Endocrine Abstracts

Background: Hypogonadism in men is associated with osteoporosis and low libido. Serum testosterone in men falls after the age of 40 years; however the benefits of replacement therapy are not established. We conducted a double-blind, placebo-controlled trial to investigate the effect of testosterone transdermal patches on bone turnover, body composition, quality of life (QoL) and well-being in men with borderline hypogonadism.Methods: 38 borderline hypogo...

AIM: To assess efficacy of GH replacement and safety of stopping treatment in patients aged over 60 years.METHODS: GH-deficient patients were started on GH 0.13 miligram per day and the dose titrated over 4 months to a serum IGF-1 in the upper half of the age-related normal range. After 4 months titration, patients were randomised to either continuing GH or placebo in a double-blind, cross-over study with 2 x 4 month periods of either GH or placebo treatment.RESULTS: 1...

Congenital adrenal hyperplasia (CAH) is a genetic disorder arising from defective steroidogenesis resulting in glucocorticoid deficiency; the commonest mutation is in the gene encoding 21-hydroxylase. Lifesaving glucocorticoid treatment was introduced in the 1950s and there is now an enlarging cohort of adult patients; however, there is no consensus on management. To address this issue, the Congenital adrenal Hyperplasia Adult Study Executive (CaHASE) was formed in 2003 to stu...

CAH is the commonest inborn endocrine disorder and associated with significant morbidity. The health status of CAH adult patients has recently been reported by the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive, CaHASE (Arlt et al. JCEM 2010 95 5110–21). Compared to the health survey for England, metabolic abnormalities were common in adult patients with CAH: obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), ost...

Cortisol secretion follows a distinct circadian rhythm, with circulating levels low at sleep onset, beginning to rise between 0200 and 0400 h, peaking within an hour of waking and then declining through the day. This circadian rhythm is determined by the central endogenous clock (pacemaker) of the hypothalamic–pituitary–adrenal (HPA) axis, located in the hypothalamic supra-chiasmatic nucleus. The HPA axis plays an important role in maintaining alertness and modulatin...

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Introduction: Leptin is a pro-inflammatory cytokine and excess leptin in obesity may induce autoimmune disease. The suppressors of cytokine signalling (SOCS) are negative regulators of cytokine signalling and therefore a target for therapy. SOCS3 modulates leptin actions but there is no data regarding other SOCS proteins and leptin signalling.Aim: To develop a bioassay and examine the actions of SOCS proteins on leptin signalling.M...

QLS-H is a new, weighted QoL questionnaire developed for patients with hypopituitarism. We evaluated QLS-H data from UK patients in the HypoCCs International surveillance study, and compared results with a sample of the general UK population (n=1090).The QLS-H questionnaire was administered at baseline and at yearly intervals. Scores were corrected for age and gender differences, and expressed as Z-scores based on UK-specific reference ranges. Using this...

The development of the growth hormone antagonist, Pegvisomant, is a story of modern drug design. The original observation was by John Kopchick, who noted that transgenic mice with a mutation in the third alpha helix of the GH molecule had a dwarf phenotype. This is the basis for the site 2 mutation (G120K) in the GH molecule that blocks GH signaling. At the same time the Genetech group of James Wells had characterised the crystal structure of the GH/receptor complex demonstrat...

Introduction: Leptin is a 16-kDa peptide hormone secreted by adipose tissue and acts as a sensor for energy stores. It feedsback at the hypothalamic arcuate nucleus to suppress appetite. Leptin treatment has been highly effective in suppressing appetite in the rare cases of leptin-deficient obesity and improving the metabolic profile in congenital generalised lipodystrophy. These patients require 2.5–10 mg once daily recombinant leptin treatment. We hypothesised that prol...