Endocrine Abstracts

Background: Inappropriately high aldosterone in patients with primary hyperaldosteronism (PHA) is due to increased aldosterone synthase (CYP11B2) activity. Selective in vivo imaging of overexpressed CYP11B2 in adrenals with positron emission tomography (PET) has not yet been achieved due to close homology of enzymes involved in aldosterone and cortisol (CYP11B1) synthesis.Aim: Synthesize a fluorine-18 labelled highly selective CYP11B2 inhibitor, [18...

Background and Aims: Type 1 diabetes mellitus (T1DM) is characterised by autoimmune destruction of pancreatic beta-cells resulting in insulin deficiency. Evaluation of novel therapies for T1DM requires reliable methods to measure beta-cell function, which is unattainable using traditional non-invasive imaging techniques. A new approach is manganese-enhanced magnetic resonance imaging (MEMRI). As a calcium analogue, manganese is taken up into pancreatic beta-cells during insuli...

G-protein subunit α-11 (Gα11), which is encoded by GNA11, plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, and germline loss-of-function mutations cause familial hypocalciuric hypercalcaemia type 2 (FHH2). Since Gα11 is ubiquitously expressed, we investigated whether FHH2 is associated with additional non-calcitropic phenotypes by analysing mice harbouring a homozygous germline deletion o...

Objectives: Noonan Syndrome (NS) is an autosomal dominant multi-system disorder characterised by short stature (SS), distinctive facial features and cardiovascular abnormalities. Mutations in multiple genes regulating the RAS-MAPK pathway have been identified in NS including 5 recently described novel LZTR1 variants. We identified 2 novel LZTR1 variants in patients with features of growth hormone insensitivity and NS. The molecular function of LZTR1 ...

Background: Primary aldosteronism is commonly caused by an aldosterone-producing adenoma (APA). Somatic mutations in the KCNJ5 gene (encoding an inwardly rectifying potassium channel) are found in around 40% of APAs, KCNJ5 germline mutations cause familial hyperaldosteronism type III. The role of KCNJ5 mutations in excessive aldosterone production is established but their role in cell growth is unclear.Objective: To study the e...

Introduction: Radioiodine (RI) is a safe and effective treatment for Graves’ disease. In the months following RI different strategies are used to gain control of thyroid status, although there is no evidence base as to the optimal approach.Objectives: To compare the incidence of dysthyroidism post-RI between three principal management strategies employed by clinicians.Study design and methods: Retrospective, observational, mul...

Objectives: Transition from paediatric (PC) to adult diabetes care (AC) is a vulnerable period for young people (YP). The West Midlands (WM) Regional Paediatric Diabetes Network conducted a region-wide study of Diabetes transition outcomes to identify 1. Areas of good practice, 2. Risk factors for poorer outcomes, 3. Regional objectives for services and 4. Provide baseline data against which future performance can be measured.Methods: Retrospective regio...

Objectives: The homozygous GHR pseudoexon (6Ψ) mutation leads to aberrant splicing of the GHR gene with clinical and biochemical heterogeneity. We investigated whether the phenotypic variability could be explained by transcript heterogeneity i.e. ratio of abnormal (6Ψ GHR) to normal (WT GHR) transcripts and/or the presence of concurrent defects in other short stature (SS) genes.Methods: 6 Ψ GHR ...

A new genetic disorder has recently been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio, constipation and a variable intellectual deficit, but exhibit a consistently severe skeletal dysplasia. Similar to these patients, Thra1PV/+ mice harbour a mutation that disrupts the C-terminal α-helix of TRα1 and express a domi...

Fluid restriction (FR) is the recommended first-line treatment for chronic hyponatraemia due to syndrome of inappropriate antidiuresis (SIAD) in expert guidelines, despite the lack of prospective data to support its efficacy. We aimed to test the hypothesis that FR was more effective than no treatment. 46 patients with chronic SIAD were randomised to either fluid restriction (1 litre/day, FR) or no specific hyponatraemia treatment (NoTx) for one month. Inclusion criteria were ...