ESPEYB20 7. Oncology and Chronic Disease Long-Term Surveillance for Endocrine Complications in Childhood Cancer Survivors (3 abstracts)
7.14. Hypothalamic-pituitary and other endocrine surveillance among childhood cancer survivors
van Iersel L , Mulder RL , Denzer C , Cohen LE , Spoudeas HA , Meacham LR , Sugden E , Schouten-van Meeteren AYN , Hoving EW , Packer RJ , Armstrong GT , Mostoufi-Moab S , Stades AM , van Vuurden D , Janssens GO , Thomas-Teinturier C , Murray RD , Di Iorgi N , Neggers SJCMM , Thompson J , Toogood AA , Gleeson H , Follin C , Bardi E , Torno L , Patterson B , Morsellino V , Sommer G , Clement SC , Srivastava D , Kiserud CE , Fernandez A , Scheinemann K , Raman S , Yuen KCJ , Wallace WH , Constine LS , Skinner R , Hudson MM , Kremer LCM , Chemaitilly W & van Santen HM
h.m.vansanten@umcutrecht.nl Endocr Rev. 2022 Sep 26;43(5):794–823.
Brief summary: In this extensive and updated review, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) report expert consensus-based guidelines that harmonize recommendations for surveillance of endocrine disorders in childhood cancer survivors.
This interdisciplinary panel of 42 international experts formulated new surveillance recommendations for hypothalamic–pituitary (HP) dysfunction. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer were summarized. The essential points of the review are:
• Whenever possible, young survivors with a history of CNS tumor or surgery near or within the HP area, or treated with radiation therapy to the HP region, should be referred to an endocrinologist or followed by a multidisciplinary team including an endocrinologist due to the high risk of developing HP dysfunction.
• The impact of chemotherapy on endocrine organs is controversial and evidence is scarce. There is low quality evidence that chemotherapy in addition to radiotherapy does not increase the risk of growth hormone deficiency, ACTH deficiency or central precocious puberty in patients with CNS tumors. No studies have robustly analyzed the risk of central hypothyroidism or hypogonadotropic hypogonadism after chemotherapy only.
• Screening should start 1 year after the completion of radiotherapy or from diagnosis in survivors with CNS tumors treated with surgery near or within the HP region.
• Screening should be scheduled every 6 months in prepubertal and pubertal survivors, and every year in post-pubertal and adult survivors.
• Hormonal tests should always include FT4, TSH and morning cortisol. Morning testosterone and LH should be added in adult males; estradiol, FSH and LH should be added in adult females.
• Height velocity and pubertal development are the most important clinical outcomes to evaluate in children.
• Although IGF-I and IGFBP-3 have high specificity to detect growth hormone deficiency in children, their sensitivity in cancer survivors is low, potentially leading to underdiagnosis. This especially happens when early or precocious puberty is present and height velocity is apparently normal, but is inappropriately low for pubertal stage. Pubertal stage and other confounders (i.e., impaired spinal growth due to previous irradiation) should be correctly evaluated when interpreting height velocity in cancer survivors.
Interestingly, the use of provocative tests to diagnose growth hormone deficiency in prepubertal and pubertal cancer survivors is not mentioned in this review. The attention is focused exclusively on height velocity, as the essential parameter to correctly diagnose growth hormone deficiency.
No recommendations are formulated for HP dysfunction following newer treatment modalities, including specific types of radiotherapy (i.e. proton vs photon therapy) or targeted biologicals and immune modulators. Immunotherapy and molecular targeted therapies are rapidly evolving and becoming standard treatment options for different types of cancer. Checkpoint inhibitors can cause hypophysitis within weeks or months after the initiation of therapy, and the resulting HP dysfunction is potentially irreversible. The adverse effects of these new drugs need to be extensively investigated to inform surveillance recommendations.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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