Thyrotoxicosis was associated with 39% higher risk for cognitive disorders.

Thyrotoxicosis, defined as a low level of serum thyroid-stimulating hormone (TSH), can result from either a primary thyroid disorder (endogenous) or overtreatment of hypothyroidism (exogenous). Evidence suggests that thyrotoxicosis is a risk factor for dementia. In this US longitudinal cohort study, researchers used data from electronic health records for 66,000 people (median age, 68 years) without low TSH levels or cognitive disorders at baseline and evaluated whether development of thyrotoxicosis was associated with excess risk for cognitive disorders.

During the study period (2014 to 2023), 2700 patients had low TSH levels (60% exogenous) and 4800 patients received diagnoses of cognitive disorders. The incidence of cognitive disorders among patients with and without thyrotoxicosis were 11% and 6% at age 75 years, and 34% and 26% at age 85 years. Adjusted for multiple variables, all-cause thyrotoxicosis was associated with a significant 39% excess risk for cognitive disorders. Exogenous thyrotoxicosis – and in particular, severe exogenous thyrotoxicosis (TSH below 0.1mIU/L) – were associated most strongly with excess risk for cognitive disorders.

Comment: Given this study’s design, residual confounding is possible, and the results do not prove causality. Nonetheless, these findings might have important public health implications, as 8% of US adults take levothyroxine. Aside from a potentially direct effect on cognition, exogenous thyrotoxicosis has adverse cardiovascular effects, which also might contribute to cognitive impairment. Clinicians should avoid overtreatment by aiming for a serum TSH level in the normal range.

Paul S. Mueller, MD, MPH, FACP, Regional Vice President – Southwest Wisconsin, Mayo Clinic Health System, La Crosse; Professor of Medicine and Biomedical Ethics, Mayo Clinic College of Medicine and Science, Rochester, USA.

Adams R, et al. Endogenous and exogenous thyrotoxicosis and risk of incident cognitive disorders in older adults. JAMA Intern Med 2023; 183: 1324-1331.

Papaleontiou M, Brito JP. Disentangling the association between excess thyroid hormone and cognition in older adults. JAMA Intern Med 2023; 183: 1332-1333.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.