Endocrine Abstracts

Rheumatoid arthritis (RA) is associated with a loss of lean mass and a corresponding increase in fat mass. How fat accumulation in RA is linked to synovial inflammation is unknown. Wnts comprise a family of secreted glycoproteins that are crucial in regulating adipocyte proliferation, apoptosis and differentiation. Recently we demonstrated that endogenously generated glucocorticoids (GCs) alter the pattern of wnt secretion by synovial fibroblasts (SFs), favouring production of...

In humans, androgen synthesis crucially depends on the enzyme CYP17A1 expressed in adrenals and gonads. The 17,20 lyase activity of CYP17A1 catalyses the key step in human androgen biosynthesis, the conversion of 17-hydroxypregnenolone to the universal sex steroid precursor dehydroepiandrosterone (DHEA). For its catalytic activity, CYP17A1 requires electron transfer from P450 oxidoreductase (POR). Mutations in CYP17A1 and POR are known to disrupt human androgen s...

Synovial fibroblasts (SFs) form a substantial component of inflamed rheumatoid synovium and generate endogenous glucocorticoids (GCs) during inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor that reduces bone formation) by SFs in response to TNFα has been proposed to be the master regulator of inflammatory osteoporosis. We have identified that in addition to TNFα, GCs potently induce DKK-1 secretion. This may provide a novel mechanism whereby lo...

Steroid 17α-hydroxylase (CYP17A1) exerts two distinct activities that catalyze conversion reactions at key branch points in steroidogenesis. CYP17A1 17α-hydroxylase activity is the key step in cortisol synthesis whereas CYP17A1 17,20 lyase activity generates sex steroid precursors. Inactivating CYP17A1 mutations result in CYP17A1 deficiency (17OHD), a rare form of congenital adrenal hyperplasia that classically presents with combined glucocorticoid and sex steroid de...

Patients receiving parenteral forms of treatment for osteoporosis (e.g. denosumab (DMAB) and zoledronic acid (ZOL)) should be vitamin D replete prior to administration, to minimise the risk of hypocalcaemia. Most patients receiving DMAB or ZOL take supplemental (calcium and) vitamin D but it is widely accepted that adherence to calcium and vitamin D is poor. Frequency of testing 25-hydoxyvitamin D (25OHD), calcium and renal function varies widely between centres in the UK. In ...

Mrs XY, 29 years. (gravida: 3 and para 2) was admitted under the obstetricians with severe hyperemesis gravidarum (HG). An ultrasonogram revealed single live foetus of 8 weeks gestation. Her two previous pregnancies were normal with no history of HG. Mrs XY was on levothyroxine 150 μg OD for autoimmune primary hypothyroidism with TPO antibodies of 259 kU/l (0–5.6). She was also taking sertraline 200 mg OD for depression. The hyperemesis settled with i.v. fluids as we...

Mrs XY, 28 years. primigravida was seen for PV bleed. Ultrasonogram confirmed live intrauterine foetus of 8 weeks gestation with no obvious cause for PV bleeding. An OGTT at 21 weeks suggested gestational diabetes. She was referred to Diabetes Nurse led clinic and treated with metformin. Hypertension was recorded and controlled with labetalol and amlodipine. Mrs XY had recurrent admissions for PV bleeds and some polycythaemia. She was seen by the haematologist and a diagnosis ...

Synthetic glucocorticoids (GCs) including dexamethasone (Dex) are potent anti-inflammatory drugs. However, long-term use of GCs results in deleterious side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The nuclear hormone receptors LXRα and LXRβ are known for their important roles in modulating whole-body cholesterol homeostasis. Recently, we have shown that liver X receptor β (LXRβ) knockout mice are protected against Dex-induced ...

18 year old female referred with 2 years history of hirsutism and secondary amenorrhoea. She was born at 37 weeks and was found to have neonatal hypothermia, hypoglycaemia and crossed hemihypertrophy, but no macroglossia. Due to the increased risk of Wilm’s tumour she had regular ultrasound scans up to the age of 11 years. She attained menarche at the age of 13 but had only two periods within 18 months. By the age of 15 she developed hirsutism and acne. Biochemistry revea...

Diabetes is a manageable but serious illness characterized by high blood sugar. In present study, comparison of treatment of metformin, insulin (biphasic isophane insulin) and insulin (biphasic isophane insulin)+metformin in the patients of type 2 diabetes mellitus with HbA1c>7% was performed. A total 45 patients of type 2 diabetes with HbA1c>7% were selected. The selected 45 patients were divided into three groups of 15 each. First group was treated with metformin (10...