Prevalence and risk factors of hypothalamic–pituitary dysfunction in infant and toddler childhood brain tumor survivors

in European Journal of Endocrinology
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  • 1 Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
  • | 2 Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
  • | 3 Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
  • | 4 Department of Pediatric Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • | 5 Department of Pediatrics, Amalia Children’s Hospital, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  • | 6 Department of Radiation Oncology, Princess Máxima Centre for Pediatric Oncology, Utrecht, The Netherlands
  • | 7 Department of Neurosurgery, University Medical Center Utrecht, The Netherlands
  • | 8 Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
  • | 9 Neurosurgical Center Amsterdam, Amsterdam University Medical Centers, AMC, Amsterdam, The Netherlands

Correspondence should be addressed to H M van Santen Email h.m.vansanten@umcutrecht.nl
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Objective

Childhood brain tumor survivors (CBTS) are at risk to develop hypothalamic–pituitary (HP) dysfunction (HPD). The risk for HPD may vary between different age groups due to maturation of the brain and differences in oncologic treatment protocols. Specific studies on HPD in infant brain tumor survivors (infant-BTS, 0–1 years at diagnosis) or toddler brain tumor survivors (toddler-BTS, ≥1–3 years) have not been performed.

Patients and methods

A retrospective nationwide cohort study in CBTS was performed. Prevalence and risk factors for HPD were compared between infant-, toddler-, and older-BTS. Subgroup analysis was performed for all non-irradiated CBTS (n = 460).

Results

In total, 718 CBTS were included, with a median follow-up time of 7.9 years. Overall, despite the less frequent use of radiotherapy (RT) in infants, no differences in the prevalence of HPD were found between the three groups. RT (OR: 16.44; 95% CI: 8.93–30.27), suprasellar tumor location (OR: 44.76; 95% CI: 19.00–105.49), and younger age (OR: 1.11; 95% CI: 1.05–1.18) were associated with HP dysfunction. Infant-BTS and toddler-BTS showed more weight gain (P  < 0.0001) and smaller height SDS (P  = 0.001) during follow-up. In non-irradiated CBTS, infant-BTS and toddler-BTS were significantly more frequently diagnosed with TSH-, ACTH-, and ADH deficiency, compared to older-BTS.

Conclusion

Infant and toddler brain tumor survivors seem to be more vulnerable to develop HP dysfunction than older children. These results emphasize the importance of special infant and toddler brain tumor treatment protocols and the need for endocrine surveillance in children treated for a brain tumor at a young age.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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  • 1

    McKinney PA Brain tumours: incidence, survival, and aetiology. Journal of Neurology, Neurosurgery, and Psychiatry 2004 75 (Supplement 2) ii12ii17. (https://doi.org/10.1136/jnnp.2004.040741)

    • Search Google Scholar
    • Export Citation
  • 2

    Siegel DA, King J, Tai E, Buchanan N, Ajani UA, Li J. Cancer incidence rates and trends among children and adolescents in the United States, 2001–2009. Pediatrics 2014 134 e945e9 55. (https://doi.org/10.1542/peds.2013-3926)

    • Search Google Scholar
    • Export Citation
  • 3

    Central Brain Tumor Registry of the United States: 2018 CBTRUS Fact Sheet [Internet], 2018 [cited 2020 May 8]. (available at https://www.cbtrus.org/www.cbtrus.org/factsheet/factsheet.html)

    • Search Google Scholar
    • Export Citation
  • 4

    Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro-Oncology 2019 21 v1v100. (https://doi.org/10.1093/neuonc/noz150)

    • Search Google Scholar
    • Export Citation
  • 5

    Turner CD, Rey-Casserly C, Liptak CC, Chordas C. Late effects of therapy for pediatric brain tumor survivors. Journal of Child Neurology 2009 24 145514 63. (https://doi.org/10.1177/0883073809341709)

    • Search Google Scholar
    • Export Citation
  • 6

    Vinchon M, Baroncini M, Leblond P, Delestret I. Morbidity and tumor-related mortality among adult survivors of pediatric brain tumors: a review. Child’s Nervous System 2011 27 697704. (https://doi.org/10.1007/s00381-010-1385-6)

