Abstract
Introduction: Endocrine disorders present a major comorbidity in pediatric brain tumors and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes. The aim of the study was to assess the prevalence of endocrine disorders among a complete childhood brain tumor survivor cohort treated between 2008 and 2018 at our national center. Methods: Children with primary brain tumors treated at the University Children’s Hospital, University Medical Center Ljubljana, between 2008 and 2018 were included and evaluated by the endocrinologist in the years 2023/2024. Data on demographics, anthropometrics, tumor type, and therapy were gathered. The presence of endocrinopathies was determined by clinical examination and laboratory data. Results: A total of 94 patients (mean age at the most recent follow-up 14.9 +/− 5.5 years, mean follow-up duration 8 +/− 3 years) were included in the study. At the time of final follow-up, 23% were diagnosed with an endocrine disorder. The most prevalent were hyposomatotropism, followed by central hypothyroidism, with panhypopituitarism affecting 10% of the cohort. Endocrine dysfunction was more frequently observed in survivors with tumors located in the suprasellar region, those who underwent radiotherapy, and those who presented with hydrocephalus. A significant decrease in height SDS was noted compared to baseline height at the time of treatment initiation (p < 0.02), with a more pronounced reduction among those who received craniospinal radiotherapy as part of the oncological treatment. Conclusion: The findings highlight a high prevalence of endocrine disorders in childhood brain tumor survivors, particularly those with suprasellar or posterior fossa tumors, or those treated with radiotherapy. These results emphasize the need for regular and ongoing endocrine monitoring in this patient population following the completion of oncological treatment.
Journal Section:
Case Report
References
1.
Madanat-Harjuoja
LM
, Pokhrel
A
, Kivivuori
SM
, Saarinen-Pihkala
UM
. Childhood cancer survival in Finland (1953-2010): a nation-wide population-based study
. Int J Cancer
. 2014
;135
(9
):2129
–34
. 2.
Smith
MA
, Altekruse
SF
, Adamson
PC
, Reaman
GH
, Seibel
NL
. Declining childhood and adolescent cancer mortality
. Cancer
. 2014
;120
(16
):2497
–506
. 3.
Hoogendijk
R
, van der Lugt
J
, van Vuurden
D
, Kremer
L
, Wesseling
P
, Hoving
E
, et al. Survival rates of children and young adolescents with CNS tumors improved in The Netherlands since 1990: a population-based study
. Neurooncol Adv
. 2022
;4
(1
):vdab183
. 4.
Oeffinger
KC
, Mertens
AC
, Sklar
CA
, Kawashima
T
, Hudson
MM
, Meadows
AT
, et al. Chronic health conditions in adult survivors of childhood cancer
. N Engl J Med
. 2006
;355
(15
):1572
–82
. 5.
Zaletel
LZ
, Bratanic
N
, Jereb
B
. Gonadal function in patients treated for leukemia in childhood
. Leuk Lymphoma
. 2004
;45
(9
):1797
–802
. 6.
Zaletel
LZ
, Bratanic
N
, Jereb
B
. Gonadal function in patients treated for Hodgkin’s disease in childhood
. Radiol Oncol
. 2010
;44
(3
):187
–93
. 7.
van Iersel
L
, Mulder
RL
, Denzer
C
, Cohen
LE
, Spoudeas
HA
, Meacham
LR
, et al. Hypothalamic-pituitary and other endocrine surveillance among childhood cancer survivors
. Endocr Rev
. 2022
;43
(5
):794
–823
. 8.
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
(8
):2761
–84
. 9.
Chemaitilly
W
, Li
Z
, Huang
S
, Ness
KK
, Clark
KL
, Green
DM
, 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
. 2015
;33
(5
):492
–500
. 10.
Brignardello
E
, Felicetti
F
, Castiglione
A
, Chiabotto
P
, Corrias
A
, Fagioli
F
, et al. Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinics
. Eur J Endocrinol
. 2013
;168
(3
):465
–72
. 11.
Ramezan
NW
, Hussain
S
, Mohamad
N
, Yaacob
NM
. Endocrine disorders in childhood brain tumour survivors: a single-centre study
. J ASEAN Fed Endocr Soc
. 2024
;39
(1
):12
–7
. 12.
Casano-Sancho
P
, Izurieta-Pacheco
AC
. Endocrine late effects in childhood cancer survivors
. Cancers (Basel)
. 2022
;14
(11
):2630
. 13.
Lawson
SA
, Horne
VE
, Golekoh
MC
, Hornung
L
, Burns
KC
, Fouladi
M
, et al. Hypothalamic-pituitary function following childhood brain tumors: analysis of prospective annual endocrine screening
. Pediatr Blood Cancer
. 2019
;66
(5
):e27631
. 14.
Clement
SC
, Schouten-van Meeteren
AYN
, Boot
AM
, Claahsen-van der Grinten
HL
, Granzen
B
, Sen Han
K
, et al. Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study
. J Clin Oncol
. 2016
;34
(36
):4362
–70
. 15.
Müller
HL
. Craniopharyngioma
. Endocr Rev
. 2014
;35
(3
):513
–43
. 16.
