Endocrine Abstracts

Background: Development of multi-steroid profiling allows comprehensive investigation into the different branches of steroid metabolism. Immunoassays only allow analysis of a single steroid per assay and suffer from problems with specificity due to cross reactivity of similar steroids. Liquid-chromatography mass spectrometry has the specificity to analyse multiple steroids in a single experiment and the dynamic range to quantify steroids at high concentrations such as those ob...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. Steroid hormones and bile acids are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. We hypothesized that AKR1D1 plays a key role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 ...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. Steroid hormones and bile acids are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. We hypothesized that AKR1D1 plays a key role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 ...

Background: In women, androgen excess is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Androgen precursors are released from the adrenal gland and converted to active androgens in peripheral tissues including adipose tissue. Although the liver plays a key role in all metabolic processes in the body, its involvement in androgen metabolism is yet to be explored. Here, we describe the investigation of androgen metabolism in human liver using norm...

Background: The detection of phaeochromocytomas evolved from autopsy finding to presentation in symptomatic/hypertensive, and genetically-predisposed individuals. Increasingly, phaeochromocytomas are diagnosed in incidental adrenal masses and the impact on the clinical, biochemical, and radiological features is unclear.Methods: Retrospective review of patients with phaeochromocytomas seen at a large tertiary referral centre between January 2010 and May 2...

Background: Primary adrenal insufficiency (PAI) can be of autoimmune origin (Addison’s disease, AD) or due to inborn disorders of steroidogenesis (congenital adrenal hyperplasia, CAH). Prognosis of patients with PAI has improved considerably after glucocorticoid replacement therapy became available. However, even in recent years, an increased risk of death has been described in both AD and CAH patients. Moreover, even with the current state-of-the-art replacement therapy,...

Background: Management of patients with CAH remains challenging. There is increasing evidence to suggest that failure to optimize treatment during childhood not only affects final height but also leads to psychological and psychiatric problems. Previous qualitative structural T2-weighted MRI studies have identified white matter hyper-intensities in up to 46% of CAH patients. The nature and functional relevance of these abnormalities remains unknown.Objec...

Background: The urinary steroid metabolome is considered the fingerprint of adrenal gland function. Novel methods using mass spectrometry profiling have seen the advent of a new era for metabolomics with powerful implications for both diagnostics and discovery. Its interpretation is difficult and performed by few specialists with the expertise to do so. This makes it a relatively inaccessible tool for the majority of Clinical Endocrinologists.Objective: ...

Background: Mutations of 21-hydroxylase (CYP21A2) cause congenital adrenal hyperplasia. Its severe (classic) form constitutes a life-threatening disease. Patients suffer a significant disease burden due to co-morbidities that are often treatment-related. The current therapeutic situation is unsatisfying and demands novel treatment approaches. In silico modelling suggests protein misfolding and intracellular retention to play a significant role in the pathogenesis of C...

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and Methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...