Spontaneous Nocturnal Growth Hormone Secretion in Anorexia Nervosa

Abstract

In anorexia nervosa, serum GH levels are increased under basal conditions and respond abnormally to provocative stimuli. We report here, for the first time, an analysis of pulsatile GH secretion in these patients performed by Cluster algorithm. Seven anorectic and six normal weight, healthy women underwent serial blood sampling at 20-min intervals form 2030-0830 h for GH estimation. The total area under the curve (AUC; micrograms per L/min) was elevated 4-fold in anorectic patients compared to controls (4743.0 +/- 1520.09 vs. 1148.6 +/- 519.27; P < 0.01), largely due to an increase in the non-pulsatile fraction (3212.5 +/- 990.45 vs. 378.7 +/- 123.27; P < 0.01). Accordingly, the valley mean value was higher in anorectic than in control subjects (5.9 +/- 2.25 vs. 1.0 +/- 1.30 micrograms/L; P < 0.01). Furthermore, pulsatile AUC was also greater in anorectic patients (1530.4 +/- 654.72 vs. 769.8 +/- 404.02; P < 0.01) due to a significant increase in GH peak frequency (5.0 +/- 0.81 vs. 3.0 +/- 0.89; P < 0.01). No correlations were observed in these patients between body mass index and any of the parameters of spontaneous GH release, whereas a positive correlation was found between insulin-like growth factor I levels and pulsatile AUC (r2 = 0.583; P < 0.05), peak height (r2 = 0.743; P = 0.01), peak increment (r2 = 0.801; P < 0.01), and GH valley mean (r2 = 0.576; P < 0.05). In conclusion, it appears that the enhanced GH secretion in anorexia nervosa is the result of an increased frequency of secretory pulses superimposed on enhanced tonic GH secretion. Although this latter is consistent with a reduction of hypothalamic SRIH tone, the former may be accounted for by an increased number of GHRH discharges. Considering that in normal weight and obese subjects parameters of GH release are negatively correlated with adiposity indexes, the lack of such a negative correlation in our patients suggests that the enhancement of spontaneous GH release in anorectic patients is not merely the consequence of malnutrition-dependent impairment of insulin-like growth factor I production, but reflects a more complex hypothalamic dysregulation of GH release.

Anorexia nervosa in female adolescents: endocrine and bone mineral density disturbances

“…Few studies have analyzed spontaneous GH secretion (SGHS) in AN patients. Scacchi et al (58) reported that increased GH secretion could be the result of an increased frequency of secretory bursts superimposed on enhanced tonic GH secretion. We studied SGHS in a group of anorexic patients at the time of diagnosis and two different times during weight recuperation and found that at the time of diagnosis SGHS is heterogeneous (59).…”

“…While decreased leptin levels in AN patients might simply reflect reduced body fat mass, increased gastric ghrelin secretion in AN might, however, reflect a physiological effort to compensate for the lack of nutritional intake and stored energy (64). Serum GH-binding protein (GHBP) levels in patients with AN are dramatically reduced (58,65,66) and tend to normalize with weight recuperation (58,67). This reduction in GH receptors is most likely one of the principal causes of GH resistance.…”

Somatostatin infusion withdrawal: studies in the acute and recovery phase of anorexia nervosa, and in obesity

“…Our present finding of a highly positive correlation between the GH responses to SSIW and to exogenous GHRH in all the subjects studied reinforces this opinion. Along this line, the enhanced GH rebound observed in AN after SSIW might be related to an enhancement of the endogenous GHRH tone (6,50). Indeed, the analysis of GH pulsatility in AN has documented an increased frequency of GH secretory pulses (6), which might be due to increased frequency of GHRH discharges (50).…”

“…Alternatively, in AN, a primary alteration in the neural control of somatotroph function involving GH-releasing hormone (GHRH) (5,6) may underlie GH hypersecretion. In fact, so far, low or absent GH response to insulin-induced hypoglycemia (17) or dopaminergic agonists (18), exaggerated GH responses to GHRH (7,8,19,20), paradoxical GH rises after glucose load (21,22), thyrotropin-releasing hormone (23), or gonadotropin-releasing hormone (GnRH) (24) have been reported.…”

“…GH secretion in AN has also been shown to be particularly refractory to the inhibitory effect of muscarinic cholinergic antagonists (7,8), as well as to the stimulatory effect of cholinergic agonists or b-adrenergic antagonists (25,26), or acute glucorticoid administration (27). As central cholinergic and b-adrenergic functions and glucorticoids would influence GH secretion via modulation of hypothalamic SS release (28), the existence of an impaired SS activity in AN has also been suggested (5,6,8,25,26). Along this line also are the low cerebrospinal fluid (CSF) concentrations of SS detected in anorectic patients (29).…”