Biondi, Fazio, and colleagues recently reported that long term T4 treatment to suppress serum TSH markedly affects cardiac function. T4-treated patients had more symptoms [12.2 +/- 3.9 (+/-SD) vs. 4.2 +/- 2.3 by quantitative questionnaire], higher mean heart rate, increased incidence of atrial extrasystoles, increased interventricular septal thickness and left ventricular mass index (LVMi), and significant diastolic dysfunction. The severity of cardiac abnormalities was highly correlated with scores of a rating scale used for assessing symptoms of thyrotoxicosis. We have duplicated their studies in 17 athyreotic patients (mean age, 45 +/- 10 yr; range, 27-63 yr) without heart disease or hypertension whose dose of T4 was titrated to suppress serum TSH to less than 0.01 microU/mL. The mean duration of T4 treatment was 9.2 +/- 5.4 yr. Controls were healthy volunteers matched for sex and age (+/-3 yr). The mean T4 dose was 2.8 +/- 0.9 micrograms/kg (0.192 +/- 0.058 mg/day). By questionnaire, patients had minimal symptoms, although their symptom score was significantly greater than the control value (4 +/- 3 vs. 2 +/- 1; P < 0.05; maximum score, 36). No differences in mean heart rate or in atrial or ventricular extrasystoles were noted. In patients, indexes of systolic and diastolic function and interventricular septal thickness were similar to control values. The mean LVMi was normal in both groups. However, the mean LVMi in patients (117 +/- 35 g/m2) was higher than that in controls (92 +/- 31; P < 0.05). In conclusion, patients were minimally affected by TSH-suppressive doses of T4. They had few symptoms and no increase in extrasystoles or basal heart rate. Based on current knowledge, the increase in LVMi observed in patients without associated significant systolic or diastolic abnormalities does not have clinical or prognostic importance. Therefore, in the absence of symptoms of thyrotoxicosis, patients treated with TSH-suppressive doses of L-T4 may be followed clinically without specific cardiac laboratory studies.