This article is more than 5 years old. Information may no longer be current.
Thyroid dysfunction increases cause-specific mortality risk in women
Women with hyperthyroidism have an increased risk for death from breast cancer, and women with hypothyroidism have an increased risk for death from diabetes and cardiovascular disease compared with women without thyroid disease, according to findings from a large, prospective 30-year follow-up study.
Cari M. Kitahara, PhD, of the radiation epidemiology branch, division of cancer epidemiology and genetics at the National Cancer Institute, and colleagues evaluated data from the U.S. Radiologic Technologists cohort study on 75,076 women to determine associations between self-reported hyperthyroidism or hypothyroidism and cause-specific mortality. Participants completed questionnaires at baseline (1983-1998) to gather information on medical history. Follow-up was a median 28 years, and participants were cancer free at baseline.
Diagnosis was made 10 or more years before study entry in 62.1% of the participants with hyperthyroidism and in 67.4% of those with hypothyroidism.
During follow-up, 3.5% of participants died from cancer, 2.4% from CV or cerebrovascular disease, 3.3% from other noncancer causes and 0.2% from unknown causes. The cumulative absolute risks for cancer (14%-16%) and noncancer mortality (43%-50%) varied little with thyroid status by age 90 years; however, participants with hyperthyroidism had almost double the cumulative absolute risks for death from breast (4.2%) and ovarian cancer (1.6%) by age 90 years compared with participants with hypothyroidism or no thyroid disease. Participants with hypothyroidism had the highest cumulative absolute risks for death from diabetes (2.2%) or CVD (19.1%) by age 90 years compared with the other participants.
Compared with participants with hypothyroidism or no thyroid disease, those with hyperthyroidism had a significantly higher risk for breast cancer mortality after age 60 years (HR = 2.04; 95% CI, 1.16-3.6), but not at younger ages, and a nonsignificant increased risk for ovarian cancer mortality (HR = 1.65; 95% CI, 0.81-3.37) in multivariable-adjusted models. Significantly higher risks for death from diabetes (HR = 1.57; 95% CI, 1.03-2.4) and CVD (HR = 1.21; 95% CI, 1.04-1.42) were associated with hypothyroidism compared with hyperthyroidism or no thyroid disease.
“No significant association was found between hyperthyroidism or hypothyroidism and other causes of death, although there was a suggestion of an elevated risk of ovarian cancer mortality among women with hyperthyroidism based on very few cases,” the researchers wrote. “These results provide evidence linking thyroid dysfunction with cause-specific mortality outcomes.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to Top
Journy and colleagues studied the relation of hyperthyroidism and hypothyroidism with cause-specific mortality in a large occupational worker cohort of women. Their findings suggest excess mortality risk of breast cancer in women with hyperthyroidism and excess risk mortality of type 2 diabetes and cardiovascular and cerebrovascular disease in women with hypothyroidism.
However, a few issues with this study call for caution. First, there is absence of laboratory thyroid function measurement data for this cohort. We know that a large proportion of patients on thyroid hormone replacement therapy are either overtreated or undertreated. This could mean, for example, that some women who report having hypothyroidism could biochemically be hyperthyroid due to overtreatment. Second, the baseline questionnaires were administered as early as 1983, and perhaps results are therefore not generalizable to women and medical care of this day and age. Lastly, the authors tested the association of hyperthyroidism and hypothyroidism with many different outcomes, which increases the risk of getting positive chance findings. Nevertheless, this study adds to the increasing body of evidence that thyroid dysfunction has implications for several important health outcomes, including mortality. The authors, therefore, rightfully conclude that, particularly with regard to breast cancer risk, further investigations are needed to explore the role of thyroid function in the pathways leading to disease and mortality.
Epidemiologic studies can provide enormous insight into disease mechanisms which then allows such revelations to be tested in a more focused way. Such insights arise when there seem to be plausible biological mechanisms to test. However, sometimes the associations are not at all obvious and the mechanisms may appear implausible, or the associations are so obvious that they provide little additional insight. This major report by Journy and colleagues appears to contain both such outcomes. In a study of 75,000 women with a self-reported history of hyper- or hypothyroidism, the authors found that hyperthyroidism was associated with an increased risk of mortality from breast cancer after 60 years of age and that hypothyroidism was associated with an increased risk of mortality from diabetes, CVD and cerebrovascular disease. To me the associations with hypothyroidism appear obvious; you gain weight and your diabetes and vascular health deteriorate. However, the association between hyperthyroidism and breast cancer has been more controversial. Previous studies have both suggested and denied such an association, but the evidence now appears to be strengthening. Take a look at the study by Søgaard and colleagues, which looked at more than 140,000 Danish women with hyper- or hypothyroidism and also found a small but significantly increased risk of breast cancer in women with a history of hyperthyroidism (Eur J Endocrinol. 2016;doi:10.1530/EJE-15-0989). Because thyroid hormones accelerate cell proliferation, including that of breast cancer cells, there is a biologically plausible explanation that women with the potential to develop breast cancer may be revealed by the hyperthyroid state. Mammography in our patients with overactive thyroid glands is clearly something that should be automatic in our practice. We should certainly already have been screening our overweight hypothyroid patients for diabetes.