Endocrine Abstracts

Case history: A previously well 45-year-old lady presented with a 3-year history of hypertension initially diagnosed at a routine health check. Her blood pressure (BP) was 170-180/90-100 mmHg.Investigations: Showed hypokalaemia (K+= 3 mmol/l; NR 3.5-5.3 mmol/l), raised aldosterone (976pmol/l; NR 100-500pmol/l) and supressed renin activity (<0.2nmol/l/h), meeting criteria for diagnosing primary aldosteronism (PA). CT adrenals showed a 2.5 cm left adre...

Successful responses to radioiodine treatment in differentiated thyroid cancer ultimately depend on uptake via the sodium-iodide symporter (NIS). However, many tumors exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transforming gene-binding factor (PBF) is partially res...

The calcium-sensing-receptor (CaSR) is a G-protein-coupled receptor that plays a fundamental role in extracellular calcium homeostasis, but is also implicated in non-calcitropic disorders including colon cancer and asthma. In addition, CaSR is highly expressed in pancreatic islets where it has a role in insulin secretion. Patients with gain-of-function CaSR mutations, and mice (referred to as Nuf) with a gain-of-function CaSR mutation (Leu723Gln), develop autosomal dominant hy...

Serum concentrations of progesterone sulphates are raised in intrahepatic cholestasis of pregnancy (ICP), the commonest pregnancy-specific liver disease. Women with ICP have increased rates of gestational diabetes mellitus (GDM). We hypothesised that raised progesterone sulphates may modulate glucose homeostasis. Progesterone sulphates were assayed in serum samples from participants of the hyperglycaemia and adverse pregnancy outcomes (HAPO) study (n=79–94), and ...

Dysfunctional regulation of sodium-iodide symporter (NIS) trafficking can result in ineffective radioiodide uptake in patients with differentiated thyroid cancer. Understanding the trafficking pathways of this key protein can be used to optimise radioiodide therapy. Recently, we identified via HiLo microscopy that the protein ADP-ribosylation Factor 4 (ARF4) helps shuttle NIS to the plasma membrane. To understand how ARF4 interacts with NIS mechanistically, we utilised advance...

The incidence of thyroid cancer is rapidly increasing worldwide. Whilst outcome in thyroid cancer is generally good, up to 25% of patients develop recurrence, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver events. Whole exome sequencing data were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatic analysis of data on N=43 patients whose tumours recurred was ...

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 5–10% of women of reproductive age, and is the major cause of anovulatory infertility. Aberrant secretion and/or action of gonadotropins are implicated but, to date, we have only limited knowledge about the precise mechanisms involved. Recent genome wide association studies have discovered signals at loci close to the genes coding for gonadotropin receptors. The functional significanc...

Whole genome sequencing (WGS) has the potential to identify nearly all forms of genetic variation. In complex disorders with multiple manifestations WGS can establish a definitive diagnosis that may change clinical management (Stavropoulos et al. 2016 Genomic Med). Here, we report on the utility of WGS in establishing the correct diagnosis in a family with hyperuricaemia. Hyperuricaemia may occur as: part of a syndromic disorder (e.g. Lowe syndrome, renal col...

Bartter’s syndrome (BS) and Gitelman’s syndrome (GS) are renal tubular disorders affecting reabsorption of sodium, potassium and chloride. Common clinical features include muscle cramps and weakness, hypokalaemia, hypochloraemic metabolic alkalosis and elevated plasma aldosterone concentrations. Urinary calcium excretion and plasma magnesium concentrations may be differentiating features, such that hypomagnesaemia and hypocalciuria are typical of GS, and hypercalciur...

Patients termed to have radioiodine-refractory differentiated thyroid cancer (RR-DTC) cannot accumulate sufficient radioiodine for a therapeutic response due to sodium iodide symporter (NIS) dysregulation via diminished expression and/or altered plasma membrane (PM) localisation. Currently, the regulation of NIS localisation remains poorly defined and despite protein-protein interactions being well-described to modulate trafficking events, the NIS interactome is limited. Previ...