Numerous investigations document that exposure to low dose external th
erapeutic radiation leads to the development of benign and malignant t
hyroid neoplasms. There is considerable controversy, however, concerni
ng whether radioactive iodine (I-131) causes thyroid cancer. The aim o
f this investigation was to examine our experience and that in the lit
erature related to this problem. From 1982 to March 1993 seven of 373
patients (1.9%) with thyroid cancer who were treated by one surgeon ha
d a history of treatment with radioactive iodine for Graves' disease a
nd toxic nodular goiter. Sixty-five patients have previously been repo
rted in the literature from 1957 to present. Our patients (five women,
two men) ranged in age from 26 to 80 years (mean 57 years). The inter
val between the exposure to the internal radiation and development of
cancer ranged from 3 to 29 years (mean 11.4 years), and the mean age a
t the time of I-131 treatment was 45 years (18-76 years). The therapeu
tic dose of I-131 was 5 to 100 mCi (mean 25.3 mCi) in our patients. Tw
o of our patients received I twice. The age of patients reported in th
e literature at the time of I-131 treatment ranged from 7 to 74 years
(mean 48 years). The mean therapeutic dose of I-131 was 20.6 mCi (1.25
-180.0 mCi) and the latent period was documented for a mean 8.7 years
(0.25-28.0 years) in these patients. Three of 29 patients in the liter
ature received I-131 twice. Fine-needle aspiration cytology of thyroid
nodules was positive for cancer in six of our patients (86%). All pat
ients were treated by total thyroidectomy, and three of them had a mod
ified neck dissection. Six of our seven patients had invasive papillar
y thyroid carcinoma (stage III disease), and the seventh patient had e
xtensive nodal metastasis and intrathyroidal invasion. Invasion into a
djacent muscle and soft tissue were found in four patients, and two ha
d tracheal invasion. Two patients had lymph node metastases. There wer
e no postoperative complications. One patient (14%), however developed
recurrent papillary and anaplastic thyroid cancer in his left neck an
d mediastinum 2 years after total thyroidectomy. He had extensive pulm
onary metastases and malignant pleural effusions and died 23 days afte
r a left modified radical neck dissection. In conclusion, radioactive
iodine in doses to treat Graves' disease may increase the risk of deve
loping thyroid cancer. These cancers are discovered at a later stage a
nd appear to be aggressive.