Guidelines for Management of Hypothalamic-Pituitary, Growth Disorders in Childhood Cancer Survivors

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Data indicate that up to half of all children who survive cancer will develop an endocrine disorder during their lifetime.
Data indicate that up to half of all children who survive cancer will develop an endocrine disorder during their lifetime.

A clinical practice guideline that addresses the diagnosis and treatment of hypothalamic–pituitary and growth disorders that are often observed in childhood cancer survivors has been issued by the Endocrine Society and published in The Journal of Endocrinology and Metabolism.

Investigators note that the 5-year survival rates for childhood cancer are currently approximately 80%, but recent data indicate that 40% to 50% of survivors will develop an endocrine disorder at some point in their lives.  While a large number of high-quality studies evaluating these issues have informed this guideline, most papers have focused on understanding the prevalence and risk factors for the various outcomes with fewer looking at diagnosis and patient management.

Their key recommendations are as follows:

  • Short stature/impaired linear growth in a childhood cancer survivor — a prospective follow-up of linear growth for childhood cancer survivors at high risk for short adult height is recommended, especially for those who were exposed to cranial radiation therapy, craniospinal irradiation, or total body irradiation at a young age, as well as patients with a history of inadequate weight gain or prolonged steroid requirement; growth hormone for short stature is not recommended in those who do not have growth hormone deficiency and/or poor linear growth following spinal irradiation. In addition, growth hormone for short stature and/or poor linear growth is not recommended in those being treated with tyrosine kinase inhibitors.
  • Growth hormone deficiency in childhood cancer survivors — lifelong periodic clinical assessment for growth hormone deficiency in survivors is recommended; discussing appropriateness of growth hormone treatment is advised as is treatment for those who are growth hormone deficient.  Relying only on serum insulin-like growth factor-1 levels in those exposed to hypothalamic-pituitary axis radiotherapy and using growth hormone alone or in combination with arginine to make a diagnosis of growth hormone deficiency is not recommended. 
  • Treatment of growth hormone deficiency in childhood cancer survivors — treatment with growth hormone in those with confirmed growth hormone deficiency is recommended.  Waiting until the patient has been disease free for 1 year after the completion of therapy for malignancy before treating with growth hormone is recommended.
  • Diagnosis of central precocious puberty in childhood cancer survivor — it is recommended that survivors be periodically assessed for evidence of central precocious puberty if they have a history of hydrocephalus, tumors developing in or near the hypothalamic region, and/or have been exposed to hypothalamic– pituitary radiation (measuring hormone levels in male survivors is recommended); treatment regimens for central precocious puberty in this population should be similar to those used in noncancer patients.
  • Diagnosis of luteinizing hormone/follicle-stimulating hormone deficiency  — screening for luteinizing hormone/follicle-stimulating hormone deficiency is recommended for those exposed to hypothalamic– pituitary axis radiation at doses of ≥30 Gy and for patients with a history of tumors or surgery affecting the hypothalamic–pituitary axis region; the treatment approach administered to the noncancer population is appropriate for survivors.
  • Diagnosis of central hypothyroidism in childhood cancer survivors — lifelong annual screening for thyroid-stimulating hormone deficiency is recommended in survivors who were treated for tumors in the hypothalamic–pituitary axis region and for those exposed to doses of hypothalamic–pituitary radiation ≥30 Gy; the same biochemical tests can be used to screen for thyroid-stimulating hormone deficiency in survivors as are used in the noncancer population. The use of triiodothyronine, thyroid-stimulating hormone surge analysis, or thyrotropin-releasing hormone stimulation is not recommended for diagnosis; the same treatment regimen can be used in survivors as is used in the noncancer population.  
  • Diagnosing adrenocorticotropic hormone deficiency in childhood cancer survivors — lifelong annual screening is recommended for adrenocorticotropic hormone deficiency in those who were treated for tumors in the hypothalamic–pituitary region and in those exposed to hypothalamic–pituitary radiation ≥30 Gy; screening for adrenocorticotropic hormone deficiency is suggested for survivors who were exposed to between 24 Gy and 30 Gy hypothalamic–pituitary radiation and who are >10 years postradiation or who have developed symptoms suggestive of adrenocorticotropic hormone deficiency. Clinicians are advised to use the same glucocorticoid regimens as replacement therapy in this population as is used in the noncancer population.

 

“Additional areas requiring further research include: management of impaired growth following spinal radiation and in those receiving long-term therapy with tyrosine kinase [inhibitors] such as imatinib; optimal frequency and duration of screening studies following [hypothalamic-pituitary] radiation; and risks and benefits of [growth hormone treatment] in adult survivors of childhood cancer,” write the authors.

Reference

Sklar CA, Antal Z, Chemaitilly W, et al. Hypothalamic–pituitary and growth disorders in survivors of childhood cancer: an Endocrine Society clinical practice guideline [published online June 29, 2018].  J Clin Endocrinol Metab. doi: 10.1210/jc.2018-01175

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