Endocrine Abstracts

Case history: A 52 year-old lady was seen for further assessment of primary hyperparathyroidism (PHPT). She complained of intermittent symptoms of bloating but was otherwise asymptomatic. She was menopausal on hormone replacement therapy (HRT) and had started lithium for bipolar disorder 4 years ago. She had no known history of nephrolithiasis and no history of fractures. Her past medical history included Hodgkin’s lymphoma treated with chemotherapy 14 years ago, bipolar ...

Objectives: Autosomal Dominant Hypocalcaemia (ADH) is due to gain-of-function mutations of the CASR resulting in constitutive activation of the GPCR Calcium Sensing Receptor (CaSR) leading to hypercalciuric hypocalcaemia, hypoparathyroidism and occasionally Bartter syndrome type V. Patients usually present with hypocalcaemic seizures at young age. Conventional treatment is with Alfacalcidol and Calcium or PTH injections. We describe a series of five patients with ADH ...

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, failure to thrive and skeletal abnormalities such as accelerated osseous development, osteopenia, bullet-shaped middle phalanges and kyphoscoliosis. MSS is caused by truncating or frameshift mutations of the nuclear factor I/X (NFIX) gene, which encodes a ubiquitously expressed transcription factor that regulates expression of viral and cellular genes, i...

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...

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, failure to thrive and skeletal abnormalities such as accelerated osseous development, osteopenia, bullet-shaped middle phalanges and kyphoscoliosis. MSS is caused by truncating or frameshift mutations of the nuclear factor I/X (NFIX) gene, which encodes a ubiquitously expressed transcription factor that regulates expression of viral and cellular genes, i...

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...

Pancreatic neuroendocrine tumours (PNETs) may occur as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome, or as a non-familial isolated endocrinopathy. Current medical treatments for PNETs are largely ineffective in preventing tumour progression, so there is a need for better therapies, which will develop from an improved understanding of the mechanisms driving PNET tumorigenesis. Cytokine-driven inflammation has been implicated in the development and progression...

Neuroendocrine tumours (NETs) may occur in multiple sites including, the pancreas, gastrointestinal tract, lung, thymus, adrenals and pituitary, and as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome. Current treatments for advanced NETs, rarely achieve a cure due to metastases at presentation and therefore additional treatments are required. Identification of cell surface receptors or binding sites that are unique to NETs could lead to novel targeted drugs, ra...

Pancreatic neuroendocrine tumours (PNETs) may occur as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome or as non-familial (sporadic) tumours. PNETs, which include gastrinomas, insulinomas and non-functioning tumours occur in more than 80% of MEN1 patients and account for 50% of disease-specific deaths. This is because 25–40% of patients with PNETs will have metastasis at presentation, and current treatments, which include surgery, chemotherapy and radiothe...

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...