Regulation of GH secretion in acromegaly: Reproducibility of daily GH profiles and attenuated negative feedback by IGF-I

GH hypersecretion is a hallmark of acromegaly. It is unknown whether the se cretory activity of somatotroph adenoma is autonomous or is still governed by central or peripheral mechanisms. In this study we investigated whether GH secretion in acromegaly 1) has a reproducible circadian pattern and 2) i s inhibited by exogenous IGF-I. Eleven patients with newly diagnosed acrome galy were studied in 2 protocols. In protocol 1, peripheral blood was sampl ed every 10 min for 48 h in 6 patients for the determination of concordance between 24-h GH profiles. There was no significant day to day variability in mean 24-h output. There was, however, a significant time effect, and the 24-h GH secretion pattern was maintained between days. In protocol 2, 5 pa tients were sampled for GH every 10 min twice, once during infusion of norm al saline and once during iv infusion of recombinant human IGF-I (10 mug/kg .h). The recombinant human IGF-I infusion increased plasma IGF-I to approxi mately 230% of the baseline concentration. This resulted in GH suppression (4220 +/- 1950 vs. 3223 +/- 1472 mug/liter.min; P=0.001), but did not alter GH secretion pattern. There were highly significant cross-correlations for 10 of the 11 of the subjects in the two protocols when the lag was 0 min. By harmonic analysis, nocturnal augmentation of GH was maintained, and maxi mum daily GH occurred at approximately 2300 h. These data demonstrate that the pattern of GH secretion in acromegaly is not random, but is highly pres erved with 24-h periodicity. In addition, negative feedback regulation by I GF-I is preserved, although the degree of negative feedback is grossly atte nuated. Thus, secretory activity of somatotroph adenomas is not autonomous or haphazard, but is still subject to both feedback and feedforward regulat ory mechanisms.