The relationship of ghrelin to biochemical and anthropometric markers of adult growth hormone deficiency.
BACKGROUND
Ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS-R) and potently stimulates GH release in humans. Ghrelin is found in the hypothalamus, but most circulating ghrelin is derived from the stomach. Ghrelin stimulates food intake but circulating levels are low in obesity. We hypothesized that GH deficiency (GHD) might be associated with increased circulating ghrelin concentrations as a result of low GH levels. We therefore measured circulating ghrelin concentrations, leptin and body composition in subjects with GHD and healthy controls.


METHODS
Subjects with GHD (n = 18) were compared to healthy control subjects (n = 18), matched for body mass index (BMI). They underwent assessment of body composition [waist circumference, BMI and percentage body fat (using bioimpedance)]. Plasma ghrelin, leptin, insulin, GH and IGF-1 were measured in the fasting state. Plasma ghrelin was measured using a specific radioimmunassay, and the other hormones using commercially available assays.


RESULTS
The groups were well-matched for BMI (GHD vs. control; 32.9 +/- 10.8 vs. 31.3 +/- 11.7, P = ns) and waist circumference (GHD vs. control; 102.9 +/- 20.0 vs. 99.8 +/- 25.2, P = ns), but percentage body fat (GHD vs. control; 37.0 +/- 9.1 vs. 29.4 +/- 13.0, P = 0.06) tended to be higher in the GHD group. As expected, IGF-1 was lower in GHD (GHD vs. control; 12.5 +/- 6.8 vs. 19.2 +/- 5.8 nmol/l, P = 0.003). Ghrelin [GHD vs. controls; geometric mean (95% CI); 828.8 (95% CI 639.9-1074.2) vs. 487.9 (95% CI 297.2-800.2) pmol/l] and leptin [GHD vs. controls; 13.2 (95% CI 6.6-26.5) vs. 7.9 (95% CI 3.7-16.9) ng/ml] were similar in the two groups. Plasma ghrelin correlated inversely with waist circumference and waist hip ratio in GHD subjects (r = -0.6, P = 0.02) but not with IGF-1 or GH concentrations. There was no significant correlation in the control subjects.


CONCLUSIONS
Circulating ghrelin concentrations are influenced by body fat distribution, but not by levels of either GH or IGF-1. However, given that obesity is associated with reduced ghrelin concentrations and that GHD is commonly associated with increased body fat, it is possible that these two opposing influences on circulating ghrelin levels result in normal concentrations in subjects with GHD.
Malik
Iqbal A
IA
Diabetes and Endocrinology Research group, University Hospital Aintree, Liverpool, UK.
English
Patrick J
PJ
Ghatei
Mohammed A
MA
Bloom
Stephen R
SR
MacFarlane
Ian A
IA
Wilding
John P H
JP
D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000097:blood / Q000601:surgery
D054439:Ghrelin; D020738:Leptin; D036361:Peptide Hormones; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone