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Hypothalamic syndrome

Nature Reviews Disease Primers volume 8, Article number: 24 (2022) Cite this article

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Abstract

Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare, non-cancerous parasellar masses, such as craniopharyngiomas, germ cell tumours, gliomas, cysts of Rathke’s pouch and Langerhans cell histiocytosis, as well as with genetic neurodevelopmental syndromes, such as Prader–Willi syndrome and septo-optic dysplasia. HS is characterized by intractable weight gain associated with severe morbid obesity, multiple endocrine abnormalities and memory impairment, attention deficit and reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition but treatments for general obesity are often used in patients with HS, including surgery, medication and counselling. However, these are mostly ineffective and no medications that are specifically approved for the treatment of HS are available. Specific challenges in HS are because the syndrome represents an adverse effect of different diseases, and that diagnostic criteria, aetiology, pathogenesis and management of HS are not completely defined.

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Fig. 1: Anatomy and connectivity of the hypothalamus.
Fig. 2: Integration of the hypothalamus with the limbic system.
Fig. 3: Neuroradiological presentations in hypothalamic syndrome.

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Acknowledgements

H.L.M. (DKS2014.13) and B.B. (DKS2018.02) are supported by the German Childhood Cancer Foundation, Bonn, Germany. M.T. has received a research grant from Pfizer. E.A.L. received an investigator initiated grant from Tonix Pharmaceuticals.

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Authors and Affiliations

  1. Department of Paediatrics and Paediatric Hematology/Oncology, University Children’s Hospital, Klinikum Oldenburg AöR, Carl von Ossietzky University, Oldenburg, Germany

    Hermann L. Müller

  2. Centre de Référence du Syndrome de Prader-Willi et autres syndromes avec troubles du comportement alimentaire, Hôpital des Enfants, CHU-Toulouse, Toulouse, France

    Maithé Tauber

  3. Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) INSERM UMR1291 - CNRS UMR5051 - Université Toulouse III, Toulouse, France

    Maithé Tauber

  4. Neuroendocrine Unit, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston, MA, USA

    Elizabeth A. Lawson

  5. Biological Psychology Laboratory, Department of Psychology, School of Medicine and Health Sciences, Carl von Ossietzky University, Oldenburg, Germany

    Jale Özyurt

  6. Research Center Neurosensory Science, Carl von Ossietzky University, Oldenburg, Germany

    Jale Özyurt

  7. Department of Neuroradiology, University Hospital Augsburg, Augsburg, Germany

    Brigitte Bison

  8. Developmental Biology and Cancer Programme, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, University College London, London, UK

    Juan-Pedro Martinez-Barbera

  9. Service de Neurochirurgie, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, Paris, France

    Stephanie Puget

  10. Service de Neurochirurgie, Hopital Pierre Zobda Quitman, Martinique, France

    Stephanie Puget

  11. Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Thomas E. Merchant

  12. Department of Paediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, Netherlands

    Hanneke M. van Santen

  13. Princess Máxima Center for Paediatric Oncology, Utrecht, Netherlands

    Hanneke M. van Santen

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  1. Hermann L. Müller
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Contributions

Introduction (H.L.M. and H.M.v.S.); Epidemiology (H.L.M.); Mechanisms/pathophysiology (E.A.L. and J.-P.M.-B.); Diagnosis, screening and prevention (H.L.M., M.T., E.A.L. and B.B.); Management (H.L.M., M.T., E.A.L., J.Ö., S.P., T.E.M. and H.M.v.S.); Quality of life (H.L.M., M.T., E.A.L., J.Ö. and H.M.v.S.); Outlook (H.L.M. and H.M.v.S.): Overview of Primer (H.L.M.).

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Correspondence to Hermann L. Müller.

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Competing interests

This manuscript was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. H.L.M. has received reimbursement of participation fees for scientific meetings and continuing medical education events from Ferring, Lilly, Pfizer, Sandoz/Hexal, Novo Nordisk, Ipsen and Merck Serono, and has received reimbursement of travel expenses from Ipsen and lecture honoraria from Pfizer. M.T. has received reimbursement of participation fees for scientific meetings and continuing medical education events as well as lecture honoraria from Millendo, Pfizer, Novo Nordisk and Merck Serono. M.T. is on the scientific advisory board of OT4B, a pharmaceutical company developing oxytocin treatment in patients with PWS. E.A.L. is on the scientific advisory board and has a financial interest in OXT Therapeutics, a company developing oxytocin-based therapeutics for obesity and metabolic disease. E.A.L.’s interests were reviewed and are managed by MGH and Mass General Brigham (formerly known as Partners Healthcare) in accordance with their conflict of interest policies. J.Ö., B.B., J.-P.M.-B., S.P., T.E.M. and H.M.v.S declare no competing interests.

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Nature Reviews Disease Primers thanks G. Chrousos, S. McCormack, S. Rose and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Müller, H.L., Tauber, M., Lawson, E.A. et al. Hypothalamic syndrome. Nat Rev Dis Primers 8, 24 (2022). https://doi.org/10.1038/s41572-022-00351-z

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