CARDIOVASCULAR EFFECTS OF GROWTH-HORMONE REPLACEMENT THERAPY IN HYPOPITUITARY ADULTS

In the present study the effects of replacement with biosynthetic human growth hormone (GH) in a large group of hypopituitary adults on cardiac structure and function were investigated. Thirty-six GH-deficient, hypopituitary patients (17 males and 19 females; aged 19-67 years) on conventional replacement therapy without GH were studied. Twenty-nine of the patients had acquired hypopituitarism in adult life, mainly due to pituitary tumours. The design of the study was a prospective, randomized, double-blind placebo-controlled trial for 6 months. Growth hormone (17 patients) was given in a daily dose of 0.02-0.05 IU/kg body wt sc (or a placebo, 19 patients) according to the patients' tolerance. Other pituitary replacement treatment was unchanged. Resting and exercise electrocardiography using the Bruce protocol, two-dimensional echocardiography, Doppler ultrasound scanning and serum insulin-like growth factor I (TGF-I) were assessed at 0 and 6 months. Resting blood pressure was measured at 0, 1, 3 and 6 months. Serum IGF-T increased significantly on GH treatment (mean +/- so) GH: 293 +/- 197 vs placebo: 82 +/- 40 mu g/l; p < 0.0001 at 6 months). Exercise time increased significantly on GH but not on placebo (GH: 8.45 +/- 3.16 to 9.38 +/- 2.42 min.sec, p < 0.01; placebo 9.08 +/- 4.35 to 9.50 +/- 4.14 min.sec, NS), although the change was not significantly different between the two. There was no change in the heart rate or the blood pressure either at rest or at the peak of exercise. No significant changes were observed in the left ventricular mass index, the left ventricular posterior wall thickness, the interventricular septal thickness, the ejection fraction or the cardiac output. Isovolumic relaxation time, a measure of the left ventricular diastolic function, decreased significantly on GH but not on placebo (GH: 98 +/- 18 to 89 +/- 11 ms, p = 0.03; placebo: 93 +/- 17 to 89 +/- 14 ms, NS), although again the change on GH was not significantly different from that on placebo. There was no significant change in the left ventricular filling. No significant changes were observed in plasma levels of urea, electrolytes or creatinine on either GH or placebo. In conclusion, six months of GH replacement therapy in hypopituitary adults had favourable cardiovascular effects, including increased exercise tolerance and improved diastolic function,