Serum free triiodothyronine as an adjunctive marker for thyroid hormone status in athyreotic patients on levothyroxine

CONTEXT: Athyreotic patients receiving levothyroxine (LT4) for hypothyroidism sometimes exhibit low serum free triiodothyronine (FT3) levels despite normal TSH, and experience hypothyroid-like symptoms and signs, suggesting reduced peripheral thyroid hormone action. OBJECTIVE: The present study aimed to identify the most reliable biochemical marker for assessing peripheral thyroid hormone status in such patients. METHODS: This was a single-center retrospective, cross-sectional study of athyreotic patients on LT4. Patients were classified according to TSH, FT3 and FT4, and selected metabolic markers potentially influenced by peripheral thyroid hormone status were compared across groups. RESULTS: In 426 athyreotic patients taking ≥1.2 μg/kg of LT4, the majority (58%) of patients exhibited normal serum FT3 and FT4, followed by 21% with normal FT3 and elevated FT4, 18% with low FT3 and normal FT4, and 2% with low FT3 and elevated FT4. This classification corresponded well with the differences in FT3/FT4 ratios that reflect the efficiency of T4 to T3 conversion. Among 156 patients not taking anti-hyperlipidemic drugs and selected with the propensity score matching using gender as a covariate, the metabolic markers of alanine transaminase, and body mass index were significantly elevated in those with low FT3 than in those with normal FT3. CONCLUSION: In our cohort, lower FT3 was associated with selected metabolic markers in LT4-treated athyreotic patients, suggesting that FT3 may provide additional information on peripheral thyroid hormone status in selected patients. Prospective studies with standardized sampling and adjustment for confounding are warranted to establish FT3 as a validated marker or support FT3-guided dosing.