Endocrine Abstracts

Background: Growing evidence suggests that hypothalamic lipid sensing plays a key role in controlling food intake, fat deposition and energy balance and that its dysregulation could lead to obesity and type 2 diabetes (T2D). Recent investigations reported that sphingosine-1-phosphate (S1P) is involved in the hypothalamic control of energy homeostasis. Intra-cerebroventricular administration of S1P decreased food intake and increased energy expenditure in rodents.<p class="...

Context: Mosaicism is a feature of several inherited tumor syndromes but is rarely systematically looked for in routine. MEN1 is an autosomal dominant hereditary syndrome characterized by several endocrine tumors affecting parathyroids, pancreas, and anterior pituitary most of the time, due to inactivating mutations in the MEN1 gene. Few cases of mosaicism in Multiple Endocrine Neoplasia type 1 (MEN1) have been described. MEN1 mosaicism is probably under-diag...

Objective: We describe two first cousins presenting with neonatal corticotropic deficiency and severe, early-onset obesity. This study aims to identify the molecular etiology of these disorders in both cases and highlights the limits of genetic investigations.Methods: We collected the clinical-biological data of the family and, more particularly, of the two first cousins (A and B). We performed several constitutive Next-generation Sequencing (NGS) protoc...

Background: The incidence of germline pathogenic/likely pathogenic variants (P/LPV) is relatively well described in low grade well differentiated neuroendocrine tumors (NETs). However, germline findings in G3 NENs including grade 3 NETs (G3NET) and poorly differentiated neuroendocrine carcinoma (NEC) is gravely understudied, and guidance related to germline testing in G3NEN is lacking.Methods: An IRB approved, single institution, retrospective chart revi...

Background: Germline pathogenic or likely pathogenic (P/LP) variants occur in approximately 10% of NEN patients with recent data suggesting a higher frequency in pancreatic NENs or paraganglioma/pheochromocytoma (PPGL). However, identification of VUS can complicate interpretation of germline results, particularly when diverse populations are under study and the optimal gene panel size for testing remains unclear.Methods: A single-center retrospective cha...

Turner syndrome (TS) is a rare condition with a high frequency of aortic dilatation (AD) and a risk of aortic dissection. Our objective was to evaluate the characteristics of the aorta in patients with TS.Methods: Analyses of aortic walls were obtained during prophylactic aortic replacement. Histological description and measurement of a standardized media degenerative score (MDC) were performed. Cytogenetic analysis quantified the level of monosomy X in ...

In the human adrenal gland, serotonin (5-HT), released by subcapsular mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R) positively coupled to cAMP/proteine kinase A (PKA) signaling pathway and calcium influx. The 5-HT4R is principally expressed in zona glomerulosa cells explaining why 5-HT strongly stimulates aldosterone production but only exerts a modest stimulatory action on cortisol. Interestingly, in primary pigmented...

Previous studies demonstrated that n-3 polyunsaturated fatty acids (PUFA) reduce insulin resistance and non-alcoholic fatty liver disease (NAFLD). However, we previously reported that transgenic expression of the fat-1 n-3 desaturase, inducing the endogenous production of n-3 PUFA, improved insulin resistance but not hepatic steatosis in a mouse model of obesity. Thus, we compared the effects of increasing n-3 PUFA levels through oral or endogenous approaches in diet-...

In human adrenals, serotonin (5-HT), released by subcapsular mast cells, increases aldosterone secretion through activation of type 4 serotonin receptors (5-HT4R) but only exerts a modest control on cortisol production. Interestingly, illicit synthesis of 5-HT in adrenocortical cells as well as overexpression of the 5-HT4R and ectopic expression of the type 7 receptor (5-HT7R) have been observed in bilateral macronodular adrenal hyperplasia res...

One third of diabetic patients suffer from Diabetic Nephropathy (DN) that leads to end-stage renal disease (ESRD). The molecular pathways involved remain underexplored. We showed that chronic phosphodiesterase-5 inhibition (PDE5i) improve vascular inflammation [1] and tissue remodelling, reducing proteinuria [2] in murine diabetes. Our aim was to investigate the effect of PDE5i on animal and human models of DN.Materials and methods: 16 mice were randomly...