Abnormalities of the thyroid in survivors of Hodgkin's disease: Data from the Childhood Cancer Survivor Study Journal Article


Authors: Sklar, C.; Whitton, J.; Mertens, A.; Stovall, M.; Green, D.; Marina, N.; Greffe, B.; Wolden, S.; Robison, L.
Article Title: Abnormalities of the thyroid in survivors of Hodgkin's disease: Data from the Childhood Cancer Survivor Study
Abstract: Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status 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 and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects 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 been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared 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 treated with 4500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.
Keywords: adolescent; adult; child; controlled study; child, preschool; retrospective studies; major clinical study; radiation dose; follow up; disease association; cohort studies; risk factor; hodgkin disease; risk assessment; survivors; infant; thyroid cancer; thyroid neoplasms; hyperthyroidism; hypothyroidism; thyroid diseases; thyroid nodule; databases, factual; thyroid hormone; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Endocrinology and Metabolism
Volume: 85
Issue: 9
ISSN: 0021-972X
Publisher: Oxford University Press  
Date Published: 2000-09-01
Start Page: 3227
End Page: 3232
Language: English
PUBMED: 10999813
PROVIDER: scopus
DOI: 10.1210/jcem.85.9.6808
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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  1. Charles A Sklar
    322 Sklar
  2. Suzanne L Wolden
    561 Wolden