Thyroid function in the euthyroid range and adverse outcomes in older adults

Abstract

Context: The appropriateness of current reference ranges for thyroid function testing in older adults has been questioned.

Objective: This study aimed to determine the relationship between thyroid function tests within the euthyroid range and adverse outcomes in older adults not taking thyroid medication.

Design, setting, and participants: US community-dwelling adults years of older (n = 2843) enrolled onto the Cardiovascular Health Study with TSH, free T4 (FT4), and total T3 concentrations in the euthyroid range.

Main outcome measures: Incidence of atrial fibrillation, coronary heart disease, heart failure, hip fracture, dementia, and all-cause death were measured.

Results: No departures from linearity were detected. Higher TSH was negatively associated (P = .03) and higher FT4 was positively associated (P = .007) with mortality. Higher FT4 was associated with atrial fibrillation (P < .001) and heart failure (P = .004). Compared with the first quartile, individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia (P < .05) and those with FT4 in the fourth quartile had higher incidences of atrial fibrillation, coronary heart disease, heart failure, and mortality (11.0, 8.0, 7.8, and 14.3 per 1000 person-years, respectively, all P < .05). Total T3 was not associated with any outcome.

Conclusions: Higher TSH and lower FT4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events in older people, including mortality. This suggests tolerance for lower thyroid hormone levels in this age group. Clinical trials are needed to evaluate the risk-benefit profile of new thresholds for initiating treatment and optimal target concentrations for thyroid hormone replacement in older people.

Figure 1.

Spline regression graphs depicting the adjusted associations of continuous concentrations of TSH (left), FT₄ (middle), and T₃ (right) with incident AF, CHD, heart failure (HF), hip fracture (Hip Fx), dementia, and total mortality. Spline regressions are adjusted for age, sex, and race.

Figure 2.

Incidence rates per 1000 person years (95% CI) for incident AF, CHD, heart failure (HF), hip fracture (Hip Fx), dementia, and total mortality by quartile of TSH (left), FT₄ (middle), and T₃ (right). For TSH, Q1 is 0.45–1.39 mU/L, Q2 is 1.40–2.00 mU/L, Q3 is 2.01–2.82 mU/L, and Q4 is 2.83–4.50 mU/L. For FT₄, Q1 is 9.20–14.20 pmol/l (0.70–1.10 ng/dL), Q2 is 14.3–15.6 pmol/L (1.11–1.21 ng/dL), Q3 is 15.7–19.0 pmol/L (1.22–1.48 ng/dL), and Q4 is 19.1–21.8 pmol/L (1.48–1.70 ng/dL). For T₃, Q1 is 1.31–1.60 nmol/L (85–104 ng/dL), Q2 is 1.61–1.77 nmol/L (105–115 ng/dL), Q3 is 1.78–1.98 nmol/L (116–129 ng/dL), and Q4 is 1.99–3.10 nmol/L (130–201 ng/dL).