The effects of growth hormone replacement therapy on overnight metabolic fuels in hypopituitary patients

OBJECTIVE Hypopituitary adults on conventional replacement have low concent rations of metabolic fuels throughout the night, possibly related to GH def iciency or to decreased cortisol levels overnight. We investigated whether GH replacement corrects the overnight fuel deficiency. DESIGN We measured circulating levels of metabolic fuels: glucose, non-este rified fatty acids (NEFA), glycerol and 3-hydroxybutyrate (3-OHB) and insul in concentrations over 24 h (from 0730 h to 0700 h) in hypopituitary adults before and after GH treatment in a randomized double-blind placebo-control led trial of 3 months' duration. PATIENTS Thirteen hypopituitary patients, 8 women and 5 men, were studied. RESULTS Six patients (4 women and 2 men) received GH and 7 patients (4 wome n and 3 men) were allocated to receive placebo. There was no difference in fasting (0730 h), area under the curve (AUC) between 2400 h and 0700 h (ove rnight) and AUC over 24 h for plasma glucose, 3-OHB, glycerol and insulin c oncentrations as a result of GH treatment. Fasting and overnight AUC for NE FA were significantly higher on GH treatment ((mean +/- SEM) 243 +/- 29 vs. 446 +/- 90 mu mol/l, P = 0.03, 1522 +/- 208 vs. 2167 +/- 123 mu mol/l H, P = 0.046, respectively), but AUC over 24 h was not affected significantly. No significant changes in any fuel were seen in the placebo group. The chan ges in fasting, overnight and 24 h AUC for glucose, 3-OHB, glycerol and ins ulin levels with GH and with placebo for 3 months were similar. The changes in fasting and overnight AUC for NEFA before and after 3 months were signi ficantly different in the group treated with GH vs. the group treated with placebo (median (lower-upper quartile) 104 (90-276) vs. -89 (-98 to 26) mu mol/l, P = 0.002; 633 (263-967) vs. -895 (-1379 to -494) mu mol/l h, P = 0. 002, respectively), but the changes in 24-h AUC for NEFA were not significa nt between the two groups. CONCLUSIONS GH replacement in hypopituitary adults increases fasting and ov ernight (between 2400 h and 0700 h) non-esterified fatty acid concentration s, consistent with the known lipolytic effect of GH. GH did not influence t he concentrations of other metabolic fuels or insulin.