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Growth Hormone Deficiency in Young Cancer Survivors

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Late Treatment Effects and Cancer Survivor Care in the Young

Abstract

Growth hormone (GH) deficiency (GHD) is the most common late endocrine complication in childhood cancer survivors (CCS). We here review the etiologies, consequences, biological assessment, and treatment of GHD in adult CCS. In summary, screening of GHD should be proposed for every patient treated by cranial irradiation and surgery of the pituitary-hypothalamic area. Since chemotherapy and any brain tumor surgery may lead to GHD, this recommendation might be extended to every CCS. GHD contributes to the alteration of quality of life (QOL) and health status observed in CCS. GH therapy improves metabolic profile, bone mineralization, muscular performance, and QOL in adult GHD. Meta-analysis and pharmaceutical companies’ prospective databases of adult GH replacement are reassuring about the risk of second malignancies and recurrence. Reimbursement of GH therapy is currently restrained in most countries to patients with severe GHD (GH <3 ng/mL during an insulin tolerance test) associated with at least another pituitary deficiency. Initiation and follow-up of GH therapy by a specialist team in adult GHD and hypopituitarism is advised. Combined clinical, biological and safety monitoring is performed in the absence of a specific marker of responsiveness in adults as is the growth rate in children.

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References

  1. Mostoufi-Moab S, et al. Endocrine abnormalities in aging survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(27):3240–7.

    Article  Google Scholar 

  2. Hudson MM, et al. Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA. 2013;309(22):2371–81.

    Article  CAS  Google Scholar 

  3. de Fine LS, et al. Long-term inpatient disease burden in the adult life after childhood cancer in Scandinavia (ALiCCS) study: a cohort study of 21,297 childhood cancer survivors. PLoS Med. 2017;14(5):e1002296.

    Article  Google Scholar 

  4. Chemaitilly W, et al. Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude lifetime cohort study. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(5):492–500.

    Article  Google Scholar 

  5. Clement SC, et al. Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(36):4362–70.

    Article  Google Scholar 

  6. de Fine Licht S, et al. Hospital contacts for endocrine disorders in adult life after childhood cancer in Scandinavia (ALiCCS): a population-based cohort study. Lancet Lond Engl. 2014;383(9933):1981–9.

    Article  Google Scholar 

  7. Rose SR, et al. Late endocrine effects of childhood cancer. Nat Rev Endocrinol. 2016;12(6):319–36.

    Article  CAS  Google Scholar 

  8. Oeffinger KC, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–82.

    Article  CAS  Google Scholar 

  9. Gurney JG, et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: childhood cancer survivor study. Cancer. 2003;97(3):663–73.

    Article  Google Scholar 

  10. Devesa J, et al. Multiple effects of growth hormone in the body: is it really the hormone for growth? Clin Med Insights Endocrinol Diabetes. 2016;9:47–71.

    Article  CAS  Google Scholar 

  11. Evans HM, Long JA. The effect of the anterior lobe administered intraperitoneally upon growth, maturity and oestrus cycles of the rat. Anat Rec. 1921;21(1):62–3.

    Google Scholar 

  12. Li CH, Evans HM. The isolation of pituitary growth hormonE. Science. 1944;99(2566):183–4.

    Article  CAS  Google Scholar 

  13. Murray PG, et al. 60 years of neuroendocrinology: the hypothalamo-GH axis: the past 60 years. J Endocrinol. 2015;226(2):T123–40.

    Article  CAS  Google Scholar 

  14. Samaan NA, et al. Hypopituitarism after external irradiation. Evidence for both hypothalamic and pituitary origin. Ann Intern Med. 1975;83(6):771–7.

    Article  CAS  Google Scholar 

  15. Shalet SM, et al. The effect of varying doses of cerebral irradiation on growth hormone production in childhood. Clin Endocrinol. 1976;5(3):287–90.

    Article  CAS  Google Scholar 

  16. Leung W, et al. Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(13):2959–64.

    Article  CAS  Google Scholar 

  17. Merchant TE, et al. Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(36):4776–80.

    Article  CAS  Google Scholar 

  18. Darzy KH, Shalet SM. Pathophysiology of radiation-induced growth hormone deficiency: efficacy and safety of GH replacement. Growth Horm IGF Res. 2006;16(Suppl A):S30–40.

    Article  CAS  Google Scholar 

  19. Mulder RL, et al. Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treat Rev. 2009;35(7):616–32.

    Article  CAS  Google Scholar 

  20. Laughton SJ, et al. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(7):1112–8.

    Article  CAS  Google Scholar 

  21. Merchant TE, et al. Radiation dose-volume effects on growth hormone secretion. Int J Radiat Oncol Biol Phys. 2002;52(5):1264–70.

    Article  CAS  Google Scholar 

  22. Appelman-Dijkstra NM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(8):2330–40.

    Article  CAS  Google Scholar 

  23. Müller HL, et al. New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma. Nat Rev Endocrinol. 2017;13(5):299–312.

