Searchable abstracts of presentations at key conferences in endocrinology

ea0050cmw2.2 | Workshop 2: Hyper and Hypocalcaemia | SFEBES2017

Familial hypocalciuric hypercalcaemia

Hannan Fadil

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), ...

ea0050cmw2.2 | Workshop 2: Hyper and Hypocalcaemia | SFEBES2017

Familial hypocalciuric hypercalcaemia

Hannan Fadil

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), ...

ea0049s1.2 | Clinical Updates in Hypoparathyroidism | ECE2017

Acquired hypoparathyroidism

Hannan Fadil

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...

ea0035s28.3 | Molecular pathophysiology for clinicians: receptor-related disorders | ECE2014

Disorders related to calcium-sensing receptor signalling

Hannan Fadil

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...

ea0055p13 | Poster Presentations | SFEEU2018

Exacerbation of hypercalcemia caused by lithium in a patient with familial hypocalciuric hypercalcemia due to a calcium sensing receptor mutation

Dede Anastasia , Hannan Fadil , Cranston Treena , Thakker Rajesh , Shotliff Kevin

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 ...

ea0028oc2.8 | Reproduction and bone | SFEBES2012

A calcium-sensing receptor (CaSR) variant, Glu250Lys, present in familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemic hypercalciuria (ADHH) probands represents a functionally neutral polymorphism: lessons for CaSR mutational analysis

Hannan Fadil , Nesbit M Andrew , Cranston Treena , Thakker Rajesh

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...

ea0050oc6.6 | Bone, Calcium and Neoplasia | SFEBES2017

Calcium-sensing receptor (CaSR) mutations in hypercalcaemic and hypocalcaemic patients cluster at the extracellular dimer interface

Olesen Mie K , Gorvin Caroline M , Thakker Rajesh V , Hannan Fadil M

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...

ea0050p044 | Bone and Calcium | SFEBES2017

Disruption of the G-protein subunit α11 (Gα11) interdomain interface causes autosomal dominant hypocalcemia type-2 (ADH2)

Gorvin Caroline , Cranston Treena , Homfray Tessa , Shine Brian , Hannan Fadil , Thakker Rajesh

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...

ea0050p045 | Bone and Calcium | SFEBES2017

Uniparental isodisomy as a cause of the autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome

Cranston Treena , Boon Hannah , Ryan Fiona , Shears Debbie , Thakker Rajesh , Hannan Fadil

The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is an autosomal recessive disorder characterized by immune deficiency and the autoimmune destruction of endocrine organs such as the parathyroids, adrenal cortex and ovaries. APECED is caused by biallelic germline mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which is expressed in thymic medullary epithelial cells and plays a key role ...

ea0050p182 | Clinical Biochemistry | SFEBES2017

Clinical evaluation of a multiple-gene sequencing panel for hypoparathyroidism

Stokes Victoria , Cranston Treena , Boon Hannah , Gorvin Caroline , Hannan Fadil , Thakker Rajesh

Hypoparathyroidism may occur as: a hereditary syndromic disorder (e.g. Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED), Hypoparathyroidism Sensorineural Deafness and Renal Disease (HDR), Autosomal Dominant Hypoparathyroidism type 1 (ADH1), or ADH type 2 (ADH2), which are due to mutations of autoimmune regulator (AIRE), GATA binding protein 3 (GATA3), calcium-sensing receptor (CASR) and G-protein sub...