Cardiac Function, Physical Exercise Capacity, and Quality of Life during Long-Term Thyrotropin-Suppressive Therapy with Levothyroxine: Effect of Individual Dose Tailoring

Abstract

As recently claimed, TSH-suppressive therapy with L-T4 may have adverse effects on the heart, but these results have not been consistently confirmed. We assessed cardiac function by clinical, echocardiographic, and ergometabolic criteria in 19 patients (16 women and 3 men) receiving long term L-T4 at a fixed daily dose ranging from 1.8-4.0 microg/kg. The results showed significant alterations in several cardiac parameters suggestive of subclinical hyperthyroidism. In particular, intraventricular septum thickness (10.0+/-1.4 vs. 8.1+/-1.1 mm), left ventricular posterior wall thickness (9.4 1.5 vs. 8.1+/-1.1 mm), end-diastolic dimension (47+/-4 vs. 44+/-3 mm), and left ventricular mass index (102+/-15 vs. 75+/-15 g/m2) were significantly increased compared to values in age- and sex-matched euthyroid controls. Exercise tolerance (expressed as maximal tolerated workload; 102+/-14 vs. 117+/-12 watts), maximal VO2 achieved at peak exercise (maximum VO2, 17.3+/-3.3 vs. 21.9+/-2.5 mL/min x kg), and anaerobic threshold (expressed as a percentage of VO2max, 46.5+/-8.4 vs. 56.2+/-6.6) were significantly reduced in L-T4-treated patients. The L-T4 dose was then reduced to the minimal amount able to keep the serum TSH concentration at 0.1 mU/L or less in 7 patients who were reevaluated 6 months after the initial study. This individual tailoring of the TSH-suppressive L-T4 dose was in all cases associated with normalization of all echocardiographic and ergometabolic parameters. In conclusion, our findings show that abnormalities of heart morphology associated with impaired exercise performance occur as a consequence of long term therapy with fixed TSH-suppressive doses of L-T4, but that these abnormalities improve or disappear after careful tailoring of TSH-suppressive therapy.

Subclinical hyperthyroidism: clinical features and treatment options

“…Similar results were obtained with individual tailoring of the TSH-suppressive dose of L-T4, although the mean score remained significantly higher than that of euthyroid healthy controls (25). Moreover, treatment for 6 months with methimazole significantly improved symptoms evaluated with the Wayne index in endogenous subclinical hyperthyroid patients, paralleling the normalization of the thyroid status (27).…”

“…Similarly, individual tailoring of the L-T4 dose in patients requiring TSH-suppressive treatment significantly decreased left ventricular mass and increased maximum workload (25). A decrease in the average 24-h heart rate, atrial premature beats, and left ventricular mass has also been reported in patients with endogenous subclinical hyperthyroidism after restoration of euthyroidism by methimazole treatment (27).…”

“…Using the bicycle ergometer test, significant reductions in the peak workload and exercise Short-term effects due to the electrophysiological action of thyroid hormone Sinus tachycardia Atrial premature beats Atrial fibrillation Long-term effects prevalently due to increased cardiac workload with enhancement of left ventricular mass Impaired diastolic function Systolic dysfunction during effort duration were found, and were associated with left ventricular systolic dysfunction on effort, as indicated by the poor increase (# 5%) or even a decreased ejection fraction during exercise (53). Similarly, using cardiopulmonary exercise testing, exercise tolerance and oxygen uptake at peak exercise and at the anaerobic threshold were significantly decreased (25).…”

The Evaluation of Left Ventricular Hypertrophy in Hypertensive Patients with Subclinical Hyperthyroidism

“…Subclinical hyperthyroidism can be the result of the same causes of overt clinical hyperthyroidism but patients with subclinical hyperthyroidism do not usually show specific symptoms and signs of hyperthyroidism [1,2]. It has been demonstrated that exogenous subclinical hyperthyroidism, in which patients treated with TSHsuppressive doses of levothyroxine, may affect the heart as in subjects with overt hyperthyroidism, but it remains controversial whether endogenous subclinical hyperthyroidism affects the heart [3][4][5].Situations in which thyroid hormones were increased have been shown to stimulate myocardial hypertrophy. Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality.…”

“…It has been demonstrated that exogenous subclinical hyperthyroidism, in which patients treated with TSHsuppressive doses of levothyroxine, may affect the heart as in subjects with overt hyperthyroidism, but it remains controversial whether endogenous subclinical hyperthyroidism affects the heart [3][4][5].…”