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Systematic screening approach may detect endocrine complications in childhood cancer survivors
As childhood cancer cure rates have substantially improved, the rate of late-onset endocrine complications among childhood cancer survivors has risen, with an estimated 50% of survivors experiencing complications ranging from thyroid dysfunction to obesity or type 2 diabetes during their lifetime, according to a recent analysis.
“Endocrine complications are among the most prevalent late-effects in [childhood cancer survivors],” wrote Wassim Chemaitilly, MD, of the division of endocrinology at St. Jude’s Children’s Research Hospital in Memphis, Tennessee, and Laurie E. Cohen, MD, of the division of endocrinology at Boston Children’s Hospital and Harvard Medical School. “A systematic screening approach should facilitate the early diagnosis and treatment of these conditions and hopefully improve health outcomes. Endocrine late-effects may continue to appear years to decades after the completion of cancer treatments; the importance of long-term follow-up cannot be overemphasized.”
Chemaitilly and Cohen outlined the prevalence and risk factors for common endocrine complications and cited best practices for diagnosis and management for each condition, including hypothalamic/pituitary axis dysfunction, growth hormone deficiency, central precocious puberty, primary ovarian insufficiency, decreased bone mineral density, obesity and type 2 diabetes.
Thyroid complications
Thyroid complications, including thyroid cancers, were cited as among the most common endocrine sequelae in the overall population of childhood cancer survivors. Patients at risk for primary hypothyroidism after exposure to radiotherapy should be screened for the condition at least yearly (more frequently in childhood) by measuring thyroid-stimulating hormone and free thyroxine levels. Screening modalities for thyroid cancer in at-risk patients remain controversial, the researchers wrote.
“Some authors argue that these issues may outweigh the hypothetical benefits of an earlier diagnosis obtained via ultrasound when compared to what can be accomplished through a careful yearly examination of the neck by an experienced provider,” they wrote. “Others have favored using ultrasound and postulated that it will result in diagnosing the disease at a less advanced stage and hence decrease the need for invasive treatments.”
Primary ovarian insufficiency
The prevalence of primary ovarian insufficiency was 11.8% among female childhood cancer survivors exposed to gonadotoxic chemotherapy drugs, such as alkylating agents and radiotherapy, the researchers wrote. Young, pubertal childhood cancer survivors at risk for primary ovarian insufficiency can be offered fertility preservation via mature oocyte cryopreservation, preferably before cancer treatment.
“Depending on the attained pubertal stage at the time of cancer diagnosis, patients with [primary ovarian insufficiency] may present with delayed puberty, interrupted puberty, primary or secondary amenorrhea, or premature menopause (ie, before 40 years of age),” the researchers wrote. “Patients undergoing cancer treatments frequently experience interruptions in their pubertal development or amenorrhea; assessments of ovarian function are generally initiated if such dysfunctions last for more than 2 years after the completion of therapy.”
Diagnosis is primarily based on elevated follicle-stimulating hormone levels contrasting with low estradiol concentrations, they wrote.
Obesity and type 2 diabetes
The risk for both obesity and type 2 diabetes were higher in cancer survivors vs. their healthy siblings in the Childhood Cancer Survivor Study, according to researchers; RR for obesity was 1.8 (95% CI, 1.7-2), RR for developing diabetes was 1.9 (95% CI, 1.6-2.4). High-risk groups include survivors of central nervous system tumors with a history of hypothalamic/pituitary tumor or surgery.
“While cranial irradiation represents a significant risk factor of obesity and diabetes mellitus in [acute lymphoblastic leukemia] survivors, those treated with chemotherapy alone continue to experience high rates of persistent obesity and overweight after many years of follow-up, likely
because of their prolonged exposure to high-dose glucocorticoids,” the researchers wrote. “Patients treated with [hematopoietic stem cell transplantation] do not seem to experience higher rates of obesity than similar-aged individuals from the general population, but they were reported to have increased risks of insulin resistance, glucose intolerance and abnormal body composition.”
The researchers noted that childhood cancer survivors should be screened every 6 to 12 months for overweight and obesity, with subsequent testing for CV risk factors following guidelines in place for the general population. Patients treated with total-body irradiation must be screened for diabetes at least every 2 years, regardless of overweight or obesity status, the researchers wrote. – by Regina Schaffer
Disclosure: Chemaitilly reports receiving consulting honoraria from Novo Nordisk and Pfizer. Cohen reports no relevant financial disclosures.