Abstract

Problem: Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid stimulating hormone (TSH) naturally increases with age. Subclinical hypothyroidism (SCH) is diagnosed when serum thyroid-stimulating hormone levels are mildly elevated while free thyroxine levels are within normal range. With uniform TSH reference ranges across the adult lifespan, a diagnosis of SCH is more likely with increasing age. Patients with SCH are often prescribed levothyroxine. This review investigates the cardiovascular and bone health impacts of levothyroxine in patients over 50 years old with a baseline diagnosis of SCH.
Approach: Systematic review and meta-analysis. An advanced search function was performed across the Cochrane, Embase, Medline, PubMed, and Web of Science databases to collate previous studies that evaluated cardiovascular and bone health outcomes in SCH patients with and without levothyroxine, from inception until the 3rd of August 2023. The remaining studies were assessed using the Cochrane Risk of Bias tool for randomised controlled trials and the Newcastle-Ottawa quality of assessment for observational studies. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was then used to assess the overall quality of each study. The results where then pooled by their odds ratios, using R-programming.
Findings: Seven studies that recruited 5,887 participants, ranging from 45.4 to 80.1 years of age were selected. Six studies for cardiovascular outcomes were pooled for meta-analysis, there was no association between levothyroxine and cardiovascular outcomes in the SCH patients aged over 65 years [pooled OR 0.99; 95% confidence interval (0.74-1.11)]. The results also showed no association between levothyroxine use and bone health outcomes for SCH patients aged over 65 years [pooled OR 0.99; 95% confidence interval (0.52-1.88)]. No heterogeneity was found between the 6 cardiovascular and the 3 bone health outcome articles (I2 =0%).
Consequences: We found no association between levothyroxine use and cardiovascular and bone health outcomes in SCH participants over 65 years, indicating that more studies are needed on levothyroxine and its implications on cardiovascular and bone health outcomes in the older population.