(CANCER RESEARCH 50. 228.1-2289. April 15. 1990| Cancer Mortality in Women with Thyroid Disease1 Marlene B. Goldman,2 Richard R. Monson, and 1aralio Maloof Department of Epidemiology, Harvard School of Public Health, Boston 02115 [M. B. 6"..R. K. M.J, and Thyroid I'nil, Massachusetts Ornerai Hospital, Boston 02114 /F. M.I, Massachusetts ABSTRACT in a study of American women (4). A mechanism for a causal relationship between the two diseases is not established, al A retrospective follow-up study of 7338 women with either nontoxic though thyroid hormones are known to influence the breast nodular goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, Hashimoto's thyroiditis, or no thyroid disease was conducted. All women either directly or through effects on thyroid-stimulating hor patients at the Massachusetts General Hospital Thyroid Clinic who were mone, prolactin, estrogens, or androgens. Researchers sug seen between 1925 and 1974 and who were treated for a minimum of 1 gested that a deficit of thyroid hormone altered the hormonal year were traced. A total of 2231 women (30.4%) were dead and 2012 milieu in a way that permitted the growth of malignant cells (1, women (27.4%) were alive as of December 31, 1978. Partial follow-up 5, 6). It is just as reasonable to hypothesize, however, that an information was available for the remaining 3095 women (42.2%). The excess of thyroid hormone may promote tumor growth. A average length of follow-up was 15.2 years. When losses to follow-up number of biochemical and clinical studies have been con were withdrawn at the time of their loss, the standardized mortality ratios ducted, but no consensus has been reached as to the role of (SMR) for all causes of death were 1.2 |95% confidence interval (CI), thyroid hormones in the initiation or promotion of cancer. 1.1-1.3) for women with nontoxic nodular goiter, 1.2 (95% CI 1.0-1.3) In addition, two thyroid treatments have been associated with for those with thyroid adenoma, 1.4 (95% CI 1.3-1.5) for women with an increased risk of cancer, "'I therapy for hyperthyroidism hyperthyroidism, 1.5 (95% CI 1.3-1.7) for hypothyroid women, 1.2 (95% CI 0.9-1.5) for those with Hashimoto's thyroiditis, and 1.5 (95% CI 1.4- and thyroid supplements for hypothyroidism. Since 1946, when I3II was introduced, there has been concern that the radiation 1.6) for those without thyroid disease. For deaths from all cancers, the standardized mortality ratios were 1.5 (95% CI 1.2-1.8) for women with may cause cancer. While there have been case reports of leu nontoxic nodular goiter, 1.5 (95% CI 1.1-1.9) for those with thyroid kemia (7-9), thyroid (10-12), breast (13), and colon cancer (14) adenoma, 1.2 (95% CI 1.0-1.4) for women with hyperthyroidism, 1.0 after '"I treatment, epidemiologie studies have not found large (95% CI 0.7-1.4) for the hypothyroid women, 1.2 (95% CI 0.7-2.1) for increases in cancer incidence or mortality among thyroid pa those with Hashimoto's thyroiditis, and 1.3 (95% CI 1.0-1.5) for those tients treated with "'I. Muñozétal.(15)found a slightly higher women without thyroid disease. When specific cancer sites were studied, than expected incidence of cancer in hyperthyroid patients who excess numbers of deaths were observed from breast cancer in women had received radioactive iodine therapy. Hoffman et al. (16), in with nontoxic nodular goiter (SMR = 1.6, 95% CI 1.0-2.6) and from a continuation of the United States Public Health Service lymphatic and hematopoietic cancer in women with nontoxic nodular goiter (SMR = 2.4, 95% CI I.2-4.3) and thyroid adenoma (SMR = 2.7, Cooperative Thyrotoxicosis Therapy Follow-up Study (Mayo 95% CI 1.I-5.2). An increase in thyroid cancer risk was observed in Clinic Center), reported no difference between radioactive io women with thyroid adenoma (SMR = 11.7, 95% CI I.3-42.1) but was dine-treated patients and surgically treated patients for total based on only two deaths. In hyperthyroid women, statistically significant cancer incidence, breast cancer, or leukemia. An elevated rate increases in the number of deaths were observed from pancreatic cancer ratio (rate ratio = 1.8, 95% CI' 1.1-3.2) was observed for (SMR = 2.6, 95% CI 1.4-4.3) and respiratory cancer (SMR = 2.2, 95% cancers of the salivary glands, digestive tract, kidney, and CI 1.3-3.5), but not breast cancer (SMR = 1.3, 95% CI 0.8-1.8). When bladder; these organs are known to concentrate radioactive the data were stratified by the time between the onset of thyroid symp iodine. Goldman et al. (17) found that women who were treated toms and death, a nonsignificant excess number of cancer deaths was with '"I at the Massachusetts