Endocrine Abstracts

Rajesh Thakker is the May Professor of Medicine at the University of Oxford, UK. He received his medical degree from the University of Cambridge in 1980, and from 1981 to 1988 he undertook postgraduate clinical and research training at The Middlesex Hospital, The Hammersmith (Royal Postgraduate Medical School, RPMS), Hospital, and Northwick Park (MRC Clinical Research Centre) Hospital (London). In 1988, he was appoint...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

Delayed puberty may occur in some boys affected with X-linked Spondyloepiphyseal dysplasia tarda (SEDT), which is caused by mutations of the gene encoding a 140 amino acid protein designated Sedlin. Sedlin interacts with the pituitary homeobox 1 (Pitx1) and steroidogenic factor 1 (SF1) transcription factors, which are involved in the development and regulation of the hypothalamic-pituitary-gonadal axis. We have therefore investigated the hypothesis that SEDT associated mutatio...

Case history: Idiopathic Infantile Hypercalcaemia (IIH) classically presents in the first year of life, usually resolves by 1 year of age and is due to mutations in 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1) or, rarely, sodium-phosphate cotransporter-2A (SLC34A1). We report a case of IIH in a Caucasian female, who was born to non-consanguineous parents, with hypercalcaemia, hypercalciuria and associated complications persisting into adulthoo...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

Current treatments, including surgery, medical therapy, radiotherapy, and radionuclide therapy for neuroendocrine tumours of the pancreas (PNETs) and bronchus (BNETs) are often unsatisfactory, leading to a 5-year survival of <50% and 5%, respectively. PNETs and BNETs frequently have mutations in chromatin-remodelling genes and the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin. Menin binds the...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

Current treatments, including surgery, medical therapy, radiotherapy, and radionuclide therapy for neuroendocrine tumours of the pancreas (PNETs) and bronchus (BNETs) are often unsatisfactory, leading to a 5-year survival of <50% and 5%, respectively. PNETs and BNETs frequently have mutations in chromatin-remodelling genes and the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin. Menin binds the...

Pancreatic neuroendocrine tumours (PNETs) have a lower mutational burden than other tumours, indicating that other mechanisms contribute to tumourigenesis. One such reported mechanism is DNA methylome dysregulation, however, inconsistencies have been observed between gene methylation and protein expression, potentially stemming from the use of standard methylation assessment methods which do not distinguish methylation (5’methylcytosine (5’mC), repressive mark) from ...