Endocrine Abstracts

The pseudo-Cushing’s syndrome that accompanies both acute alcohol ingestion and alcohol withdrawal is an important differential diagnosis of hypercortisolism that is poorly understood. Two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) interconvert hormonally active cortisol (F) and inactive cortisone (E). Previously we have shown higher urinary F:E metabolite ratios (a reflection of total body 11βHSD activity) in patients with alcoholic liver disea...

Excessive glucocorticoid exposure has been implicated in the pathogenesis of obesity and the metabolic syndrome. The in vivo conversion of inactive to active glucocorticoids is catalysed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), requiring NADPH as a cofactor. Hexose-6-phosphate dehydrogenase (H6PDH) is co-localised with 11β-HSD1 in the lumen of the endoplasmic reticulum and controls local NADPH availability. Thus H6PDH plays an important role...

During the luteal phase of the menstrual cycle aldosterone increases mainly due to the antagonistic properties of progesterone at the MR and due to estrogen-mediated stimulation of angiotensinogen. Little is known about other steroid-metabolizing enzymes that may influence steroid receptor binding, eg 11beta-HSDs, A-ring reductases. Therefore a group of ten normotensive female volunteers with regular menstrual cycles were studied on day 7 (follicular phase) and day 21 (luteal ...

Glucocorticoids have potent but paradoxical effects on bone. In vitro they are required for the differentiation of osteoblasts but in excess can cause suppression of the mature osteoblast phenotype by reducing proliferation and inducing apoptosis. In vivo, glucocorticoids are anabolic at physiological concentrations, but in excess have an adverse effect on the skeleton most clearly seen in steroid-induced osteoporosis. We have postulated that this paradox may be ...

Background: The adverse effects of corticosteroid therapy are similar to those of endogenous glucocorticoid excess. Previous studies have established the usage patterns of oral corticosteroids in the primary healthcare setting, but these have concentrated on corticosteroid-induced osteoporosis. The aim of this study was to investigate the prevalence and morbidity of long-term oral corticosteroids in a General Practice setting.Methods: From a population ...

A 31 year old female with no prior history of thyroid disease presented to hospital four days after 2nd dose Pfizer vaccination with fever, myalgia, neck discomfort and chest pain; which was relieved by sitting forwards. A small goitre and tachycardia were noted on physical examination. CXR and echocardiogram were normal. ECG revealed sinus tachycardia. Troponin T was elevated (32 ng/l, normal <5). Free T4 was raised (26.6 pmol/l, reference 10-22) with an undetectable TSH ...

Delayed wound healing (WH), characterized by ischemia, is exacerbated by glucocorticoid (GC) excess. Local GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates the GC cortisol from inactive cortisone. We previously reported improved WH in 11β-HSD1-null mice but regulation of 11β-HSD1 by hypoxia in human skin remains unknown. Primary human dermal fibroblasts (HDF, biological n=3), were treated...

Turner’s syndrome (TS) results from a genetic abnormality in phenotypical female individuals where the second X chromosome is either absent or present in a mosaic form. The most obvious consequences are short stature and primary amenorrhoea, although there are often dysmorphic features as well as cardiovascular and genitourinary complications. 90% of TS patients experience primary amenorrhoea with subsequent infertility. Spontaneous recovery of ovarian function in patient...

Chronic wounds contribute significantly to patient morbidity, mortality and associated healthcare costs. Glucocorticoid (GC) excess and hypoxia are both associated with impaired wound healing (WH) outcomes. The cyclooxygerase 2 (COX2) pathway is an integral component of inflammation and WH. Locally, GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates cortisol from inactive cortisone. Although we recently demon...

Hexose-6-phosphate dehydrogenase is an important factor in setting the redox status of the endo-/sarcoplasmic reticulum (ER/SR) lumen by generating the NADPH:NADP+ ratio for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediated glucocorticoid (GC) activation. H6PDH knockout mice (H6KO) clearly demonstrate the obligate nature of 11β-HSD1 for H6PDH, and display a vacuolating of type IIb fiber myopathy, elevated glycogen storage and type II to type...