DOI: 10.12688/f1000research.179360.2 ISSN: 2046-1402

Early initiation of thyroid hormone therapy versus watchful waiting or delayed treatment or no treatment in subclinical hypothyroidism: A systematic review and meta-analysis protocol

Aravind P Gandhi, Kalyani P Deshmukh, Anupriya Kaliyappan, Akash Bang, Neha Gangane
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Background The prevalence of subclinical hypothyroidism (SCH) in the general population is notably high, ranging from 4% to 20%, and varies according to sex and age. SCH has been reported to be associated with multiple adverse pregnancy outcomes in pregnant women. While the therapeutic decision for overt hypothyroidism is fairly straightforward, treatment of SCH, especially the timing of the initiation of therapy, has been a point of discussion. Objective To assess the effect of early initiation of treatment (thyroid hormone therapy) compared to watchful waiting, delayed initiation, or no treatment on progression to overt hypothyroidism, prevention of complications, and associated adverse outcomes through a "systematic review and meta-analysis (SRMA)”. Methods The SRMA protocol adhered to the “Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P 2015)” guidelines. Only “randomized controlled trials (RCTs)” will be included. The databases “PubMed, Scopus, EMBASE, and the Cochrane Library” will be searched from inception until 30.12.2025. Two stages (title abstract followed by full-text review) and two-pass screening (two authors independently) with a third reviewer adjudication of conflicts will be adopted. Data will be extracted, and the risk of bias will be assessed independently by two authors using a process to resolve differences. The risk of bias for RCTs will be assessed using Cochrane ROB 2.0. Pooled estimates will be calculated for meta-analysis. Subgroup analysis and meta-regression will be performed if heterogeneity was present. The certainty of the evidence will be ascertained through “GRADE (Grading of Recommendations, Assessment, Development, and Evaluation)”. Intended outcomes The SRMA can inform the framing of clinical guidelines for SCH management for all population groups and also intends to bring out gaps in the existing literature for future studies. PROSPERO ID: CRD420251270021 (Date: 08 February 2026)

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