Thyroid Hormone Replacement Increases Mortality Risk

Jennifer Mammen, MD, PhD

Use of thyroid hormone replacement therapy in older patients was associated with an increased risk of mortality compared to no treatment, according to the findings of new research to be presented at the Endocrine Society (ENDO) 2020 Annual Scientific Sessions

Principal investigator Jennifer Mammen, MD, PhD, and colleagues from Johns Hopkins University, analyzed the thyroid status of more than 1000 participants in the Baltimore Longitudinal Study of Aging (BLSA) to determine the effects of levothyroxine (LT4) on survival among older adults. The team found that treating thyrotropin changes associated with aging adaptation could adversely alter key homeostatic compensations.

Older adults typically have elevated thyrotropin with normal thyroid levels. Findings to previous research showed that the elevation could reflect the development of hypothyroidism in some adults, while for others, it was adaptation to age-related changes in health—not thyroid disease.

“As a result, some of these older people may be receiving inappropriate or excessive thyroid hormone therapy, treatment that may counteract important adaptations needed for healthy aging,” Mammen, an assistant professor of medicine at Johns Hopkins School of Medicine, said in a statement.

Mammen and the team of investigators defined the thyroid status for 1054 participants in the BLSA >65 years old with >1 thyrotropin and FT4 level since 2003. Participants were excluded if they used interfering medications other than LT4 or had a history of thyroid cancer.

The investigators evaluated the risk of dying during one-year periods from 2003-2018 and adjusted their analyses for demographic and health factors that could have influenced survival.

Among the participants, the mean age was 78,7 years old and 43.3% were women. Nearly 70% of the visits occurred in untreated, euthyroid individuals with an untreated isolated elevated thyrotropin level found in 7.8%. Of the visits, treatment with LT4 was present in 13.7%. Overall, follow-up time was 8483.3 years.

During the study period, 245 deaths occurred. Visits of LT4, no matter the thyrotropin levels, contributed to a 55% higher hazard of death than those who were euthyroid and not on a thyroid hormone (HR, 1.55; 95% CI, 1-2.38). What’s more, after adjusting their model for other covariates, the team found that such patients also had an estimated doubled risk compared to patients with untreated isolated elevated thyrotropin (HR, 2.23; 95% CI, 1.05-4.73). The findings were the same when limited to patients who were never over-treated (HR, 2.5; 95% CI, 1.18-5.3).

“We were surprised that we were able to demonstrate harm associated with thyroid hormone supplementation,” Mammen said. “Our work supports the growing calls to use age-specific (thyroid-stimulating hormone) reference intervals to determine the threshold for thyroid hormone treatment.”

Mammen recommended repeating testing after finding isolated elevation of thyroid-stimulating hormones in older adults.

“We advocate being cautious and conservative when considering thyroid hormone treatment,” she concluded.

The study, “Thyroid Hormone Use and Relative Survival Among the BLSA Cohort,” will be presented at the Endocrine Society (ENDO) 2020 Annual Scientific Sessions.