Endocrine Abstracts

A 52 years old man was referred to the renal clinic for persistent proteinurea and leg swelling with suspicion of nephrotic syndrome. He had a history of Hypertension and chronic depression and was taking olanzapine, venlafaxine, Ramipril.He also had diarrhoea of 5–6 stools per day over the last 6 months. He was getting short of breath and had lost weight. On examination he had erythematous rash over the face, limbs and abdomen which he mentioned was exacerbated by stress...

Vitamin D-dependent rickets type-1 (VDDR1) is an autosomal recessive disorder characterised by onset of rickets by 2 years of age, accompanied by poor growth and hypotonia, muscle weakness, seizures, hypocalcaemia with secondary hyperparathyroidism, hypophosphataemia and normal plasma 25-hydroxyvitamin D (25(OH2)D) concentration that distinguishes VDDR1 from vitamin D deficient rickets. VDDR1 is caused by loss-of-function mutations of the 25-hydroxyvitamin D 1-alpha...

The calcium-sensing receptor (CaSR), a class C G-protein coupled receptor (GPCR) is critical for calcium homeostasis. The presence of CaSR at the plasma membrane (PM) is regulated by a balance between internalisation via clathrin-mediated endocytosis, and agonist-induced PM insertion from intracellular receptor pools, in a mechanism known as agonist-driven insertional signalling. Recently, mutations of the clathrin-mediated endocytic adaptor protein-2 sigma subunit, AP2σ,...

Familial hypocalciuric hypercalcaemia type-3 (FHH3) is caused by loss-of-function mutations of the sigma subunit of adaptor protein-2 (AP2), a ubiquitously expressed heterotetrameric protein with a fundamental role in endocytosis of transmembrane proteins. FHH3-associated AP2σ mutations impair internalisation of calcium-sensing receptor (CaSR) giving rise to FHH. CaSR predominantly signals via Gαq/11 leading to intracellular calcium release, and activation...

Hereditary hypercalcaemia can be a diagnostic challenge. We present a family with autosomal dominant hypercalcaemia that illustrates this. A 48-year-old man was referred with asymptomatic long standing hypercalcaemia (2.8–3.04 mmol/l), with plasma PTH levels between 45 and 48 ng/l (normal 15–65), and a high urinary calcium excretion, (24 h calcium collection 10.4 mmol/l (2.5–7.5), with high calcium excretion indexes) all consistent with primary hyperparathyroidi...

Background: Diabetes mellitus is the commonest endocrinopathy, Worldwide. Inspite of its commonality, the genetic basis of etiopathogenesis and pathophysiology are ever evolving and enigmatic. Amongst the protean genetic variations, cubulin gene and megalin gene mutations in diabetes are important in dictating genotype—phenotypic correlations and natural clinical course of diabetes. The genetic studies in this area are especially very sparse from Indian sub-continent. In...

Mutational analysis of the calcium-sensing receptor (CaSR) is frequently undertaken to confirm a diagnosis of familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemic hypercalciuria (ADHH). However, functional characterization of these CaSR mutations to demonstrate loss-of-function for FHH mutations and gain-of-function for ADHH mutations is infrequently performed. We demonstrate the importance of pursuing in vitro studies that investigate the functiona...

Introduction: Di George’s syndrome is a rare congenital disease that is usually diagnosed in childhood due to its presentation with velo-cardio-facial abnormalities.Case report: A 42-year-old man was incidentally found to be hypocalcaemic (corrected calcium 1.71 mmol/l) during a ‘well-man check’. A subsequent parathyroid hormone (PTH) was inappropriately low at 0.8 pmol/l (reference range 0.5–4.4 pmol/l).He was ...

Case report: A 67-year-old female with untreated congenital adrenal hyperplasia (21-hydoxylase deficiency) was diagnosed with bilateral vulval carcinomata. She was referred to another unit with serum sodium of 121 mmol/l, potassium 4.6 mmol/l and 17-hydroxyprogesterone of 714 nmol/l (0–14 nmol/l). A short synacthen test performed in the evening demonstrated a baseline cortisol of 558 nmol/l, rising to 643 nmol/l at 80 min. The baseline cortisol was deemed adequate but in ...

Background: Primary hyperparathyroidism (PHPT) is commonly diagnosed after the fifth decade of life. Current guidelines suggest that young patients with apparently sporadic PHPT should be screened as potential index cases for the multiple endocrine neoplasia type 1 (MEN-1) syndrome.Aim: To determine the prevalence of mutations in the MEN1 gene in young patients presenting with apparently sporadic PHPT before the age of 40 years.Met...