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

Abstract

Objective: Changes in GH/IGF-I axis activity occur in both anorexia nervosa (AN) and obesity (OB). A GH hypersecretory state with very low plasma IGF-I levels is present in AN, whereas in morbid OB, GH secretion is dull and plasma IGF-I levels are generally preserved. Endogenous GHRH activity in AN and OB has never been directly studied, although indirect evidence would indicate that GHRH function is altered in either condition, possibly enhanced and reduced respectively. Somatostatin (SS) infusion withdrawal (SSIW) is followed by a rebound rise of plasma GH in animals and humans, an event which, allegedly, is mediated by endogenous GHRH release. Methods: In the present study, 28 young women, eight with active AN (A-AN), six with AN in the recovery phase (R-AN), eight with morbid OB, and six healthy age-matched normal weight subjects (NW), were studied. All subjects underwent, on different occasions, the following two tests: (i) acute GHRH injection (1 mg/kg, i.v.); (ii) infusion of SS (9 mg/kg per h i.v. over 60 min), with blood samples drawn prior to and at different intervals after drug injections. Plasma GH levels were measured at each time interval in all sessions, and, in addition, baseline plasma estradiol, free triiodothyronine, TSH, IGF-I and insulin were measured at 2 30 min. Results: Baseline plasma GH concentrations were significantly higher in A-AN than in NW ð4:7^0:7 vs 2:1^0:6 mg=l; P , 0:01Þ: Baseline GH levels in R-AN were also higher than in NW, but the difference did not reach statistical significance (5:6^1:7 mg=l; not significant (NS)). Baseline plasma GH concentrations were significantly lower in OB than in NW ð0:3^0:1 mg=l; P , 0:01Þ: GHRH-stimulated GH release was significantly higher in A-AN than in NW (mean change in area under the curve (DAUC) 1904:9^626:1 vs 613:9^75:9 mg=l per min, P , 0:01), whereas no statistically significant difference was present between R-AN and NW (mean DAUC 638:2^293:0 mg=l per min, NS); in OB, GHRH failed to evoke a plasma GH rise (mean DAUC 239:8^89:9 mg=l per min vs A-AN, R-AN, and NW, P , 0:01). SS infusion markedly reduced plasma GH concentrations in both A-AN and R-AN and, to a lesser extent, in NW, but failed to do so in OB. In A-AN, SSIW was followed by a plasma GH rise markedly higher than that present in NW (mean DAUC 193:0^42:3 vs 60:1^11:4 mg=l per min, P , 0:01), whereas in R-AN the GH response after SSIW was nearly superimposable on that registered in NW (mean DAUC 72:9^22:8 mg=l per min, NS). There were no changes in plasma GH levels after SSIW in OB (mean DAUC 22:8^9:7 mg=l per min). In all groups, DAUCs of the GH response to GHRH and after SSIW were highly positively correlated ðr ¼ 0:7; P , 0:01Þ: Conclusions: These data support the view that a high endogenous GHRH tone, which subsides in the recovery phase of the disease, is present in AN, whereas GHRH hypofunction, possibly associated with pituitary impairment, might indicate OB.

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

“…SSTR1-4) in these effects. Finally, a direct interaction between SRIF14 and SSTR5 may not be ruled out in our study, as the pharmacological dose of SRIF used in this study was capable of strikingly inhibiting GH secretion in A-AN and R-AN (41).…”

“…The dose of SRIF was chosen based on its effectiveness to inhibit GH secretion in A-AN (41). Anyway, serum GH levels were measured before, during, and after SRIF infusion (i.e.…”

Influence of Body Mass Index on the Growth Hormone Response to Provocative Testing in Short Children without Growth Hormone Deficiency

“…The low GH level in obese people or in those with a high BMI may result from a shortened half-life of GH or decreased GH production and secretion (16). The possible causes of decreased GH production and secretion are dysregulation of the GHRH, somatostatin, and ghrelin pathways (17, 18), hyperinsulinemia (19), or increased free fatty acid (FFA) level. In obese patients, inhibition of FFA production by administration of the antilipolytic drug acipimox ameliorated the effect of obesity on GH secretion (19, 20).…”

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients

“…Reportedly, GH secretion is increased in the florid phase of the disease, and, although this has been related to a loss of the feedback action of circulating IGF-I (Berelowitz et al 1981, Counts et al 1992, Ross & Chew 1995, Gianotti et al 2000, a primary hyperfunction of GHRH-secreting neurons cannot be disregarded (Scacchi et al 1997, Stoving et al 1999a, 1999b, Gianotti et al 2000, Pincelli et al 2002. If this were the case, one cannot rule out the possibility that GHRH-secreting neurons are, in turn, under an enhanced stimulation by hypothalamic ghrelin-secreting neurons (Hewson & Dickson 2000).…”