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Survivors of Childhood Cancer at Risk for Developing Hormone Deficiencies as Adults

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Key Points

  • Researchers found that 51.4% of survivors were deficient in at least one of the hormones included in this study, and 10.9% had multiple deficiencies.
  • The most common deficits involved gonadotropins, but other deficiencies included thyroid-stimulating hormone and adrenocorticotropic hormone.
  • Untreated survivors with these deficiencies are more likely to experience muscle weakness, low energy, abdominal obesity, poor fitness, reduced bone density, high blood pressure, and elevated cholesterol levels.

Decades after undergoing cranial irradiation for childhood cancer, St. Jude Children's Research Hospital investigators found that adult survivors of pediatric cancer remain at risk for pituitary hormone deficiencies, which may diminish their health and quality of life. Chemaitilly et al published their findings in the Journal of Clinical Oncology.

The study included 748 St. Jude survivors of leukemia, brain, and other cancers whose treatment included brain irradiation. The research is the most comprehensive effort yet to assess the long-term impact of the treatment on pituitary function.

“This study provides much needed long-term follow-up data and shows that the risk of pituitary problems follows these survivors into adulthood,” said Wassim Chemaitilly, MD, an assistant member of the St. Jude Department of Pediatric Medicine. Dr. Chemaitilly estimated that a significant proportion of childhood cancer survivors exposed to cranial radiotherapy are at risk for hormone deficiencies as adults. Although St. Jude has dropped cranial irradiation for treatment of acute lymphoblastic leukemia, the most common childhood cancer, it remains important for treatment of pediatric brain tumors.

Study Details

Survivors were enrolled in the St. Jude Lifetime Cohort Study (St. Jude LIFE). The study goal is to improve medical care and the quality of life for current and future childhood cancer survivors. The average survivor in this study was 34 years old and was an average of 27 years from the diagnosis of childhood cancer.

Researchers found that 51.4% of survivors were deficient in at least one of the hormones included in this study, and 10.9% had multiple deficiencies.

The most common deficits involved gonadotropins, which were also the hormone deficiencies most likely to have gone undiagnosed. Untreated survivors with those deficiencies were also more likely than other survivors to experience muscle weakness, poor fitness, heart disease risk factors, and other factors associated with an increased risk of frailty and early death.

More than 46% of the survivors in this study were diagnosed with growth hormone deficiency. In 212 survivors—almost 61% of those identified with the deficiency—this was a first-time diagnosis of such a deficiency. Of the 731 participants checked for low levels of gonadotropins, and the resulting low levels of estrogen and testosterone, researchers identified deficiencies in 79 participants, or nearly 11%. In 46 of the 79 survivors, this was a first-time diagnosis. Obese white men were at greatest risk of having low testosterone levels.

Deficiencies in other pituitary hormones were less common. Blood tests showed that about 7%, or 56 of the 743 survivors included in the screening, had low levels of thyroid-stimulating hormone. The deficit was previously unrecognized in about 14% of patients. Adrenocorticotropic hormone deficiencies were found in almost 4% of survivors, or 29 of the 748 individuals screened.

Long-Lasting Implications

Researchers also reported that the younger survivors were when they underwent cranial irradiation and the higher the radiation dose they received, the greater their risk for pituitary problems later.

This analysis found an association between untreated growth hormone deficiency and reduced strength and muscle size, low energy, poor fitness, and abdominal obesity. Some of the same factors are associated with early aging and an increased risk of premature death. Untreated gonadotropin deficiencies were associated with reduced bone mineral density, reduced fitness, high blood pressure, abdominal obesity, and elevated cholesterol and other blood lipid levels.

“The findings also underscore the need for the nation's growing population of childhood cancer survivors to get recommended health screenings and the challenges they face in trying to navigate the health-care system and follow that advice,” said Dr. Chemaitilly.

Children’s Oncology Group guidelines recommend survivors treated with cranial irradiation have their pituitary function checked annually. Dr. Chemaitilly said the high percentage of survivors with previously undiagnosed hormone deficiencies highlights the need for new strategies to ensure survivors receive recommended health checks.

Additional research is needed to help guide management of adults with growth hormone deficiency. Treatment is expensive, and the long-term benefits in adults are uncertain, Dr. Chemaitilly said.

Dr. Chemaitilly is the corresponding author of the Journal of Clinical Oncology article.

This study was supported by the National Cancer Institute and ALSAC. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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