Endocrine Abstracts

Objectives: The variability of thyroid hormone levels during long-term antithyroid drug (ATD) therapy and its possible association with adverse health outcomes has not been previously studied. The aim of this study was to evaluate the association of thyroid function test (TFT) variability and cardiovascular disease (CVD) morbidity during long-term ATD therapy. Furthermore, clinical factors related to high TFT variability during the ATD therapy were identified.

Design: Retrospective cohort study.

Methods: Patients (n = 394) treated for hyperthyroidism with a first-line long-term ATD therapy at Tampere University Hospital between March 2016 and December 2018 were included and followed up until March 2019. The medians and coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined and evaluated in relation to baseline clinical factors. The associations of TFT variability and baseline clinical factors with CVD-associated hospital visits were assessed with logistic regression analyses.

Results: In the multivariable analyses, age (odds ratio [OR] 1.06, 95 % confidence interval [CI] 1.02-1.09), median fT4 (OR 1.09, 95 % CI 1.0-1.16) and median fT3 values (OR 1.34, 95 % CI 1.09-1.65), and fT4-CV (OR 1.02, 95 % CI 1.01-1.04) were independent risk factors for CVD morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAb) protected from CVD morbidity (OR 0.29, 95 % CI 0.13-0.66). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with CVD morbidity (OR 1.03, 95 CI 1.00-1.05), but median fT4 or fT3 levels were not. The patients with positive baseline TRAbs or thyroid peroxidase antibodies (TPOAbs) had higher fT4-CV and median fT4 levels, compared to the patients with negative TRAb or TPOAb measurements (P = 0.002 and P = 0.024, respectively).

Conclusions: During long-term ATD therapy for hyperthyroidism, fT4 variability is associated with an increased CVD morbidity. Patients with autoantibody-related hyperthyroidism have a higher variability of fT4 values compared to patients without thyroid autoantibodies. Although positive TRAbs are associated with a lower CVD morbidity compared to hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with CVD morbidity also in patients with positive TRAbs.