Thyrotoxicosis Associated With Risk for Cognitive Disorders

Lower thyrotropin levels due to thyrotoxicosis are associated with a higher risk for cognitive disorder among adults 65 years and older, according to study findings published in JAMA Internal Medicine. 

Previous study findings suggest an association between excess thyroid hormone and dementia risk. However, these data are inconsistent and cast doubt on the significance of thyrotoxicosis for cognitive disorder risk. 

To clarify the association between thyrotoxicosis and risk for cognitive disorders, researchers at Johns Hopkins University School of Medicine conducted a retrospective cohort study using the electronic health records of patients from the Johns Hopkins Community Physicians Network between January 2014 and May 2023. Patients were aged 65 years or older with at least 30 days between their first and last primary care physician visits.

Exclusion criteria included a diagnosis of mild cognitive impairment or dementia and a low thyrotropin measurement before or within 6 months after the first eligible visit. 

The researchers separated low thyrotropin values according to either endogenous hyperthyroidism, overtreatment of hypothyroidism, or unknown causes. The outcome cognitive disorder incidence, including mild cognitive impairment and all-cause dementia. The researchers used a time-varying Cox model to assess the relationship between thyrotoxicosis and cognitive disorder. 

The study included a total of 65,931 patients, of whom 56.4% were women, and 69.9% were White. The median age at the first visit was 68 years (interquartile range [IQR], 65-74) and the median time from first to last visit was 3.9 years (IQR, 1.6-1.7). The researchers recorded low thyrotropin measurements from 4.1% of patients, of which 60% were exogenous, 17% were endogenous, and 24% were unknown. 

During follow-up, 7.2% of patients received a cognitive disorder diagnosis. The researchers identified a higher cognitive disorder incidence risk among patients with prior thyrotoxicosis (hazard ratio [HR], 1.48; 95% CI, 1.27-1.73; P <.001). Cumulative cognitive disorder incidences according to age were:

• 11% (95% CI, 8.4-14.2; aged 75 years with thyrotoxicosis);
• 6.4% (95% CI, 6.0-6.8; aged 75 years without thyrotoxicosis);
• 34.2% (95% CI, 29.2-39.9; aged 85 years with thyrotoxicosis); and,
• 25.9% (95% CI, 25-26.8; aged 85 years without thyrotoxicosis). 

After adjustment, risk for cognitive disorder incidence was significantly associated with:

• All-cause thyrotoxicosis (adjusted HR, 1.39; 95% CI, 1.18-1.64; P <.001); 
• Exogenous thyrotoxicosis (adjusted HR 1.34; 95% CI, 1.10-1.63; P =.003);
• Moderate exogenous thyrotoxicosis (adjusted HR, 1.23; 95% CI, 0.97-1.55; P =.08); and,
• Severe exogenous thyrotoxicosis (adjusted HR, 1.65; 95% CI, 1.20-2.28; P =.02). 

Study limitations include possible measurement errors, missing data biases, and potential misclassifications of abnormal thyrotropin levels. 

The researchers concluded, “[I]ncreased risk of cognitive disorders is among the potential negative consequences of thyroid hormone excess, a common consequence of thyroid hormone treatment.” 

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Endocrinology Advisor