Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Abstract

Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P ϭ 0.002), nadir (P ϭ 0.0006), and valley levels (P ϭ 0.002). On deconvolution analysis, secretory burst amplitude (P ϭ 0.03) and burst mass (P ϭ 0.04) were higher in AN, resulting in higher pulsatile (P ϭ 0.05) and total ghrelin secretion (P ϭ 0.03). Fasting ghrelin independently predicted GH burst frequency (r ϭ 0.44, P ϭ 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency. growth hormone; cortisol; total triiodothyronine; estradiol; luteinizing hormone; insulin resistance GHRELIN, A 28-AMINO ACID PEPTIDE, is a growth hormone (GH) secretagogue (2, 4, 25, 26, 50 -53) that is also orexigenic (40,56). It is unknown whether elevated ghrelin values are an important contributing factor to the elevated GH levels that occur in anorexia nervosa (AN), a unique model of chronic undernutrition. We have demonstrated higher fasting ghrelin levels in adolescent girls with AN compared with healthy adolescents and higher nadir ghrelin levels following an oral glucose load (36). Girls with AN also have higher GH concentrations, a consequence of increased basal GH secretion and secretory burst frequency (33). Similarly, elevated ghrelin (21, 39) and GH concentrations (47, 49) have been reported in adult women with AN. Negative feedback from low IGF-I levels has been hypothesized to cause increased GH secretion, and the relationship between ghrelin and GH secretion in AN has not been explored.Administration of a single dose of intravenous ghrelin causes an increase in GH secretion in both rodent models (51, 66) and healthy adults (4, 50, 52). Howe...

Effect of somatostatin infusion on peptide YY secretion: studies in the acute and recovery phase of anorexia nervosa and in obesity

“…reduced PYY DAUC). This pattern contrasts the SRIF-induced inhibition of fasting and postprandial PYY levels of patients with Prader-Willi syndrome, who share with A-AN the hyperghrelinemia (45,50).…”

Surviving Starvation: Essential Role of the Ghrelin-Growth Hormone Axis

“…There is one clinical condition in which such depletion does occur, namely, in patients with anorexia nervosa. It is therefore intriguing that such patients have been demonstrated to maintain threefold elevations of plasma ghrelin and of growth hormone (Tanaka et al 2004;Misra et al 2005;Nass et al 2011). We speculate that these elevations may be responsible for the maintenance of blood glucose in these adipose-deficient subjects.…”

Fasting total ghrelin levels are increased in patients with adolescent idiopathic scoliosis

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