Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging

Background: Both endogenous and exogenous thyrotoxicosis has been associated with atrial fibrillation and low bone mineral density. Therefore, this study investigated the risk factors associated with prevalent and incident thyrotoxicosis and the initiation of thyroid hormone therapy in a healthy, aging cohort. Methods: A total of 1450 ambulatory community volunteer participants in the Baltimore Longitudinal Study of Aging examined at the NIA Clinical Research Unit in Baltimore, MD, have undergone longitudinal monitoring of serum thyrotropin (TSH) and thyroid hormone (free thyroxine and free triiodothryonine) levels as well as medication use every one to four years, depending on age, between 2003 and 2014. Results: The prevalence of low TSH was 9.6% for participants on thyroid hormone and 0.8% for nontreated individuals (p < 0.001). New cases occurred at a rate of 17.7/1000 person-years of exposure to thyroid hormone therapy [CI 9-32/1000] and 1.5/1000 person-years in the unexposed population [CI 0.7-2.9/1000]. Women were more likely to be treated and more often overtreated than men were. The adjusted hazard ratio (HR) for thyrotoxicosis between treated and untreated women was 27.5 ([CI 7.2-105.4]; p < 0.001) and 3.8 for men ([CI 1.2-6.3]; p < 0.01). White race/ethnicity and older age were risk factors for thyroid hormone therapy but not overtreatment. Body mass index was not associated with starting therapy (HR = 1.0). Thyroid hormone initiation was highest among women older than 80 years of age (3/100 person-years). For one-third of treated participants with follow-up data, overtreatment persisted at least two years. Conclusions: Iatrogenic thyrotoxicosis accounts for approximately half of both prevalent and incident low TSH events in this community-based cohort, with the highest rates among older women, who are vulnerable to atrial fibrillation and osteoporosis. Physicians should be particularly cautious in treating subclinical hypothyroidism in elderly women in light of recent studies demonstrating no increased risk of cardiovascular morbidity or death for individuals with elevated TSH levels <10 mIU/L.