Endocrine Abstracts

Carpal tunnel syndrome (CTS) in acromegaly is caused, in part, by median nerve (MN) swelling. Pegvisomant (Peg), a growth hormone receptor (GHR) antagonist, lowers serum insulin-like growth factor-I (IGF-I) concentrations in patients with acromegaly, but serum GH levels rise and Peg is detected by most GH assays. Demonstrating that normalisation of serum IGF-I by Peg is associated with improvement/reversal of the consequences of GH excess is desirable. We documented changes in...

Vascular endothelial growth factor (VEGF) is involved in the activation of the matrix metalloproteinase system (MMP) which in turn degrades the extracellular matrix involved in development, morphogenesis and tissue remodelling. Increased activity of MMPs has been implicated in atherosclerosis and cardiovascular disease. This study assessed plasma MMP and VEGF levels in patients with active acromegaly (IGF-I >130%ULN), and on treatment with pegvisomant.<p class="abstext"...

Pegvisomant is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Insulin resistance is an important factor in the increased cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to compare insulin sensitivity (IS) in a group of 7 patients with acromegaly (3 male, mean age 59+/-13 years, SD), treated first with a stable dose of depot octreotide (OT) (median dose 20mg four weekly, range 10-20) for at least t...

5beta-Reductase is a key glucocorticoid metabolising enzyme. In humans, urinary steroid metabolite profiles suggest an inverse relationship between 5beta-reductase and 11beta-hydroxysteroid dehydrogenase (11HSD1) in obesity and congenital deficiency of 11HSDs. Indeed in the obese Zucker rat hepatic 11HSD1 is decreased and 5beta-reductase increased. Here we use animal models with well characterised alterations in 11HSD1 to explore the link between these enzymes.11HSD1 was m...

Obese humans and rats exhibit altered glucocorticoid metabolism; increased regeneration of glucocorticoid by adipose 11HSD1 and inactivation by hepatic A-ring reductases. The mechanisms remain unclear; candidates include resistance to insulin-mediated regulation, and secondary effects of adipose products eg TNFalpha. To explore temporal associations between changes in glucocorticoid metabolism, insulin resistance and obesity, we examined effects of high-fat feeding in rats.<br...

Patients with acromegaly treated with medical therapy intermittently discontinue therapy to allow assessment of underlying disease activity. This is particularly so in patients treated with pituitary irradiation. Typical 'washout' times include 5 weeks for bromocriptine and 2 weeks for short-acting sc octreotide; longer periods are required for cabergoline and slow-release somatostatin analogues. Pegvisomant is a novel medical therapy for acromegaly that functions as a GH rece...

Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in children in association with the increasing prevalence of obesity. The underlying mechanisms are incompletely understood, however the accumulation of cholesterol and fatty acid lipotoxins plays an important role. 5-hydroxymethylcytosine (5hmC) is an epigenetic modification generated from 5-methylcytosine (5mC) by the Ten-eleven translocase isoenzymes (Tets). Tet ...

Section 1: Case history: We present the case of a 21-year-old lady known to harbour a homozygous inactivating mutation of the calcium sensing receptor (CaSR) which led to uncontrolled hypercalcaemia in infancy, necessitating emergency total parathyroidectomy. The CaSR plays an important role in calcium homeostasis. Inactivating mutations result in a higher calcium “set-point” and various degrees of hypercalcaemia based on the severity of functional impairment. In the...

Background: Adrenal Insufficiency (AI) is an inadequate production of cortisol hormone from the adrenal glands. The most common form is secondary AI (suppression of the hypothalamic-pituitary-adrenal axis), with a prevalence of approximately 300 cases per million. Patients with AI require lifelong corticosteroid replacement, which poses a risk of a life-threatening adrenal crisis (AC) event. AC presents with low blood pressure, hypoglycaemia and even loss of consciousness. Thi...

Background: Primary aldosteronism (PA) is a common, curable and high-risk subset of hypertension, mandating detection. In all but the most severe cases, learned society guidelines recommend confirmatory testing. Whilst a variety of confirmatory tests exist, data describing their safety are limited. Concerns centre around the potential of some tests to precipitate hypokalaemia or a hypertensive emergency in a patient with PA on sub-optimal anti-hypertensive medication. In this ...