Ann Pediatr Endocrinol Metab.  2023 Jun;28(2):116-123. 10.6065/apem.2244028.014.

Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiency

• Shin C
• Jang MJ
• Kim S
• Lee JW
• Chung NG
• Cho B
• Jung MH
• Suh BK
• Ahn MB

• KMID: 2543292
• DOI: http://doi.org/10.6065/apem.2244028.014

Abstract

Purpose
Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment.
Methods
A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population.
Results
Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment.
Conclusion
GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.

Keyword

Leukemia; Growth hormone deficiency; Growth hormone treatment; Height

Figure

• 

  Fig. 1. Difference in height status between growth hormone-treated patients and untreated patients. SDS, standard deviation score.

Reference

References

1. Chemaitilly W, Cohen LE, Mostoufi-Moab S, Patterson BC, Simmons JH, Meacham LR, et al. Endocrine late effects in childhood cancer survivors. J Clin Oncol. 2018; 36:2153–9.

2. Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004; 350:1535–48.

3. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015; 373:1541–52.

4. Tallman MS. Myeloid diseases. Curr Opin Hematol. 2005; 12:31–2.

5. Diller L, Chow EJ, Gurney JG, Hudson MM, Kadin-Lottick NS, Kawashima TI, et al. Chronic disease in the Childhood Cancer Survivor Study cohort: a review of published findings. J Clin Oncol. 2009; 27:2339–55.

6. Schriock EA, Schell MJ, Carter M, Hustu O, Ochs JJ. Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia. J Clin Oncol. 1991; 9:400–5.

7. Sklar CA, Antal Z, Chemaitilly W, Cohen LE, Follin C, Meacham LR, et al. Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103:2761–4.

8. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab. 2000; 85:3990–3.

9. Ranke MB. Short and long-term effects of growth hormone in children and adolescents with GH deficiency. Front Endocrinol (Lausanne). 2021; 12:720419.

10. Brämswig JH, Schlösser H, Kiese K. Final height in children with growth hormone deficiency. Horm Res. 1995; 43:126–8.

11. MacGillivray MH, Blethen SL, Buchlis JG, Clopper RR, Sandberg DE, Conboy TA. Current dosing of growth hormone in children with growth hormone deficiency: how physiologic? Pediatrics. 1998; 102(2 Pt 3):527–30.

12. Ranke MB, Lindberg A, Mullis PE, Geffner ME, Tanaka T, Cutfield WS, et al. Towards optimal treatment with growth hormone in short children and adolescents: evidence and theses. Horm Res Paediatr. 2013; 79:51–67.

13. Ranke MB, Wit JM. Growth hormone - past, present and future. Nat Rev Endocrinol. 2018; 14:285–300.

14. Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab. 1998; 83:379–81.

15. Mukherjee A, Tolhurst-Cleaver S, Ryder WD, Smethurst L, Shalet SM. 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; 90:1542–9.

16. Darzy KH, Shalet SM. Radiation-induced growth hormone deficiency. Horm Res. 2003; 59 Suppl 1:1–11.

17. Haddy TB, Mosher RB, Nunez SB, Reaman GH. Growth hormone deficiency after chemotherapy for acute lymphoblastic leukemia in children who have not received cranial radiation. Pediatr Blood Cancer. 2006; 46:258–61.

18. Didi M, Brennan B, Shalet S. Growth hormone replacement in children treated for leukemia in childhood. Horm Res. 1997; 48:65.

19. Adan L, Souberbielle JC, Blanche S, Leverger G, Schaison G, Brauner R. Adult height after cranial irradiation with 24 Gy: factors and markers of height loss. Acta Paediatr. 1996; 85:1096–101.

20. Kim JH, Yun S, Hwang SS, Shim JO, Chae HW, Lee YJ, et al. The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr. 2018; 61:135–49.

21. Hyun SE, Lee BC, Suh BK, Chung SC, Ko CW, Kim HS, et al. Reference values for serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Korean children and adolescents. Clin Biochem. 2012; 45:16–21.

22. Viana MB, Vilela MI. Height deficit during and many years after treatment for acute lymphoblastic leukemia in children: a review. Pediatr Blood Cancer. 2008; 50(2 Suppl):509–16. discussion 517.

23. Tamhane S, Sfeir JG, Kittah NEN, Jasim S, Chemaitilly W, Cohen LE, et al. GH therapy in childhood cancer survivors: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2018; 103:2794–801.

24. Gurney JG, Ness KK, Sibley SD, O'Leary M, Dengel DR, Lee JM, et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006; 107:1303–12.

25. Follin C, Thilén U, Ahrén B, Erfurth EM. 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; 91:1872–5.

26. Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994; 125:29–35.

27. Vimpani GV, Vimpani AF, Lidgard GP, Cameron EH, Farquhar JW. Prevalence of severe growth hormone deficiency. Br Med J. 1977; 2:427–30.

28. Mulder RL, Kremer LC, van Santen HM, Ket JL, van Trotsenburg AS, Koning CC, et al. Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treat Rev. 2009; 35:616–32.

29. Damasio I, Cavaco D, Maciel J, Dias D, Donato S, Pinheiro S, editors. Growth hormone deficiency in childhood acute lymphoblastic leukemia survivors–should systematic stimulation test be performed in all irradiated children? Endocr Abstr. 2020; 70:AEP620.

30. Cianfarani S. Risk of cancer in patients treated with recombinant human growth hormone in childhood. Ann Pediatr Endocrinol Metab. 2019; 24:92–8.

31. Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, et al. Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med. 2008; 149:461–71. W83–8.

32. Endogenous Hormones and Breast Cancer Collaborative Group, Key TJ, Appleby PN, Reeves GK, Roddam AW. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol. 2010; 11:530–42.

33. Rinaldi S, Cleveland R, Norat T, Biessy C, Rohrmann S, Linseisen J, et al. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int J Cancer. 2010; 126:1702–15.

34. Chen B, Liu S, Xu W, Wang X, Zhao W, Wu J. IGF-I and IGFBP-3 and the risk of lung cancer: a meta-analysis based on nested case-control studies. J Exp Clin Cancer Res. 2009; 28:89.

35. Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol. 2011; 7:11–24.

36. Nishi Y, Tanaka T. Growth hormone treatment and adverse events. Pediatr Endocrinol Rev. 2017; 14 Suppl 1(Suppl 1):235–9.

37. Brignardello E, Felicetti F, Castiglione A, Fortunati N, Matarazzo P, Biasin E, et al. GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution. J Endocrinol Invest. 2015; 38:171–6.