General Hospital between 1946 observed in hyperthyroid women who died 20 or more years after their and 1964 had a standardized rate ratio for developing breast symptoms began. The standardized mortality ratio for deaths from breast cancer of 1.9 (95% CI 0.9-4.1), compared with those never cancer was 1.1 (95% CI 0.5-2.3) for all hypothyroid women and 1.0 treated with I3II. The standardized rate ratios were 0.7 for (95% CI 0.4-2.1) for hypothyroid women with a history of thyroid replacement hormone use. deaths due to cancer and 1.0 for incident cases of cancer. After treatment for hyperthyroidism, a majority of patients develop iatrogenic hypothyroidism and may require treatment INTRODUCTION with thyroid supplements. In 1976, Kapdi and Wolfe (18) For the last 30 years investigators have been interested in reported that women who were seen at a mammography screen what relationship, if any, there is between thyroid diseases and ing clinic and who used thyroid supplements were at high risk their treatments and the development of cancer, especially of developing breast cancer. The likelihood that selection bias breast cancer. In the 1950s, clinical investigators reported that, occurred in the design of this study prompted the American while breast cancer seldom occurred in hyperthyroid women, it Thyroid Association to urge the National Cancer Institute to seemed to occur more frequently than expected in hypothyroid support further research on the role of thyroid diseases and women (1, 2). More recently, Itoh and Maruchi (3) suggested their treatments in the etiology of cancer, particularly breast that Japanese women with Hashimoto's thyroiditis had an cancer (19). In 1978, we began a retrospective follow-up study to measure increased incidence of breast cancer, but no increase was noted mortality in women with thyroid disease who were diagnosed Received 5/17/89; revised 12/14/89. at the Massachusetts General Hospital Thyroid Clinic between The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in 1925 and 1974. This paper presents the cancer mortality results accordance with 18 LJ.S.C. Section 1734 solely to indicate this fact. for women with nontoxic nodular goiter, thyroid adenoma, 1Supported by National Cancer Institute Contract NCI-CB-84230. M. B. G. hyperthyroidism, hypothyroidism, or Hashimoto's thyroiditis. was also supported by an award from the Exxon Corporation Fellowship Program in Epidemiology. For comparison, a group of women who were referred to the 2To whom requests for reprints should be addressed, at Department of Epidemiology. Harvard School of Public Health. 677 Huntington Avenue, Bos ' The abbreviations used are: CI, confidence interval; MGH, Massachusetts ton. MA 02115. General Hospital: SMR. standardized mortality ratio. 2283 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 1990 American Association for Cancer Research. CANCER MORTALITY AFTER THYROID DISEASE Thyroid Clinic for examination but who were found not to have whichever came first. Since very few women reached age 80 or 90 prior thyroid disease were also included. to the closing date. Assumptions 3 and 4 had little effect. Assuming the losses to be alive until the closing date inflated the number of woman-years. The most reasonable estimates were obtained when the SUBJECTS AND METHODS losses were withdrawn at their date of loss. Definition of Period of Observation. Woman-years of follow-up were Population accrued starting from the first anniversary of the date of diagnosis of thyroid disease at MGH. The observation period ended at the common The study population was 7338 women with nontoxic nodular goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, Hashimoto's thy- closing date of the study (December 31, 1978), at the date a woman was last known to be alive, or at her date of death, whichever occurred roiditis, or no thyroid disease who were first seen at the MGH Thyroid first. Women who were lost to follow-up were withdrawn at their date Clinic between January 1, 1925, and December 31, 1974; who were Massachusetts residents; and who were followed by the Hospital for at of loss. least 1 year. These women were identified from a roster of all patients Statistical Analysis that has been kept since the Clinic opened in 1920. Observed numbers of deaths were compared with those that were Diagnosis Confirmation and Medical Record Review expected based on race-, sex-, age-, calendar time-, and cause-specific The diagnosis of thyroid disease was confirmed by a review of the mortality rates using the USDR computer program (21). This program calculated the number of woman-years of follow-up and the number of MGH medical record.