Abnormalities of the thyroid in survivors of Hodgkin's disease: Data from the childhood cancer survivor study

Treatment for Hodgkin's disease (HD) is associated with a variety of thyroi d abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neo plasms. Due to the small sample size and short follow-up time of most publi shed studies, it has been difficult to appreciate the full extent of the pr oblem and to characterize the interaction between various patient and treat ment variables. To overcome these limitations we have assessed thyroid stat us in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood an d adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. S urvivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a m edian of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subj ects were treated with radiation (median dose of radiation to the thyroid, 3500 cGy; range, 0.37-5500 cGy). Control data were available from 2,808 (1, 346 males) sibling controls. Thirty-four percent of the entire cohort has b een diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compare d to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treat ed with 4500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism wa s reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than t he incidence reported by the controls. Thyroid dose of 3500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid n odules was 27 times (P < 0.0001) that in sibling controls. Female sex and r adiation dose to the thyroid of 2500 cGy or more were independent risk fact ors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagno sed in 20 survivors, which is 18 times the expected rate for the general po pulation. After taking into account the possibility that some of the relati ve risk estimates may be exaggerated due to ascertainment bias, abnormaliti es of the thyroid are still extremely common in young adult survivors of ch ildhood HD, particularly among females treated with high doses of radiation to the neck.