Discontinuation of levothyroxine therapy in patients with subclinical hypothyroidism: a pilot randomized clinical trial.

IF 2.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2025-07-30 DOI:10.1007/s12020-025-04371-z

Spyridoula Maraka, Richard R Owen, Naykky M Singh Ospina, Micheal Knox, Terri Dodds, Jeff D Thostenson, Katherine Dishongh, Rebecca A Raciborski, Arwa Albashaireh, Aashka Shah, Sabah Syed, Syeda Naqvi, Hooman Motahari, Soumya Thumma, Freddy Toloza, Elena Ambrogini, Juan P Brito

{"title":"Discontinuation of levothyroxine therapy in patients with subclinical hypothyroidism: a pilot randomized clinical trial.","authors":"Spyridoula Maraka, Richard R Owen, Naykky M Singh Ospina, Micheal Knox, Terri Dodds, Jeff D Thostenson, Katherine Dishongh, Rebecca A Raciborski, Arwa Albashaireh, Aashka Shah, Sabah Syed, Syeda Naqvi, Hooman Motahari, Soumya Thumma, Freddy Toloza, Elena Ambrogini, Juan P Brito","doi":"10.1007/s12020-025-04371-z","DOIUrl":null,"url":null,"abstract":"Purpose: 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.Methods: 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.Results: 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).Conclusion: 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.Clinical trial registration number: NCT04288115.","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364413/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-025-04371-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Clinical trial registration number: NCT04288115.

查看原文本刊更多论文

亚临床甲状腺功能减退患者停用左旋甲状腺素治疗：一项随机临床试验

目的：随机临床试验（rct）显示，左甲状腺素治疗亚临床甲状腺功能减退（SCH）在改善幸福感、心血管结局或死亡率方面没有益处。我们的目的是评估研究程序的可行性、安全性和在成人sch患者中停用左甲状腺素的初步效果。方法：我们在退伍军人事务医疗中心进行了一项试点、双盲、安慰剂对照的随机对照试验，随访6个月。每日左旋甲状腺素≤75微克的SCH患者被随机分为继续左旋甲状腺素组或改用安慰剂组。主要结果是可行性。结果：随机纳入50例受试者（入组率32%）；5人因未证实的SCH而被排除在随机分组后，共45名参与者（21名左旋甲状腺素，24名安慰剂）。安慰剂组有一名患者因个人原因退出治疗（完成率98%）。参与者的平均年龄为68.2岁（SD 9.7）；男性占80%，白人占86.7%。6个月时，安慰剂组和左旋甲状腺素组在甲状腺素-甲状腺功能减退症状[28.3（22.8）比22.9(19.5)]、疲劳[27.6（22.8）比32.8(22.1)]和EQ-5D评分[0.750（0.232）比0.741(0.180)]方面无统计学差异。唯一值得注意的不良事件是安慰剂组参与者的肋骨骨折（6个月时TSH 3.04 mIU/L）。安慰剂组2例患者重新开始左旋甲状腺素治疗(n = 1， TSH为10 mIU/L；N = 1，疲劳)。结论：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，并获得了对健康的初步影响。不良事件的低发生率表明左甲状腺素停药可能耐受良好。这些发现支持进行更大规模的多地点随机对照试验，以全面评估左甲状腺素停药的影响。临床试验注册号：NCT04288115。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.