Skip to main content
SpringerLink
Log in

Clinical experience of growth hormone replacement for pediatric intracranial germ cell tumor

  • Original Article
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Purpose

Intracranial germ cell tumors (IGCTs) account for 8–15% of brain tumors in children in Eastern Asia and typically occur at the age of puberty. Recently, adjuvant therapy has been modified to ameliorate post-treatment complications such as cognitive dysfunction, in patients with IGCT. However, endocrine problems remain to be resolved. There is reluctance to use growth hormone (GH) at an early stage after treatment for IGCT because of the risk of tumor recurrence; however, GH replacement must be administered before the onset of puberty in children with short stature. There is little guidance on this issue due to a lack of literature on the risks of GH replacement therapy in patients with IGCT. This study aimed to evaluate the safety of GH replacement.

Methods

In this retrospective study, 6 patients with IGCT who were under the age of 18 years when they started GH replacement therapy were reviewed. Histopathological analysis and/or analysis of tumor markers was used to confirm a diagnosis.

Results

All six cases who underwent GH replacement therapy showed no recurrence. GH replacement therapy was administered in 5 patients for short stature and all achieved a height within ± 2.0 standard deviation.

Conclusion

GH replacement for children with IGCT was safe in our case series. Placental alkaline phosphatase levels in cerebrospinal fluid can be used to facilitate the decision on when to initiate GH replacement.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Liu B, Arakawa Y, Yokogawa R, Tokunaga S, Terada Y, Murata D, Matsui Y, Fujimoto KI, Fukui N, Tanji M, Mineharu Y, Minamiguchi S, Miyamoto S (2018) PD-1/PD-L1 expression in a series of intracranial germinoma and its association with Foxp3+ and CD8+ infiltrating lymphocytes. PLoS One 13:e0194594

    Article  PubMed  PubMed Central  Google Scholar 

  2. Phi JH, Wang KC, Kim SK (2018) Intracranial germ cell tumor in the molecular era. J Korean Neurosurg Soc 61:333–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Odagiri K, Omura M, Hata M, Aida N, Niwa T, Ogino I, Kigasawa H, Ito S, Adachi M, Inoue T (2012) Treatment outcomes, growth height, and neuroendocrine functions in patients with intracranial germ cell tumors treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys 84:632–638

    Article  CAS  PubMed  Google Scholar 

  4. Packer RJ, Cohen BH, Cooney K (2000) Intracranial germ cell tumors. Oncologist 5:312–320

    Article  CAS  PubMed  Google Scholar 

  5. Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86:446–455

    Article  CAS  PubMed  Google Scholar 

  6. Liu APY, Hastings C, Wu S, Bass JK, Heitzer AM, Ashford J, Vestal R, Hoehn ME, Ghazwani Y, Acharya S, Conklin HM, Boop F, Merchant TE, Gajjar A, Qaddoumi I (2019) Treatment burden and long-term health deficits of patients with low-grade gliomas or glioneuronal tumors diagnosed during the first year of life. Cancer 125:1163–1175

    Article  PubMed  Google Scholar 

  7. Bogarin R, Steinbok P (2009) Growth hormone treatment and risk of recurrence or progression of brain tumors in children: a review. Childs Nerv Syst 25:273–279

    Article  PubMed  Google Scholar 

  8. Sklar CA, Mertens AC, Mitby P, Occhiogrosso G, Qin J, Heller G, Yasui Y, Robison LL (2002) 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 87:3136–3141

    Article  CAS  PubMed  Google Scholar 

  9. Gleeson HK, Stoeter R, Ogilvy-Stuart AL, Gattamaneni HR, Brennan BM, Shalet SM (2003) Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. J Clin Endocrinol Metab 88:3682–3689

    Article  CAS  PubMed  Google Scholar 

  10. Geffner M, Lundberg M, Koltowska-Haggstrom M, Abs R, Verhelst J, Erfurth EM, Kendall-Taylor P, Price DA, Jonsson P, Bakker B (2004) Changes in height, weight, and body mass index in children with craniopharyngioma after three years of growth hormone therapy: analysis of KIGS (Pfizer International Growth Database). J Clin Endocrinol Metab 89:5435–5440

    Article  CAS  PubMed  Google Scholar 

  11. Indini A, Schiavello E, Biassoni V, Bergamaschi L, Magni MC, Puma N, Chiaravalli S, Pallotti F, Seregni E, Diletto B, Pecori E, Gandola L, Poggi G, Massimino M (2017) Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns. J Neuro-Oncol 131:349–357

    Article  CAS  Google Scholar 

  12. Darendeliler F, Karagiannis G, Wilton P, Ranke MB, Albertsson-Wikland K, Anthony Price D, On Behalf Of The Kigs International B (2006) Recurrence of brain tumours in patients treated with growth hormone: analysis of KIGS (Pfizer International Growth Database). Acta Paediatr 95:1284–1290

    Article  PubMed  Google Scholar 

  13. Swerdlow AJ, Reddingius RE, Higgins CD, Spoudeas HA, Phipps K, Qiao Z, Ryder WD, Brada M, Hayward RD, Brook CG, Hindmarsh PC, Shalet SM (2000) Growth hormone treatment of children with brain tumors and risk of tumor recurrence. J Clin Endocrinol Metab 85:4444–4449

    CAS  PubMed  Google Scholar 

  14. Friend KE, Radinsky R, McCutcheon IE (1999) Growth hormone receptor expression and function in meningiomas: effect of a specific receptor antagonist. J Neurosurg 91:93–99

