Hypothyroidism and mortality among dialysis patients

Connie M Rhee, Erik K Alexander, Ishir Bhan, Steven M Brunelli, Connie M Rhee, Erik K Alexander, Ishir Bhan, Steven M Brunelli

Abstract

Background and objectives: Hypothyroidism is highly prevalent among ESRD patients, but its clinical significance and the benefits of thyroid hormone replacement in this context remain unclear.

Design, setting, participants, & measurements: This study examined the association between hypothyroidism and all-cause mortality among 2715 adult dialysis patients with baseline thyrotropin levels measured between April of 2005 and April of 2011. Mortality was ascertained from Social Security Death Master Index and local registration systems. The association between hypothyroidism (thyrotropin greater than assay upper limit normal) and mortality was estimated using Cox proportional hazards models. To reduce the risk of observing reverse-causal associations, models included a 30-day lag between thyrotropin measurement and at-risk time.

Results: Among 350 (12.9%) hypothyroid and 2365 (87.1%) euthyroid (assay within referent range) patients, 917 deaths were observed during 5352 patient-years of at-risk time. Hypothyroidism was associated with higher mortality. Compared with thyrotropin in the low-normal range (0.4-2.9 mIU/L), subclinical hypothyroidism (thyrotropin >upper limit normal and ≤10.0 mIU/L) was associated with higher mortality; high-normal thyrotropin (≥3.0 mIU/L and ≤upper limit normal) and overt hypothyroidism (thyrotropin >10.0 mIU/L) were associated with numerically greater risk, but estimates were not statistically significant. Compared with spontaneously euthyroid controls, patients who were euthyroid while on exogenous thyroid replacement were not at higher mortality risk, whereas patients who were hypothyroid were at higher mortality risk. Sensitivity analyses indicated that effects on cardiovascular risk factors may mediate the observed association between hypothyroidism and death.

Conclusions: These data suggest that hypothyroidism is associated with higher mortality in dialysis patients, which may be ameliorated by thyroid hormone replacement therapy.

Figures

Figure 1.
Figure 1.
Time to death based on baseline thyroid functional status. Survival curves are adjusted for age, sex, race, diabetes, and hospitalization for noncardiovascular indication in the preceding year. (A) shows results of the primary analysis in which the start of at-risk time began 30 days after thyrotropin (TSH) measurement. (B) shows estimates from an analogous model that did not consider the 30-day lag period. 95% CI, 95% confidence interval; HR, hazard ratio.
Figure 2.
Figure 2.
Secondary analyses of adjusted associations between gradations in TSH and mortality. (A) presents HRs (95% CIs) for low-normal TSH, high-normal TSH, subclinical hypothyroidism, and overt hypothyroidism. (B) shows TSH analyzed as a restricted cubic spline with knots at 1.1, 1.7, 2.4, 3.9, and 10.0 mIU/L; a histogram of observed TSH values is overlaid. All analyses considered a 30-day lag between TSH assessment and the start of the at-risk time, and they were adjusted for age, sex, race, diabetes, and hospitalization for noncardiovascular indication within the preceding year. ULN, upper limit normal.
Figure 3.
Figure 3.
Adjusted HRs (95% CIs) for mortality based on baseline functional thyroid status and exogenous thyroid hormone status. Analyses considered a 30-day lag between TSH assessment and the start of the at-risk time, and they were adjusted for age, sex, race, diabetes, and hospitalization for noncardiovascular indication within the preceding year.

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