CORRESPONDENCE: LETTER TO THE EDITOR
Hyperthyroidism and Mortality
Henry Völzke, MD*
* Institute of Epidemiology and Social Medicine, Ernst Moritz Arndt University, Walther Rathenau Strasse 48, D-17487 Greifswald, Germany (Email: voelzke{at}uni-greifswald.de).
Hyperthyroidism is associated with systemic inflammation (1) atrial fibrillation (2), and vascular and left ventricular hypertrophy (3,4). It is therefore reasonable to assume an increased mortality in patients with overt hyperthyroidism compared to euthyroid subjects. The effects of hyperthyroidism on all-cause and circulatory mortality, however, are a matter of debate and subject to ongoing controversy. Some investigations demonstrated increased mortality in hyperthyroid compared to euthyroid subjects (5,6), but others did not confirm this finding (7–9). One study even revealed lower mortality in hyperthyroid compared to euthyroid elderly subjects (10).
In a previous issue of JACC, Osman et al. (11) analyzed mortality of 393 patients with overt hyperthyroidism and 393 age- and gender-matched euthyroid subjects. During the 66.6 months of follow-up, 26 patients died, 7 of them from circulatory causes, whereas 12 euthyroid subjects died, 4 of them from circulatory causes. Unfortunately, risk estimates, including levels of statistical significance, were not given.
As correctly stated by Osman et al. (1), interpretation of their results is hampered by the low number of deceased subjects. Further limitations, however, should be considered and discussed. First, a number of potential factors confound the association between hyperthyroidism and mortality. Osman et al. (11) controlled for gender and age by study design. In addition, imbalances between hyperthyroid and euthyroid subjects with regard to current smoking (29% vs. 15%, p < 0.0001) and diabetes mellitus (6% vs. 3%, p = 0.1) will have strong effects on the group-specific mortality risk in their study. Thus, analyses should also be controlled for at least these 2 factors.
Second, the outcome in patients who undergo a specific treatment depends upon various characteristics, including risk factors for the disease, the disease itself, comorbidities influencing the choice of a specific therapy, and desired and undesired treatment effects. Increased mortality in patients with hyperthyroidism seen in the study by Osman et al. (11) might therefore be explained at least hypothetically by, for example, the type of and the indication for a specific antithyroid therapy and the status of thyroid function following treatment.
Third, Osman et al. (11) recruited patients with hyperthyroidism from a university hospital, whereas euthyroid subjects were selected either from staff members working at the hospital or from a community center. Patients referred to university hospitals more often exhibit (not only cardiovascular) co-morbidities than do ambulatory-treated patients or patients referred to general hospitals. Thus, patients with overt hyperthyroidism recruited for this investigation (11) are probably not representative of hyperthyroid patients living in the study region. Likewise, with regard to control subjects, medical staff might in general behave healthier than the rest of the population. As a result, excess mortality among cases compared to controls might be explained by selection bias.
Taken together, the association between overt hyperthyroidism and mortality found in the study of Osman et al. (11) likely results from bias and confounding and should not necessarily be interpreted as a biological, causal relationship.
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