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Left Ventricular Diastolic Dysfunction in Patients with Subclinical Hypothyroidism

Departments of Internal Medicine (S.F., E.A.P., A.C., F.B., L.S.) and Endocrinology (B.B., N.P., G.L.) of the University Federico II, and Department of Endocrinology (C.C.) of the Second University, Naples, Italy

Address all correspondence and requests for reprints to: Luigi Saccà, M.D., Department of Internal Medicine, via Pansini, 5, 80131 Naples, Italy.

Although subclinical hypothyroidism is frequently diagnosed, the decision to institute a substitutive therapy with L-T₄ remains controversial. Because the cardiovascular system is considered a main target for the action of thyroid hormone, we investigated whether subclinical hypothyroidism induces cardiovascular abnormalities.

Twenty-six patients (mean age, 36 ± 12 yr) were evaluated by Doppler-echocardiography, whereas a subgroup of 10 patients, randomly selected, were reevaluated after 6 months of L-T₄ substitutive therapy (mean dose, 68 µg daily). Thirty subjects (matched for age, sex, and body surface area) served as controls.

Mean plasma TSH was significantly higher in patients (P < 0.001), whereas mean serum free T₄ and free T₃ concentrations, although in the normal range, were significantly lower (P < 0.001 and P < 0.005, respectively). Blood pressure and heart rate did not differ from control values. Echocardiogram examination showed no abnormalities of the left ventricular morphology and a slight, but not significant, reduction in the systolic function in the patient group. In contrast, Doppler-derived indices of diastolic function showed significant prolongation of the isovolumic relaxation time (94 ± 13 vs. 84 ± 8 msec; P < 0.001), increased A wave (55 ± 13 vs. 48 ± 9 cm/sec; P < 0.05), and reduced early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.4 ± 0.3 vs. 1.7 ± 0.3; P < 0.001). In the subgroup of 10 patients, thyroid hormone profile was normalized by 6 months of L-T₄ substitutive therapy, whereas no changes were observed in the left ventricular morphology. Systolic function was significantly enhanced, as compared with pretreatment values (P < 0.01) but did not differ from control values. Also, systemic vascular resistance was significantly decreased by L-T₄ replacement therapy. Assessment of diastolic function showed significant shortening of isovolumic relaxation time (77 ± 15 vs. 91 ± 8; P < 0.05), reduction of A wave (51 ± 13 vs. 60 ± 12; P < 0.01), and increase of early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.7 ± 0.4 vs. 1.3 ± 0.3; P < 0.001). These indices, however, were comparable with those of control subjects.

These findings indicate that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T₄ substitutive therapy.

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