    Article  CAS  PubMed  Google Scholar 

  15. Sklar CA, Antal Z, Chemaitilly W, Cohen LE, Follin C, Meacham LR, Murad MH (2018) Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 103:2761–2784

    Article  PubMed  Google Scholar 

  16. Child CJ, Conroy D, Zimmermann AG, Woodmansee WW, Erfurth EM, Robison LL (2015) Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the hypopituitary control and complications study. Eur J Endocrinol 172:779–790

    Article  CAS  PubMed  Google Scholar 

  17. Yuen KCJ, Biller BMK, Radovick S, Carmichael JD, Jasim S, Pantalone KM, Hoffman AR (2019) American Association of Clinical Endocrinologists and American College of endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care. Endocr Pract 25:1191–1232

    Article  PubMed  Google Scholar 

  18. Aihara Y, Watanabe S, Amano K, Komatsu K, Chiba K, Imanaka K, Hori T, Ohba T, Dairoku H, Okada Y, Kubo O, Kawamata T (2018) Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors. J Neurosurg:1–8

  19. Richmond EJ, Rogol AD (2008) Growth hormone deficiency in children. Pituitary 11:115–120

    Article  CAS  PubMed  Google Scholar 

  20. Ogata T, Tanaka T, Kagami M (2007) Target height and target range for Japanese children: revisited. Clin Pediatr Endocrinol 16:85–87

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cameron N (1993) The Tanner-Whitehouse II skeletal maturity method: rationale and applicability. Clin Pediatr Endocrinol 2:9–18

    Article  Google Scholar 

  22. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pfaffle R (2015) Hormone replacement therapy in children: the use of growth hormone and IGF-I. Best Pract Res Clin Endocrinol Metab 29:339–352

    Article  PubMed  Google Scholar 

  24. Li Q, You C, Liu L, Rao Z, Sima X, Zhou L, Xu J (2013) Craniopharyngioma cell growth is promoted by growth hormone (GH) and is inhibited by tamoxifen: involvement of growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R). J Clin Neurosci 20:153–157

    Article  CAS  PubMed  Google Scholar 

  25. Cohen P, Clemmons DR, Rosenfeld RG (2000) Does the GH-IGF axis play a role in cancer pathogenesis? Growth Hormon IGF Res 10:297–305

    Article  CAS  Google Scholar 

  26. Karavitaki N, Warner JT, Marland A, Shine B, Ryan F, Arnold J, Turner HE, Wass JA (2006) GH replacement does not increase the risk of recurrence in patients with craniopharyngioma. Clin Endocrinol 64:556–560

    Article  CAS  Google Scholar 

  27. Alotaibi NM, Noormohamed N, Cote DJ, Alharthi S, Doucette J, Zaidi HA, Mekary RA, Smith TR (2018) Physiologic growth hormone-replacement therapy and craniopharyngioma recurrence in pediatric patients: a meta-analysis. World Neurosurg 109:487–496 e481

    Article  PubMed  Google Scholar 

  28. Niu DM, Guo WY, Pan HC, Wong TT (2002) Rapid enlargement of a residual craniopharyngioma during short-term growth hormone replacement. Childs Nerv Syst 18:164–165

    Article  PubMed  Google Scholar 

  29. Olsson DS, Buchfelder M, Wiendieck K, Kremenevskaja N, Bengtsson BA, Jakobsson KE, Jarfelt M, Johannsson G, Nilsson AG (2012) Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up. Eur J Endocrinol 166:1061–1068

    Article  CAS  PubMed  Google Scholar 

  30. Calaminus G, Kortmann R, Worch J, Nicholson JC, Alapetite C, Garre ML, Patte C, Ricardi U, Saran F, Frappaz D (2013) SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro-Oncology 15:788–796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Muller HL, Gebhardt U, Schroder S, Pohl F, Kortmann RD, Faldum A, Zwiener I, Warmuth-Metz M, Pietsch T, Calaminus G, Kolb R, Wiegand C, Sorensen N, study committee of K (2010) Analyses of treatment variables for patients with childhood craniopharyngioma--results of the multicenter prospective trial KRANIOPHARYNGEOM 2000 after three years of follow-up. Horm Res Paediatr 73:175–180

    Article  PubMed  Google Scholar 

  32. Gupta S, Bi WL, Giantini Larsen A, Al-Abdulmohsen S, Abedalthagafi M, Dunn IF (2018) Craniopharyngioma: a roadmap for scientific translation. Neurosurg Focus 44:E12

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Kostadin Karagiozov, Mr. David Hang, and the staff of the Department of Neurosurgery at Tokyo Women’s Medical University for their guidance and assistance in preparing this paper.

Funding

This study was supported by research funds from the Department of Neurosurgery at Tokyo Women’s Medical University.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Tokyo Women’s Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo, 162-8666, Japan

    Kentaro Chiba, Yasuo Aihara & Takakazu Kawamata

Authors
  1. Kentaro Chiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuo Aihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takakazu Kawamata
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Kentaro Chiba, Yasuo Aihara, and Takakazu Kawamata. The first draft of the manuscript was written by Kentaro Chiba and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yasuo Aihara.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This study was approved by the Human Investigation Committee at our hospital and performed in accordance with the Declaration of Helsinki. Because of the retrospective nature of the study, the institutional review board waived the requirement for informed consent. To protect patient privacy, we removed all identifiers from our records upon completion of our analyses.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chiba, K., Aihara, Y. & Kawamata, T. Clinical experience of growth hormone replacement for pediatric intracranial germ cell tumor. Childs Nerv Syst 36, 1755–1760 (2020). https://doi.org/10.1007/s00381-020-04549-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-020-04549-y

Keywords

Search

Navigation