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Cardiovascular Consequences of Early-Onset Growth Hormone Excess

Department of Molecular and Clinical Endocrinology and Oncology (A.Co., R.P., C.D.S., G.L.) and Internal Medicine I (L.S., D.B.), and Nuclear Medicine Center of the National Council of Research, Department of Biomorphological and Functional Sciences (A.Cu., M.S.) Federico II University, 80131 Naples, Italy; Operative and Echo-Guided Surgery Unit, S. Maria del Popolo degli Incurabili Hospital (S.S.) and Scientific Institute for Research and Care Neuromed (A.Cu., R.P.), 86077 Pozzilli, Italy

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy. E-mail: . colao{at}unina.it

Abstract

Acromegaly has relevant effects on the cardiovascular system, but few data deal with the early effects of GH and IGF-I excess. To study the early stage of acromegalic cardiomyopathy and give indirect evidence of the mechanisms underlying GH and IGF-I action on the human heart, 25 patients with uncomplicated acromegaly [15 young subjects with short-term (5 yr) disease and 10 with long-term (>5 yr) disease] and 25 sex- and age-matched controls were studied.

Cardiovascular risk parameters were studied by standard methods; cardiac morphology by M-mode and Doppler echocardiography, cardiac function at rest and at peak exercise by equilibrium radionuclide angiography, and vascular disease at common carotid arteries by Doppler ultrasonography. In the patient group these measurements were repeated after 6 months of treatment with octreotide-LAR (20–40 mg, im, every 28 d).

Glucose, glycosylated hemoglobin, insulin, low density lipoprotein cholesterol, triglycerides, and fibrinogen levels were higher, and high density lipoprotein cholesterol levels were lower in acromegalic patients than in controls. Resting blood pressure was similar in patients and controls, whereas heart rate at rest and systolic blood pressure at peak exercise were higher in the patients. The left ventricular mass index was higher in acromegalic patients than in controls (123.3 ± 8.9 vs. 81.5 ± 4.3 g/m²; P < 0.001); seven patients had left ventricular hypertrophy. Diastolic function was similar in the two groups. The ejection fraction at rest, but not at peak exercise, was significantly increased in the patients compared with controls. As a consequence the exercise-induced changes in the ejection fraction were lower in patients than controls (8.7 ± 1.1% vs. 21.9 ± 3.5%; P < 0.001). At common carotid ultrasonography, young patients with acromegaly had increased diastolic peak velocity and increased intima media thickness, even if neither patient nor controls had atherosclerotic plaques.

Six months after OCT-LAR treatment, GH and IGF-I levels remarkably decreased in all patients; 8 (53.3%) achieved disease control. Insulin, total cholesterol, and fibrinogen levels reduced, whereas high density lipoprotein cholesterol levels increased. Both at rest and at peak exercise, heart rate significantly decreased, whereas systolic and diastolic blood pressures did not change. The left ventricular mass index was significantly reduced, but it was still higher than the control value (101.6 ± 3.5 g/m²; P < 0.01). The left ventricular ejection fraction at rest was significantly reduced, but its response at peak exercise was increased (16.3 ± 2.4%), becoming similar to the control value. At common carotids, the intima media thickness of right and left arteries was significantly reduced as was the diastolic peak velocity without any change in systolic peak velocity.

Short-term GH excess, despite causing enhanced cardiac performance at rest, reduces cardiac performance on effort and impairs vascular morphology. These deleterious effects of early-onset acromegaly are ameliorated by suppressing GH/IGF-I levels for 6 months.

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