Adequacy of thyroid hormone replacement for people with hypothyroidism in real-world settings: A systematic review and meta-analysis of observational studies

Objective: Thyroid hormone under-replacement and over-replacement are associated with adverse health outcomes. This systematic review aimed to evaluate the extent of thyroid hormone replacement adequacy for patients with known hypothyroidism in real-word settings, excluding those receiving thyroid hormone suppressive therapy as thyroid cancer treatment. Design: Four electronic databases (Embase [Ovid], Medline [Ovid], PubMed and SCOPUS) were searched for published and unpublished observational studies until 12 December 2022. The results of the studies were meta-analysed to calculate pooled prevalence estimates for thyroid hormone supplementation adequacy, over-replacement and under-replacement. Quality assessment of studies was performed using the Joanna-Briggs appraisal tool for prevalence studies. Results: Seven studies with a total of 4230 patients were eligible for quantitative synthesis. The pooled prevalence estimates of adequate thyroid replacement, over-replacement and under-replacement were 0.55 (95% confidence interval [CI]: 0.49-0.60, p =.001), 0.20 (95% CI: 0.14-0.27, p =.001) and 0.24 (95% CI: 0.13-0.36, p =.001), respectively. Four studies subclassified hypothyroidism and hyperthyroidism into overt and subclinical. The pooled prevalence of overt and subclinical hyperthyroidism was 0.04 (95% CI: 0.00-0.11, p =.01) and 0.17 (95% CI: 0.09-0.27 p =.001), respectively. For overt and subclinical hypothyroidism, the pooled prevalence was 0.02 (95% CI: 0.01-0.03, p =.001) and 0.20 (95% CI: 0.12-0.29, p =.001), respectively. Conclusions: On average, approximately half of patients with hypothyroidism are only treated to target euthyroidism. In real-world practice, a significant number of patients are over-treated or under-treated, leading to adverse healthcare outcomes. It is imperative that more effective thyroid monitoring strategies be implemented, with an emphasis on primary care thyroid function monitoring, to minimise inappropriate thyroid replacement treatments and optimise healthcare outcomes at a population level.