    • Search Google Scholar
    • Export Citation
  • 7

    Armstrong GT Long-term survivors of childhood central nervous system malignancies: the experience of the childhood cancer survivor study. European Journal of Paediatric Neurology 2010 14 298303. (https://doi.org/10.1016/j.ejpn.2009.12.006)

    • Search Google Scholar
    • Export Citation
  • 8

    Sklar CA Overview of the effects of cancer therapies: the nature, scale and breadth of the problem. Acta Paediatrica 1999 88 14. (https://doi.org/10.1111/j.1651-2227.1999.tb14395.x)

    • Search Google Scholar
    • Export Citation
  • 9

    Rutter MM, Rose SR. Long-term endocrine sequelae of childhood cancer. Current Opinion in Pediatrics 2007 19 48048 7. (https://doi.org/10.1097/MOP.0b013e3282058b56)

    • Search Google Scholar
    • Export Citation
  • 10

    Clement SC, Schouten-van Meeteren AY, Boot AM, Claahsen-van der Grinten HL, Granzen B, Sen Han K, Janssens GO, Michiels EM, van Trotsenburg AS, Vandertop WP et al. Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. Journal of Clinical Oncology 2016 34 436243 70. (https://doi.org/10.1200/JCO.2016.67.5025)

    • Search Google Scholar
    • Export Citation
  • 11

    Lustig RH, Post SR, Srivannaboon K, Rose SR, Danish RK, Burghen GA, Xiong X, Wu S, Merchant TE. Risk factors for the development of obesity in children surviving brain tumors. Journal of Clinical Endocrinology and Metabolism 2003 88 6116 16. (https://doi.org/10.1210/jc.2002-021180)

    • Search Google Scholar
    • Export Citation
  • 12

    Shalitin S, Gal M, Goshen Y, Cohen I, Yaniv I, Phillip M. Endocrine outcome in long-term survivors of childhood brain tumors. Hormone Research in Paediatrics 2011 76 1131 22. (https://doi.org/10.1159/000327584)

    • Search Google Scholar
    • Export Citation
  • 13

    Ishida Y, Sakamoto N, Kamibeppu K, Kakee N, Iwai T, Ozono S, Maeda N, Okamura J, Asami K & Inada H et al. Late effects and quality of life of childhood cancer survivors: part 2: impact of radiotherapy. International Journal of Hematology 2010 92 95104. (https://doi.org/10.1007/s12185-010-0611-z)

    • Search Google Scholar
    • Export Citation
  • 14

    Demoor-Goldschmidt C, Allodji RS, Journy N, Rubino C, Zrafi WS, Debiche G, Llanas D, Veres C, Thomas-Teinturier C & Pacquement H et al. Risk factors for small adult height in childhood cancer survivors. Journal of Clinical Oncology 2020 38 178517 96. (https://doi.org/10.1200/JCO.19.02361)

    • Search Google Scholar
    • Export Citation
  • 15

    Gurney JG, Ness KK, Stovall M, Wolden S, Punyko JA, Neglia JP, Mertens AC, Packer RJ, Robison LL, Sklar CA. Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study. Journal of Clinical Endocrinology and Metabolism 2003 88 4731473 9. (https://doi.org/10.1210/jc.2003-030784)

    • Search Google Scholar
    • Export Citation
  • 16

    World Health Organization growth reference 5–19 years [Internet]. (available at: https://www.who.int/growthref/who2007_bmi_for_age/en/)

    • Search Google Scholar
    • Export Citation
  • 17

    De Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bulletin of the World Health Organization 2007 85 660667. (https://doi.org/10.2471/blt.07.043497)

    • Search Google Scholar
    • Export Citation
  • 18

    Grigorenko EL Brain development: the effect of interventions on children and adolescents. In Disease Control Priorities, Third Edition (Volume 8): Child and Adolescent Health and Development, pp. 1191 32, 2017. Bundy DAP, Silva Nd, Horton S, et al. (Eds); Washington DC, USA: The International Bank for Reconstruction and Development / The World Bank.

