Management of Acquired Hypothalamic Dysfunction and the Hypothalamic Syndrome

Hanneke M van Santen and Hermann L Müller
Endocrine Reviews, First published online August 1, 2025, bnaf025
https://doi.org/10.1210/endrev/bnaf025

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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