Excess Mortality in Patients Diagnosed With Hypothyroidism: A Nationwide Cohort Study of Singletons and Twins

Background: Although hypothyroidism is associated with increased morbidity, an association with increased mortality is still debated. Our objective was to investigate, at a nationwide level, whether a diagnosis of hypothyroidism influences mortality. Methods: In an observational cohort study from January 1, 1978 until December 31, 2008 using record-linkage data from nationwide Danish health registers, 3587 singletons and 682 twins diagnosed with hypothyroidism were identified. Hypothyroid individuals were matched 1: 4 with nonhypothyroid controls with respect to age and gender and followed over a mean period of 5.6 years (range 0-30 years). The hazard ratio (HR) for mortality was calculated using Cox regression analyses. Comorbidity was evaluated using the Charlson score (CS). Results: In singletons with hypothyroidism, the mortality risk was increased (HR 1.52; 95% confidence interval [CI]: 1.41-1.65). Although the effect attenuated, hypothyroidism remained associated with increased mortality when evaluating subjects with a CS = 0 (HR 1.23; 95% CI: 1.05-1.44). In twin pairs discordant for hypothyroidism, the hypothyroid twin had excess mortality compared with the corresponding euthyroid cotwin (HR 1.40; 95% CI 0.95-2.05). However, after stratifying for zygosity, hypothyroidism was associated with excess mortality in dizygotic twin pairs (HR 1.61; 95% CI 1.00-2.58), whereas the association attenuated in monozygotic pairs (HR 1.06; 95% CI 0.55-2.05). Conclusions: Hypothyroidism is associated with an excess mortality of around 50%, which to some degree is explained by comorbidity. In addition, the finding of an association between hypothyroidism and mortality within disease discordant dizygotic but not monozygotic twin pairs indicates that the association between hypothyroidism and mortality is also influenced by genetic confounding. (J Clin Endocrinol Metab 98: 1069-1075, 2013)