Childhood cancer survivors should be screened long-term for endocrine disorders, according to new clinical practice guidelines from the Endocrine Society.
The document, published in the Journal of Clinical Endocrinology & Metabolism, notes that recent research suggests that as many as 50% of cancer survivors diagnosed in adolescence will develop an endocrine disorder later in life, due to the type of cancer and the treatment effects on endocrine organs, particularly those affecting the hypothalamus and pituitary gland.
Taking into account the individual patient’s clinical characteristics, cancer history, and treatment exposures, providers should regularly assess their patients for a wide range of endocrine disorders. For example, some of the most common endocrinopathies seen in childhood cancer survivors are growth disorders including short stature, growth hormone deficiency, central precocious puberty, hypogonadotropic hypogonadism, central hypothyroidism and thyroid stimulating hormone (TSH) deficiency, and adrenocorticotropic hormone deficiency (ACTHD).
“Our new guideline addresses the growing risk of endocrine disorders among childhood cancer survivors and suggests best practices for managing pituitary and growth disorders commonly found in this population,” the chairman of the writing committee, Charles Sklar, MD, of Memorial Sloan Kettering Cancer Center in New York City, said in a statement. “The guideline stresses the importance of life-long screening of these survivors for earlier detection and optimal patient care.”
Childhood cancer survivors are at a particularly high risk for impaired growth — highest for survivors of brain tumors — and should be regularly followed up to assess linear growth, including standing and sitting height, the guideline states. Exposure to treatments that include radiation involving the hypothalamic-pituitary region, spinal irradiation, total body irradiation, glucocorticoids, tyrosine kinase inhibitors, and retinoic acid are all tied to an increased risk for impaired growth. The document recommends against using growth hormones in patients without growth hormone deficiency or who are being treated with tyrosine kinase inhibitors, a suggestion based on lower-quality evidence.
As for survivors with growth hormone deficiency, those who were treated for tumors in the hypothalamic-pituitary axis and those exposed to hypothalamic-pituitary axis radiation at a dose of ≥18 Gy should be periodically assessed for growth hormone levels throughout the patient’s life, the guideline states. Height should also be assessed every 6 to 12 months in these patients. The guideline also recommends growth hormone treatment, but waiting until the patient is disease-free for 1 year before initiation.
Patients with a history of hydrocephalus, tumors developing in or close to the hypothalamic region, and/or who have been exposed to hypothalamic-pituitary radiation at a dose of ≥18 Gy should be regularly assessed for central precocious puberty, a recommendation based on moderate evidence. The guideline suggests measuring serum testosterone via liquid chromatography-tandem mass spectroscopy and luteinizing hormone levels as opposed to using testicular volume to assess for this condition causing early onset of puberty.
Patients who were exposed to hypothalamic-pituitary axis radiation at doses of ≥30 Gy, as well as patients with a history of tumors or surgery affecting the hypothalamic-pituitary axis region should undergo lifelong annual screening for luteinizing hormone and follicle-stimulating hormone deficiency, TSH deficiency, and ACTHD. Typical treatment strategies are recommended for managing all these conditions. However, when diagnosing a TSH deficiency, the guidelines advise against using serum triiodothyronine, TSH surge analysis, or thyrotropin-releasing hormone stimulation, a recommendation based on moderate evidence.
In order to better inform future clinical practice, the guideline also called for further research on the endocrine effects of some of the newer cancer treatments, such as targeted biologicals, immune modulators, and conformal radiation with protons.
The guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society, and endorsed by the Pituitary Society.
The guideline was supported by the Endocrine Society.
Primary Source
The Journal of Clinical Endocrinology & Metabolism
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