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Subclinical thyroid dysfunction and mortality: An estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies

P Haentjens, CEBAM, Belgian Centre for Evidence Based Medicine, Vrije Universiteit Brussel, Belgium
A Van Meerhaeghe, ISPPC, CHU A. Vesale, Charleroi, Belgium
K Poppe, Endocrinology, UZ Brussel, Brussels, Belgium
B Velkeniers, Endocrinology, UZ Brussel, Brussels, Belgium

Correspondence: Patrick Haentjens, Email: patrick.haentjens{at}uzbrussel.be

Abstract

Objectives: To determine excess mortality among patients with subclinical hyper- or hypothyroidism.

Methods: We searched electronic reference databases through 31 July 2007. Cohort studies reporting the hazard ratio for all-cause mortality in patients with subclinical thyroid dysfunction vs. euthyroid controls were included.

Results: Based on seven cohorts including 290 participants with subclinical hyperthyroidism, random effects models estimated that the pooled hazard ratio (HR) for all-cause mortality was 1.41 (95% confidence interval [CI], 1.12-1.79; P=0.004). Using the pooled HR and standard life-table methods, we estimated that a white US woman, when diagnosed with subclinical hyperthyroidism at age 70, has an excess mortality of 1.5%, 4.0%, and 8.7% at 2, 5, and 10 years after diagnosis, respectively. Likewise, a white US man, has an excess mortality of 2.3%, 5.7%, and 10.7 %.

For the nine cohorts including 1580 participants with subclinical hypothyroidism, observed heterogeneity (Q test P=0.006; I-squared=63%) disappeared after pooling cohorts in predefined subgroups. The pooled HR was 1.03 in cohorts from the community (95% CI, 0.78-1.35; P=0.83), and 1.76 (95% CI, 1.36-2.30; P<0.001) in cohorts of participants with co-morbidities (P=0.014 for heterogeneity among groups).

Conclusions: Individuals with subclinical hyperthyroidism demonstrate a forty percent increase in relative mortality from all causes vs. euthyroid control subjects. Mathematical modelling indicates that absolute excess mortality after diagnosis might depend on age, with an increase beyond the age of sixty, especially in ageing men. For patients with subclinical hypothyroidism, the relative risk of all-cause mortality is increased only in patients with co-morbid conditions.