To investigate the effects of long term thyroid hormone suppressive therapy on the heart, 20 patients were evaluated by noninvasive techniques. Of them, 10 were athyreotic after surgery for differentiated thyroid cancer, and 10 had diffuse or nodular goiter. The mean age of the group was 39 +/- 11 yr. Twenty age- and sex-matched subjects served as controls. The mean dose of levothyroxine was 163 +/- 34 micrograms daily. Plasma TSH was undetectable in all patients. Mean serum T4, free T4, and sex hormone-binding globulin were significantly higher (P < 0.001), whereas mean serum T3, free T3, and osteocalcin did not differ from control levels. Cardiac evaluation consisted of a standard 12-lead electrocardiogram, an ambulatory electrocardiographic monitoring (Holter), and an echocardiographic study. Two patients showed abnormal electrocardiograms for left ventricular hypertrophy. Holter demonstrated an increase in average heart rate (84 +/- 7 vs. 70 +/- 6 beats/min; P < 0.01). Prevalence of atrial premature beats was higher in the patient group than in the control group (100% vs. 60%; P < 0.006). The echocardiogram showed an increased left ventricular mass index in the patient group (97 +/- 24 vs. 80 +/- 18 g/m2; P < 0.02). Furthermore, left ventricular systolic function was enhanced, with higher values of fractional shortening (38 +/- 7% vs. 34 +/- 4%; P < 0.05) and rate-adjusted velocity of shortening (1.2 +/- 0.13 vs. 1.05 +/- 0.14 circumferences/sec; P < 0.01). These findings indicate that long term levothyroxine therapy at suppressive doses markedly affects cardiac function.