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Iodine-131, as therapy for hyperthyroidism, was introduced in the 1940s
and is still a common therapy (16,17). In many clin-ics, 131I
is the therapy of choice for both Graves' disease and toxic nodular goiter,
largely because serious side effects are uncommon. However, there are still
concerns as to the possible carcinogenic effect of the isotope, but no
clear pattern of an increased cancer risk has been observed (18-20) and
most noteworthy, leukemia has never been found to be in excess among 131I
treated hyper-thyroid patients (18,19). An increased risk of leukemia has
been described among patients with hyperthyroidism but there was no difference
in risk related to type of therapy, e.g. patients operated or receiving
131I had the same risk of leukemia (18). It was concluded that
the risk of leukemia was related to the underlying disease and not to the
given treatment.
The risk of leukemia and solid tumors has been evaluated in 10,552 Swedish patients treated with 131I for hyperthyroidism (21). The patients were less than 75 years of age at the time of treatment, mean age at exposure 57 years, and the follow-up 15 years. Only average organ doses were calculated and stomach (0.25 Gy), salivary gland (0.20 Gy), and bladder (0.14 Gy) received more than 0.10 Gy. A total of 1,543 cancers was found more than 1 year after exposure and sites that showed significantly elevated risks were lung (n=105), kidney (n=66), and parathyroid gland (n=30) (Table 3). However, stomach cancer was the only site with an increased risk related to 131I exposure since a significant dose- response relationship was noted. Atrophic gastritis is an autoimmune disorder that could be a confounding factor being related both to Graves’ disease and stomach cancer. However, the increased risk of stomach cancer was found among the patients with toxic nodular goiter (SIR=1.35) and not in those with Graves’ disease (SIR=0.87). The risk of lymphoma was significantly lower than expected and no in-creased risk of leukemia was noticed. The risk of kidney cancer was slightly elevated but did not vary with organ dose (Table 3).
Mortality other than cancer has also been studied in the Swedish cohort of hyperthyroid patients (22). A total of 5,400 deaths was observed and overall standardized mortality ratio was 1.47 (95% CI 1.43-1.51; Table 4). The most common cause of death was cardiovascular diseases [61%; standardized mortality ratio (SMR) 1.65] and significantly elevated risks were also seen for tumors, diseases of the endocrine system, cardiovascular system, respiratory system, gastro-intestinal system, and congenital malformations (Table 4). Patients given higher 131I activity and younger patients had higher risks than those given lower activity and older patients.
Cancer mortality was highest during the first year of follow-up and probably reflects the increased medical surveillance. A higher incidence of smoking in patients with Graves’ disease could be the explanation to the higher risk among those patients (23,24) but unfortunately information on smoking habits was not available for these patients. Fortynine percent of the patients dying from endocrine disorders died of complications to a long standing diabetes, an autoimmune disease related to Graves' disease. Of the 22 individuals dying from congenital malformations, 21 died from congenital heart failures. Hyperthyroidism increases stroke volume, heart rate, and systolic blood pressure and might therefore complicate congenital heart malformations as well as occult heart disease. The finding of a sharp decline of SMR for the cardiovascular system 1 year after 131I treatment favors this hypothesis. The significantly increased risk of respiratory disorders could be explained by the immunosuppressive effect of hyperthyroidism in itself and antithyroid medication. Whether these factors could have contributed to our findings of 67% of the deaths in respiratory disorders were due to infections remain unclear. This population represents a selected group of patients who did not qualify for surgery. Young patients and women of childbearing age are less likely to receive 131I and this selection bias might influence the risk. Younger patients are rarely treated with 131I if their medical condition permits surgery and this condition could thus be the cause of death instead of the 131I treatment. Patients receiving the highest activities of 131I also revealed the highest mortality probably reflecting the severity of the hyperthyroidism. A possible effect of 131I was thus likely hidden by the severity of the underlying disorder. |
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