Abnormalities of the Thyroid in Survivors of Hodgkin’s Disease: Data from the Childhood Cancer Survivor Study1
Charles Sklar,
John Whitton,
Ann Mertens,
Marilyn Stovall,
Daniel Green,
Neyssa Marina,
Brian Greffe,
Suzanne Wolden and
Leslie Robison
Departments of Pediatrics (C.S.) and Radiation Oncology (S.W.),
Memorial Sloan-Kettering Cancer Center, New York, New York 10021;
Department of Biostatistics, Fred Hutchinson Cancer Research Center
(J.W.), Seattle, Washington 98104; Department of Pediatrics,
University of Minnesota (A.M., L.R.), Minneapolis, Minnesota
55455; Department of Radiation Physics, University of Texas,
M. D. Anderson Cancer Center (M.S.), Houston, Texas 77030;
Department of Pediatrics, Roswell Park Cancer Institute (D.G.),
Buffalo, New York 14263; Department of Pediatrics, Stanford
University Medical Center (N.M.), Stanford, California 94304;
and Department of Pediatrics, Children’s Hospital, University of
Colorado Health Sciences Center (B.G.), Denver, Colorado
80218
Address all correspondence and requests for reprints to: Charles Sklar, M.D., Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. E-mail:
sklarc{at}mskcc.org
Treatment for Hodgkin’s disease (HD) is associated witha
variety of thyroid abnormalities, including hypothyroidism,
hyperthyroidism,and thyroid neoplasms. Due to the small sample size
and shortfollow-up time of most published studies, it has been
difficultto appreciate the full extent of the problem and to
characterizethe interaction between various patient and treatment
variables.To overcome these limitations we have assessed thyroid
statusin 1,791 (959 males) HD survivors from among 13,674 participants
inthe Childhood Cancer Survivor Study, a cohort of 5-yr survivorsof
childhood and adolescent cancer diagnosed between 1970 and1986.
Thyroid abnormalities were ascertained as part of a 22-page
questionnairesent to participants. Survivors were a median of 14 yr
(range,2–20 yr) at diagnosis of HD and a median of 30 yr (range,
12–47yr) at follow-up. Seventy-nine percent of subjects were treated
withradiation (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 entirecohort has
been diagnosed with at least one thyroid abnormality.Hypothyroidism
was the most common disturbance, with a relativerisk of 17.1
(P < 0.0001) compared to sibling controls.
Increasingdose of radiation, older age at diagnosis of HD, and female
sexwere all independently associated with an increased risk of
hypothyroidism.Actuarial risk of hypothyroidism for subjects treated
with 4500cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism
wasreported by 5% of survivors, which was 8-fold greater
(P <0.0001) than the incidence reported by the
controls. Thyroiddose of 3500 cGy or more was the only risk factor
identifiedfor hyperthyroidism. The risk of thyroid nodules was 27
times(P < 0.0001) that in sibling controls.
Female sex and radiationdose to the thyroid of 2500 cGy or more were
independent riskfactors for thyroid nodules. The actuarial risk of a
femalesurvivor developing a thyroid nodule is 20% at 20 yr from
diagnosis.Thyroid cancer was diagnosed in 20 survivors, which is 18
timesthe expected rate for the general population. After taking into
accountthe possibility that some of the relative risk estimates maybe
exaggerated due to ascertainment bias, abnormalities of the
thyroidare still extremely common in young adult survivors of
childhoodHD, particularly among females treated with high doses of
radiationto the neck.
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