New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Séparation parentale et autres facteurs de stress au cours de l'enfance :Lien éventuel avec l'apparition du diabète de type 1. Une revue systématique de la literature

Introduction :Type 1 diabetes mellitus (T1DM) results from an interaction between genetic and environmental factors. Its worldwide pediatric incidence is increasing annually by 2-5%, and given this rapid rate, the most likely explanation would be the influence of the environment. According to the ß cell stress hypothesis, psychological stress could be one of the risk factors for the disease. Parental separation is associated with increased health problems in childhood. Aims :Clarify the link between T1DM and childhood stress, including parental separation, as an environmental risk factor. Methods :Consultation of quaternary to primary databases with the following MeSH terms :« Child Adolescent Marital Status Diabetes Mellitus, Type 1 Life Change Events Stress, Psychological Risk Factors ». Results :Inclusion of 23 observational studies. Description of outcomes according to various factors: Parental separation, loss of relative, stressful events, parental stress, psychological dysfunction, and socio-economic status. Discussion :The majority of studies support the involvement of psychological stress in the pathogenesis of T1DM. The experience of stressful events could triple the risk of diagnosis. Hill's causality criteria support a link between T1DM and parental separation or the experience of stressful events. Conclusions :Parental separation and psychological stress in childhood appears to be an environmental factor influencing T1DM which should be considered in primary care medicine.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Does sleep apnea disappear once acromegaly is adequately treated?

Acromegaly is a rare hormonal disease related to excessive growth hormone secretion. It can result in a range of complications, including cardiovascular, respiratory, metabolic, articular and neoplastic disorders. Among patients with the condition, obstructive sleep apnea syndrome occurs frequently and the effect of treatment is inconstant: improvement, statu quo or deterioration can be observed. We here report three clinical cases, which illustrate the unpredictable evolution of this condition.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Histologically surprising nasal polyps

info:eu-repo/semantics/published15th European Congress of Endocrinologie – ECE 2013. Copenhaguen, Denmar

T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: The lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Adénome hypophysaire non sécrétant: faut-il traiter un résidu après chirurgie?

Diagnosis of non-functioning pituitary adenoma is generally posted when there is a compression of the ophthalmic nerve or when a hypopituitarism occurred. Surgery will be the first treatment but complete removal can be achieved in less than 50% of the patients. In the great majority of the patients, there is a recurrence and a new treatment is proposed. The question is when we must treat a residue after surgery. We performed a retrospective study reviewing a series of 111 patients with a non-functioning pituitary adenoma. All patients had a pre- and post-operative MRI (1.5 T). A statistical analysis was done to determine the influence of the resection, the age of the patient on the recurrence. A complete removal was achieved for 45 patients and 11 of these present a recurrence. 39 patients out of 66 patients who had a partial removal presented also a recurrence. The mean age of the population is 53 years. The statistical analysis demonstrates that patients with a complete removal had less recurrence. Patient with an age below 60 years had more frequently a recurrence compared with older than 60 years old. In conclusion, treatment for non-functioning pituitary adenoma is a transsphenoidal approach surgery. A complete surgery must be the aim of the neurosurgeon. And when a residue is present, a secondary treatment must be given for patient with an age below 60 years old like radiosurgery or radiation therapy.English AbstractEvaluation StudiesJournal Articleinfo:eu-repo/semantics/publishe

Minimally invasive endoscopic unilateral transsphenoidal surgery for pituitary adenomas

Objective: The aim of this study was to analyse the results of minimally invasive endoscopic unilateral transsphenoidal surgery for pituitary adenomas. Methods: A series of 83 patients presenting with a pituitary lesion was reviewed retrospectively. Surgical procedures were performed between February 2007 and December 2010. The extent of resection was evaluated on post-operative contrast-enhanced MRI. We also reviewed our complications and compared them with the literature. Results: Our series included 10 micro- and 73 macro-adenomas, with cavernous sinus invasion in 60.3%. Fifty-three per cent were non-secreting. Complete resection of the macro-adenomas was achieved in 22.5% of the cases. Complications were as follows: 2 deaths (2.5%), 2 sinusitis (2.5%), 5 CSF leaks (6.2%), 1 meningitis (1.2%), 16 post-operative anterior lobe insufficiency (19.8%) and 4 persistent diabetes insipidus (4.9%). Thirty-seven patients (44.6%) presented with a compression of optical pathways with an improvement of visual acuity in 94.3%. Conclusions: Purely endoscopic unilateral endonasal transsphenoidal adenoma resection is minimally invasive surgery leading to a good rate of gross total tumour resection and it is associated with a low complication rate.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Unexpected presentation of diabetes insipidus following pineal tumor resection: A case report

