Somatotropin Pulse Frequency and Basal Concentrations Are Increased in Acromegaly and Are Reduced by Successful Therapy*

Abstract

Alterations in pulsatile GH release in 13 acromegalic patients (7 men and 6 women) were studied by measuring serum GH concentrations in blood sampled every 5 min over 24 h. Specific properties of pulsatile GH release were quantitated by Cluster analysis, and Fourier expansion time series analysis was used to resolve fixed periodicities underlying GH secretion. Compared with sex-matched controls, 24-h integrated GH concentrations (IGHC; min·mg/L) were elevated 15-fold in the acromegalic men (40 ± 27 vs. 2.6 ± 0.35; P = 0.02) and 10-fold in the acromegalic women (43 ± 19 vs. 4.1 ± 0.35; P = 0.01). The increase in integrated GH concentrations was accounted for by an increase in the nonpulsatile fraction [men, 31 ± 20 vs. 0.65 ± 0.10 (P = 0.001); women, 35 ± 14 vs. 1.2 ± 0.10 (P = 0.0008)]; the pulsatile component was not different from that in normal subjects. Acromegalics had an increased number of pulses per 24 h [men, 17 ± 1.5 vs. 6.7 ± 1.4 (P = 0.0001); women, 19 ± 1.6 vs. 11 ± 1.0 (P = 0.002)] and increased basal GH concentrations [men, interpulse valley mean, 22 ± 14 vs. 1.4 ± 0.30 μg/L (P = 0.0006); women, 27 ± 12 vs. 1.3 ± 0.20 μg/L (P = 0.0001)]. The proportion of the mean GH concentration attributable to 24-h rhythmicity was decreased in the acromegalic patients. Five patients studied during biochemical remission (4 after transsphenoidal surgery and 1 during bromo-criptine therapy) had GH profiles that resembled those of normal subjects. Pulsatile GH secretion in acromegaly is characterized by augmented basal GH concentrations, increased GH pulse frequency, and an attenuation of the underlying 24-h rhythm. Such a pattern may be secondary to the intrinsic pathology of ade-nomatous somatotrophs and/or the effects of altered hypothalamic regulation.