Assessment of GH/IGF-I axis in obesity by evaluation of IGF-I levels and the GH response to GHRH+arginine test

The GH response to provocative stimuli in obese is often as low as in panhypopituitaric patients with severe GHD; however, IGF-I levels are normal or slightly reduced. In 53 patients with simple obesity (11 M and 42 F, age: 40.3 ± 1.6 yr, BMI: 39.1 ± 1.0 Kg/m²), we evaluated the GH response to GHRH (1 μg/kg iv) + arginine (ARG, 0.5 g/kg iv), and total IGF-I levels. The mean (± SE) GH peak after GHRH + ARG was markedly lower (74% reduction, p < 0.0001) in obese (16.8 ± 2.0 μg/l) than in normal subjects (62.7 ± 4.3 μg/l). IGF-I levels in obese patients (134.0 ± 7.6 μg/l) were lower (33% reduction, p < 0.001) than in normal subjects (200.8 ± 5.7 μg/l). Taking into account the 3rd centile limit of normal response, the GH response to GHRH + ARG was reduced in 62.3% (33/53) of the obese patients, and 21.2% (7/33) of them had low IGF-I levels. Assuming the 1st centile limit, it was reduced in 33.9% (18/53) obese subjects, and 22% (4/18) of them had low IGF-I levels. Considering 3.0 μg/L as arbitrary cut-off, the GH response was reduced in 5.7% (3/53) of the obese patients, and still one of them had low IGF-I levels. Our findings: a) confirm that the secretory capacity of somatotroph cells is often deeply impaired in obesity; b) demonstrate that IGF-I assay generally rules out severe impairment of GH/IGF-I axis in obese patients with marked reduction of the GH secretion; c) indicate that the percentage of obese patients with concomitant reduction of GH secretion and IGF-I levels is not negligible. Thus, IGF-I assay should be routinely performed in obese patients; those presenting with low IGF-I levels should undergo further evaluation of their hypothalamo-pituitary function and morphology, particularly in the presence of empty sella.