    • Search Google Scholar
    • Export Citation
  • 19

    Van Iersel L, Li Z, Srivastava DK, Brinkman TM, Bjornard KL, Wilson CL, Green DM, Merchant TE, Pui CH & Howell RM et al. Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. Journal of Clinical Endocrinology and Metabolism 2019 104 61016115. (https://doi.org/10.1210/jc.2019-00834)

    • Search Google Scholar
    • Export Citation
  • 20

    Sklar CA, Antal Z, Chemaitilly W, Cohen LE, Follin C, Meacham LR, Hassan Murad MH. Hypothalamic–pituitary and growth disorders in survivors of childhood cancer: an Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism 2018 103 27612784. (https://doi.org/10.1210/jc.2018-01175)

    • Search Google Scholar
    • Export Citation
  • 21

    Gan HW, Phipps K, Aquilina K, Gaze MN, Hayward R, Spoudeas HA. Neuroendocrine morbidity after pediatric optic gliomas: a longitudinal analysis of 166 children over 30 years. Journal of Clinical Endocrinology and Metabolism 2015 100 37873799. (https://doi.org/10.1210/jc.2015-2028)

    • Search Google Scholar
    • Export Citation
  • 22

    Chemaitilly W, Li Z, Huang S, Ness KK, Clark KL, Green DM, Barnes N, Armstrong GT, Krasin MJ & Srivastava DK et al. Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the st Jude lifetime cohort study. Journal of Clinical Oncology 2015 33 492500. (https://doi.org/10.1200/JCO.2014.56.7933)

    • Search Google Scholar
    • Export Citation
  • 23

    Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, Robison LL, Sklar CA. Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study. Journal of Pediatrics 2007 150 370375, 375.e1. (https://doi.org/10.1016/j.jpeds.2006.11.036)

    • Search Google Scholar
    • Export Citation
  • 24

    Pietilä S, Mäkipernaa A, Koivisto AM, Lenko HL. Growth impairment and gonadal axis abnormalities are common in survivors of paediatric brain tumours. Acta Paediatrica 2017 106 16841693. (https://doi.org/10.1111/apa.13975)

    • Search Google Scholar
    • Export Citation
  • 25

    Chemaitilly W, Merchant TE, Li Z, Barnes N, Armstrong GT, Ness KK, Pui CH, Kun LE, Robison LL & Hudson MM et al. Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes. Clinical Endocrinology 2016 84 361371. (https://doi.org/10.1111/cen.12964)

    • Search Google Scholar
    • Export Citation
  • 26

    Ong KK, Emmett P, Northstone K, Golding J, Rogers I, Ness AR, Wells JC, Dunger DB. Infancy weight gain predicts childhood body fat and age at menarche in girls. Journal of Clinical Endocrinology and Metabolism 2009 94 15271532. (https://doi.org/10.1210/jc.2008-2489)

    • Search Google Scholar
    • Export Citation
  • 27

    Shalet SM, Brennan BMD. Growth and growth hormone status after a bone marrow transplant. Hormone Research 2002 58 (Supplement 1) 8690. (available at https://www.ncbi.nlm.nih.gov/pubmed/12373020). (https://doi.org/10.1159/000064768)

    • Search Google Scholar
    • Export Citation
  • 28

    Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M & Morrison J et al. Obesity and the metabolic syndrome in children and adolescents. New England Journal of Medicine 2004 350 23622374. (https://doi.org/10.1056/NEJMoa031049)

    • Search Google Scholar
    • Export Citation
  • 29

    Allcock DM, Gardner MJ, Sowers JR. Relation between childhood obesity and adult cardiovascular risk. International Journal of Pediatric Endocrinology 2009 2009 108187. (https://doi.org/10.1155/2009/108187)

    • Search Google Scholar
    • Export Citation
  • 30

    Langeveld N, Ubbink M, Smets E & Dutch Late Effects Study Group. ‘I don’t have any energy’: the experience of fatigue in young adult survivors of childhood cancer. European Journal of Oncology Nursing 2000 4 2028. (https://doi.org/10.1054/ejon.1999.0063)

    • Search Google Scholar
    • Export Citation