Journal Information
Vol. 80. Issue 6.
Pages 357-364 (01 June 2014)
Vol. 80. Issue 6.
Pages 357-364 (01 June 2014)
Original Article
Full text access
Endocrinological outcome in children and adolescents survivors of central nervous system tumours after a 5 year follow-up
Secuelas endocrinológicas en niños y adolescentes supervivientes de tumores del sistema nervioso central tras 5 años de seguimiento
Visits
4455
M. Güemes Hidalgoa, M.T. Muñoz Calvoa,b,c,d,
Corresponding author
maitemunozcalvo@gmail.com

Corresponding author.
, L. Fuente Blancoa, C. Villalba Castañoa, G.A. Martos Morenoa,b,c,d, J. Argentea,b,c,d,
Corresponding author
jesus.argente@uam.es

Corresponding author.
a Servicio de Endocrinología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
b Servicio de Pediatría, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
c Departamento de Pediatría, Universidad Autónoma de Madrid, Madrid, Spain
d Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
This item has received
Article information
Abstract
Bibliography
Download PDF
Statistics
Abstract
Introduction

Given the successful increase in survival rates with the current treatments for central nervous system tumours (CNST), survivors are at high risk for late adverse effects.

Purpose

To evaluate the endocrine sequelae in children with CNST according to the type of tumour and treatment received.

Patients and methods

A retrospective review of the clinical features, auxology, hormone determinations and imaging findings of 38 patients (36.8% females, 63.2% males) with CNST, with a minimum of 5 years follow-up, was performed.

Results

The mean age at diagnosis was 5.34±3.07 years, with 76.3% of the patients having at least one hormone deficiency, of which growth hormone (GH) (73.7% of all patients) was the most prevalent, followed by thyrotropin (TSH) (68.4%), corticotropin (31.6%), antidiuretic hormone (28.9%), and gonadotropin (LH/FSH) (21.1%) deficiency. Precocious puberty was found in 21.1% of patients. After 5 years of follow-up, 28.9% were obese. Craniopharyngioma had more hormone deficiency, obesity and recurrence rates. The most frequently administered treatment was surgery + chemotherapy + radiotherapy, in 47.4% of the patients. Mean fi height (20 patients) was -1.2 1.6 SDS, with a mean difference of -0.53 SDS regarding their target height.

Conclusions

1) The type of tumour and treatment received influence the endocrinological sequelae. 2) The most frequent hormone deficiencies in all types of CNST, regardless of the treatment received, were GH and TSH. 3) Early diagnosis and prompt intervention of endocrine dysfunction can reduce the morbidity and improve quality of life over the long term.

Keywords:
Childhood brain tumours
Endocrine late effects
Hypothalamic pituitary axis
Cancer survivors
Resumen
Introducción

Con las terapias actuales, la supervivencia de los tumores del sistema nervioso central (TSNC) es cada vez mayor y, con ello, las complicaciones a largo plazo.

Objetivo

Evaluar las secuelas endocrinológicas en niños con TSNC en relación con el tipo de neoplasia y el tratamiento recibido.

Sujetos y métodos

Se revisaron retrospectivamente los datos clínicos, auxológicos, analíticos y radiológicos de 38 pacientes (36,8% mujeres y 63,2% varones) con antecedente de TSNC y seguimiento mínimo de 5 años.

Resultados

La media ± desviación estándar de edad al diagnóstico fue de 5,34 ± 3,07 años. El 76,3% de los casos presentó al menos un déficit hormonal, siendo el más prevalente el de hormona de crecimiento (GH) (73,7%), seguido de los déficits de tirotropina (TSH) (68,4%), corticotropina (31,6%), hormona antidiurética (28,9%) y gonadotropinas (LH/FSH) (21,1%). El 21,1% de los pacientes presentaron pubertad precoz. A los 5 años de seguimiento, el 28,9% presentaba obesidad. El craneofaringioma fue el tipo tumoral que registró mayor número de casos con deficiencias hormonales, obesidad y tasa de recurrencia. El tratamiento más frecuentemente administrado fue la combinación de cirugía + quimioterapia + radioterapia, empleado en el 47,4% de los pacientes. La talla final media ± desviación estándar (20 pacientes) fue −1,2 ± 1,6; con una disminución media de −0,53 DE respecto de su talla diana.

Conclusiones

1) El tipo tumoral y el tratamiento recibido influyen sobre las secuelas endocrinológicas; 2) las deficiencias hormonales más frecuentes en todos los tipos de TSNC, independientemente del tratamiento recibido, fueron GH y TSH; 3) el diagnóstico precoz y la intervención temprana sobre la disfunción endocrina, reducen la morbilidad y mejoran la calidad de vida a largo plazo.

