Endogenous or exogenous thyrotoxicosis associated with higher risk of incident cognitive disorder

A groundbreaking cohort study conducted by researchers at the Johns Hopkins Community Physicians Network has uncovered a significant association between thyroid hormone imbalances, also known as thyrotoxicosis, and the risk of cognitive disorders in older adults. The study found that both endogenous and exogenous thyrotoxicosis are associated with a higher risk of cognitive disorders, particularly in patients aged 65 and older. 

The study results were published in the journal JAMA Internal Medicine. 

Thyroid hormone medications are among the most commonly prescribed drugs, with millions of patients relying on them to manage various thyroid conditions. Past research revealed that endogenous hyperthyroidism is a risk factor for dementia. Hence, researchers from the Johns Hopkins Community Physicians Network conducted a cohort study to understand whether thyrotoxicosis, both endogenous and exogenous, is associated with increased risk of cognitive disorders and raised important questions about the potential consequences of overtreating these conditions, particularly in individuals aged 65 and older.

The study involved a comprehensive analysis of electronic health records for 65,931 patients aged 65 and older, each of whom had at least two visits to their primary care physician with a 30-day gap. None of these patients had a history of low thyrotropin (TSH) levels or cognitive disorders diagnosed within six months of their initial visit, ensuring a clean slate for the investigation.

The exposure variable of interest in this study was a low TSH level, a biomarker for thyroid function. Researchers categorized low TSH levels based on their cause, which could be attributed to either endogenous thyrotoxicosis (resulting from the thyroid gland itself), exogenous thyrotoxicosis (caused by external factors, such as medication), or of unknown origin. Cases of low TSH linked to acute illness or other medical factors were excluded from the analysis.

The primary outcome measure was the incidence of cognitive disorders, encompassing both mild cognitive impairment and all-cause dementia. This inclusive approach aimed to account for the potential underdiagnosis of dementia in primary care settings.

Key findings: 

• Patients exposed to thyrotoxicosis were shown to have a significantly higher incidence of cognitive disorders compared to those who were not exposed.
• By the age of 75, 11.0% of patients exposed to thyrotoxicosis were diagnosed with cognitive disorders, in contrast to 6.4% of those not exposed.
• Moreover, the study's results indicated a robust association between all-cause thyrotoxicosis and the risk of cognitive disorder diagnosis, even after adjusting for various confounding factors. The adjusted hazard ratio was 1.39. 
• This heightened risk persisted when considering the causes and severity of thyrotoxicosis.
• Notably, exogenous thyrotoxicosis, often resulting from external factors like medication, remained a significant risk factor with an adjusted hazard ratio of 1.34.
• Furthermore, the point estimates in the study hinted at a possible dose-response relationship, indicating that higher levels of thyrotoxicosis might be associated with an even greater risk of cognitive disorders.

Thus, the study underscores the importance of closely monitoring thyroid hormone levels in older patients, as well as the need to minimize the risk of cognitive disorders associated with thyrotoxicosis. It serves as a wake-up call for healthcare providers to consider the potential risks and benefits of thyroid hormone therapy more carefully, and to avoid overtreatment, especially in light of the prevalence of thyroid hormone prescriptions in the United States.

Further reading: Adams R, Oh ES, Yasar S, Lyketsos CG, Mammen JS. Endogenous and Exogenous Thyrotoxicosis and Risk of Incident Cognitive Disorders in Older Adults. JAMA Intern Med. Published online October 23, 2023. doi:10.1001/jamainternmed.2023.5619