Amplified and orderly growth hormone secretion characterizes lean adolescents with polycystic ovary syndrome

Objective: The present study evaluated the hypothesis that pulsatile GH secretion is altered in adolescents with polycystic ovary syndrome (PCOS). Design and patients: Thirteen adolescent girls with PCOS (ages 13-19 years) and ten eumenorrheic controls (ages 14-19 years) matched for a range of body mass index (BMI) values underwent blood sampling every 20 min for 12 h overnight. Methods: Serum concentrations of GH and LH were measured by specific immunofluorometric assays (IFMA). Pulsatile secretion was quantitated by deconvolution analysis and pattern orderliness by the approximate entropy (ApEn) statistic. Fasting serum androstenedione, testosterone, 17-hydroxy-progesterone, estrone, estradiol, insulin and IGF-I concentrations were measured by RIA, GH-binding protein (GHBP) by IFMA and IGF-binding protein (IGFBP)-1 and IGFBP-3 by IRMA. Results: Twelve-hour mean and integrated GH concentrations, the mass of GH secreted per burst, and the GH pulse frequency were not distinguishable in patients with PCOS and controls as a whole. Subanalysis of non-obese (BMI < 25 kg/m²) PCOS and healthy volunteers disclosed elevated 12-h GH production rates (P = 0.03) and integrated serum GH concentrations (P = 0.04) in (lean) patients with PCOS. ApEn analysis of the orderliness of GH release showed remarkably more regular GH secretion patterns (lower ApEn of GH release) in girls with PCOS compared with controls (P = 0.02). Serum GHBP, IGF-I and IGFBP-3 concentrations were similar in both groups, whether lean or obese. However, IGFBP-1 levels were lower in the combined group of PCOS subjects compared with BMI-matched controls (P < 0.05). In volunteers with PCOS, mean (12-h) serum GH concentrations correlated positively with mean serum LH levels (P = 0.006). Based on deconvolution analysis, the 12-h production rate and the mass of GH secreted per burst also correlated strongly with the cognate LH measure (both predicted) (P = 0.004) in PCOS. Androstenedione levels were also related to the 12-h GH secretion rate (P = 0.02). Conclusions: This study shows that non-obese adolescents with PCOS secrete GH at a higher rate and with more orderly patterns, resembling a male profile. Determining whether this pattern reflects an intrinsic hypothalamic abnormality or is secondary to androgen excess in PCOS will require further studies.