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Hyperthyroidism: Is Radioactive Iodine Safe?


I have read that radioactive iodine treatment of hyperthyroidism is associated with excess mortality. Many specialists recommend radioactive iodine as first-line therapy--is this safe?

I have read that radioactive iodine treatment of hyperthyroidism is associated with excess mortality. Many specialists recommend radioactive iodine as first-line therapy-is this safe?

Hyperthyroidism affects 2% of women and 0.2% of men.1 Treatment strategies include radioactive iodine (RAI), thionamides (such as methimazole), and surgery. In the United States, thyroid specialists strongly favor RAI (69% use it as a first choice).2 In their follow-up of a cohort of 7209 patients with hyperthyroidism who received RAI from 1950 through 1989, Franklyn and coworkers3 found excess mortality. To determine whether RAI is safe over the long term, these investigators conducted a population-based study of 2668 persons aged 40 years or older who had received this treatment for hyperthyroidism.4 Although 487 deaths were predicted for this group, 554 of the RAI-treated patients died; thus, the risk of dying was 1.14 times greater than in controls who were not similarly treated.

At first glance, these data seem to suggest that RAI is not an appropriate first-line therapy for patients with hyperthyroidism. However, when the data were "crunched" further (that is, when persons treated with RAI were placed into 2 groups, those given subsequent thyroid replacement therapy and those who did not receive it), an interesting pattern emerged. The excess mortality did not occur in RAI-treated patients who were given thyroid replacement.

The real risk seems to reside in the insidious development of subclinical and clinical hypothyroidism as a result of RAI ablation. It is hypothyroidism-with its attendant lipid disorders, diastolic hypertension, and left ventricular dysfunction-not the RAI per se, that seems to increase the risk of death.

Reassure patients that RAI is a safe, effective treatment for hyperthyroidism. However, they will need to be monitored closely for resultant subclinical (elevated thyroid-stimulating hormone level without clinical signs of hypothyroidism) and clinical hypothyroidism. If either develops, thyroid replacement is indicated and protects against the risks of induced hypothyroidism.



1. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7:481-493.
2. Wartofsky L, Glinoer D, Solomon B, et al. Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States. Thyroid. 1991;1:129-135.
3. Franklyn JA, Maisonneuve P, Sheppard MC, et al. Mortality after the treatment of hyperthyroidism with radioactive iodine. N Engl J Med. 1998;338:712-718.
4. Franklyn JA, Sheppard MC, Maisonneuve P. Thyroid function and mortality in patients treated for hyperthyroidism. JAMA. 2005;294:71-80.

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