Quality of Life and Mood in Relation to Free T3, Free T4 and the FT3/FT4 Ratio in Levothyroxine-Treated Hypothyroidism: A Cross-Sectional Study

Background and Objectives: Many levothyroxine (LT4)-treated hypothyroid patients report persistent symptoms. We examined thyroid-related quality of life (QoL) and anxiety and depression symptoms in LT4-treated patients with Hashimoto thyroiditis or after thyroidectomy, and their associations with free triiodothyronine (FT3), free thyroxine (FT4), the FT3/FT4 ratio and thyrotropin (TSH). Materials and Methods: In this single-centre cross-sectional study, 219 consecutive adults (63 clinic comparison participants without known thyroid disease, 110 LT4-treated Hashimoto patients and 46 LT4-treated post-thyroidectomy patients) completed a Turkish ThyPRO short-form version (nine scales plus an overall QoL-impact item) and the Hospital Anxiety and Depression Scale (HADS). Fasting blood was drawn before the daily LT4 dose. Linear models were adjusted for diagnostic group, age, sex, body-mass index and TSH, with ratio × group interaction testing and group-specific slopes. Results: TSH, FT3 and FT4 were all within the reference range in 79% of the comparison group, 57% of Hashimoto and 24% of thyroidectomy patients. ThyPRO and HADS scores differed across groups (all p < 0.001). In the primary group-adjusted analysis, each one-unit lower FT3/FT4 ratio was associated with a higher ThyPRO composite (β = −8.6, 95% CI −9.1 to −8.1), HADS-depression (β = −1.4, −1.7 to −1.0) and HADS-anxiety score (β = −1.7, −2.0 to −1.3; all Holm-adjusted p < 0.001). Slopes differed between groups for ThyPRO and HADS-anxiety, but point estimates were negative in every group, and associations persisted among participants with all three tests in range (n = 124) and after excluding comparison participants with high FT4. TSH was not associated with the outcomes. Conclusions: Lower FT3 and FT3/FT4 ratio, but not TSH, were associated with worse thyroid-related QoL and more anxiety and depression symptoms; the association with the ratio persisted in participants with all thyroid tests in range. These cross-sectional associations require confirmation in independent prospective cohorts.