左甲狀腺素（LT4）對大多數甲狀腺功能低下症患者有效。然而，有少數患者在血清甲狀腺刺激素水平恢復正常後仍有症狀。包括所有類型甲狀腺功能低下症患者的隨機臨床試驗顯示，左甲狀腺素和利甲狀腺素（LT4+LT3）合併治療安全，是患者首選，相比單獨使用LT4。許多未能完全從LT4中受益的患者在轉換至LT4+LT3後經歷生活品質和認知的改善。對於這些患者，正在測試提供穩定血清三碘甲腺原氨酸水平的新型緩釋LT3配方。此外，再生技術的進展使得人類甲狀腺有器官在移植至甲狀腺功能低下小鼠後能恢復到正常功能。最後，根據新的認識，在某些情況下，T3信號可能在特定組織中受損，而全身甲狀腺功能保持正常。例如，對於代謝（功能）相關脂肪肝患者，肝選擇性T3樣分子已在臨床試驗中成功應用。《醫學年度評論》第75卷的預期最終在線出版日期是2024年1月。請參閱http://www.annualreviews.org/page/journal/pubdates進行修訂的估計。

Levothyroxine (LT4) is effective for most patients with hypothyroidism. However, a minority of the patients remain symptomatic despite the normalization of serum thyrotropin levels. Randomized clinical trials including all types of patients with hypothyroidism revealed that combination levothyroxine and liothyronine (LT4+LT3) therapy is safe and is the preferred choice of patients versus LT4 alone. Many patients who do not fully benefit from LT4 experience improved quality of life and cognition after switching to LT4+LT3. For these patients, new slow-release LT3 formulations that provide stable serum T3 levels are being tested. In addition, progress in regenerative technology has led to the development of human thyroid organoids that restores euthyroidism after being transplanted into hypothyroid mice. Finally, there is a new understanding that, under certain conditions, T3 signaling may be compromised in a tissue-specific fashion while systemic thyroid function is preserved. This is seen, for example, in patients with metabolic (dysfunction)-associated fatty liver disease, for whom liver-selective T3-like molecules have been utilized successfully in clinical trials. Expected final online publication date for the Annual Review of Medicine, Volume 75 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.