Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group

JAMA. 1998 Jul;280(4):347-55. doi: 10.1001/jama.280.4.347.


Context: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation.

Objective: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment.

Design: A retrospective cohort study.

Setting: Twenty-five clinics in the United States and 1 clinic in England.

Patients: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I.

Main outcome measure: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism.

Results: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86).

Conclusions: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthyroidism / complications*
  • Hyperthyroidism / therapy*
  • Iodine Radioisotopes / adverse effects
  • Iodine Radioisotopes / therapeutic use*
  • Likelihood Functions
  • Male
  • Neoplasms / complications*
  • Neoplasms / etiology
  • Neoplasms / mortality*
  • Neoplasms, Radiation-Induced / epidemiology
  • Poisson Distribution
  • Retrospective Studies
  • Risk


  • Iodine Radioisotopes