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This version published online on November 14, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1587
A more recent version of this article appeared on February 1, 2007
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Submitted on July 21, 2006
Accepted on November 3, 2006

Treatment with GH receptor antagonist in acromegaly: Effect on cardiac structure and performance

Rosario Pivonello, Maurizio Galderisi, Renata S. Auriemma, Maria Cristina De Martino, Mariano Galdiero, Antonio Ciccarelli, Arcangelo D'Errico, Ione Kourides, Pia Burman, Gaetano Lombardi, and Annamaria Colao*

Department of Molecular and Clinical Endocrinology and Oncology (R.P., R.S.A., M.C.D.M., M.G., A.Ci., G.L., A.Co.), Department of Experimental Medicine (M.G., A.D.), "Federico II" University of Naples, Italy, and Pfizer Inc. (P.B., I.K.), New York, USA

* To whom correspondence should be addressed. E-mail: colao{at}unina.it.

Aim: The aim of the current study was to evaluate the effect of short-term (6 months) and long-term (18 months) treatment with pegvisomant on cardiac structure and function in patients with acromegaly.

Patients: Seventeen patients (9 women, 8 men, 27-61 yr) with active acromegaly entered and 12 completed the long-term study. After a baseline evaluation, including measurement of hemodynamic, biochemical, hormonal parameters, and a standard Doppler echocardiography, treatment with pegvisomant was started at the initial dose of 10 mg/day, increasing by 5 mg/day every 6 weeks on the basis of IGF-I levels until normalization or the achievement of a maximal dose of 40 mg/day.

Results: After short-term treatment, IGF-I levels were normalized in 10 of the 17 (59%) patients. Left ventricular (LV) mass index (LVMi) was significantly decreased, without changes in diastolic and systolic performance. After long-term treatment, IGF-I levels were normalized in 10 of the 12 (83%) patients. Blood glucose and serum insulin levels were decreased compared with baseline. LVMi was further decreased compared with short-term treatment, so that the prevalence of LV hyperthrophy decreased from 53% at baseline to 17% after 18 months of treatment. Moreover, ejection fraction (EF), as well as early to late (atrial) peak velocity ratio (E/A), were significantly increased whereas isovolumic relaxation time (IVRT) was significantly decreased compared with baseline, demonstrating an improvement of both diastolic and systolic function. A significant correlation was found between the change in IGF-I levels and that of left ventricular EF. In general, the prevalence of cardiac insufficiency was present in 13 of the 17 (76%) patients at baseline and in 1 (8%) patient after 18 months of treatment.

Conclusions: Long-term treatment with the GH receptor antagonist improves acromegalic cardiomyopathy, by decreasing cardiac hypertrophy and enhancing diastolic and systolic function, and consequently partially or completely reverting the cardiac insufficiency.
Key words: GH receptor antagonist • pegvisomant • heart • cardiac structure • cardiac function • GH • IGF-I • acromegaly




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