Age-related changes in thyroid physiology influence hormone levels

Thyroid function is linked with age-related changes in pituitary and thyroid physiology in older adults, according to data recently published in Thyroid.

Based on their findings, researchers advise the use of caution when prescribing thyroid hormone supplements, as higher thyroid-stimulating hormone levels may not always indicate subclinical hypothyroidism in this patient population.

“Multiple large population studies have demonstrated that mean circulating thyrotropin (TSH) levels are higher in older populations. Consequently, older patients are started on thyroid hormone therapy at higher rates than those who are younger,” Jennifer S. Mammen, MD, PhD, of the Johns Hopkins University School of Medicine, and colleagues wrote. “When the hypothalamic-pituitary-thyroid axis is intact, TSH rises in response to thyroid hormone deficiency to increase thyroid hormone production. However, higher TSH levels during aging may reflect changes other than primary thyroid gland failure.”

The researchers evaluated changing TSH and free thyroxine levels among 640 participants who took part in the Baltimore Longitudinal Study of Aging. All patients had at least three recorded measurements of TSH and free thyroxine over a mean 7 years of follow-up. The researchers developed slope estimates for annual change in thyroid phenotype using linear regression of TSH and FT4 and used quintiles for both slopes to identify participants with changing thyroid phenotypes. Multivariate Cox regression was used to identify survival across phenotypes.

Thyroid function remained stable among most participants at all ages; however, older adults showed more changes compared with younger groups, the researchers reported. Nearly one-third (32.3%) of participants aged older than 80 years showed changing thyroid function that fell into the highest and lowest quintiles, Mammen and colleagues wrote, compared with just 9.5% of participants younger than 60 years. In some cases, regression to the mean accounted for change; increased baseline TSH was associated with a pattern of decreasing TSH (OR = 1.4 per 1 mIU/L; 95% CI, 1.1-1.7).

The researchers reported a higher risk for death in changing thyroid function in the upper or lower quintiles of slope for TSH and FT4, compared with stable thyroid functioning (HR = 5.4; 95% CI, 3.1-9.5).

“In summary, our results suggest that thyroid function tests change for many reasons: reversion to the mean, aging and disease-related changes in pituitary and thyroid function, and in response to other comorbidities,” the researchers wrote. “This diversity of pathophysiology complicates the interpretation of thyroid tests in older individuals. … Phenotyping will also be critical to studies evaluating the appropriate use of therapy in this population, since the efficacy of thyroid hormone replacement may vary depending on the underlying physiologic mechanisms.” – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures.