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Submitted on March 21, 2005
Accepted on August 18, 2005
Departments of Endocrinology (JS, CE-R, EC, AP, JR), Clinical Chemistry (MF) and Cardiology (GB, JH, EW, JB) Leiden University Medical Center, Leiden
* To whom correspondence should be addressed. E-mail: jwasmit{at}lumc.nl.
Background: Subclinical hyperthyroidism has been reported to affect systolic- and diastolic cardiac function. However, the reversibility of these effects is not well established.
Objective: To investigate the presence and reversibility of cardiac abnormalities in patients with long-term exogenous subclinical hyperthyroidism.
Design: Prospective, single-blinded placebo-controlled randomized trial of 6 months duration with 2 parallel groups.
Setting: University Medical Center, tertiary referral center for thyroid carcinoma.
Patients: As a model for subclinical hyperthyroidism, 25 patients with a history of differentiated thyroid carcinoma with >10 yr TSH (TSH) suppressive therapy with L-thyroxin were studied.
Interventions: L-Thyroxin dose was replaced by study medication containing L-thyroxin or placebo. Medication was titrated in a single-blinded fashion to establish continuation of TSH suppression (low-TSH group) or euthyroidism (euthyroid group).
Measurements: Serum levels of free-thyroxin (free T4) and TSH. ECHO Doppler cardiography including tissue Doppler to establish left ventricular dimensions and function as well as diastolic function. Baseline Echocardiography data were compared with 24 controls.
Results: There were no differences in baseline cardiac parameters and TSH levels between the two groups. Although mean LVMI was increased as compared with 24 controls, only 4 patients had left ventricular hypertrophy at baseline. This was not improved by restoration of euthyroidism. At baseline, diastolic function was impaired in all patients as indicated by abnormal values for the peak flow of the early filling phase (E, 55.3±9.5 mm/s), the ratio of E and the peak flow of the atrial filling phase (E /A ratio, 0.87±0.13), the early diastolic velocity obtained by tissue Doppler (E', 5.7±1.3 cm/s) and the peak atrial filling velocity obtained by tissue Doppler (A', 6.8±1.4 cm/s), prolonged E deceleration time (234± 34 ms) and isovolumetric relaxation time (IVRT, 121± 15 ms).
After 6 months, significant improvements were observed in the euthyroid group in the E/A ratio (+41%, P < 0.001), E deceleration time (-18%, P = 0.006), IVRT (-25%, P < 0.001), E' (+31%, P < 0.001) and the E'/A' ratio (+40%, P < 0.001).
Conclusions: We conclude that prolonged subclinical hyperthyroidism is accompanied by diastolic dysfunction that is at least partly reversible after restoration of euthyroidism. As isolated diastolic dysfunction may be associated with increased mortality, this finding is of clinical significance.
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