Use of the 36-Point Thyroid Symptom Questionnaire to Potentially Guide Optimal Thyroid Hormone Replacement Therapy

Objective: To determine the association between a transition from levothyroxine (LT4) to combination therapy and change in the Thyroid Symptom Questionnaire (TSQ-36). Methods: We performed a post hoc subgroup analysis of 2 previous randomized, double-blind, crossover studies (total n = 143) to evaluate patient symptoms on treatment with LT4, desiccated thyroid extract (DTE), and levothyroxine + liothyronine (LT4+LT3). The TSQ-36 was completed at the end of each treatment period in the context of normal thyroid stimulating hormone levels. Patients were stratified based on their TSQ-36 score on LT4: Low Symptoms (TSQ-36: 0-12), Moderate Symptoms (TSQ-36: 13-24), and High Symptoms (TSQ-36: 25-36). Mean TSQ-36 scores were compared on LT4, LT4+LT3, and DTE. Treatment-blinded preference of therapy was also stratified by TSQ-36 score on LT4. Results: In cohort 1, the Moderate-High Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (P = .01). In cohort 2, the High Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (P < .01) and on LT4+LT3 vs LT4 (P < .001). The Moderate Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (P = .02). The Low Symptoms group had significantly lower TSQ-36 scores on LT4 vs DTE (P = .03) and LT4+LT3 (P = .02). Patients who preferred combination therapy had significantly higher TSQ-36 scores than patients who preferred LT4. Persistent symptoms may be due to a relative deficiency in triiodothyronine, which could be remedied by combination therapy. Conclusion: The TSQ-36 can potentially be used to quantify patient symptoms and guide thyroid hormone therapy. Patients on LT4, with moderate-to-severe symptoms despite normalization of thyroid stimulating hormone, could consider a trial of combination therapy. Patients with low symptoms on LT4 should generally avoid combination therapy.