    Article  Google Scholar 

  24. Fleck SK, et al. Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland. BMC Endocr Disord. 2013;13:51.

    Article  Google Scholar 

  25. van den Heijkant S, et al. Effects of growth hormone therapy on bone mass, metabolic balance, and Well-being in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2011;33(6):e231–8.

    Article  CAS  Google Scholar 

  26. Román J, et al. Chemotherapy-induced growth hormone deficiency in children with cancer. Med Pediatr Oncol. 1995;25(2):90–5.

    Article  Google Scholar 

  27. Rose SR, et al. Hypothalamic dysfunction after chemotherapy. J Pediatr Endocrinol Metab. 2004;17(1):55–66.

    Article  Google Scholar 

  28. Jarfelt M, et al. Young adult survivors of childhood acute lymphoblastic leukemia: spontaneous GH secretion in relation to CNS radiation. Pediatr Blood Cancer. 2004;42(7):582–8.

    Article  CAS  Google Scholar 

  29. Haddy TB, et al. Growth hormone deficiency after chemotherapy for acute lymphoblastic leukemia in children who have not received cranial radiation. Pediatr Blood Cancer. 2006;46(2):258–61.

    Article  Google Scholar 

  30. Ceppi F, et al. Opportunities and challenges in the immunological therapy of pediatric malignancy: a concise snapshot. Eur J Pediatr. 2017;176(9):1163–72.

    Article  CAS  Google Scholar 

  31. Majzner RG, et al. Harnessing the immunotherapy revolution for the treatment of childhood cancers. Cancer Cell. 2017;31(4):476–85.

    Article  CAS  Google Scholar 

  32. Ring EK, et al. Checkpoint proteins in pediatric brain and extracranial solid tumors: opportunities for immunotherapy. Clin Cancer Res. 2017;23(2):342–50.

    Article  CAS  Google Scholar 

  33. Faje A. Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights. Pituitary. 2016;19(1):82–92.

    Article  CAS  Google Scholar 

  34. Merchant MS, et al. Phase I clinical trial of ipilimumab in pediatric patients with advanced solid tumors. Clin Cancer Res. 2016;22(6):1364–70.

    Article  CAS  Google Scholar 

  35. Mulrooney DA, et al. The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude lifetime cohort study. Lancet Haematol. 2019;6(6):e306–16.

    Article  Google Scholar 

  36. Gurney JG, et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006;107(6):1303–12.

    Article  CAS  Google Scholar 

  37. Jarfelt M, et al. Body composition in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol. 2005;153(1):81–9.

    Article  CAS  Google Scholar 

  38. Maiter D, et al. Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database. Eur J Endocrinol. 2006;155(2):253–60.

    Article  CAS  Google Scholar 

  39. Murray RD, et al. GH-deficient survivors of childhood cancer: GH replacement during adult life. J Clin Endocrinol Metab. 2002;87(1):129–35.

    Article  CAS  Google Scholar 

  40. Ness KK, et al. Body composition, muscle strength deficits and mobility limitations in adult survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2007;49(7):975–81.

    Article  Google Scholar 

  41. Follin C, et al. Cardiovascular risk, cardiac function, physical activity, and quality of life with and without long-term growth hormone therapy in adult survivors of childhood acute lymphoblastic leukemia. J Clin Endocrinol Metab. 2010;95(8):3726–35.

    Article  CAS  Google Scholar 

  42. Taskinen M, et al. Insufficient growth hormone secretion is associated with metabolic syndrome after allogeneic stem cell transplantation in childhood. J Pediatr Hematol Oncol. 2007;29(8):529–34.

    Article  CAS  Google Scholar 

  43. Follin C, et al. Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy. Eur J Endocrinol. 2011;164(5):695–703.

    Article  CAS  Google Scholar 

  44. Link K, et al. Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood. J Clin Endocrinol Metab. 2004;89(10):5003–12.

    Article  CAS  Google Scholar 

  45. Kargi AY, Merriam GR. Diagnosis and treatment of growth hormone deficiency in adults. Nat Rev Endocrinol. 2013;9(6):335–45.

    Article  CAS  Google Scholar 

  46. Molitch ME, et al. Endocrine Society. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587–609.

    Article  CAS  Google Scholar 

  47. Darzy KH, et al. The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab. 2003;88(1):95–102.

    Article  CAS  Google Scholar 

  48. Sfeir JG, et al. Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers. J Clin Endocrinol Metab. 2018;103(8):2785–93.

    Article  Google Scholar 

  49. Garcia JM, et al. Macimorelin as a diagnostic test for adult GH deficiency. J Clin Endocrinol Metab. 2018;103(8):3083–93.

    Article  Google Scholar 

  50. Ho KKY. 2007 GH deficiency consensus workshop participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH research society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. 2007;157(6):695–700.

    Article  CAS  Google Scholar 

  51. Philip S, et al. An audit of growth hormone replacement for GH-deficient adults in Scotland. Clin Endocrinol. 2013;78(4):571–6.

    Article  CAS  Google Scholar 

  52. Clayton PE, et al. Consensus statement on the management of the GH-treated adolescent in the transition to adult care. Eur J Endocrinol. 2005;152(2):165–70.

