Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois, USA.
Department of Medicine, Rush University Medical Center, Chicago, Illinois, USA.
Thyroid. 2020 Oct;30(10):1399-1413. doi: 10.1089/thy.2020.0153. Epub 2020 May 12.
The basis for the treatment of hypothyroidism with levothyroxine (LT4) is that humans activate T4 to triiodothyronine (T3). Thus, while normalizing serum thyrotropin (TSH), LT4 doses should also restore the body's reservoir of T3. However, there is evidence that T3 is not fully restored in LT4-treated patients. For patients who remain symptomatic on LT4 therapy, clinical guidelines recommend, on a trial basis, therapy with LT4+LT3. Reducing the LT4 dose by 25 mcg/day and adding 2.5-7.5 mcg liothyronine (LT3) once or twice a day is an appropriate starting point. Transient episodes of hypertriiodothyroninemia with these doses of LT4 and LT3 are unlikely to go above the reference range and have not been associated with adverse drug reactions. Trials following almost a 1000 patients for almost 1 year indicate that similar to LT4, therapy with LT4+LT3 can restore euthyroidism while maintaining a normal serum TSH. An observational study of 400 patients with a mean follow-up of ∼9 years did not indicate increased mortality or morbidity risk due to cardiovascular disease, atrial fibrillation, or fractures after adjusting for age when compared with patients taking only LT4. Desiccated thyroid extract (DTE) is a form of combination therapy in which the LT4/LT3 ratio is ∼4:1; the mean daily dose of DTE needed to normalize serum TSH contains ∼11 mcg T3, but some patients may require higher doses. The DTE remains outside formal FDA oversight, and consistency of T4 and T3 contents is monitored by the manufacturers only. Newly diagnosed hypothyroid patients should be treated with LT4. A trial of combination therapy with LT4+LT3 can be considered for those patients who have unambiguously not benefited from LT4.
左旋甲状腺素（LT4）治疗甲状腺功能减退症的依据是人体将 T4 转化为三碘甲状腺原氨酸（T3）。因此，在使血清促甲状腺激素（TSH）正常化的同时，LT4 剂量也应恢复体内 T3 的储备。然而，有证据表明，在接受 LT4 治疗的患者中，T3 并未完全恢复。对于在 LT4 治疗后仍有症状的患者，临床指南建议在试用的基础上进行 LT4+LT3 治疗。减少 LT4 剂量 25 mcg/天，并每天添加 2.5-7.5 mcg 左甲状腺素（LT3）一次或两次，是一个合适的起点。这些 LT4 和 LT3 剂量下的短暂高三碘甲状腺原氨酸血症不太可能超过参考范围，也与药物不良反应无关。对近 1000 名患者进行近 1 年的试验表明，与 LT4 相似，LT4+LT3 治疗可以在维持正常血清 TSH 的同时恢复甲状腺功能正常。一项对 400 名患者进行的观察性研究，平均随访时间约为 9 年，与服用 LT4 的患者相比，在调整年龄后，并未因心血管疾病、心房颤动或骨折而增加死亡率或发病率风险。干甲状腺提取物（DTE）是一种联合治疗形式，其中 LT4/LT3 比值约为 4:1；使血清 TSH 正常化所需的 DTE 平均日剂量包含约 11 mcg T3，但一些患者可能需要更高剂量。DTE 仍未受到 FDA 的正式监管，只有制造商监测 T4 和 T3 含量的一致性。新诊断的甲状腺功能减退症患者应接受 LT4 治疗。对于那些明确未从 LT4 中获益的患者，可以考虑尝试 LT4+LT3 联合治疗。
