Which Factors Influence the Link Between Hyperthyroidism and Increased Mortality?

The Roles of Genetic Factors and Comorbidity

The word hyperthyroidism on a tablet with a stethoscopeIs hyperthyroidism associated with increased mortality? If so, is it the condition itself, genetic factors, or comorbidity that influences this increase?

Danish researchers set out to answer these questions in a study titled, “Excess mortality in hyperthyroidism: the influence of preexisting comorbidity and genetic confounding. A Danish nationwide register-based cohort study of twins and singletons.” The study was published in August 2012 online ahead of print in The Journal of Clinical Endocrinology & Metabolism.

The research efforts were led by experts at Odense University Hospital in Odense, Denmark. Researchers relied on data obtained from Danish health registries. They used data on 4,850 individual participants, and 926 twins diagnosed with hyperthyroidism. Only same-sex twin pairs were used in the study.

Participants were matched with controls based on their age and gender. All of the cases and their controls were followed up with for an average of 10 years (0-31 years) to check for comorbidity and mortality. Comorbidity was measured using the Charlson comorbidity index (calculated on an individual level using diagnoses made at discharge). Cox regression analyses were used to calculate mortality hazard ratios (HR).

The results of the data analysis showed that there was significantly higher mortality in individuals (non-twins) with hyperthyroidism than the controls [HR 1.37]. These results held even after the researchers adjusted for preexisting comorbidity [HR 1.28].

Additionally, in twin pairs where 1 twin had hyperthyroidism and the other did not (625 pairs), the twin who did have the condition had increased mortality compared to the other twin [HR 1.43]. However, the result only held in dizygotic (“fraternal”) twin pairs, not in monozygotic (“identical”) pairs.

The researchers state that their study findings demonstrate an association between hyperthyroidism and increased mortality, regardless of pre-existing comorbidity. Additionally, the results from the hyperthyroidism discordant twin pairs demonstrate that genetic confounding may influence this association.

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