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Cited by 21Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesPituitary Gland Disorders and Treatments

Management of Acquired Hypothalamic Dysfunction and the Hypothalamic Syndrome; It Is More Than Obesity

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van Santen, Hanneke M, Müller, Hermann L·2025·Endocrine Reviews
DOI 10.1210/endrev/bnaf025PMC PMC12640713
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Abstract

The hypothalamus is the key regulator of human energy balance. Hypothalamic dysfunction leads to (morbid) hypothalamic obesity, but may have many more consequences such as hypopituitarism, adipsia, disruption of the circadian rhythm, decreased energy expenditure, low core body temperature, and behavioral changes. Many patients with hypothalamic dysfunction experience chronic fatigue, increased daytime sleepiness, headaches, inactivity, and mood disorders, all of which may contribute to the development of obesity. Adipsic arginine vasopressin deficiency, severe hypothermia, uncontrollable hyperphagia, and severe mood disorders may require 24/7 management. Signs and symptoms may be severe or mild. Severe hypothalamic dysfunction is usually readily diagnosed, but less severe hypothalamic dysfunction is much harder to recognize because, among other things, of its multifaceted presentation. Through raising awareness and by better categorization of the different clinical signs and symptoms of hypothalamic dysfunction within different domains, the underlying cause for fatigue and obesity observed in patients with hypothalamic dysfunction may be better understood, which in turn, will open new perspectives on successful management options. In this review, the state of the art for diagnostics and management of acquired hypothalamic dysfunction is summarized and a new management algorithm is suggested. The lessons learned from pediatric patients with acquired hypothalamic dysfunction, including hypothalamic obesity management through the different clinical domains, may also prove to be useful for patients with congenital or genetic forms of hypothalamic dysfunction resulting in fatigue and obesity, as well as for children with presumed “common” obesity.

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  • Methylphenidate, dextroamphetamine, and modafinil and combinations of modafinil and dextroamphetamine have been used to treat narcolepsy and excessive sleepiness.

    “Methylphenidate, dextroamphetamine, and modafinil and combinations of modafinil and dextroamphetamine have been used to treat narcolepsy and excessive sleepiness; practice parameters for their use have been published (4, 77).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [4]

    The Management of Hypothalamic Sleep Disorders section (page unavailable) says central stimulating agents improved sleep disorders in patients with secondary narcolepsy. The obesity-treatment section names methylphenidate and dextroamphetamine as stimulants, but for hypothalamic obesity, not specifically for narcolepsy. Our copy does not substantiate modafinil, its combination with dextroamphetamine, or the cited practice parameters. (LLM, conf=0.84)

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References 170 · Cited by 21

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Authors
van Santen, H. M., & Müller, H. L.
Affiliations
  • Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, UMC Utrecht , Utrecht 3508XB ,
  • Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR , Oldenburg 26133 ,
ORCID
van Santen, Hanneke M
Venue
Endocrine Reviews
Publisher
The Endocrine Society
Published
2025-08-01
Volume
46
Issue
6
Pages
891-907
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
DOI
10.1210/endrev/bnaf025
PMC
PMC12640713
OpenAlex
W4412842979
Cited by
21
References
170
Citations by year
2026: 19 · 2025: 2
FWCI
2.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Reviews (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • KRANIOPHARYNGEOM
  • German Childhood Cancer Foundation, Bonn, Germany (DKS2014.13)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
hypothalamic obesity, hypopituitarism, adipsia, central diabetes insipidus, hypothermia, hyperphagia, circadian rhythm disruption, energy balance, chronic fatigue, mood disorders, management algorithm, diagnosis
MeSH terms
Humans, Hypothalamic Diseases, Hypothalamus, Obesity

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