78%. Non-adenomatous AIs with rapid contrast wash-out were exclusively benign pseudocysts and pheochromocytomas, suggesting that classical thresholds of 60% and 40% for APW and RPW, respectively, can be safely used for patients with normal metanephrine values. Inter-observer reproducibility of all parameters was excellent (intra-class correlation coefficients: 0.96-0.99). CONCLUSIONS: Our study, the largest conducted in AIs recruited in an endocrinological setting, suggests safe thresholds for quantitative CT parameters to avoid false diagnoses of benignity.

13/04/2018 | Mol Metab   IF 6.3
mTORC1-dependent increase in oxidative metabolism in POMC neurons regulates food intake and action of leptin.
Haissaguerre M, Ferriere A, Simon V, Saucisse N, Dupuy N, Andre C, Clark S, Guzman-Quevedo O, Tabarin A, Cota D

OBJECTIVE: Nutrient availability modulates reactive oxygen species (ROS) production in the hypothalamus. In turn, ROS regulate hypothalamic neuronal activity and feeding behavior. The mechanistic target of rapamycin complex 1 (mTORC1) pathway is an important cellular integrator of the action of nutrients and hormones. Here we tested the hypothesis that modulation of mTORC1 activity, particularly in Proopiomelanocortin (POMC)-expressing neurons, mediates the cellular and behavioral effects of ROS. METHODS: C57BL/6J mice or controls and their knockout (KO) littermates deficient either for the mTORC1 downstream target 70-kDa ribosomal protein S6 kinase 1 (S6K1) or for the mTORC1 component Rptor specifically in POMC neurons (POMC-rptor-KO) were treated with an intracerebroventricular (icv) injection of the ROS hydrogen peroxide (H2O2) or the ROS scavenger honokiol, alone or, respectively, in combination with the mTORC1 inhibitor rapamycin or the mTORC1 activator leptin. Oxidant-related signal in POMC neurons was assessed using dihydroethidium (DHE) fluorescence. RESULTS: Icv administration of H2O2 decreased food intake, while co-administration of rapamycin, whole-body deletion of S6K1, or deletion of rptor in POMC neurons impeded the anorectic action of H2O2. H2O2 also increased oxidant levels in POMC neurons, an effect that hinged on functional mTORC1 in these neurons. Finally, scavenging ROS prevented the hypophagic action of leptin, which in turn required mTORC1 to increase oxidant levels in POMC neurons and to inhibit food intake. CONCLUSIONS: Our results demonstrate that ROS and leptin require mTORC1 pathway activity in POMC neurons to increase oxidant levels in POMC neurons and consequently decrease food intake.

01/04/2018 | ann biol clin (paris)   IF 0.4
Serum GH concentration must now be expressed in mass units in France like in the rest of the world.
Chanson P, Reynaud R, Coutant R, Linglart A, Nicolino M, Rodien P, Borson-Chazot F, Tabarin A, Le Bouc Y, Piketty ML, Gauchez AS, Chevenne D, Porquet D, Souberbielle JC


04/2018 | Eur J Endocrinol   IF 4.3
Preoperative medical treatment in Cushing's syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN.
Valassi E, Franz H, Brue T, Feelders RA, Netea-Maier R, Tsagarakis S, Webb SM, Yaneva M, Reincke M, Droste M, Komerdus I, Maiter D, Kastelan D, Chanson P, Pfeifer M, Strasburger CJ, Toth M, Chabre O, Krsek M, Fajardo C, Bolanowski M, Santos A, Trainer PJ, Wass JAH, Tabarin A

BACKGROUND: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.