Hyperthyroidism, Hypothyroidism, and Cause-Specific Mortality in a Large Cohort of Women

Abstract

Background: The prevalence of hyperthyroidism and hypothyroidism is 0.5–4% in iodine-replete communities, but it is 5–10 times higher in women than in men. Those conditions are associated with a broad range of metabolic disorders and cardiovascular diseases. Biological evidence of a role of thyroid hormones in carcinogenesis also exists. However, the association between thyroid dysfunction and cardiovascular disease or cancer mortality risk remains controversial. In a large cohort of women, the associations of hyperthyroidism and hypothyroidism with cause-specific mortality were evaluated after nearly 30 years of follow-up. Methods: The prospective study included 75,076 women aged 20–89 years who were certified as radiologic technologists in the United States in 1926–1982, completed baseline questionnaires in 1983–1998 from which medical history was ascertained, and reported no malignant disease or benign thyroid disease except thyroid dysfunction. A passive follow-up of this cohort was performed through the Social Security Administration database and the National Death Index-Plus. Cause-specific mortality risks were compared according to self-reported thyroid status, with proportional hazards models adjusted for baseline year and age, race/ethnicity, body mass index, family history of breast cancer, and life-style and reproductive factors. Results: During a median follow-up of 28 years, 2609 cancer, 1789 cardiovascular or cerebrovascular, and 2442 other non-cancer deaths were recorded. Women with hyperthyroidism had an elevated risk of breast cancer mortality after 60 years of age (hazard ratio [HR] = 2.04 [confidence interval (CI) 1.16–3.60], 13 cases in hyperthyroid women) compared to women without thyroid disease. Hypothyroid women had increased mortality risks for diabetes mellitus (HR = 1.58 [CI 1.03–2.41], 27 cases in hypothyroid women), cardiovascular disease (HR = 1.20 [CI 1.01–1.42], 179 cases), and cerebrovascular disease (HR = 1.45 [CI 1.01–2.08], 35 cases, when restricting the follow-up to ≥10 years after baseline). Other causes of death were not associated with hyperthyroidism or hypothyroidism, though there was a suggestion of an elevated risk of ovarian cancer mortality in hyperthyroid women based on very few cases. Conclusion: The excess mortality risks observed in a large, prospective 30-year follow-up of patients with thyroid dysfunction require confirmation, and, if replicated, further investigation will be needed because of the clinical implications.