Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adults

OBJECTIVE To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. PATIENTS AND METHODS Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean +/- SD: 0.3 +/- 0.1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0.025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. RESULTS Group A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31.4 +/- 2.5 vs. 26.4 +/- 1.3, P < 0.05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193.9 +/- 27.1 vs. 298.1 +/- 32.5 pmol/l, respectively, P = 0.02), while ApN levels were similar (10.2 +/- 1.1 and 9 +/- 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193.9 +/- 27.1 to 232.4 +/- 26.3 pmol/l (P < 0.01) and from 8.6 +/- 0.8 to 10.3 +/- 1.1 mg/l (P < 0.05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. CONCLUSION GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release.