Discussion

Myelodysplastic syndrome has been previously reported in a 67-years old woman after 820 mCi of ¹³¹I for thyroid cancer (and who ultimately evolved to leukaemia)1 and in another patient who also received external beam radiation therapy.2

Leukemia after treatment for thyrotoxicosis has been previously reported,3–5 even if the 36-yr follow-up of 116 patients under the age of 20 yr with Graves' disease who were treated with radioiodine between 1953 and 1973 did not disclose any leukaemia case.6

Leukemia as a second malignancy after treatment of thyroid cancer is rare and was first reported in 1955.8 Most cases in the literature are represented by acute leukemia8–13 and have occurred after cumulative doses higher than 800 mCi,14 with a case of M6 AML occurring after as long as 8 years.7 Despite this, 2 cases of acute myeloid leukaemia (AML) (one M2 and the other M3) have been reported after single dosage of only 150 mCi,9 and a third case after 2 doses of 150 mCi.15 The risk associated with microdoses has also been suggested by Laurenti et al, who reported a 45-years old female who developed M2 AML 14 months after a single dose of just 23 mCi.7 At least 2 cases of acute promyelocytic leukaemia (AML M3, APL) have been reported : Kolade et al reported a 51-year-old woman who developed APL within 27 months of completing a cumulative dose of radioiodine of 22.1 mCi,16 while Roldan et al reported APL after single dosage of only 150 mCi.9

Chronic leukaemia has also been reported after ¹³¹I treatment. At least 10 cases of chronic myeloid leukemia (CML) have been reported after radioiodine treatment of thyroid cancer with a total dose less than 150 mCi,17–20 one 13 years after a cumulative dose of 670 mCi18 and another 14 years after.19

A general recommendation is that the bone marrow should not receive a total dose which exceeds 1000 mCi, and there should be an interval of at least one year between doses.15 Almost all cases reported in the literature occurred after a total dose of more than 800 mCi and with an interval between doses of 2 and 6 months.15,22 Total quantities up to 1 Ci or more may be used, with a limiting factor being a 200 rad acute exposure to the bone marrow.^{21 131}I at any dose could cause sublethal damage to the bone marrow, but individual susceptibility cannot be excluded in patients developing leukemia after ¹³¹I treatment.

Since ¹³¹I was introduced for hyperthyroidism, no apparent increase in the incidence of leukaemia has been detected,14,23 although an increased (but not statistically significant) risk was observed for both chronic lymphocytic leukemia (CLL) and non-CLL in two large retrospective studies from Sweden;10,14,24 leukemia has also been reported in rare cases as a complication of ¹³¹I treatment for metastatic thyroid cancer, although epidemiological analyses show conflicting results.15,22,25 As a matter of fact, the incidence of leukemia after ¹³¹I treatment for thyroid cancer is estimated at around 2% in large series,2,12,13 while the incidence of leukemia after ¹³¹I treatment for hyperthyroidism, which is a relatively benign condition, is still a matter of debate.14,24

On the other hand, lymphoma is an extremely rare occurrence after ¹³¹I treatment. Wiseman et al reported two cases of lymphoma of the parotid gland 10 and 3 years after 675 mCi and 350 mCi radioiodine therapy for thyroid carcinoma, respectively.26

¹³¹I is widely used in the treatment of hyperthyroidism and for remnant ablation in patients with differentiated thyroid cancers,27 and it is considered an efficacious and safe approach, although recently some authors prudentially restrict its use to older patients after surgery or medical failure. In conclusion, since the benefits of radioactive iodine therapy in the treatment of hyperthyroidism and thyroid cancer are proven and the use of ¹³¹I appears to be increasing for nonmalignant thyroid diseases,6 a strict hematological follow-up of patients submitted to ¹³¹I is warranted in order to accurately detect the incidence of leukemias and lymphomas. Although the development of these malignancies can be due to aging or other causes rather than exposure to ¹³¹I treatment, its role could have been underestimated. Radioprotectants such as amifostine could eventually be used to reduce extrathyroid toxicity.