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TOPLINE:

An individual participant data analysis of 31 prospective cohort studies found that age-related changes in thyroid function were generally modest, but variability increased after age 65. All patterns of changing thyroid function — whether thyroid-stimulating hormone (TSH) and free thyroxine (FT4) increased or decreased together or in opposite directions — were associated with higher all-cause mortality compared with stable thyroid function.

METHODOLOGY:

• Researchers conducted both cross-sectional and longitudinal analyses of individual participant data to evaluate age-related changes in thyroid function and their association with all-cause mortality in adults.
• They included 137,488 adults (median age, 60 years; 49.7% women) with at least one TSH measurement from 31 population-based cohorts across Europe, the US, Asia, Brazil, and Australia; 110,382 of these participants also had FT4 measurements.
• Individuals on thyroid-altering medications or with thyroid disease at baseline or during follow-up were excluded.
• The longitudinal analysis included 40,026 participants with at least two thyroid function measurements (median follow-up duration, 7.4 years). Iodine status for each cohort was determined based on the median urine iodine concentration (sufficient, ≥ 100 μg/L or insufficient, < 100 μg/L); when urine data were unavailable, the study relied on previous regional studies or data from the Iodine Global Network.
• Mean annual changes in TSH and FT4 levels were estimated and categorized into quintiles, with the lowest and highest quintiles defined as decreasing and increasing thyroid function, respectively.

TAKEAWAY:

• In the cross-sectional analysis, mean TSH levels increased with age in iodine-sufficient regions but decreased with age in iodine-insufficient regions. In the longitudinal analysis, TSH levels increased modestly with age in both iodine-sufficient and iodine-insufficient regions.
• Cross-sectionally, FT4 levels increased with age in both iodine-sufficient and iodine-insufficient regions but the association was nonlinear. Longitudinally, FT4 levels increased with age only in iodine-sufficient regions.
• Among individuals aged 18-39 years and 40-64 years, 71.1% and 72.5%, respectively, maintained stable TSH concentrations, whereas only 41.1% of those aged 65-79 years and 34.7% of those aged 80 years or older had stable TSH over time; stability of TSH and FT4 combined also declined with age.
• Four patterns of changes in thyroid function were identified on the basis of combined TSH and FT4 status: increasing TSH with stable or decreasing FT4, increasing TSH with increasing FT4, decreasing TSH with stable or increasing FT4, and decreasing TSH with decreasing FT4. Compared with stable thyroid function, all change patterns were significantly associated with a higher risk for all-cause mortality (adjusted hazard ratios, 1.80-2.45).

IN PRACTICE:

“These findings suggest that individual longitudinal trajectories of thyroid function might provide more clinical relevant information than single age-specific limit alone. Therefore, cautions should be exercised when applying generalised cutoffs, as individuals with high TSH concentrations might not be regarded as a homogeneous group,” the authors wrote.

“Tracking individual trajectories of thyroid function over time might be helpful in making decisions about initiating hypothyroidism treatment,” Elizabeth N. Pearce, MD, endocrinologist and epidemiologist specializing in thyroid disorders at Boston Medical Center, Boston, wrote in an accompanying editorial.

SOURCE:

This study was led by Yanning Xu, MD, Erasmus University Medical Center, Rotterdam, Netherlands. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The study lacked serum triiodothyronine measurements and did not obtain direct urine iodine measurements in most cohorts. Individuals treated with levothyroxine were not included. Most data came from Europe and the US, limiting the generalizability of the findings.

DISCLOSURES:

This study declared no funding source. Some authors reported receiving research grants, consulting fees, personal fees, or research support from; serving in leadership and advisory roles for; and having other ties with various pharmaceutical companies and organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.