Thomas
H
, Timmermann
B
. Paediatric proton therapy
. Br J Radiol
. 2020
;93
(1107
):20190601
. 17.
Wilson
JS
, Main
C
, Thorp
N
, Taylor
RE
, Majothi
S
, Kearns
PR
, et al. The effectiveness and safety of proton beam radiation therapy in children and young adults with Central Nervous System (CNS) tumours: a systematic review
. J Neuro Oncol
. 2024
;167
(1
):1
–34
. 18.
Grimberg
A
, DiVall
SA
, Polychronakos
C
, Allen
DB
, Cohen
LE
, Quintos
JB
, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency
. Horm Res Paediatr
. 2016
;86
(6
):361
–97
. 19.
Castets
S
, Thomas-Teinturier
C
, Villanueva
C
, Amsellem
J
, Barat
P
, Brun
G
, et al. Diagnosis and management of congenital hypopituitarism in children
. Arch Pediatr
. 2024
;31
(3
):165
–71
. 20.
Persani
L
, Brabant
G
, Dattani
M
, Bonomi
M
, Feldt-Rasmussen
U
, Fliers
E
, et al. 2018 European thyroid association (ETA) guidelines on the diagnosis and management of central hypothyroidism
. Eur Thyroid J
. 2018
;7
(5
):225
–37
. 21.
Reznik
Y
, Barat
P
, Bertherat
J
, Bouvattier
C
, Castinetti
F
, Chabre
O
, et al. SFE/SFEDP adrenal insufficiency French consensus: introduction and handbook
. Ann Endocrinol
. 2018
;79
(1
):1
–22
. 22.
González Briceño
LG
, Kariyawasam
D
, Samara-Boustani
D
, Giani
E
, Beltrand
J
, Bolle
S
, et al. High prevalence of early endocrine disorders after childhood brain tumors in a large cohort
. J Clin Endocrinol Metab
. 2022
;107
(5
):e2156
–66
. 23.
Chemaitilly
W
, Cohen
LE
. Diagnosis of endocrine disease: endocrine late-effects of childhood cancer and its treatments
. Eur J Endocrinol
. 2017
;176
(4
):R183
–203
. 24.
Merchant
TE
, Rose
SR
, Bosley
C
, Wu
S
, Xiong
X
, Lustig
RH
. Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors
. J Clin Oncol
. 2011
;29
(36
):4776
–80
. 25.
Aldrich
KD
, Horne
VE
, Bielamowicz
K
, Sonabend
RY
, Scheurer
ME
, Paulino
AC
, et al. Comparison of hypothyroidism, growth hormone deficiency, and adrenal insufficiency following proton and photon radiotherapy in children with medulloblastoma
. J Neuro Oncol
. 2021
;155
(1
):93
–100
. 26.
Eaton
BR
, Esiashvili
N
, Kim
S
, Weyman
EA
, Thornton
LT
, Mazewski
C
, et al. Clinical outcomes among children with standard-risk medulloblastoma treated with proton and photon radiation therapy: a comparison of disease control and overall survival
. Int J Radiat Oncol Biol Phys
. 2016
;94
(1
):133
–8
. 27.
Rose
SR
. Improved diagnosis of mild hypothyroidism using time-of-day normal ranges for thyrotropin
. J Pediatr
. 2010
;157
(4
):662
–7.e1
. 667.e1.28.
Eaton
BR
, Esiashvili
N
, Kim
S
, Patterson
B
, Weyman
EA
, Thornton
LT
, et al. Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma
. Neuro Oncol
. 2016
;18
(6
):881
–7
. 29.
Merchant
TE
, Wu
S
, Onar-Thomas
A
, Gajjar
A
, Delaney
A
. Hypogonadism after treatment for medulloblastoma: results from the SJMB03 trial of risk-adapted radiation therapy
. Int J Radiat Oncol Biol Phys
. 2023
;116
(3
):569
–78
. 30.
Wei
C
, Crowne
E
. The impact of childhood cancer and its treatment on puberty and subsequent hypothalamic pituitary and gonadal function, in both boys and girls
. Best Pract Res Clin Endocrinol Metab
. 2019
;33
(3
):101291
. 31.
Hartley
KA
, Li
C
, Laningham
FH
, Krasin
MJ
, Xiong
X
, Merchant
TE
. Vertebral body growth after craniospinal irradiation
. Int J Radiat Oncol Biol Phys
. 2008
;70
(5
):1343
–9
. 32.
Mizumoto
M
, Oshiro
Y
, Pan
H
, Wang
F
, Kaste
SC
, Gajjar
A
, et al. Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors
. Pediatr Blood Cancer
. 2020
;67
(10
):e28617
. 33.
Beckers
D
, Thomas
M
, Jamart
J
, Francois
I
, Maes
M
, Lebrethon
MC
, et al. Adult final height after GH therapy for irradiation-induced GH deficiency in childhood sur vivors of brain tumors: the Belgian experience
. Eur J Endocrinol
. 2010
;162
(3
):483
–90
. 34.
Shalet
SM
, Gibson
B
, Swindell
R
, Pearson
D
. Effect of spinal irradiation on growth
. Arch Dis Child
. 1987
;62
(5
):461
–4
. © 2025 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2025
You do not currently have access to this content.
