Endocrine Abstracts (2005) 10 OC21

Neuroendocrine response to ghrelin in patients with anorexianervosa (AN)

D Miljic1, S Pekic1, M Djurovic1, M Doknic1, N Milic1, FF Casanueva2 M Ghatei3 & V Popovic1


1Institute of Endocrinology, Belgrade, Serbia and Montenegro , 2Department of Medicine, Santiago de Compostella, Spain , 3Department of Metabolic Medicine Imperial College, London, United Kingdom.


Ghrelin stimulates growth hormone (GH), prolactin (PRL) and cortisol release in rodents and healthy humans.

Aim: to determine the effects of ghrelin on neuroendocrine response in patients with AN in this cross-sectional hospital based study, approved by the Local Ethical Committee. Twenty-five young women were studied: AN with very low body weight (BMI 12.0±0.4 kg/m2), partially recovered AN (PRAN 17.2±1.3 kg/m2) and constitutionally thin subjects (CTS 17.6±0.4 kg/m2) with menstrual cycles. During five hours of ghrelin 5 pmol/kg/min iv infusion (Bachem, UK) blood was sampled at 15 min. intervals for the first two hours and then every 30 min. for ghrelin (“in house assay” Hammersmith Hospital, London, UK), GH (RIA Cis USA), cortisol (RIA Cis USA) and PRL (RIA Cis USA) measurements. Leptin was measured at baseline (RIA, Linco USA). At baseline, AN had significantly higher ghrelin, GH and cortisol levels and lower leptin (2.1±0.2 ng/ml) than PRAN (4.6±0.8* ng/ml; p<0.05) and CTS (9.6±1.8** ng/ml; p<0.01). GH response to ghrelin was attenuated in patients with AN/PRAN compared to CTS (ΔGHmax AN 6.6±3.7 and PRAN 14.9±6.2 vs CTS 22.0±8.6 μg/l; p<0.01) despite similar levels of ghrelinemia during infusions. Ghrelin did not induce significant increase in PRL and cortisol levels in AN, PRAN and CTS.

Our results suggest that AN patients are insensitive to ghrelin in terms of GH response, probably due to desensitization by chronic hyperghrelinemia and increased activation of GH and HPA axes.

VariableAN (n=9)PRAN (n=6)CTS (n=10)
Ghrelin (pg/ml)985.3±165.4685.2±78.0443.7±78.7**
GH (μg/l)8.5±3.71.4±0.4 *0.6±0.2**
Cortisol (nmol/l)744.0±59.9502.7±52.5**425.8±39.1**
PRL (mU/l)538.8±266.6426.3±224.7353.6±75.5

VariableAN (n=9)PRAN (n=6)CTS (n=10)
Ghrelin (pg/ml)985.3±165.4685.2±78.0443.7±78.7**
GH (μg/l)8.5±3.71.4±0.4 *0.6±0.2**
Cortisol (nmol/l)744.0±59.9502.7±52.5**425.8±39.1**
PRL (mU/l)538.8±266.6426.3±224.7353.6±75.5

*p<0.05 PRAN/CTS vs AN; **p<0.01 PRAN/CTS vs AN

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