Palabras clave:
Tumores cerebrales infantiles
Secuelas endocrinas
Eje hipotálamo-hipofisario
Supervivientes de cáncer
Full text is only aviable in PDF
References
[1]
S. Shalitin, M. Gal, Y. Goshen, I. Cohen, I. Yaniv, M. Phillip.
Endocrine outcome in long-term survivors of childhood brain tumors.
Horm Res Paediatr., 76 (2011), pp. 113-122
[2]
Martínez González MJ, García Ribes A, Garaizar Axpe C. Tumores cerebrales infantiles: diagnóstico y semiología neurológica. In: Narbona García J, Casas Fernández C.(eds.) Protocolos de neurología. Protocolos de la AEP. 2nd. Madrid: Ediciones AEP; 2008. 203-9.
[3]
D.M. Anderson, K.M. Rennie, R.S. Ziegler, J.P. Neglia, L.R. Robison, J.G. Gurney.
Medical and neurocognitive late effects among survivors of childhood central nervous system tumors.
Cancer., 92 (2001), pp. 2709-2719
[4]
P.K. Duffner, M.E. Cohen.
Long-term consequences of CNS treatment for childhood cancer Part II. Clinical consequences.
Pediatr Neurol., 7 (1991), pp. 237-242
[5]
P.K. Duffner, M.E. Horowitz, J.P. Krischer, H.S. Friedman, P.C. Burger, M.E. Cohen, et al.
Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors.
N Engl J Med., 328 (1993), pp. 1725-1731
[6]
T. Pasqualini, R. Rey, S. Gottlieb.
Secuelas endocrinológicas del tratamiento de las enfermedades oncológicas en la infancia y adolescencia.
Revista Argentina de Endocrinología y Metabolismo., 46 (2009), pp. 24-38
[7]
Ries L, Eisner MP, Kosary CL. SEER Cancer Statistics Review, 1975-2002. Bethesda: National Cancer Institute; 2005.
[8]
J.G. Gurney, N.S. Kadan-Lottick, R.J. Packer, J.P. Neglia, C.A. Sklar, J.A. Punyko, et al.
Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survey Study.
Cancer, 97 (2003), pp. 663-673
[9]
B. Jereb, R. Korenjak, C. Krzisnik, G. Petric-Grabnar, L. Zadravec- Zaletel, J. Anzic, et al.
Late sequelae in children treated for brain tumors and leukemia.
Acta Oncologica., 33 (1994), pp. 159-164
[10]
K.C. Oeffinger, D.A. Eshelman, G.E. Tomlinson, M. Tolle, G.W. Schneider.
Providing primary care for long-term survivors of childhood acute lymphoblastic leukemia.
J Fam Pract., 49 (2000), pp. 1133-1146
[11]
G.T. Armstrong, J.A. Whitton, A. Gajjar, L.E. Kun, E.J. Chow, M. Stovall, et al.
Abnormal timing of menarche in survivors of central nervous system tumors. A report from the Childhood Cancer Survivor Study.
Cancer, 115 (2009), pp. 2562-2570
[12]
E.A. Livesey, P.C. Hindmarsh, C.G. Brook, A.C. Whitton, H.J. Bloom, J.S. Tobias, et al.
Endocrine disorders following treatment of childhood brain tumours.
Br J Cancer., 61 (1990), pp. 622-625
[13]
S.M. Shalet, C.G. Beardwell, B.M. Aarons, D. Pearson, P.H. Jones.
Growth impairment in children treated for brain tumours.
Arch Dis Child., 53 (1978), pp. 491-497
[14]
P.K. Duffner, M.E. Cohen, M.L. Voorhess, M.H. MacGillivray, M.L. Brecher, A. Panahon, et al.
Long-term effects of cranial irradiation on endocrine function in children with brain tumors. A prospective study.
Cancer., 56 (1985), pp. 2189-2193
[15]
L.S. Constine, P.D. Woolf, D. Cann, G. Mick, K. McCormick, R.F. Raubertas, et al.
Hypothalamic-pituitary dysfunction after radiation for brain tumors.
N Engl J Med., 328 (1993), pp. 87-94
[16]
M. Schmiegelow, U. Feldt-Rasmussen, A.K. Rasmussen, M. Lange, H.S. Poulsen, J. Muller.
Assessment of the hypothalamo-pituitary-adrenal axis in patients treated with radiotherapy and chemotherapy for childhood brain tumor.
J Clin Endocrinol Metab., 88 (2003), pp. 3149-3154
[17]
H.A. Spoudeas, P.C. Hindmarsh, D.R. Matthews, C.G. Brook.
Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: A prospective study.
J Endocrinology., 150 (1996), pp. 329-342
[18]
H.K. Gleeson, S.M. Shalet.
The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours.
Endocrine-Related Cancer., 11 (2004), pp. 589-602
[19]
S.M. Shalet, B. Gibson, R. Swindell, D. Pearson.
Effects of spinal irradiation on growth.
Arch Dis Child., 62 (1987), pp. 461-464
[20]
H.K. Gleeson, R. Stoeter, A.L. Ogilvy-Stuart, H.R. Gattamaneni, B.M. Brennan, S.M. Shalet.
Improvements in fi height over 25 years in growth hormone (GH)-defi childhood survivors of brain tumours receiving GH replacement.
J Clin Endocrinol Metab., 88 (2003), pp. 3682-3689
[21]
B.F. Danoff, F.S. Cowchock, C. Marquette, L. Mulgrew, S. Kramer.
