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JOURNAL ARTICLE

Unstable thyroid function in older adults is caused by alterations in both thyroid and pituitary physiology and associated with increased mortality

Jennifer Sophie Mammen, John McGready, Paul W Ladenson, Eleanor M Simonsick
Thyroid: Official Journal of the American Thyroid Association 2017 August 30
28854871

BACKGROUND: Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time.

METHODS: Individual patterns of changing TSH and free thyroxine (FT4) were determined in 640 participants in the Baltimore Longitudinal Study of Aging who had at least three measures of serum TSH and FT4, not on medications, over an average of 7 years follow up. We identified participants with changing phenotypes based on quintiles for both slopes. Those with alterations in primary thyroid gland function demonstrated intact negative feedback (rising TSH with declining FT4 or declining TSH with rising FT4). Other participants had a parallel rise or fall of TSH and FT4 levels, consistent with pituitary dysfunction. Predictors of phenotype were analyzed by logistic regression. Differential survival between thyroid aging phenotypes was analyzed using multivariate Cox regression.

RESULTS: While the majority of participants at all ages had stable thyroid function, changes were more common among older adults, with 32.3% of those over 80 but only 9.5% of those younger than 60 demonstrating thyroid function changes in the highest and lowest quintiles. Regression to the mean accounts for some of the changes, for example increased baseline TSH was associated with a falling TSH pattern OR=1.4 (95% CI 1.1-1.7) per 1 mIU/L. Importantly, changing thyroid function in either the upper or lower quintiles of slope for TSH and FT4 was associated with increased risk of death compared to stable thyroid status with HR=5.4 (95% CI: 3.1-9.5).

CONCLUSIONS: Changing thyroid hormone function is increasingly common at older ages and associated with decreased survival. Nonetheless, the tendency for abnormal thyroid function tests to resolve, along with altered pituitary responsiveness underlying some TSH elevations, suggests that an elevated TSH level should be not assumed to represent subclinical hypothyroidism in older adults. Thus, caution is appropriate when determining the need for thyroid hormone supplements in older adults.

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