Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing's syndrome: indirect evaluation of sensitivity to GH

Abstract

Objective: To verify the hypothesis of an increased sensitivity to GH in obesity (OB) and Cushing's syndrome (CS). Design: We studied the effects of short-term administration of low-dose rhGH on circulating IGF-I levels in patients with simple OB or CS and in normal subjects (NS 2 ) underwent s.c. administration of 5 mg/kg per day rhGH at 2200 h for four days. Serum IGF-I, IGF-binding protein-3 (IGFBP-3), GHbinding protein (GHBP), insulin and glucose levels were determined at baseline and 12 h after the first and the last rhGH administration. Results: Basal IGF-I levels in NS 239X3^22X9 mgal were similar to those in OB 181X5^13X7 mgal and CS 229X0^29X1 mgalX Basal IGFBP-3, GHBP and glucose levels in NS, OB and CS were similar while insulin levels in NS were lower P , 0X01 than those in OB and CS. In NS, the low rhGH dose induced a sustained rise of IGF-I levels (279X0^19X5 mgalY P , 0X001Y a non-significant IGFBP-3 increase and no change in GHBP, insulin and glucose levels. In OB and CS, the IGF-I response to rhGH showed progressive increase (246X2^17X2 and 311X0^30X4 mgal respectively, P , 0X01 vs baseline). Adjusting by ANCOVA for basal values, rhGH-induced IGF-I levels in CS (299.4 mg/l) were higher than in OB (279.1 mg/l, P , 0X01), which, in turn, were higher P , 0X05 than in NS (257.7 mg/l). In OB, but not in CS, IGFBP-3 and insulin levels showed slight but significant P , 0X05 increases during rhGH treatment, which did not modify glucose levels in any group; thus, in the OB patient group a significant fall in glucose/insulin ratio was observed. Conclusions: Short-term treatment with low-dose rhGH has enhanced stimulatory effect on IGF-I levels in OB and, particularly, in hypercortisolemic patients. These findings support the hypothesis that hyperinsulinism and hypercortisolism enhance the sensitivity to GH in humans.

Effects of gastric bypass on the GH/IGF-I axis in severe obesity – and a comparison with GH deficiency

“…The levels were elevated in severely obese subjects (5,35) and this has been suggested to compensate for the low GH secretion (34). Others have found levels of GHBP to be similar in obese and lean subjects (36). IGFBP-1 levels are known to be inversely related to insulin levels and thus lower in obese subjects (37).…”

“…Few studies have addressed tissue responsiveness to GH in morbid obesity. By using IGF-I generation tests, Maccario et al (36) found a more prominent response in obese women compared with lean women. Among the obese subjects, a subgroup with Cushing's disease had the most marked response, leading the authors to conclude that both hyperinsulinemia and hypercortisolism enhance sensitivity to GH.…”

Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects

“…Based on these results on GH secretion in obesity, our results suggest that the reduction in GH secretion is only partially translated into reduced IGF-I secretion. The reason for this is unclear, but again, an increase in GH sensitivity has been discussed (25). In a population-based study with 400 subjects, a negative correlation of IGF-I with BMI was found that disappeared after adjustment for age (26).…”

“…Obesity is characterized by blunted GH secretion (16,19) but reports of IGF-I levels in obese subjects are divergent. Some authors have reported decreased levels of IGF-I (20)(21)(22), while others have found normal levels (23)(24)(25), which could be due to an increased GH sensitivity in obese subjects (25). Negative correlations of IGF-I levels to visceral fat areas, assessed by computed tomography scan (23,26,27) have been reported even in the absence of significant correlations between body mass index (BMI) and IGF-I (23), suggesting that the amount of visceral fat is an important determinant of IGF-I levels.…”

Eixos hormonais na obesidade: causa ou efeito?

“…Há evidên-cias de maior sensibilidade da ação do GH, tais como maior nível de GHBPs (e conseqüentemente de receptores de GH) e o achado de que administração de baixas doses de rhGH tem efeito estimulatório na produção de IGF1 maior em obesos do que em indivídu-os de peso normal (42). Além disso, a redução do peso após cirurgia bariátrica acarreta elevação marcante de parâmetros do perfil de secreção de 24 horas de GH (ritmo) em obesas grau III sem alteração do nível de ghrelina, sugerindo um papel limitado desta na regulação fisiológica do eixo somatotrófico (43).…”