Endocrine Abstracts

Introduction: Dysregulated glucocorticoid (GC) metabolism has been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). NAFLD extends from simple steatosis, to inflammation (steatohepatitis/NASH), fibrosis and consequent cirrhosis. It is often regarded as the hepatic manifestation of the metabolic syndrome and is independently associated with increased liver and cardiovascular mortality. Changes in GC metabolism have thus far been described in small num...

Steroid hormones and BAs are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in the liver where it inactivates steroid hormones and catalyses a fundamental step in bile acid (BA) synthesis. We have hypothesised that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 was performed in human liver HepG2 and Huh7 cells. Expression changes were confirmed by qPCR and western blotting, ...

In patients with autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion; patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this...

Introduction: Immune dysregulation is a feature of Cushing’s syndrome (CS). We report a case of CS that presented with rapidly developing cutaneous Kaposi’s sarcoma (KS).Case description: A previously well 59-year-old heterosexual man presented with a two-month history of proximal muscle weakness, recurrent mouth ulcers, and purplish skin lesions. He had a background history of hypertension. Skin biopsies were compatible with KS. History of pas...

Context: Differentiating adrenocortical adenoma (ACA) from adrenocortical carcinoma (ACC) represents a continuous challenge in patients with (often incidentally discovered) adrenal masses, with unfavorable sensitivities and specificities provided by tumor size, imaging and even histology. We have previously developed urine steroid metabolomics as a tool for the detection of adrenal malignancy employing gas chromatography mass spectrometry (GC-MS) for the detection of 32 distin...

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

Patients with adrenal insufficiency require increased hydrocortisone (HC) replacement doses during surgery, trauma and infection to avoid life-threatening adrenal crisis. However, currently administered HC doses are chosen empirically rather than on rational grounds, with huge variability in administration modes, total dose and dosing intervals. To conclusively determine serum cortisol levels observed under stress conditions, we firstly collected blood samples from healthy con...

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate around the optimum glucocorticoid replacement therapy.Objective: To assess the effect of glucocorticoid replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.Design and patients: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body ...

Human sulfation depends on provision of the universal sulfate donor PAPS by the two PAPS synthase isoforms PAPSS1 and PAPSS2. Mutations in PAPSS2 have been identified as a monogenic cause of androgen excess presenting with premature adrenarche and polycystic ovary syndrome, due to decreased sulfation of the androgen precursor DHEA by DHEA sulfotransferase (SULT2A1) and hence increased conversion of DHEA to active androgens (New Eng J Med 2009 360 (22)...

Background: Treatment of CAH in childhood focuses on growth and development; however the impact of final height (FH) on adult health is not known. We examined the relationship between FH, adiposity, cardiometabolic risk and quality of life (QoL) in a cohort of adult patients.Methods: Cross-sectional analysis of 199 adults with CAH. FH, waist circumference (WC) and QoL were expressed as z-scores adjusted for mid-parental target height (FHTH<...