Childhood cancer survivors at risk for endocrine disorders

The risk for endocrinopathies increased substantially over time among childhood cancer survivors, especially among those who received high-risk therapies, according to the results of an analysis from the Childhood Cancer Survivor Study.

The current 5-year survival for childhood cancer exceeds 80%. However, research has shown that survivors are at increased risk for a broad spectrum of serious health conditions.

“Late endocrine effects frequently occur many years after cancer treatment,” Sogol Mostoufi-Moab, MD, MSCE, assistant professor of pediatrics at Perelman School of Medicine of University of Pennsylvania, and colleagues wrote. “And although an increase in the occurrence of endocrinopathies in aging survivors is expected, currently, there are few long-term follow-up data with respect to endocrinopathies in childhood cancer survivors as they age beyond young adulthood.”

To assess the development of endocrinopathies in survivors based on treatment exposure, Mostoufi-Moab and colleagues used the Childhood Cancer Survivor Study to analyze self-reported conditions in 14,290 (46% female) 5-year survivors.

Patients’ median age at diagnosis was 6 years (range, less than 1 to 20), and their median age at last follow-up was 32 years (range, 5-58). The survivors had been diagnosed with leukemia (33%), Hodgkin lymphoma (13%), central nervous system tumor (13%), Wilms’ tumor (9%), soft tissue sarcoma (9%), bone cancer, (8%), non-Hodgkin lymphoma (8%) and neuroblastoma (7%).

Researchers used simple random sampling to generate a cohort of 4,031 siblings (52% female) who had no history of cancer. The median age of siblings at last follow-up was 34 years (range, 5-62).

Researchers used the Children’s Oncology Group Long-Term Follow-Up Guidelines to identify high-risk therapeutic exposures.

Forty-four percent of survivors developed at least one endocrinopathy, 16.7% had at least two and 6.6% had three or more endocrinopathies.

Endocrinopathies occurred most frequently among survivors of Hodgkin lymphoma (60.1%), followed by survivors of CNS tumor (54%), leukemia (45.6%), sarcoma (41.3%), non-Hodgkin lymphoma (39.7%), neuroblastoma (31.9%), Wilms’ tumor (28.5%) and bone cancer (27.8%).

Risk for endocrine disorders appeared significantly increased among survivors exposed to high-risk therapies. These survivors had a greater risk for:

primary hypothyroidism (HR = 6.6; 95% CI, 5.6-7.8);

hypothyroidism (HR = 1.8; 95% CI, 1.2-2.8);

thyroid nodules (HR = 6.3; 95% CI, 5.2-7.5);

thyroid cancer (HR = 9.2; 95% CI, 6.2-13.7);

growth hormone deficiency (HR = 5.3; 95% CI, 4.3-6.4);

obesity (RR = 1.8; 95% CI, 1.7-2); and

diabetes (RR = 1.9; 95% CI, 1.6-2.4).

Female survivors appeared more likely to have primary ovarian insufficiency following high-risk therapies (RR = 6.3; 95% CI, 5-8). Further, they had greater likelihood of having hypothalamic pituitary after receiving irradiation of at least 30 Gy (RR = 6; 95% CI, 4.2-8.5).

Among men, those who received 20 Gy or more of testicular irradiation or 20 mg/m² or more of cyclophosphamide-equivalent dose were more likely to need testosterone replacement therapy (RR = 10.8; 95% CI, 8.2-14.2), and those who received 30 Gy or more irradiation were more likely to have hypothalamic pituitary (RR = 5.7; 95% CI, 4.2-7.7).

Researchers noted these risks appeared to increase over time.

Regardless of treatment exposure, all survivors had increased risk for thyroid disorders and diabetes compared with their siblings (P < .001 for all).

“The risks are particularly great for . . . high-dose irradiation of the head, neck or pelvis, and after exposure to high doses of alkylating agents,” Mostoufi-Moab and colleagues wrote. “For many outcomes, even survivors exposed to non–high-risk therapies were significantly more likely to develop an endocrine disorder compared with siblings.”

Researchers acknowledged the self-reported nature of the data, lack of hormone data, and possible surveillance and selection bias may have limited findings. – by Nick Andrews

Disclos ure: Mostoufi-Moab reports no relevant financial disclosures. Other researchers report research funding and travel accommodations and expenses from Merck and Sandoz.