Cardiac Disease in Acromegaly

Visit our website at: http://pituitary.mgh.harvard.edu Patients with acromegaly are known to have reduced life expectancy. Prior to effective treatment for acromegaly, more than 80% of acromegalic patients died of cardiovascular disease before age 60 (1,2). Even in the modern era with available therapy, mortality in active acromegaly is still increased about twoto three-fold and the major cause of death remains cardiovascular disease, comprising 40 to 60 percent of mortality in acromegalic patients (3). Several studies have shown, however, that mortality rates can be decreased to levels expected in the general population by normalization of serum growth hormone (GH) and insulin-like growth factor (IGFI) (3,4,5,6). Huchard first described cardiac abnormalities associated with acromegaly in 1895 (7), not long after Marie’s initial description of acromegaly (8). In addition to myocardial hypertrophy and congestive heart failure, other cardiovascular disorders prevalent in acromegalic patients include hypertension, diastolic dysfunction, valvular heart disease, ventricular arrhythmia, and endothelial dysfunction. Post-mortem pathological studies found the increase in heart size was related to duration of acromegaly and occurred in both hypertensive and nonhypertensive patients (9). Cardiac histopathology showed myocardial hypertrophy (in 93% of patients examined), interstitial fibrosis (85%), and lymphomononuclear cell infiltrate (59%). Possible etiologic factors for cardiac hypertrophy in acromegaly include hypertension, direct hormonal effects of growth hormone or IGF-I, or the combination of hypertension and hormonal effects. Hypertension, a well-established cause of left ventricular hypertrophy, is very common in acromegaly. In normal rat heart in vivo, the administration of recombinant IGF-I causes ventricular chamber enlargement and hypertrophy in a dose-responsive manner (10). Some authors have proposed a separate entity of “acromegalic cardiomyopathy” since hypertrophic cardiomyopathy can be seen independent of hypertension, diabetes mellitus, valvular heart disease, or atherosclerosis in acromegaly. Early on, as the myocardium hypertrophies, diastolic dysfunction is detectable. Later, ventricular remodeling with chamber enlargement and systolic heart failure can ensue. The prevalence of regurgitant valvular heart disease, especially aortic valve regurgitation and mitral valve regurgitation, is Comparison of a normal sized heart (on the left) with an acromegalic heart (on the right). Reprinted from American Heart Journal (9) with permission from Elsevier.