Association of Thyroid Hormone Therapy with Mortality in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis

Context: Benefits of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism remain undetermined. Objective: To summarize the impact of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism. Data sources: PubMed, Embase, Scopus, Web of Science, and Clinicaltrials.gov from inception until April 25, 2020. Study selection: Studies comparing the effect of thyroid hormone therapy with that of placebo or no therapy in adults with subclinical hypothyroidism on all-cause and/or cardiovascular mortality. Data extraction: Two reviewers independently extracted data and performed quality assessments. Random-effects models for meta-analyses were used. Data synthesis: Five observational studies and 2 randomized controlled trials with 21 055 adults were included. Overall, thyroid hormone therapy was not significantly associated with all-cause (pooled relative risk [RR] = 0.95, 95% confidence interval [CI]: 0.75-1.22, P = .704) or cardiovascular (pooled RR = 0.99, 95% CI: 0.82-1.20, P = .946) mortality. Subgroup analyses revealed that in younger adults (aged <65-70 years), thyroid hormone therapy was significantly associated with a lower all-cause (pooled RR = 0.50, 95% CI: 0.29-0.85, P = .011) and cardiovascular (pooled RR = 0.54, 95% CI: 0.37-0.80, P = .002) mortality. However, no significant association between thyroid hormone therapy and mortality was observed in older adults (aged >= 65-70 years). Conclusions: Use of thyroid hormone therapy does not provide protective effects on mortality in older adults with subclinical hypothyroidism. However, thyroid hormone therapy for subclinical hypothyroidism may show benefits on morality in adults aged <65 to 70 years.