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Cited by 11Pituitary Gland Disorders and TreatmentsGlioma Diagnosis and TreatmentHypothalamic control of reproductive hormones

The many different clinical faces of acquired hypothalamic dysfunction: a retrospective cohort study in the Netherlands

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van Roessel, Ichelle M.A.A., Hulsmann, Sanne C., Schouten-van Meeteren, Antoinette Y.N., Hoving, Eelco W., Janssens, Geert O., Raphael, Martine F., Zijtregtop-Blom, Eline A.M., de Vos-Kerkhof, Evelien +3 more·2025·eClinicalMedicine
DOI 10.1016/j.eclinm.2025.103313PMC PMC12270709
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Abstract

Background: Acquired hypothalamic dysfunction, occurring at diagnosis or after treatment for a childhood (supra)sellar brain tumor, can have severe consequences. While morbid obesity and pituitary dysfunction are easily recognized, the other consequences of hypothalamic dysfunction (HD), such as hypothermia, sleep disturbance, or behavioral issues, are less well-known and may be overlooked. In addition, hypothalamic dysfunction may present differently in each patient hampering diagnostic and therapeutic efficacy. These different faces of hypothalamic dysfunction have, however, never been described systematically. Here, we systematically describe the different faces of acquired HD and its association with patient, tumor, or treatment-related factors. Methods: We conducted a retrospective cohort study in children diagnosed with a (supra)sellar brain tumor across four centres in the Netherlands between January 2003 and January 2023. We included three cohort of patients younger than 18 years (at time of diagnosis) with at least 1 year of follow-up: Dutch supratentorial midline Low Grade Glioma (LGG) cohort, including patients with a diagnosis of supratentorial midline LGG (thalamic or suprasellar location); Dutch Childhood Craniopharyngioma (cCP) cohort, including patients with a diagnosis of craniopharyngioma; and Dutch Suprasellar Germ Cell tumor (GCT) cohort including patients with a diagnosis of suprasellar non-germinomatous germ cell tumors or germinoma. Patients were assessed using the diagnostic hypothalamic score; the percentage of patients with severe or mild symptoms was reported for each domain. The different presentations of acquired hypothalamic dysfunction were described per tumor group. Findings: 336 paediatric patients were included in total; 220 patients diagnosed with LGG, 88 patients with cCP, and 28 with GCT. Acquired hypothalamic dysfunction was present in 81.3% of patients (273 of 336). In 38.1% (106 of 278) the hypothalamic syndrome (HS) was present, as defined by the van Santen 2023 criteria. Within these 106 patients, 42 different clinical presentations or faces of hypothalamic dysfunction were observed. The most common combination of signs and symptoms was hyperphagia, hypothalamic obesity, with pituitary dysfunction (n = 9, 8.5%), followed by a combination of signs and symptoms (at least minor) on all of the six domains (n = 8, 7.5%). Of patients presenting with overweight or obesity at brain tumor diagnosis, 28.6% had pituitary dysfunction, but 71.4% had adequate pituitary function. Associated factors with presence of HS, identified by multivariate analyses, were any neurosurgical resection (OR 4.61, 95% CI 2.45-8.67), targeted therapy (OR 2.57, 95% CI 1.39-4.77), and longer follow-up time (OR 1.09, 95% CI 1.03-1.16). Interpretation: Hypothalamic dysfunction has many different clinical faces and concerns a far broader perspective than hypothalamic obesity alone. Obesity can be caused by a suprasellar tumor, even if pituitary function is still intact. Vice versa, hypothalamic dysfunction can be present without obesity. Recognition of the different faces of hypothalamic dysfunction may reduce delay in diagnosis and enable more personalized management. Funding: None.

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  • A growing body of evidence supports the heterogeneity of acquired hypothalamic syndrome, with individuals experiencing many distinct and unique combinations of problems.

    “A growing body of evidence supports the heterogeneity of this condition, with individuals experiencing many distinct and unique combinations of problems (3).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [3]

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Authors
van Roessel, I. M. A. A., Hulsmann, S. C., Schouten-van Meeteren, A. Y. N., Hoving, E. W., Janssens, G. O., Raphael, M. F., Zijtregtop-Blom, E. A. M., de Vos-Kerkhof, E., Bakker, B., Tissing, W. J. E., & van Santen, H. M.
Affiliations
  • Princess Máxima Center (NL)
  • University Medical Center Utrecht (NL)
  • Wilhelmina Children's Hospital (NL)
  • University Medical Center Groningen (NL)
ORCID
Venue
eClinicalMedicine
Publisher
Elsevier BV
Published
2025-07
Volume
85
Pages
103313
ISSN
2589-5370 (ISSN-L)
DOI
10.1016/j.eclinm.2025.103313
PMC
PMC12270709
OpenAlex
W4412006858
Cited by
10
References
13
Citations by year
2026: 8 · 2025: 2
FWCI
6.82
Type
journal article
Language
en
Open access
Licence
Locations
  • EClinicalMedicine (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
hypothalamic obesity, pituitary dysfunction, hypothalamic syndrome, low-grade glioma, craniopharyngioma, hyperphagia, hypothermia, sleep disorders, behavioral problems, treatment complications, diagnostic score, pediatric neuro-oncology, germinoma

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