Clinical factors predicting the successful discontinuation of hormone replacement therapy in patients diagnosed with primary hypothyroidism

BACKGROUND: Although reversible in some patients, primary hypothyroidism is considered a permanent condition requiring lifelong hormone therapy. This study aimed to investigate the factors predicting the successful discontinuation of levothyroxine (L–T4) therapy in patients with primary hypothyroidism. METHODS: A retrospective study was performed in primary hypothyroidism patients who met inclusion criteria: patients who maintained stable L–T4 therapy for more than 1 year, following gradual dose reduction of L–T4 based on the clinical decision (L–T4 tapering); patients receiving either no L–T4 or a fixed minimum dose for more than 1 year after L–T4 tapering. Reduction in L–T4 dosage by 12.5–50 μg within 3 months was considered as L–T4 tapering. Serum free T4, TSH, and clinical symptoms were evaluated before, during and after tapering. Logistic regression and decision tree analyses were performed to predict the successful discontinuation of L–T4. RESULTS: Among 382 patients, 22.5% and 58.4% showed successful discontinuation (T4–Discontinued) and dose reduction (T4–Reduced) of L–T4 therapy, while other did not obtained any reduction of L–T4 dose (T4–Unchanged). The median number of tapering visit was 1.0 (range, 1.0–4.0). In T4–Discontinued group, the TSH level and the positive rate of anti-thyroperoxidase at the time of L–T4 initiation were lower, the duration of L–T4 therapy was shorter, and the maintenance dose of L–T4 at the time of tapering was lower than those in the T4–Unchanged group. In ultrasonography, normal parenchyma was preserved in the T4–Discontinued group while others showed higher rates of heterogeneous or hypoechoic parenchymal changes. Among those different characteristics, the longer duration of L–T4 therapy and the higher maintenance dose of L–T4 at the time of tapering significantly predicted the failure of discontinuation of L–T4 in multivariate analysis. A decision tree showed that patients with a duration of L–T4 therapy >4.6 years had lower success rate of discontinuation. CONCLUSION: Shorter duration of L–T4 therapy and lower L–T4 dose at the time of tapering are the predictable factors for successful L–T4 tapering in stably maintained primary hypothyroidism patients.