Her soccer dreams didn’t change. Her brain did.
Not all obesity is the same. Injury to the hypothalamus can cause acquired hypothalamic obesity, a challenging, long-term disease demanding specialized support and management.
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Symptoms and Causes
Acquired hypothalamic obesity (HO) is a unique form of obesity caused by injury to the hypothalamus1-4
The hypothalamus plays a key role in many diverse functions, including
regulating satiety, hunger, and energy expenditure.5
Hypothalamic injury can lead to5,6:
Accelerated, sustained weight gain
Hyperphagia
Decreased energy expenditure
Differences in type, location, and extent of hypothalamic injury may result in variable time to onset and progression of weight gain.7,8
of patients with acquired HO reported they struggle with the burden of hyperphagia.9 Hyperphagia is a chronic, pathological, insatiable hunger and impaired satiety accompanied by persistent and abnormal food-seeking behavior.5,6
There are several causes of acquired HO.10
KNOWN common causes10:
- Brain tumors, including craniopharyngioma, astrocytoma, and macroadenoma of the pituitary
- Brain tumor treatment, including surgical resection and radiotherapy
Other causes10:
- Traumatic brain injury
- Stroke
- Disorders that cause inflammation to the hypothalamus
While HO can be congenital or acquired, most cases are acquired.10
Know who is at risk—acquired HO occurs in up to 75% of patients with craniopharyngioma following treatment.11
Questions about acquired HO?
Disease Mechanism
Acquired HO has an underlying
pathophysiology that distinguishes
it from general obesity1-4
Acquired HO can occur when hypothalamic injury impairs MC4R pathway function.1-4
The MC4R pathway regulates hunger, satiety, and energy expenditure.12-14
Injury to the hypothalamus can disrupt MC4R pathway signaling,
ultimately leading to accelerated and sustained weight gain.9,15
Interested in learning more about the distinct underlying pathophysiology of acquired HO?
Patient and Caregiver Burden
Acquired HO carries significant, long-term burden for people with hypothalamic injury15,16
There is a strong and significant correlation between increased weight and
decreased quality of life for patients with acquired HO and their caregivers.9,15
Physical burden
Significant burden on patients’ and caregivers' day-to-day lives:
- Hyperphagia
- Chronic fatigue
- Decreased physical activity
- Weight gain, even in the absence of increased caloric intake
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Emotional burden
Distressing emotional and social challenges for patients:
- Poor body image perceptions
- Fewer positive social interactions
- Negative impact on mental health
- Frustration due to difficulty losing weight
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Acquired HO is a major risk factor for related morbidity and mortality.16,17
Long-term Effects of Obesity-related Sequelae in Craniopharyngioma Survivors18-20
Nonalcoholic fatty liver disease
Hypertension
Sleep apnea
Glycemic disturbance
Dyslipidemia
Cardiovascular disease
“When you're actively watching your child suffer, it's pretty impactful on [your] wellbeing. It’s… the grief, the sadness, the fear for what this means for his future health, both physical health and mental health.”
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Rhythm InTune provides one-on-one educational support for patients and family members navigating the burdens of acquired HO.
Early Detection and Management
Screening for acquired HO is critical in
cases of hypothalamic injury
A clinical diagnosis of acquired HO is characterized by accelerated
and sustained weight gain, most often within the initial 6 to 12 months
following injury to the hypothalamus.1,6,10,17,21,22
Monitor Proactively in New Patients
Early signs and symptoms that can help identify patients with acquired HO include5,6,9,23:
- Accelerated and sustained weight gain, even in the absence of increased caloric intake
- Increased hunger or hyperphagia
- Decreased physical activity
- Increased levels of fatigue or daytime sleepiness
Follow Up with EXISTING Patients
Patients with a past brain injury may1,6,14:
Experience persistent obesity that is resistant to calorie restriction, exercise, or other weight loss interventions
Many patients may not be aware of acquired HO as a risk following hypothalamic injury or may only be focused on other post-treatment concerns.
