Maraka Spyridoula, Owen Richard R, Singh Ospina Naykky M, Knox Micheal, Dodds Terri, Thostenson Jeff D, Dishongh Katherine, Raciborski Rebecca A, Albashaireh Arwa, Shah Aashka, Syed Sabah, Naqvi Syeda, Motahari Hooman, Thumma Soumya, Toloza Freddy, Ambrogini Elena, Brito Juan P
Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
Endocrine. 2025 Jul 30. doi: 10.1007/s12020-025-04371-z.
Randomized clinical trials (RCTs) have shown no benefit of levothyroxine for subclinical hypothyroidism (SCH) in improving well-being, cardiovascular outcomes, or mortality. We aimed to evaluate study procedures' feasibility, safety, and preliminary effects of levothyroxine discontinuation in adults with SCH.
We conducted a pilot, double-blind, placebo-controlled RCT with 6-month follow-up at a Veterans Affairs Medical Center. Adults with SCH on levothyroxine ≤75 mcg daily were randomized to continue levothyroxine or switch to placebo. The primary outcome was feasibility.
Fifty participants were randomized (32% enrollment rate); five were excluded post-randomization due to unconfirmed SCH, yielding 45 participants (21 levothyroxine, 24 placebo). One patient in the placebo group withdrew for personal reasons (98% completion rate). Participants' mean age was 68.2 years (SD 9.7); 80% were male, and 86.7% were White. At 6 months, there was no statistically significant difference between the placebo and levothyroxine groups in ThyPRO-Hypothyroid Symptoms [28.3 (22.8) vs. 22.9 (19.5)], Tiredness [27.6 (22.8) vs. 32.8 (22.1)], and EQ-5D score [0.750 (0.232) vs. 0.741 (0.180)]. The only notable adverse event was rib fractures in a placebo group participant (TSH 3.04 mIU/L at 6 months). Two participants in the placebo group restarted levothyroxine (n = 1, TSH > 10 mIU/L; n = 1, fatigue).
We demonstrated feasibility of study procedures for discontinuing levothyroxine in patients with SCH and obtained preliminary effects on well-being. The low occurrence of adverse events suggests that levothyroxine discontinuation may be well-tolerated. These findings support conducting a larger multi-site RCT to comprehensively assess the effects of levothyroxine discontinuation.
NCT04288115.
随机临床试验（RCT）表明，左甲状腺素对亚临床甲状腺功能减退症（SCH）在改善健康状况、心血管结局或死亡率方面并无益处。我们旨在评估左甲状腺素停药在成年SCH患者中的研究程序的可行性、安全性及初步效果。
我们在一家退伍军人事务医疗中心进行了一项为期6个月随访的试点、双盲、安慰剂对照RCT。每日服用左甲状腺素≤75微克的成年SCH患者被随机分为继续服用左甲状腺素或改用安慰剂组。主要结局是可行性。
50名参与者被随机分组（入组率32%）；5名参与者在随机分组后因SCH未得到确认而被排除，最终有45名参与者（21名服用左甲状腺素，24名服用安慰剂）。安慰剂组有1名患者因个人原因退出（完成率98%）。参与者的平均年龄为68.2岁（标准差9.7）；80%为男性，86.7%为白人。在6个月时，安慰剂组和左甲状腺素组在甲状腺功能减退症患者症状评分（ThyPRO-Hypothyroid Symptoms）[28.3（22.8）对22.9（19.5）]、疲劳感[27.6（22.8）对32.8（22.1）]和EQ-5D评分[0.750（0.232）对0.741（0.180）]方面无统计学显著差异。唯一值得注意的不良事件是安慰剂组一名参与者发生肋骨骨折（6个月时促甲状腺激素[TSH]为3.04 mIU/L）。安慰剂组有2名参与者重新开始服用左甲状腺素（1名TSH>10 mIU/L，1名因疲劳）。
我们证明了在SCH患者中停用左甲状腺素的研究程序的可行性，并获得了对健康状况的初步影响。不良事件发生率低表明停用左甲状腺素可能耐受性良好。这些发现支持开展一项更大规模的多中心RCT，以全面评估停用左甲状腺素的效果。
NCT04288115。
