Primary hypothyroidism after treatment for childhood cancer in the Dutch Childhood Cancer Survivor Study: Hypothyroidism in childhood cancer survivors

PURPOSE: Primary hypothyroidism is common in childhood cancer survivors (CCS). Exposure to radiation and hematopoietic stem cell transplantation (HSCT) are known risk factors; however, the impact of chemotherapy and the role of thyroid peroxidase antibodies (anti-TPO) remain unclear. The prevalence of primary hypothyroidism, anti-TPO, and treatment-related risk factors in a cohort of CCS was assessed.

METHODS: In total, 1774 five-year CCS were included. The prevalence of primary hypothyroidism according to treatment strategy was evaluated: radiotherapy involving the thyroid gland (±chemotherapy), chemotherapy only, HSCT, and controls. Multivariable logistic regression was performed to identify risk factors for hypothyroidism.

RESULTS: After a median follow-up time of 25.3 years (range, 14.8-54.7), primary hypothyroidism was present in 8.2%. When evaluating subgroups specifically, the prevalence of primary hypothyroidism increased to 28% in CCS treated with radiotherapy and 30.6% after HSCT. In multivariable analyses, survivors treated with chemotherapy only were not at increased risk of hypothyroidism (odds ratio [OR], 0.74; 95% CI, 0.28-2.00), whereas survivors treated with radiotherapy had an almost 14-fold increased risk (OR, 13.91; 95% CI, 5.34-36.22). In irradiated CCS, the use of platinating agents was associated with an increased risk of hypothyroidism (OR, 3.25; 95% CI, 1.39-7.59). The prevalence of anti-TPO did not differ between the treatment groups (p = .42).

CONCLUSIONS: Primary hypothyroidism is prevalent after radiation exposure and HSCT. Chemotherapy only does not increase the risk for primary hypothyroidism. The use of platinating agents combined with radiotherapy may increase its risk. Treatment for childhood cancer does not increase the risk of anti-TPO.