Endocrine Abstracts

New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow...

Background: Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours, and carries a poor prognosis (mean survival <4 years), with standard chemotherapeutic regimens showing limited efficacy. However, recent evidence suggests that temozolomide, an orally active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. Low levels of expression of the DNA-repair enzyme ...

Context: Hypertension is one of the most preventable risk factors for cardiovascular disease and death. Up to 42.1% of non-Hispanic African-American subjects have hypertension. We recently found that germline ARMC5 variants may play a role in primary aldosteronism, particularly in African-Americans.Objective: We investigated a cohort of participants in the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) stud...

Background: Congenital Hyperinsulinism (CHI) is a disease of severe hypoglycaemia due to insulin hypersecretion, that can be recognised either early or late in childhood. CHI is associated with adverse neurodevelopmental outcomes. The Vineland Adaptive Behaviour Scales Second Edition (VABS-II) is a parent-report measure of intellectual and developmental functioning, which could be used to screen children with CHI for impairments.Aims: To investigate reli...

Background: Diminished sodium iodide symporter (NIS) activity at the plasma membrane (PM) is frequently associated with suboptimal radioiodide (RAI) uptake and poor prognosis in differentiated thyroid cancer (DTC). Endocytosis is a key determinant of symporter activity, with our recent study demonstrating specific interaction of NIS with Adaptor Protein 2 (AP2) – a central player in endocytosis. Here, our objective was to determine whether NIS endocytosis...

Introduction: New approaches to improve radioiodide (RAI) uptake are urgently required in RAI-refractory thyroid cancer. We previously identified disulfiram as a leading candidate to induce sodium iodide symporter (NIS) activity and promote RAI uptake. In vivo, DSF is metabolised to diethyldithiocarbamate (DDC) which binds metal ions. Here, we aimed to gain a mechanistic understanding of how DSF and it’s related metabolite Cu(DDC)2 imp...

Familial hypocalciuric hypercalcaemia types 1, 2, and 3 (FHH1, FHH2, and FHH3) are caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), G-protein subunit α11 (Gα11) and adaptor protein 2 sigma subunit (AP2σ), respectively; whilst autosomal dominant hypocalcaemia types 1 and 2 (ADH1 and ADH2) are due to gain-of-function mutations of CaSR and Gα11, respectively. We therefore hypothesised that gain-of-function AP2σ mutations may re...

Familial hypocalciuric hypercalcaemia (FHH) comprises three types: FHH1, FHH2, and FHH3, which are due to mutations of the calcium-sensing receptor (CaSR), G-protein α 11 subunit (Gα11), and adaptor protein-2 sigma subunit (AP2σ), respectively. The aims of this study were: to assess for genotype–phenotype correlations among the three reported FHH3-causing AP2σ mutations, which all involve the Arg15 residue, and comprise Arg15Cys, Arg15His, and Arg15Leu...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by hypercalcaemia and inappropriately low urinary calcium excretion, and is occasionally associated with acute pancreatitis. FHH can be classified into three types: FHH type 1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), which accounts for >65% of cases; FHH type 2, due to loss-of-function mutations of the G-protein α 11 subunit (Gα11), of ...

The role of progesterone in male physiology is mainly unknown. We recently observed that progesterone was the most abundant sex hormone in orchiectomized (ORX) mice with most of it stored in white adipose tissue (WAT) (1). The aim of the present study was to use a sensitive and validated gas chromatography/tandem mass spectroscopy method to determine the origins of progesterone in male mice. Tissue levels of progesterone were high in adrenals of male mice, indicating that male...