Background: Neuroendocrine dysfunction is a common complication of several neurosurgical conditions. In particular, central diabetes insipidus (CDI) can occur subsequent to traumatic brain injury, subarachnoid hemorrhage, cerebral tumors or as a result of a complication following pituitary neurosurgery. In contrast, surgical resection of non-sellar tumors does not commonly result in CDI, with only a few cases reported in the literature. Case description: We report the case of a 40-year-old man who presented a transient CDI following surgical resection of a pineal papillary tumor via an occipital interhemispheric trans-tentorial approach. The underlying pathogenesis of CDI occurring post resection of tumors arising at a distance from the sella is not yet clearly understood, especially since there is no evidence of direct compression of the pituitary stalk. With regards to our case, we hypothesize that restauration of the initial obstructive hydrocephalus might induce a rapid intracranial pressure variation leading to hemodynamics changes of the portal hypophyseal vascular system. Postoperative air entrapment in the sellar region might also lead to irritation of the pituitary stalk. Conclusion: This case highlights that CDI may happen as a consequence of pineal tumor resection and advocates for a careful postoperative monitoring.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland.

Genetic inactivation of ClC-5, a voltage-gated chloride channel prominently expressed in the kidney, leads to proteinuria because of defective apical endocytosis in proximal tubular cells. Because thyroid hormone secretion depends on apical endocytosis of thyroglobulin (Tg), we investigated whether ClC-5 is expressed in the thyroid and affects its function, using Clcn5-deficient knockout (KO) mice. We found that ClC-5 is highly expressed in wild-type mouse thyroid ( approximately 40% of mRNA kidney level). The protein was immunolocalized at the apical pole of thyrocytes. In Percoll gradients, ClC-5 overlapped with plasma membrane and early endosome markers, but best codistributed with the late endosomal marker, Rab7. ClC-5 KO mice were euthyroid (normal T4 and TSH serum levels) but developed a goiter with parallel iodine and Tg accumulation (i.e. normal Tg iodination level). When comparing ClC-5 KO with wild-type mice, thyroid 125I uptake after 1 h was doubled, incorporation into Tg was decreased by approximately 2-fold, so that trichloroacetic acid-soluble 125I increased approximately 4-fold. Enhanced 125I- efflux upon perchlorate and presence of 125I-Tg as autoradiographic rings at follicle periphery demonstrated delayed iodide organification. Endocytic trafficking of 125I-Tg toward lysosomes was not inhibited. Expression of pendrin, an I-/Cl- exchanger involved in apical iodide efflux, was selectively decreased by 60% in KO mice at mRNA and protein levels. Thus, ClC-5 is well expressed in the thyroid but is not critical for apical endocytosis, contrary to the kidney. Instead, the goiter associated with ClC-5 KO results from impaired rate of apical iodide efflux by down-regulation of pendrin expression

Pituitary stalk thickening: neoplastic or not? - author's response to the letter by Wang et al.

We thank Dr Shirui Wang and colleagues for their interest in our recent publication on the distinction of neoplastic from non-neoplastic lesions in adult patients presenting with central diabetes insipidus (CDI) and pituitary stalk thickening (PST) (1). We acknowledge the fact that they could not confirm in their population our previous observation that a higher prolactin (PRL) concentration at diagnosis increases the likelihood of a neoplastic origin (2). As they mentioned, such an association of CDI and PST represents a rare and heterogeneous disorder, raising challenging issues in both diagnosis and management. It is interesting to mention that only 46 out of their original cohort of 321 patients with PST (3) were eligible for this comparative analysis. As there are limited data about the prevalence and significance of hyperprolactinemia in such patients, any additional insight is most welcome and worth to debate. [...