Management strategies for patients with subclinical hypothyroidism:a protocol for an umbrella review

Background: Subclinical hypothyroidism is a thyroid disorder diagnosed from the laboratory blood test results of otherwise asymptomatic patients. It has been associated with poor cardiovascular outcomes, mortality and progression to overt thyroid hormone deficiency. Current guidelines on the management of subclinical hypothyroidism differ because of conflicting evidence on long-term treatment benefits. Even though there are several existing systematic reviews on its clinical outcomes, no definitive conclusion has been reached yet. As such, a new synthesis could help provide more insight and consensus on this topic. To this purpose, this umbrella review will evaluate and synthesise current evidence on the long-term clinical outcomes of the different management strategies for subclinical hypothyroidism.Methods: This is a protocol for an umbrella review on the management strategies for subclinical hypothyroidism. We will conduct literature searches in multiple electronic databases (from inception onwards), namely MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, JBI Evidence Synthesis, Epistemonikos database, PDQ Evidence and the PROSPERO register. There will be no restriction on the date or language of publication. Additional material will be identified through grey literature searches and citation chaining. Review inclusion criteria will be patients with subclinical hypothyroidism, receiving treatment or monitoring, no restrictions on the comparators used and with cardiovascular events, frailty fractures, quality of life and all-cause mortality as primary outcomes of interest. Two reviewers will independently screen all citations, full-text articles and abstract data on a pre-piloted form in duplicate. Methodological quality (or bias) of included studies will be appraised using AMSTAR-2. Any conflicts that arise will be resolved through discussion or involving a third reviewer. A narrative synthesis will be provided with information presented in the main text and tables to summarise and explain the characteristics and findings of the included reviews. Even so, it is not expected that a meta-analysis will be performed due to review variability. Study limitations and methodological quality assessments will also be reported to provide context for the overall summary of evidence.Discussion: This review will provide a comprehensive summary of the effects of the pharmacological and non-pharmacological management of subclinical hypothyroidism on specific long-term clinical outcomes. It is anticipated that the findings of this umbrella review will aid in the development of consensus-based clinical recommendations for subclinical hypothyroidism, as well as highlight areas for future research. Review findings will be disseminated primarily through peer-reviewed publications.