Assessment of the long-term effects of primary radiation therapy for brain tumors in children.
Cancer., 49 (1982), pp. 1580-1586
[22]
G. Costin.
Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic–pituitary function.
Am J Dis Child., 142 (1988), pp. 847-852
[23]
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. J Clin Endocrinol Metab. 2000; 85:3990-3.
[24]
S. Nivot, C. Benelli, J.P. Clot, C. Saucet, L. Adan, J.C. Souberbielle, et al.
Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy.
J Clin Endocrinol Metab., 78 (1994), pp. 597-601
[25]
B.C. Thomas, R. Stanhope, P.N. Plowman, A.D. Leiper.
Growth following single fraction and fractionated total body irradiation for bone marrow transplantation.
Eur J Pediatrics., 152 (1993), pp. 888-892
[26]
J.G. Gurney, K.K. Ness, M. Stovall, S. Wolden, J.A. Punyko, J.P. Neglia, et al.
Final height and body mass index among adult survivors of childhood brain cancer: Childhood Cancer Survivor Study.
J Clin Endocrinol Metab., 88 (2003), pp. 4731-4739
[27]
S.R. Rose.
Endocrinopathies in childhood cancer survivors.
The Endocrinologist., 13 (2003), pp. 488-495
[28]
A.L. Ogilvy-Stuart, S.M. Shalet, H.R. Gattamaneni.
Thyroid function after treatment of brain tumors in children.
J Pediatr., 119 (1991), pp. 733-737
[29]
C.A. Sklar.
Endocrine complications of the successful treatment of neoplastic diseases in childhood. Growth.
Genetics and Hormones., 17 (2001), pp. 37-45
[30]
M. Schmiegelow, U. Feldt-Rasmussen, A.K. Rasmussen, H.S. Poulsen, J. Muller.
A population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor.
J Clin Endocrinol Metab., 88 (2003), pp. 136-140
[31]
E.A. Livesey, C.G. Brook.
Thyroid dysfunction after radiotherapy and chemotherapy of brain tumours.
Arch Dis Child., 64 (1989), pp. 593-595
[32]
D. Chin, C. Sklar, B. Donahue, N. Uli, N. Geneiser, J. Allen, et al.
Thyroid dysfunction as a late effect in survivors of pediatric medulloblastoma/primitive neuroectodermal tumors: A comparison of hyperfractionated versus conventional radiotherapy.
Cancer., 80 (1997), pp. 798-804
[33]
K.H. Darzy, S.M. Shalet.
Hypopituitarism following radiotherapy revisited.
Endocr Dev., 15 (2009), pp. 1-24
[34]
J. Byrne, J.J. Mulvihill, M.H. Myers, R.R. Connelly, M.D. Naughton, M.R. Krauss, et al.
Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer.
N Engl J Med., 317 (1987), pp. 1315-1321
[35]
W. Chemaitilly, C.A. Sklar.
Endocrine complications in long-term survivors of childhood cancers.
Endocrine-Related Cancer., 17 (2010), pp. 141-159
[36]
R.H. Lustig, S.R. Post, K. Srivannaboon, S.R. Rose, R.K. Danish, G.A. Burghen, et al.
Risk factors for the development of obesity in children surviving brain tumors.
J Clin Endocrinol Metab., 88 (2003), pp. 611-616
[37]
P.K. Duffner, J.P. Krischer, M.E. Horowitz, M.E. Cohen, P.C. Burger, H.S. Friedman, et al.
Second malignancies in young children with primary brain tumors following treatment with prolonged postoperative chemotherapy and delayed irradiation: A Pediatric Oncology Group study.
Ann Neurol., 44 (1998), pp. 313-316
[38]
J.P. Neglia, D.L. Friedman, Y. Yasui, A.C. Mertens, S. Hammond, M. Stovall, et al.
Second malignant neoplasms in five-year survivors of childhood cancer: Childhood cancer survivor study.
J Natl Cancer Inst., 93 (2001), pp. 618-629

Previous presentation of the work: certain aspects of this research were presented as a poster at the 51st Annual Meeting of the European Society of Paediatric Endocrinology (ESPE), held in Leipzig (Germany) held 20-23 September 2012. The authors and title of this communication were: Güemes M, Fuente L, Caballero FJ, Martos-Moreno G, Muñoz-Calvo MT, Argente J. Endocrinological effects in survivors of central nervous system tumours after a 5 year follow-up”.

Please cite this article as: Güemes Hidalgo M, Muñoz Calvo MT, Fuente Blanco L, Villalba Castaño C. Martos Moreno GA, Argente J. Secuelas endocrinológicas en niños y adolescentes supervivientes de tumores del sistema nervioso central tras 5 años de seguimiento. An Pediatr (Barc). 2014;80:357-364.

Copyright © 2013. Asociación Española de Pediatría
Idiomas
Anales de Pediatría (English Edition)
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?