Endocrine Abstracts

Carriage of the exon 3 deletion in the GH receptor (GHR) gene has been reported to enhance growth response to GH therapy in a range of conditions. JAK2 and PI3Kinase are involved in signal transduction from the GH (JAK2/PI3Kinase) and IGF-1 (PI3Kinase) receptors. We have investigated whether single nucleotide polymorphisms within these genes influence growth response to GH therapy. DNA was taken, with ethical approval, from 97 children treated with GH therapy in a single growt...

Severe growth hormone (GH) deficiency in adults is associated with adverse changes in quality of life (QoL), body composition and cardiovascular risk profile. NICE guidance restricts GH replacement in the UK to those with impaired QoL, defined by a score of >11 in the QoL-AGHDA questionnaire.Aims: To assess whether the NICE guidance differentiates other clinical or biochemical features in GH deficient adults.Patients and...

GH deficiency (GHD) in adults shares several clinical features with syndromes of glucocorticoid excess. Many patients with GHD also receive glucocorticoid therapy. GH inhibits the generation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), but the confounding effect of ACTH deficiency/ cortisol replacement therapy has not been evaluated.Aims: To assess corticosteroid exposure and metabolism and body composition in...

3-M syndrome is an autosomal recessive disorder characterised by severe pre- and post-natal growth failure, a characteristic facial appearance (triangular shaped face, fleshy tipped nose) and radiological features (slender long bones and tall vertebrae). 3-M syndrome is known to be caused by mutations throughout the Cullin 7 gene, identified in a range of ethnic groups including Brazilian, European, Moroccan, Yakutskian and Indian.We have now identified ...

Introduction: The aetiology of obesity-related nephropathy (ORN) is uncertain but may involve hyperfiltration and systemic inflammation.Aims: To define ORN using novel urinary biomarkers that can identify damage to specific regions of the nephron.Methods: Clinical data, blood and urine samples were collected from a consecutive series of 22 patients attending a weight-management clinic (excluding those with diabetes), and from a con...

The use of the simplified IM glucagon stimulation test (IMGST) over its standard counterpart in the diagnosis of GH and cortisol deficiency has been advocated. Despite apparent comparable diagnostic utility, the simplified IMGST is capable of producing false positive results, raising the potential for misdiagnosis if relied upon exclusively.The aim of this study was to re-evaluate the diagnostic utility of the two forms of the IMGST, ascertaining the mag...

Females release 2–3 fold greater GH compared with males whilst maintaining similar IGF-I levels. IGF-I generation tests in healthy subjects suggest this discordancy results from resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF-I and higher GH maintenance doses during replacement. GHD adults of childhood- (CO) and adult-onset (AO) show CO-GHD adults to have lower basal IGF-I values and require higher ma...

Heparan sulphate (HS) is a highly complex linear polysaccharide found attached to core proteins both on the cell surface and in the extracellular matrix. Newly synthesized HS chains are modified by a family of enzymes, many of which have multiple isoforms with differing substrate preferences. These modifications include the addition of sulphate groups at up to four positions on each disaccharide unit. The pattern of modifications a HS saccharide undergoes alters its structure,...

A few studies have suggested that radiation-induced growth hormone neurosecretory dysfunction (GHNSD) exists in children irradiated for leukemia (18–24 Gy). The presence or absence of GHNSD in adult cancer survivors has not been studied before. Thus, 24-hour spontaneous GH secretion was studied by 20 min sampling both in the fed state (n=16; 6 women) and the last 24 hours of 33-hour fast (n=10; 3 women) in adult cancer survivors, of normal GH status defined ...

Ion and fluid transport mechanisms within the eye are important for several key physiological processes including the maintenance of corneal transparency and the regulation of intraocular pressure (IOP). The mechanism involved in epithelial sodium transport in the eye is regulated by corticosteroids and at a pre-receptor level, by 11β-hydroxysteroid dehydrogenase (11β-HSD) activity. Recent studies localised type 1 (11β-HSD1), an oxo-reductase that activates cort...