ABSENCE OF DESENSITIZATION BY HEXARELIN TO SUBSEQUENT GH RELEASING HORMONE-MEDIATED GH SECRETION IN PATIENTS WITH ANOREXIA-NERVOSA

OBJECTIVE Both the basal levels and the neuroregulation of GH secretio n are perturbed in patients with anorexia nervosa. It is unknown if th ese alterations are due to severe undernutrition or if they reflect ba sic neurotransmitter alterations of the patient's neural pathways. On the other hand, prior administration of the GH secretagogue hexarelin in normal subjects blocks the GH-releasing capability of GH releasing hormone (GHRH) administered 2 hours later. In the present work a seque ntial test was performed using the administration of hexarelin as firs t stimulus followed 120 minutes later by GHRH. The two aims of the stu dy were: (a) to evaluate the interaction of GHRH and hexarelin, and (b ) to further understand the alterations in GH neuroregulation in patie nts with anorexia nervosa. DESIGN The GH stimuli used were hexarelin ( 1 mu g/kg i.v.), a GH stimulus whose main action is hypothalamic, foll owed 120 minutes later by GHRH (1 mu g/kg i.v.) as a pituitary stimulu s. Each woman was tested once. PATIENTS Thirty-two women matched for a ge participated in the study: six normal-weight women as controls, 14 women with anorexia nervosa, seven women with secondary amenorrhoea du e to voluntary weight loss for aesthetic reasons, and five normal-weig ht women after 72 hours of a controlled hypocaloric diet (800 cal/day) . MEASUREMENTS Plasma GH levels were measured by time-resolved fluoroi mmunosasay, each value shown is the mean +/- SE in mU/l. RESULTS The a dministration of hexarelin to the normal-weight women induced a clear- cut GH secretion (expressed as mean +/- SE of GH peak in mU/l of 77.5 +/- 21.8, but blocked the GH-releasing capability of GHRH administered 120 minutes later (6.6 +/- 2.8, P < 0.05). In contrast, the women wit h anorexia nervosa showed a normal GH response after the two stimuli: hexarelin 64.8 +/- 9.2. GHRH 71.1 +/- 14.2. The absence of heterologou s desensitization was specific to anorexia nervosa, because the women with amenorrhoea due to voluntary weight loss but with a normal energy intake showed a pattern similar to the controls (GH after hexarelin 6 0.3 +/- 9.5 and to GHRH 120 minutes later 6.2 +/- 1.0 (P < 0.05)). Sim ilarly, the women after the short-term hypocaloric diet showed a hexar eiin-mediated GH secretion of 99.6 +/- 17.8, which blunted the subsequ ent administration of GHRH (GH mean peak of 9.9 +/- 2.9, P < 0.05 vs h exarelin). CONCLUSIONS In the normal subjects, the administration of h exarelin induced clear-cut GH secretion, but inhibited the action of G HRH when administered 120 min later, while this heterologous desensiti zation was not observed in the patients with anorexia nervosa. This se quentially delayed test may be of some value in the clinical setting f or assessing the status of patients with anorexia nervosa.