Endocrine Abstracts

Although adrenal vein sampling (AVS) remains the gold-standard for distinguishing unilateral and bilateral disease in primary hyperaldosteronism (PHA), it is technically demanding and not always feasible. Metomidate (MTO), a potent inhibitor of CYP11B1 and CYP11B2, can be C11H3-labelled as a PET tracer (11C-MTO), and we have previously shown it to be an alternative to AVS for localising unilateral aldosterone-producing adenomas (APAs) (Burton <...

The causative link between circulating glucocorticoid excess and osteoporosis is established. Although circulating cortisol levels do not change significantly with age, local tissue metabolism may be implicated in age-related bone loss. The enzyme11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) increases local cortisol production, is expressed in human osteoblasts and its activity increases with age leading to a decrease in bone formation. We hypothesised that sele...

Introduction: Loss-of-function mutations in AIP are associated with familial isolated pituitary adenoma, often leading to gigantism due to invasive GH-secreting pituitary adenomas. One challenging problem in the management of patients carrying a missense AIP variant is to determine whether the missense variant is a disease-causing mutation or not. As most of the molecular mechanisms involved in the control of growth and the cell cycle are well-conserved, we p...

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor with an extracellular bilobed venus flytrap domain (VFTD) predicted to contain five calcium-binding sites. The major site for calcium-binding is comprised of amino acid residues that line the cleft between the two lobes of the VFTD. We investigated the structure-function relationships of VFTD CaSR mutations identified in patients with familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperpa...

Orexin-A and orexin-B orchestrate their diverse central and peripheral effects via two G-protein coupled receptors, OX1R and OX2R, which activate multiple G-proteins. They are involved in a host of physiological processes including, steroidogenesis, appetite control and energy regulation. Whilst some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatial...

Inbred laboratory mice are widely used to generate, by homologous recombination, transgenic and chemical mutagenesis routes, genetic models of human disease. However, physiological studies of such models are hampered by the lack of normal ranges for serum and urinary biochemistry, particularly in relation to acclimatisation following placement in metabolic cages. To establish such values, we investigated urinary and serum parameters in forty, 24–30 week-old C3H/HeH, BALB/...

Background: Consumption of a high-meat, low carbohydrate diet in late pregnancy is associated with fetal growth restriction, and raised blood pressure and glucose intolerance in the offspring. In a recent study in Motherwell, Scotland, where pregnant women had been advised to eat one pound (0.45 kg) of red meat per day during pregnancy and to avoid carbohydrate-rich foods, we found elevated fasting plasma cortisol levels in men and women whose mothers reported higher protein c...

The gut plays an important role in energy homeostasis, and gut function is under intensive neuroendocrine control. The non-invasive imaging techniques contrast enhanced ultrasound (CEUS) imaging and super resolution ultrasound (SRUS) have the potential visualise the gut and provide novel insight into its structure and function. We aimed to demonstrate that changes in duodenal villi structure can be monitored using CEUS and SRUS, providing an insight into the structural of the ...

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,...

Background: Primary aldosteronism (PA) is an important, potentially curable, cause of hypertension. Distinguishing unilateral and bilateral causes is a critical step in determining who should be considered for adrenalectomy. Adrenal vein sampling (AVS) remains the gold standard for lateralisation. However, AVS is technically challenging with limited availability. To address this, we have introduced molecular imaging using PET/CT with the radiotracer [11C]Metomidate ...