Abstract

Hypothyroidism is a prevalent endocrine disorder managed primarily with levothyroxine (LT4) monotherapy. While this treatment effectively restores serum thyroid hormone levels in most patients, approximately 10–20% continue to experience persistent symptoms, such as cognitive dysfunction, fatigue, and metabolic abnormalities, despite normalized TSH levels. This review explores recent advances in hypothyroidism management, including combination therapy with LT4 and liothyronine (LT3), development of slow-release T3 formulations, and personalized treatment approaches based on genetic polymorphisms such as DIO2 Thr92Ala. Additionally, novel strategies including thyroid organoid transplantation, tissue-specific T3 delivery systems, and thyromimetic agents targeting THRβ in hepatic tissue are discussed. These innovations aim to improve therapeutic efficacy, address residual symptoms, and advance individualized care in hypothyroidism. The article highlights both the scientific rationale and the clinical evidence behind these emerging therapies, signaling a paradigm shift from hormone normalization toward restoring thyroid hormone action at the tissue level.

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