Endocrine Abstracts

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...

Background and aims: The mechanisms in HIV by which mitochondrial dysfunction occurs, leading to impaired energy homeostasis and metabolic regulation, are unclear; although similarities are noted in T2DM. Therefore, we investigated the effect of HIV status and ARV therapy on several mitochondrial and nuclear encoded genes related to mitochondrial metabolism and energy homeostasis.Materials and methods: Subcutaneous AT biopsies from the ileac crest were o...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite increasing use of GCs as therapeutic agents, the precise molecular mechanisms that underpin GC-induced insulin resistance are unknown. Within skeletal muscle, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to the active GC, cortisol (corticosterone in rodents) and thus amplifies local GC act...

In adipose tissue, glucocorticoids (GC) are known to regulate lipogenesis and lipolysis. Hexose-6-phosphate dehydrogenase (H6PDH), a protein located in the endoplasmic reticulum (ER) provides co-factor for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thus regulating the set point of its activity and allowing for tissue specific activation of GCs. The aim of this study was to examine the effect of lack of H6PDH on adipose tissue biology using the H6P...

The pre-receptor regulation of glucocorticoids is mediated by 11β-hydroxysteroid dehydrogenases (11β-HSD). The type 1 isoform is primarily responsible for the generation of active cortisol in tissues such as liver and adipose, whereas 11β-HSD2 regulates sodium and ion transport. Recently, we have shown the presence of functional 11β-HSD1 in the ciliary body of the eye where it is important in control of sodium transport, aqueous humour production and intrao...

Microsomal glucose-6-phosphatase (G6Pase) and glucose-6-phosphate transporter (G6PT) are key enzymes in regulation of blood glucose concentration. Deficiency of G6Pase gives rise to glycogen storage disease type Ia (GSDIa) whilst mutations in G6PT cause GSDIb. Both are characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly. G6Pase shares its substrate (G6P) with hexose-6-phosphate-dehydrogenase (H6PDH), an ER enzyme functionally coupled with, and which c...

Case history: A 38-year-old woman presented with blepharospasm, cramping of the hands, and paraesthesia primarily affecting the face and hands. Symptoms had been present for 10 years but had been progressive over the previous 12 months. Symptoms were consistent with neuromuscular instability. Hypocalcaemia and elevated Parathyroid hormone (PTH) were confirmed. Past medical history was notable for anorexia nervosa in remission. Family history was non-contributary. Hypocalcaemia...

Background and aims: HNF1A-MODY causes monogenic diabetes with a lean, insulin sensitive phenotype. Altered glucocorticoid (GC) metabolism has been implicated in the pathogenesis of type 2 diabetes (T2D) and inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active cortisol from inactive cortisone have been trialled as a therapeutic approach. 11β-HSD1 is down-regulated in hepatocytes from Hnf1a knock-out mice but the role...

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is reported to be common in patients undergoing bariatric surgery, but the diagnostic accuracy of non-invasive NAFLD biomarkers to stage disease and track progress longitudinally has not been assessed.Methods: 274 patients undergoing bariatric surgery were included in the study. Intra-operative liver biopsies were taken from 163 patients and histologically graded using t...

Idiopathic intracranial hypertension (IIH) is a condition of unknown aetiology characterised by raised intracranial pressure, chronic headaches and blindness. Akin to polycystic ovary syndrome (PCOS), IIH patients are almost exclusively obese females of reproductive age. A distinct androgen excess profile has been noted in PCOS. Here, we aimed to delineate androgen metabolism in IIH compared to PCOS and simple obesity.Women w...