Endocrine Abstracts

More than 190 disease-causing mutations of V2 vasopressin receptor (AVPR2) have been identified in patients with X-linked nephrogenic diabetes insipidus (NDI). About half of the mutations lead to a loss or truncation of the receptor protein whereas missense mutations present a variety of functional alterations such as reduced binding and signaling abilities and improper cell surface trafficking. To date, the therapy of NDI focuses mainly on treating clinical symptoms with thia...

Objective: Growth hormone (GH) has long been known to have neuroprotective properties. Hypophysectomy (Hx) completely abolishes circulating endocrine GH. Also neuronal (non-erythrocyte) haemoglobin beta chain (Hbb) in the hippocampus decreases following Hx while GH infusions and injections robustly increase the levels approximately 2-4-fold in male rat hippocampus. Recently it has been revealed that Hbb protein is present in mitochondria in the mammalian brain. Current investi...

Nephrolithiasis is a major clinical and economic health burden. We performed a genome-wide association study in British and Japanese nephrolithiasis populations and identified twenty nephrolithiasis-associated loci, five of which (DGKD, DGKH, WDR72, GPIC1 and BCR) were predicted to influence calcium-sensing receptor (CaSR) signalling. Gain-of-function CaSR-signalling pathway mutations cause enhanced signalling via intracellular calcium ([Ca2+]...

Diacylglycerol kinase delta (DGKD) has been implicated in calcium homeostasis and nephrolithiasis by genome-wide association studies. We have previously demonstrated that alterations in expression of DGKD cause biased calcium-sensing receptor (CaSR) signalling in vitro. To further elucidate the physiological role of DGKD we examined the biochemical phenotype of a Dgkd-haploinsufficient (+/-) mutant mouse developed by the International Mouse Phenotyping Consor...

Introduction: The pathogenesis of kidney stone disease (KSD) is poorly understood and has been linked to features of metabolic syndrome (MetS). Using conventional and genetic epidemiological analyses we studied associations of MetS phenotypes with risk of KSD.Methods: Multivariate Cox-proportional hazard models were used to assess association of BMI and waist-hip ratio (WHR) with KSD in 492,380 UK Biobank participants. Causal relationships between WHR, B...

Background: Kidney stone disease (KSD) has been linked to obesity, metabolic syndrome and higher serum calcium concentration (SCa). The mechanisms underlying these associations are uncertain. Using conventional and genetic epidemiological techniques, we aimed to investigate the effects of adiposity on KSD.Methods: Observational associations between adiposity and incident KSD in 479, 405 people from the UK Biobank were assessed. Genome-wide association st...

Introduction: The treatment of Graves’ disease is represented principally by anti-thyroid drugs, radioiodine ablation or thyroidectomy. Methimazole is the most used drug for the initial treatment. It is rare to encounter patients with resistant hyperthyroidism despite high doses of MMI.Case presentation: A 41-year-old woman was referred to our unit for resistant thyrotoxicosis. She had a confirmed Graves’ disease with positive serum Trab. Whils...