Endocrine Abstracts

Familial hypocalciuric hypercalcaemia (FHH) is a rare but highly penetrant autosomal dominant condition, which is characterised by lifelong mild-to-moderate hypercalcaemia in association with normal or mildly raised serum parathyroid hormone (PTH) concentrations. FHH is considered to be a benign and asymptomatic condition, which in general requires no specific treatment. However, as this disorder has a similar serum biochemical phenotype to primary hyperparathyroidism (PHPT), ...

Familial hypocalciuric hypercalcaemia (FHH) is a rare but highly penetrant autosomal dominant condition, which is characterised by lifelong mild-to-moderate hypercalcaemia in association with normal or mildly raised serum parathyroid hormone (PTH) concentrations. FHH is considered to be a benign and asymptomatic condition, which in general requires no specific treatment. However, as this disorder has a similar serum biochemical phenotype to primary hyperparathyroidism (PHPT), ...

Hypoparathyroidism is characterized by absent or low circulating concentrations of parathyroid hormone (PTH), which results in hypocalcaemia, hyperphosphataemia and impaired renal reabsorption of calcium. Hypoparathyroidism has a prevalence of ~20–40 cases per 100 000 individuals, and anterior neck surgery accounts for around 75% of cases. Postsurgical hypoparathyroidism may arise in patients undergoing total thyroidectomy, radical neck dissection for head and neck malign...

The extracellular calcium (Cao2+)-sensing receptor (CaSR) is a family C G-protein-coupled receptor (GPCR) that regulates Cao2+ homeostasis by detecting alterations in Cao2+ concentrations and triggering Gq/11 signaling cascades, which modulate parathyroid hormone (PTH) secretion and urinary calcium excretion. Loss-of-function mutations of the CASR gene, located on chromosome 3q21.1, lead to familial h...

Lactation is a hormonally controlled process that promotes infant growth and development and reduces the long-term maternal risk of diabetes, cardiovascular disease and breast cancer. Hormones, such as prolactin and progesterone, mediate mammary development during pregnancy and are critical for initiating copious milk secretion during postpartum days 1-4. However, the hormone concentrations and mechanisms mediating lactation onset during this period of secretory activation are...

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 ...

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...

The onset of lactation after childbirth is a key determinant of successful breastfeeding. Copious milk secretion occurs by postpartum day 4 and is mediated by a decline in serum progesterone and high serum prolactin. However, the threshold prolactin concentration required is unclear. It is also unknown if changes in mammary prolactin sensitivity contribute to the initiation of lactation. To investigate this, we recruited 52 healthy pregnant women aged 26-42 years following inf...

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...

Heterotrimeric G-proteins are important molecular switches that transduce extracellular ligand-binding at G-protein-coupled receptors (GPCRs) to intracellular signals. G-protein alpha-subunits (Gα) have two domains, a helical and GTPase domain, which provide structural stability and mediate GTPase activity, respectively. Gain-of-function Gα mutations cause endocrine conditions including McCune-Albright Syndrome, due to Gαs mutations, and a...