Endocrine Abstracts

Reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2D) from 25-hydroxyvitamin D (25OHD) in end stage renal disease (ESRD) results in low serum 1,25(OH)2D. This appears to be due to reduced renal cell function and elevated serum fibroblast growth factor 23 (FGF23). Treatment strategies have therefore focussed on 1,25(OH)2D or its synthetic analogues, alfacalcidol or paricalcitol. However this overlooks 25-hydroxyv...

Recent in-vitro studies have shown that vitamin D metabolites undergo conjugation reactions by sulfation and glucuronidation and may be important mechanisms for the inactivation, storage and excretion of analytes. However the circulating concentrations and clinical significance of phase II vitamin D conjugation is unclear as current analysis has almost exclusively been restricted to measuring their unconjugated metabolite forms. In this study we aimed to develop an analytical ...

Objectives: Endogenous Cushing’s Syndrome (CS) is a rare, chronic condition that results in high morbidity, caused by prolonged exposure to elevated levels of circulating free cortisol levels. Osilodrostat, a newly approved steroidogenesis inhibitor, has been shown to achieve fast and high rates of cortisol normalization, improving manifestations of hypercortisolism in patients with Cushing’s Disease (CD), a form of CS. We evaluated relative complete response (CR) ou...

Background: We aim to test whether plasma copeptin (copeptin), the C-terminal fragment of vasopressin, has predictive value of cardiovascular events in patients with type 2 diabetes without previous cardiovascular disease who were treated in primary care.Methods: We measured copeptin in 697 patients who participated in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes – a Prospective Study in Primary Care; Clin...

Vitamin D exists as two forms; D3 (UV) and D2 (plant derived). Measuring the metabolite 25-hydroxyvitamin D (25OHD) is routinely applied in research and clinical laboratories to assess vitamin D status. The Institute of Medicine and Society for Endocrinology have previously set recommended vitamin D guidelines based on combined 25OHD3 and 25OHD2 serum concentrations. In order to achieve accurate quantitation of these metabolites, the respective C3 epimers must be separately qu...

Vitamin D-deficiency during pregnancy has been associated with increased complications of pregnancy including a high risk of pre-eclampsia (PET). Current analysis of vitamin D ‘status’ is based exclusively on analysis of maternal serum 25-hydroxyvitamin D3 (25(OH)D3), the circulating precursor form of vitamin D. We hypothesised that comprehensive profiling of vitamin D metabolites may provide a more accurate determination of vitamin D function i...

Vitamin D metabolites such as 25-hydroxyvitamin D (25D) circulate bound primarily to vitamin D binding protein (DBP). However, for most extra-renal tissues 25D uptake is independent of DBP, even though the ‘free’ 25D fraction is very small. DBP has a lower binding affinity for 25D2 compared to 25D3. We hypothesized that this would increase serum free 25D2, with possible variations in vitamin D function. Mice were placed on diets containing equal amounts (1000 IU/kg) ...

Although a complex metabolic pathway for vitamin D exists, serum measurement of inactive 25-hydroxyvitamin D3 (25OHD3) continues to be the most common determinant of vitamin D ‘status’. However, several other metabolites contribute to the physiological role of vitamin D, notably the active form 1α,25-dihydroxyvitamin D (1α,25(OH)2D3), inactive 3-epi-25OHD3 and chiral 23R and 24R,25(OH)2D3 metabolites. Quantification of these additional metabolites could pro...

Background: The effects of glucocorticoids (GC) on the developing zebrafish embryo (Zfe) are poorly characterised. We have assessed the effects of pharmacological and genetic manipulation of cortisol and glucocorticoid receptors (GR) on global development and stress response during the first 120 hpf.Methods: Cortisol production was modulated by inhibiting the enzyme 11b hydroxylase using morpholino gene knockdown (MO) or incubation in the drug metyrapone...

Glial cells missing B (GCMB), which is the mammalian homologue of the Drosophila GCM gene, encodes a 506 amino acid parathyroid-specific transcription factor that contains: a DNA-binding domain (residues 21–174); a predicted nuclear localization signal (residues 176–193); an inhibitory domain (residues 258–347); and two transactivation domains (residues 174–263, and residues 428–506). To date only two different GCMB m...