Talk to your patients about signs and symptoms to watch out for.
There is a critical need to recognize the urgency to diagnose and manage
acquired HO due to its impact on patients and families.1,7,8,15-17
Patients may experience short-term weight loss with lifestyle modifications, anti-obesity medications, or surgery,
but these approaches have shown limited efficacy in producing sustained results in acquired HO.1,6,10,17,21,22,24
Diet
Exercise
Anti-obesity medications
Bariatric surgery
Currently, there is no FDA-approved treatment specifically indicated for acquired HO.17,25,26
While acquired HO can be challenging to manage, early identification and proactive intervention may help to slow the progression of weight gain and help patients better understand their disease.1,10,17
Patient Support Resources
Connect patients and family members with someone who understands acquired HO
and its challenges
Rhythm InTune—a program that provides one-on-one educational support
for people with acquired HO and their family members.
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Patient Education Managers (PEMs)* are trained to:
- Provide resources, education, and information tailored to the unique needs of patients with acquired HO
- Help patients and family members connect to a community of others living with acquired HO
* Patient Education Managers are employees of Rhythm Pharmaceuticals and do not provide medical care or advice. We encourage patients to always speak to their healthcare providers regarding their medical care.
Many patients may be unprepared for the impact of acquired HO, so accessing
tailored resources and 1:1 education can make a meaningful difference.
Tell your patients about Rhythm InTune.
Sign Up for Updates
Sign up to get timely updates
about acquired HO
Sign up to receive practice and patient resources, and hear about updates
in acquired HO.
Join a directory of healthcare
professionals who manage acquired HO.
α-MSH=alpha-melanocyte-stimulating hormone, MC4R=melanocortin-4 receptor, POMC=pro-opiomelanocortin.
REFERENCES
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- Roth CL. Hypothalamic obesity in patients with craniopharyngioma: profound changes of several weight regulatory circuits. Front Endocrinol (Lausanne). 2011;2:49. Published 2011 Oct 14. doi:10.3389/fendo.2011.00049
- Roth CL, Enriori PJ, Gebhardt U, et al. Changes of peripheral alpha-melanocyte-stimulating hormone in childhood obesity. Metabolism. 2010;59(2):186-194. doi:10.1016/j.metabol.2009.06.031
- Roth CL, Gebhardt U, Müller HL. Appetite-regulating hormone changes in patients with craniopharyngioma. Obesity (Silver Spring). 2011;19(1):36-42. doi:10.1038/oby.2010.80
- van Santen HM, van Schaik J, van Roessel IMAA, Beckhaus J, Boekhoff S, Müller HL. Diagnostic criteria for the hypothalamic syndrome in childhood. Eur J Endocrinol. 2023;188(2):lvad009. doi:10.1093/ejendo/lvad009
- Roth CL. Hypothalamic obesity in craniopharyngioma patients: disturbed energy homeostasis related to extent of hypothalamic damage and its implication for obesity intervention. J Clin Med. 2015;4(9):1774-1797. Published 2015 Sep 9. doi:10.3390/jcm4091774
- Roth CL, Eslamy H, Werny D, et al. Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity. Obesity (Silver Spring). 2015;23(6):1226-1233. doi:10.1002/oby.21067
- Müller HL. Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):81-89. doi:10.1097/MED.0000000000000214
- Kayadjanian N, Hsu EA, Wood AM, Carson DS. Caregiver burden and its relationship to health-related quality of life in craniopharyngioma survivors. J Clin Endocrinol Metab. 2023;109(1):e76-e87. doi:10.1210/clinem/dgad488
