title: Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study.
abstract: Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients with craniopharyngeoma or a pituitary gland tumor were excluded. Results of all endocrine investigations, which were performed at diagnosis and during follow-up, were collected from patient charts. Multivariable logistic regression was used to study associations between demographic and tumor- and treatment-related variables and the prevalence of early endocrine disorders. Results After a median follow-up of 6.6 years, 178 CBTS (24.8%) were diagnosed with an endocrine disorder. A total of 159 CBTS (22.1%) presented with at least one endocrine disorder within the first 5 years after diagnosis. The most common endocrine disorders were growth hormone deficiency (12.5%), precocious puberty (12.2%), thyroid-stimulating hormone deficiency (9.2%), and thyroidal hypothyroidism (5.8%). The risk of hypothalamic-pituitary dysfunction (n = 138) was associated with radiotherapy (odds ratio [OR], 15.74; 95% CI, 8.72 to 28.42), younger age at diagnosis (OR, 1.09; 95% CI, 1.04 to 1.14), advanced follow-up time (OR, 1.10; 95% CI, 1.02 to 1.18), hydrocephalus at diagnosis (OR, 1.77; 95% CI, 1.09 to 2.88), and suprasellar (OR, 34.18; 95% CI, 14.74 to 79.29) and infratentorial (OR, 2.65; 95% CI, 1.48 to 4.74) tumor site. Conclusion The prevalence of early endocrine disorders among CBTS is high. The observation that 22.1% of CBTS developed at least one endocrine disorder within the first 5 years after diagnosis stresses the importance of early and regular assessment of endocrine function in CBTS who are at risk for endocrine damage.
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Clement
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Antoinette Y N
authors.initials: AY
authors.lastname: Schouten-van Meeteren
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Boot
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Claahsen-van der Grinten
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Bernd
authors.initials: B
authors.lastname: Granzen
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Sen Han
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Geert O
authors.initials: GO
authors.lastname: Janssens
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Erna M
authors.initials: EM
authors.lastname: Michiels
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: W Peter
authors.initials: WP
authors.lastname: Vandertop
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Dannis G
authors.initials: DG
authors.lastname: van Vuurden
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Leontien C M
authors.initials: LC
authors.lastname: Kremer
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Hubert N
authors.initials: HN
authors.lastname: Caron
authors.affiliation: Sarah C. Clement, K. Sen Han, and Hanneke M. van Santen, University Medical Center Utrecht, Utrecht; Sarah C. Clement, Antoinette Y.N. Schouten-van Meeteren, A.S. Paul van Trotsenburg, W. Peter Vandertop, Leontien C.M. Kremer, and Hubert N. Caron, Academic Medical Center, University of Amsterdam; W. Peter Vandertop and Dannis G. van Vuurden, Vrije Universiteit University Medical Center, Amsterdam; Annemieke M. Boot, University Medical Center Groningen, University of Groningen, Groningen; Hedy L. Claahsen-van der Grinten and Geert O. Janssens, Radboud University Nijmegen Medical Center, Nijmegen; Bernd Granzen, Maastricht University Medical Center, Maastricht; and Erna M. Michiels, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Hanneke M
authors.initials: HM
authors.lastname: van Santen
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D001932:Brain Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004700:Endocrine System Diseases / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D006785:Hospitals, University; D006801:Humans; D007006:Hypogonadism / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D007037:Hypothyroidism / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands; D016017:Odds Ratio; D015995:Prevalence; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis; D055815:Young Adult