    Article  CAS  Google Scholar 

  53. Appelman-Dijkstra NM, et al. Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. Eur J Endocrinol. 2013;169(1):R1–14.

    Article  CAS  Google Scholar 

  54. van Bunderen CC, et al. Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity. Clin Endocrinol. 2014;81(1):1–14.

    Article  CAS  Google Scholar 

  55. Filipsson Nyström H, et al. Discontinuing long-term GH replacement therapy—a randomized, placebo-controlled crossover trial in adult GH deficiency. J Clin Endocrinol Metab. 2012;97(9):3185–95.

    Article  CAS  Google Scholar 

  56. Götherström G, et al. Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency. Eur J Endocrinol. 2007;156(1):55–64.

    Article  CAS  Google Scholar 

  57. Follin C, et al. Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after two years of growth hormone (GH) treatment in GH-deficient adult survivors of childhood-onset acute lymphoblastic leukemia. J Clin Endocrinol Metab. 2006;91(5):1872–5.

    Article  CAS  Google Scholar 

  58. Tamhane S, et al. GH therapy in childhood cancer survivors: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2018;103(8):2794–801.

    Article  Google Scholar 

  59. Mukherjee A, et al. The characteristics of quality of life impairment in adult growth hormone (GH)-deficient survivors of cancer and their response to GH replacement therapy. J Clin Endocrinol Metab. 2005;90(3):1542–9.

    Article  CAS  Google Scholar 

  60. Huisman J, et al. The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study. BMC Pediatr. 2008;8:25.

    Article  Google Scholar 

  61. Gasco V, et al. Management of GH treatment in adult GH deficiency. Best Pract Res Clin Endocrinol Metab. 2017;31(1):13–24.

    Article  CAS  Google Scholar 

  62. Clayton PE, et al. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol. 2011;7(1):11–24.

    Article  CAS  Google Scholar 

  63. Olsen JH, et al. Lifelong cancer incidence in 47,697 patients treated for childhood cancer in the Nordic countries. J Natl Cancer Inst. 2009;101(11):806–13.

    Article  Google Scholar 

  64. Krzyzanowska-Mittermayer K, et al. New Neoplasm During GH Replacement in Adults With Pituitary Deficiency Following Malignancy: A KIMS Analysis. J Clin Endocrinol Metab. 2018;103(2):523–31.

    Article  Google Scholar 

  65. Sklar CA, et al. Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study. J Clin Endocrinol Metab. 2002;87(7):3136–41.

    Article  CAS  Google Scholar 

  66. Stochholm K, Kiess W. Long-term safety of growth hormone-A combined registry analysis. Clin Endocrinol (Oxf). 2018;88:515–28.

    Article  Google Scholar 

  67. Stochholm K, Johannsson G. Reviewing the safety of GH replacement therapy in adults. Growth Horm IGF Res. 2015;25(4):149–57.

    Article  CAS  Google Scholar 

  68. Ergun-Longmire B, et al. Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab. 2006;91(9):3494–8.

    Article  CAS  Google Scholar 

  69. Patterson BC, et al. Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J Clin Endocrinol Metab. 2014;99(6):2030–7.

    Article  CAS  Google Scholar 

  70. Erfurth EM. Update in mortality in GH-treated patients. J Clin Endocrinol Metab. 2013;98(11):4219–26.

    Article  CAS  Google Scholar 

  71. Olsson DS, et al. Life expectancy in patients with pituitary adenoma receiving growth hormone replacement. Eur J Endocrinol. 2017;176(1):67–75.

    Article  CAS  Google Scholar 

  72. Stochholm K, et al. Socioeconomic factors do not but GH treatment does affect mortality in adult-onset growth hormone deficiency. J Clin Endocrinol Metab. 2014;99(11):4141–8.

    Article  CAS  Google Scholar 

  73. Carel J-C, et al. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab. 2012;97(2):416–25.

    Article  CAS  Google Scholar 

  74. Allen DB, et al. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol. 2016;174(2):P1–9.

    Article  CAS  Google Scholar 

  75. Stochholm K, et al. Mortality and socioeconomic status in adults with childhood onset GH deficiency (GHD) is highly dependent on the primary cause of GHD. Eur J Endocrinol. 2012;167(5):663–70.

    Article  CAS  Google Scholar 

  76. Cook DM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients—2009 update. Endocr Pract. 2009;15(Suppl 2):1–29.

    Article  Google Scholar 

  77. Barbosa EJL, et al. Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults. Eur J Endocrinol. 2010;162(5):869–78.

    Article  CAS  Google Scholar 

  78. Leung K-C, et al. Estrogen regulation of growth hormone action. Endocr Rev. 2004;25(5):693–721.

    Article  CAS  Google Scholar 

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Espiard, S., Jarfelt, M., Johannsson, G. (2021). Growth Hormone Deficiency in Young Cancer Survivors. In: Beck, J.D., Bokemeyer, C., Langer, T. (eds) Late Treatment Effects and Cancer Survivor Care in the Young. Springer, Cham. https://doi.org/10.1007/978-3-030-49140-6_7

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  • DOI: https://doi.org/10.1007/978-3-030-49140-6_7

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