- Rose SR, Horne VE, Bingham N, Jenkins T, Black J, Inge T. Hypothalamic obesity: 4 years of the International Registry of Hypothalamic Obesity Disorders. Obesity (Silver Spring). 2018;26(11):1727-1732. doi:10.1002/oby.22315
- Lustig RH. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment. Front Endocrinol (Lausanne). 2011;2:60. Published 2011 Nov 3. doi:10.3389/fendo.2011.00060
- Timper K, Brüning JC. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis Model Mech. 2017;10(6):679-689. doi:10.1242/dmm.026609
- Vlaardingerbroek H, van den Akker ELT, Hokken-Koelega ACS. Appetite- and weight-inducing and -inhibiting neuroendocrine factors in Prader-Willi syndrome, Bardet-Biedl syndrome and craniopharyngioma versus anorexia nervosa. Endocr Connect. 2021;10(5):R175-R188. Published 2021 May 19. doi:10.1530/EC-21-0111
- Haliloglu B, Bereket A. Hypothalamic obesity in children: pathophysiology to clinical management. J Pediatr Endocrinol Metab. 2015;28(5-6):503-513. doi:10.1515/jpem-2014-0512
- Craven M, Crowley JH, Chiang L, et al. A survey of patient-relevant outcomes in pediatric craniopharyngioma: focus on hypothalamic obesity. Front Endocrinol (Lausanne). 2022;13:876770. Published 2022 May 9. doi:10.3389/fendo.2022.876770
- Bereket A. Postoperative and long-term endocrinologic complications of craniopharyngioma. Horm Res Paediatr. 2020;93(9-10):497-509. doi:10.1159/000515347
- van Isrel L, Brokke KE, Adan RAH, Bulthuis LCM, van den Akker ELT, van Santen HM. Pathophysiology and individualized treatment of hypothalamic obesity following craniopharyngioma and other suprasellar tumors: a systematic review. Endocr Rev. 2019;40(1):193-235. doi:10.1210/er.2018-00017
- Dogra P, Bedatsova L, Van Gompel JJ, Giannini C, Donegan DM, Erickson D. Long-term outcomes in patients with adult-onset craniopharyngioma. Endocrine. 2022;78(1):123-134. doi:10.1007/s12020-022-03134-4
- Crowley RK, Woods C, Fleming M, et al. Somnolence in adult craniopharyngioma patients is a common, heterogeneous condition that is potentially treatable. Clin Endocrinol (Oxf). 2011;74(6):750-755. doi:10.1111/j.1365-2265.2011.03993.x
- Pereira AM, Schmid EM, Schutte PJ, et al. High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma. Clin Endocrinol (Oxf). 2005;62(2):197-204. doi:10.1111/j.1365-2265.2004.02196.x
- Rosenfeld A, Arrington D, Miller J, et al. A review of childhood and adolescent craniopharyngiomas with particular attention to hypothalamic obesity. Pediatr Neurol. 2014;50(1):4-10. doi:10.1016/j.pediatrneurol.2013.09.003
- Van Roessel IMAA, Van Den Brink M, Dekker J, Ruitenburg-van Essen BG, Tissing WJE, van Santen HM. Feasibility, safety, and efficacy of dietary or lifestyle interventions for hypothalamic obesity: a systematic review. Clin Nutr. 2024;43(8):1798-1811. doi:10.1016/j.clnu.2024.05.028
- Kim RJ, Shah R, Tershakovec AM, et al. Energy expenditure in obesity associated with craniopharyngioma. Childs Nerv Syst. 2010;26(7):913-917. doi:10.1007/s00381-009-1078-1
- Dimitri P. Treatment of acquired hypothalamic obesity: now and the future. Front Endocrinol (Lausanne). 2022;13:846880. Published 2022 Apr 6. doi:10.3389/fendo.2022.846880
- Shoemaker AH, Tamaroff J. Approach to the patient with hypothalamic obesity. J Clin Endocrinol Metab. 2023;108(5):1236-1242. doi:10.1210/clinem/dgac678
- Roth CL, Zenno A. Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon. Front Endocrinol (Lausanne). 2023;14:1256514. Published 2023 Sep 13. doi:10.3389/fendo.2023.1256514