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. 2025 May 15;26(1):161.
doi: 10.1186/s13063-025-08857-z.

Efficacy and safety of levothyroxine monotherapy in lowering the risk of cardiovascular disease in older adults with subclinical hypothyroidism: research protocols of a multicenter, open-label, randomized controlled trial

Chong Xu #  1 , Hui Zhou #  1 , Xiaofan Lu  1 , Shuhang Xu  2 , Yu Sun  3
Affiliations

Efficacy and safety of levothyroxine monotherapy in lowering the risk of cardiovascular disease in older adults with subclinical hypothyroidism: research protocols of a multicenter, open-label, randomized controlled trial

Chong Xu et al. Trials. .

Abstract

Objective: This multicenter, open-label, randomized controlled trial (RCT) aims to assess the efficacy and safety of levothyroxine monotherapy in lowering the risk of cardiovascular disease (CVD) in untreated older adults with subclinical hypothyroidism (SCH) who are diagnosed according to population-specific TSH reference values.

Methods: A total of 254 patients with SCH who meet the diagnostic criteria will be recruited, and the baseline clinical data of the patients will be collected. Then, a total of 127 patients will be randomly divided into each of the treatment and control groups, and the treatment group will receive daily levothyroxine doses (Merck Euthyrox® levothyroxine 50 mcg tablet). Specifically, 50 µg of levothyroxine per day will be administered to patients in the treatment group (or 25 µg to patients with a body weight < 50 kg) for at least 48 weeks to maintain thyroid-stimulating hormone (TSH) levels within the normal range. The participants in the control group will be subjected only to thyroid status evaluation, and the results will be recorded. The participants will complete five visits before and after the start of the trial, and differences in the change in carotid intima-media thickness (CIMT), maximum mean change in plaque burden, and changes in lipid profiles, bone mineral densities, and incidences of fatal and nonfatal cardiovascular events between the initial visit and the last follow-up visit will be evaluated via vascular ultrasound.

Discussion: We will explicitly address whether levothyroxine replacement therapy provides cardiovascular benefits for older adults with subclinical hypothyroidism.

Clinical trial registration: ClinicalTrials.gov, No. ChiCTR2400092634. Registered on 30 November 2024. Recruitment for this study began on December 1, 2024, and continues until at least until November 30, 2025.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study will follow the tenets of the Declaration of Helsinki, and the protocol was approved by the ethics committees of the Affiliated Suqian Hospital of Xuzhou Medical University and the Affiliated Nanjing University of Chinese Medicine Nanjing Integrated Traditional Chinese and Western Medicine Hospital (No. ChiCTR2400092634) on November 30, 2024. Informed consent will be obtained from all the participants. Informed consent procedures will be stratified by cognitive status: participants with MMSE scores ≥ 25 will provide autonomous consent, whereas those with scores < 25 will require consent from legally authorized representatives per institutional protocols. Any changes to the protocol resulting from data revision will be communicated to the Research Ethics Committee, and approval for the modifications will be obtained before implementing any adjustments to the study. Additionally, significant changes to the study protocol will require reconsent from participants. Consent for publication: Not applicable. Competing interests: The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of this work.

Figures

Fig. 1
Fig. 1
Study flowchart. CIMT, carotid intima–media thickness
See this image and copyright information in PMC

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    Hou X, Sun X, Xu S, Li Y. Hou X, et al. Endocr Connect. 2025 Aug 5;14(8):e250393. doi: 10.1530/EC-25-0393. Print 2025 Aug 1. Endocr Connect. 2025. PMID: 40709715 Free PMC article. No abstract available.

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