Effects of theophylline infusion on the growth hormone (GH) and prolactin response to GH-releasing hormone administration in acromegaly

Abstract

Since theophylline has been shown to blunt the GH response to growth hormone-releasing hormone (GHRH) in normal subjects, we investigated whether the same effect of theophylline administration could be reproduced in patients with active acromegaly. Ten acromegalic patients received on two different days 100 μg GHRH iv alone and the same GHRH dose during a constant infusion of theophylline (3.56 mg/min), beginning 2 h before GHRH administration. In the whole group theophylline did not affect basal GH secretion significantly (from a mean of 44.6 ± 14.4 at 0 min to 41.8 ± 13.5 ng/ml at 120 min). However, the amount of GH released after GHRH stimulation was lower when theophylline was concomitantly infused (7525 ± 3709 ng min/ml vs. 12038 ± 6337 ng min/ml; p < 0.05). The inhibitory effect of theophylline was not homogeneous, since either marked or minimal reductions of the GHRH-stimulated GH secretion occurred. Serum PRL levels increased after GHRH administration in 6 patients and theophylline infusion had no influence upon this response. Peak GHRH levels were not different in both studies (14.9 ± 1.7 and 1 1 ± 4.0 ng/ml, respectively). Free fatty acid levels rose progressively during theophylline administration (from 0.66 ± 0.10 at 0 min to 1.04 ± 0.10 mEq/I at 240 min) and were significantly higher than after GHRH stimulation alone from 180 min up to the end of the test. Our results demonstrate that in active acromegaly theophylline blunts the GH response to GHRH, though this effect is not uniformly seen in all patients. However, even if only theophylline sensitive patients are considered, both basal GH secretion and PRL response to GHRH are not affected by infusion of the drug.