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 secretion are perturbed in patients with anorexia nervosa. It is unknown if these alterations are due to severe undernutrition or if they reflect basic 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 sequential test was performed using the administration of hexarelin as first stimulus followed 120 minutes later by GHRH. The two aims of the study were: (a) to evaluate the interaction of GHRH and hexarelin, and (b) to further understand the alterations in GH neuroregulation in patients with anorexia nervosa.

DESIGN

The GH stimuli used were hexarelin (1 micrograms/kg i.v.), a GH stimulus whose main action is hypothalamic, followed 120 minutes later by GHRH (1 micrograms/kg i.v.) as a pituitary stimulus. Each woman was tested once.

PATIENTS: Thirty-two woman matched for age participated in the study: six normal-weight women as controls, 14 women with anorexia nervosa, seven women with secondary amenorrhoea due to voluntary weight loss for aesthetic reasons, and five normal-weight women after 72 hours of a controlled hypocaloric diet (800 cal/day).

MEASUREMENTS: Plasma GH levels were measured by time-resolved fluoroimmunosasay, each value shown is the mean +/- SE in mU/l.

RESULTS

The administration 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 with anorexia nervosa showed a normal GH response after the two stimuli: hexarelin 64.8 +/- 9.2. GHRH 71.1 +/- 14.2. The absence of heterologous 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 60.3 +/- 9.5 and to GHRH 120 minutes later 6.2 +/- 1.0 (P < 0.05)). Similarly, the women after the short-term hypocaloric diet showed a hexarelin-mediated GH secretion of 99.6 +/- 17.8, which blunted the subsequent administration of GHRH (GH mean peak of 9.9 +/- 2.9, P < 0.05 vs hexarelin).

CONCLUSIONS

In the normal subjects, the administration of hexarelin induced clear-cut GH secretion, but inhibited the action of GHRH when administered 120 min later, while this heterologous desensitization was not observed in the patients with anorexia nervosa. This sequentially delayed test may be of some value in the clinical setting for assessing the status of patients with anorexia nervosa.