Malignant and Benign Neoplasms of the Thyroid in Patients Treated for Hyperthyroidism: A Report of the Cooperative Thyrotoxicosis Therapy Follow-up Study

Abstract
Data concerning the occurrence of malignant and benign thyroid neoplasms in patients treated for hyperthyroidism have been collected at 26 medical centers in the Cooperative Thyrotoxicosis Therapy Follow-up Study. There was 98.8% follow-up in 36,050 patients treated for hyperthyroidism between 1946 and 1968. The analysis is based on 34,684 patients treated by 131I, thyroidectomy, antithyroid drugs, X-irradiation or various combinations of these therapeutic measures. Cases were classified as: Graves' disease without palpable nodules, Graves' disease with palpable nodules, toxic adenoma(s) or unclassified types. The interval of time for the occurrence of a neoplasm (identified by removal) was classified as occurring either at the time of or within 1 year of initial therapy or at sometime greater than 1 yr following therapy. There were 86 malignant thyroid neoplasms found among 34,684 patients. Of those few malignant neoplasms found in Graves' disease, many were of the occult variety, the clinical potential of which is unknown. There were 9 malignant thyroid neoplasms found within 1 yr of treatment in 21,714 patients treated by 131I, 50 in 11,732 patients treated by thyroidectomy, and none in 1,238 patients treated with antithyroid drugs. After an interval of more than 1 yr there were 19 malignant thyroid neoplasms following 131I, 4 following thyroidectomy, and 4 following antithyroid therapy in these respective populations. If the occurrence of 19 malignant lesions found 1 yr or more after 131I is viewed from the standpoint of the incidental malignant lesions found in patients treated primarily by thyroidectomy, the risk from 131I is not significant. There were five anaplastic carcinomas found more than 1 yr following 131I therapy and one fibrosarcoma following thyroidectomy plus 131I therapy. The anaplastic neoplasms occurred within 5 yr of therapy and in patients with an average age of 69.4 yr. No anaplastic lesions were found within 1 yr of any treatment. There were four deaths from malignant thyroid neoplasms among 11,732 patients treated by thyroidectomy, six deaths from malignant neoplasms in 21,704 patients treated with 131I, and no deaths from malignant lesions in 1,238 patients treated more than 1 yr with antithyroid drugs. The occurrence of thyroid adenomas is higher when 131I therapy is used for treatment in the first two decades of life than when used in older individuals.