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What steps do you take when seeing a patient who is a childhood cancer survivor?
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Focus on cancer treatment history
When seeing a childhood cancer survivor, important history includes age at diagnosis and times of treatments; radiation to hypothalamus and pituitary (for growth hormone, other pituitary hormone deficiencies and precocious puberty); radiation to spine (for impaired spine growth); radiation to thyroid (for hypothyroidism or hyperthyroidism and thyroid nodules); radiation to ovaries or testes and/or alkylating agents (for infertility, hypogonadism); total body irradiation or abdominal radiation (for insulin resistance/diabetes); and corticosteroids or methotrexate (for decreased bone mineral density).
Physical examination should include height, weight and BMI; sitting height if a patient received spinal radiation; thyroid palpation for nodules if a patient received thyroid radiation; Tanner staging of breasts and pubic hair; and testicular size by orchidometry. Pubertal onset should be judged in relation to the patient’s prior growth pattern and family history, rather than population norms. Testicular size may not reflect the stage of puberty if there is Sertoli cell damage.
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Depending on the potential axis affected, screening laboratory testing may include insulin-like growth factor I level to assess growth hormone status; free T4 and thyroid-stimulating hormone to assess thyroid function; luteinizing hormone; follicle-stimulating hormone; estradiol/testosterone to assess gonadal function; 8 a.m. cortisol level to assess adrenal function; fasting lipid profile; fasting blood glucose; and HbA1c to assess metabolic syndrome. It should be remembered that normal labs may not rule out pathology, especially at the low and high ends of normal, and clinical correlation is always needed.
Patients at risk should — at least — be seen yearly; more often if endocrinopathies arise.
Laurie Cohen, MD, is Director of the Neuroendocrinology Program and Assistant Professor of Pediatrics at Harvard Children’s Hospital.
Focus on obtaining detailed, accurate history
Obtaining a detailed and accurate history is crucial in the assessment of a childhood cancer survivor, with special attention to treatment exposures and the chronology of events because many complications may occur years following the exposure to treatments. In this context, the importance of long-term follow-up of childhood cancer survivors cannot be overemphasized.
Patients at risk need to be seen at least yearly and care needs to be coordinated with all other providers. The physical examination includes elements particular to survivorship. The growth velocity should be assessed with as many growth points as possible, given that precocious puberty can mask by increasing the growth rate of concomitant growth hormone deficiency. Increased waist–to–hip and waist–to–height ratios are predictors of metabolic syndrome and should be obtained. A sitting height should be measured in patients with a history of irradiation to the spine (as following total body irradiation). Depending on the type of exposure, pubertal assessment in boys and men cannot entirely rely on testicular volume measurements given the risk of germ cell failure.
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Based on the history, the child’s complaints, growth pattern and clinical examination, further investigations can be planned. If growth hormone deficiency is suspected, children should undergo growth hormone stimulation testing as include insulin-like growth factor I levels do not represent a reliable screening tool in this population. Additional tests include: fasting glucose and insulin; lipids; thyroid-stimulating hormone; free T4; cortisol and adrenocorticotropic hormone drawn at 8 a.m.; luteinizing hormone; follicle-stimulating hormone; testosterone; estradiol; and a bone age X-ray for children who have not completed their growth. Bone mineral density studies using DXA are periodically performed in patients deemed at risk for osteoporosis (long-term exposure to systemic steroids, patients with a history of multiple or non-provoked fractures) and interpreted using the z score for chronologic age.
Wassim Chemaitilly, MD, is Assistant Professor of Pediatric Endocrinology at Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center.