Cardiovascular consequences of early-onset growth hormone excess(420 views) Colao A, Spinelli L, Cuocolo A, Spiezia S, Pivonello R, Di Somma C, Bonaduce D, Salvatore M, Lombardi G
Department of Molecular and Clinical Endocrinology and Oncology, Italy
Nuclear Medicine Center of the National Council of Research, Department of Biomorphological and Functional Sciences, Italy
Federico II University, 80131 Naples, Italy
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Osterziel, K. J., Strohm, O., Schuler, J., Friedrich, M., Hanlein, D., Willenbrock, R., Anker, S. D., Dietz, R., Randomised, double-blind placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy (1998) Lancet, 351, pp. 1233-1237
Prysor-Jones, R. A., Jenkins, J. S., Effects of excessive secretion of growth hormone on tissue of the rat, with particular reference to the heart and skeletal muscle (1980) J Endocrinol, 85, pp. 75-82
Cittadini, A., Str mer, H., Katz, S. E., Clark, R., Moses, A. C., Morgan, J. P., Douglas, P. S., Differential cardiac effects of growth hormone and IGF-I in the rat: A combined in vivo and in vitro evaluation (1996) Circulation, 93, pp. 800-809
Str mer, H., Cittadini, A., Douglas, P. S., Morgan, J. P., Exogenously administered growth hormone and IGF-I alter intracellular calcium handling and enhance cardiac performance: In vitro evaluation in the isolated isovolumic buffer perfused rat heart (1996) Circ Res, 79, pp. 227-236
Sahn, D. J., De Maria, A., Kissio, J., Weyman, A., The committee on M-mode standardization of the American Society of Echocardiography. Recommendations regarding quantification in M-mode echocardiography: Results of a survey of echocardiography measurements (1978) Circulation, 58, pp. 1072-1083
Devereux, R. B., Detection of left ventricular hypertrophy by M-mode echocardiography. Anatomic validation, standardization, and comparison to other methods (1987) Hypertension, 9 (SUPPL. 2), pp. 19-26
Sacc, L., Cittadini, A., Fazio, S., Growth hormone and the heart (1994) Endocr Rev, 15, pp. 555-573
M ller, J., J rgensen, J. O. L., M ller, N., Hansen, K. W., Pedersen, E. B., Christiansen, J. S., Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man (1991) J Clin Endocrinol Metab, 72, pp. 768-772
Gunal, A. I., Isik, A., Celiker, H., Eren, O., Celebi, H., Gunal, S. Y., Luleci, C., Short term reduction of left ventricular mass in primary hypertrophic cardiomyopathy by octreotide injections (1996) Heart, 76, pp. 418-421
Crick, S. J., Sheppard, M. N., Ho, S. Y., Anderson, R. H., Localisation and quantitation of autonomic innervation in the porcine heart. I. Conduction system (1999) J Anat, 195, pp. 341-357
Cardiovascular consequences of early-onset growth hormone excess
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/m 2; 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/m 2; 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.
Cardiovascular consequences of early-onset growth hormone excess