Late Complications

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The main long-term complications of 131I are damage to the gonads, bone marrow, and lungs, and the induction of other carcinomas.

Ovarian Damage

The risk of permanent damage to the ovaries after ablative radioiodine treatment appears to be low and most patients can be reassured they can have normal pregnancies after 131I treatment. During the first year after 131I therapy, middle-aged women may developed temporary amenorrhea and elevated serum gonadotropin concentrations [153] and women of all ages have a higher than expected rate of spontaneous miscarriage [154], yet there are no measurable effects of 131I on fertility, birth defect, birth-weight and prematurity rates [155]. Still, 131I therapy may be associated with early menopause [156]. In a study by Vini et al. [157] of 496 women under the age of 40 at the time of diagnosis, 65% of whom had received 3 GBq (81mCi) of 131I while the remainder had received subsequent treatment with a cumulative activity of 8.5-59 GBq (230-1595 mCi) for persistent disease, transient amenorrhea or menstrual irregularities lasting up to 10 months occurred in 83 patients (17%). No cases of permanent ovarian failure were recorded. There were 427 children born to 276 women; only one patient was unable to achieve a successful pregnancy. Four premature births and 14 miscarriages occurred but no congenital abnormalities were reported. In a study of 33 children treated at an average age of 14.6 years with a mean dose of 7252MBq (196mCi) of 131I, the frequency of infertility (12%), miscarriage (1.4%), prematurity (8%), and major congenital anomalies (1.4%) after an average follow-up of almost 19 years was not significantly different from that in the general population [158]. See Chapter 16 for an excellent review of this by Dr Vini.

Testicular Damage

In men, gonadal damage may be more severe

[159], with permanent testicular damage or transiently reduced sperm counts roughly proportional to the 131I dose administered

[160]. Serum follicle-stimulating hormone (FSH) levels usually do not change or rise transiently, although they may remain high [161]. Serum testosterone concentrations and fertility are usually not affected [162]. In a longitudinal analysis of 21 men, six had no change or only a slight increase in serum FSH after 131I therapy while 11 others had a transient rise above normal 6 to 12 months after treatment. Four men treated with several doses of 131I had a progressive increase in serum FSH, which eventually became permanent. Semen analysis performed in a small subgroup of men showed a consistent reduction in sperm motility, but the serum testosterone concentrations in the treated and normal men were similar. A survey of 59 men treated with 131I found they had fathered 106 children, none of whom was reported to have had major congenital malformations [162]. In another study, fertility was normal in 30 patients who were aged 30 years or less when treated; they had 44 live births [163]. Two men who had received a total of 35.9 and 52.98 GBq (972 and 1432mCi) between ages 10 and 19 years had fathered two and three children, respectively, up to 13 and 24 years later. Another treated at age 24 with 25.2 GBq (680 mCi) had oligospermia with an elevated serum FSH. Thus, 131I therapy occasionally impairs testicular germinal cell function, posing a significant risk of infertility. Young men should consider banking sperm specimens before therapy, particularly if larger cumulative doses of 131I are to be given [159].

Bone Marrow Damage

This and the induction of other tumors are the most serious late hazards of 131I therapy. Large amounts of 131I (>37000MBq, 1000mCi) can cause a small but significant excess of deaths, especially from bladder cancer and leukemia [163]. Bladder cancer occurs more often in those with relatively little 131I uptake in the neck or metastases [163]. In one report, 80% of 35 patients treated with 131I had bone marrow abnormalities, including three with acute myeloid leukemia [164]. Those with pancytopenia had received cumulative 131I activities over 37.0GBq (1000mCi) [164]. In 13 large series comprising a total of 2753 patients with thyroid carcinoma, 14 cases of leukemia were detected

[165], resulting in a prevalence of about five cases per 1000 patients (0.5%), which is higher than expected in the general population. Acute myeloid leukemia tends to occur within 10 years of treatment and is less likely when 131I is given annually rather than every few months, and when total blood doses per administration are less than 2Gy (200rad) [165]. The lifetime risk of leukemia is so small (0.33%) that it does not outweigh the benefit of 131I therapy [166]. The risk of life lost because of recurrent thyroid cancer exceeds that from leukemia by fourfold to 40-fold, and is greatest in younger patients

[166]. Few cases of leukemia occur when 131I is given at 12-month intervals and cumulative amounts are less than 22.0 to 29.6GBq (600 to 800mCi) [151]. Still, 131I therapy is not stopped for patients with serious metastatic tumor who have reached these limits.

Pulmonary Fibrosis

This rarely occurs in patients with diffuse pulmonary metastases treated with 131I [167]. It can be avoided by using 131I in amounts that result in a whole-body retention of less than 2.96GBq (80 mCi) 48 hours after its administration when there is diffuse 131I uptake in the lungs seen on the DxWBS. However, retention of >50% at 48 hours is uncommon [136].

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