Medications for Hypothalamic Obesity | Marci Serota, RDN

Medications and Hypothalamic Obesity – What Does the Literature Say?

Hypothalamic obesity is considered a treatment-resistant condition. A limited number of studies have looked at pharmacological treatments for hypothalamic obesity. Although no one medication can “cure” hypothalamic obesity, the following medications MAY help, although more studies are needed.

• Dextroamphetamine, long acting
• Naltrexone
• Intranasal Oxytocin
• Carbetocin
• Exantide, Victoza
• Contrave

Stimulants

Stimulants, such as dextroamphetamine and methylphenidate have been shown to provide a modest reduction in the velocity of weight gain in patients with hypothalamic obesity​​ (1).

Oxytocin and Naltrexone: Case Study Demonstrates Efficacy of Combination Therapy

Based on the experience of a case-based study, ​Eugenie A. Hsu, PhD, a psychologist at Kaiser Permanente Oakland Medical Center in California, achieved success with a combination of low-dose intranasal oxytocin and naltrexone in a 13-year old child with hypothalamic obesity, post craniopharngioma resection.​ Naltrexone, an opiate antagonist, ​appears effective in deterring hedonic eating, enhancing the effects of oxytocin (2).

Oxytocin is a ​hypothalamic ​neuropeptide responsible for energy regulation​ and has been shown to exert anorexigenic effects in animal studies: however, unlike other hypothalamic and pituitary hormones, oxytocin is not routinely replaced in patients diagnosed with hypopituitary craniopharyngioma. ​

In this case report, the patient exhibited improved satiety and decreased preoccupation with food following therapeutic treatment with a combination of oxytocin and naltrexone, says Dr. Hsu. “In addition, this patient achieved a decreased body mass index from obese to normal, which is one of the primary interests of individuals with hyperphagia and hypothalamic obesity. It’s important to note that the diet (lower carb, and limited access to sugar) remained the same from one year prior to initiation of the study and through the 48-week trial; otherwise, the patient was permitted an open kitchen with free access to food after oxytocin’s effect started to kick in,” Dr. Hsu tells us.

Oxytocin treatment in children with Prader–Willi syndrome: A double‐blind, placebo‐controlled, crossover study

Jennifer Miller, et al, conducted a double‐blind, placebo‐controlled, crossover study in 24 children with PWS. “The results from this study suggest that low dose intranasal oxytocin is safe for individuals with PWS and may result in reduction in appetite drive, and improvements in socialization, anxiety, and repetitive behaviors. Further, long‐term studies with a larger population of participants are necessary to confirm these findings. The results of this study are encouraging that oxytocin may be a safe and effective treatment for many of the issues that negatively impact individuals with PWS.” (3)

Carbetocin

Another promising treatment is carbetocin, an oxytocin analogue; Dykens and Miller, et al, recently completed a small, randomized, placebo-controlled trial demonstrating significant improvement in hyperphagia during treatment with carbetocin in 17 children who were between 10-18 years with Prader-Willi syndrome (4).

Liraglutide for the treatment of hypothalamic obesity

One case report demonstrated that a 23 year old female with hypothalamic obesity and panhypopituitarism who was treated with liraglutide noted marked improvement in polyphagia and increased satiety after meals, as well as a 20 pound weight loss that she was able to maintain over 27 months without adverse effects (5). Liraglutide has been approved for long-term treatment of obesity.

Other Medications

A variety of medications may prove useful in this specific patient population, such bupropion/naltrexone, phentermine/topiramate, pram​i​lintide, as well as other common weight loss agents, such as orlistat, which have not been studied in this population.

Ongoing Trials

GLP-1R Agonist (Exantide)

Christian L. Roth, MD, professor of medicine at the University of Washington in Seattle, is currently studying the prescribing of the GLP-1R agonist, exenatide, in children and adults with hypothalamic obesity so we should look out for these results to inform treatment going forward.

Intranasal Oxytocin in Hypothalamic Obesity

Dr. Shana McCormack, MD, MTR, attending physician and Scientific Director of the Neuroendocrine Center in the Division of Endocrinology and Diabetes at Children’s Hospital of Philadelphia (CHOP) is currently studying the effects of intranasal oxytocin on children with hypothalamic obesity.

My Personal Opinion

HO patients report frustration with their healthcare professionals’ unwillingness to “think outside the box” and to try “cutting-edge approaches” that may help them live healthier, longer lives. Most researches and clinicians agree that additional research is necessary before widespread treatment is undertaken. However, it seems to me that the majority of patients with hypothalamic obesity feel that the risk:benefit ratio of trialing promising treatments is quite low when compared to the risk:benefit ratio of doing nothing. Which, most assuredly, will lead to development of fatty liver disease, type 2 diabetes, sleep apnea, high blood pressure, cardiovascular disease and metabolic syndrome.

I can attest to the fact that my son with HO suffered from most of these conditions by the time he was nine years old. I understand that liability is a concern and no physician wants to risk causing harm to a patient by prescribing a mediation that has not been adequately studied. I however, would not hesitate to sign away my rights to seek compensation or retribution for any damages that may result from trialing a relatively safe medication that could potentially improve my son’s quality of life.

Our Personal Anecdotal Report

Instituting a carbohydrate-controlled, very low sugar, low flour diet that focuses on nature-made, unprocessed foods (in the context of locking access to food 24 hours per day), and adding exercise have decreased my son’s food cravings and aided in weight loss (6).

Additionally, maximizing his thyroid replacement (he is panhyopituitary) – keeping his Free T4 in the top third of of the normal range and adding liothyronine, both helped to further decrease his BMI and increased his energy levels. Decreasing his hydrocortisone dose to the lowest safe amount lessened his food-seeking and aided in weight loss even more (6).

However, it wasn’t until starting my son on 30 mg Naltrexone per day, that we saw a life-changing decrease in food-seeking and food preoccupation. So much so, that we no longer have to lock the refrigerator in our home. This has provided tremendous relief in our whole family’s quality of life.

A Few Words from the Trenches

A few adults with hypothalamic obesity have reported to me substantial weight loss using Contrave (naltrexone/buproprion). There have also been a few adults and children with HO that have reported that Victoza (liraglutide) injections have led to substantial weight loss.

Marci Serota, RDN

“In my experience, treatment of hypothalamic obesity is most successful when it is attacked from several angles simultaneously. Therefore, a multimodal plan that includes: diet, physical activity, and pharmacologic. In addition, panhypopituitary patients benefit from aggressive thyroid replacement to maximize metabolism, prescribing the lowest glucocorticoid dose possible, and consideration of adult doses of human growth hormone supplementation, even in the absence of a growth hormone deficiency.” – Marci Serota, RDN.

Eugenie Hsu, PhD

“Until hypothalamic obesity sufferers can rely upon a gold standard intervention, I assert that successfully treating hypothalamic obesity demands thinking outside the box with cutting-edge approaches. I am sure glad I did.” -Eugenie Hsu, Ph.D.

Philip Zeitler, MD

Dr. Philip Zeitler, Professor of Pediatrics, and Medical Director at Children’s Hospital Colorado Clinical & Translational Research Center Section Head Endocrinology, treats and researches severe childhood obesity and its effects on children’s health (though not hypothalamic obesity). He has published several studies on the safety and efficacy of using medications such as metformin and rosiglitazone to treat Type 2 Diabetes in obese children. Type 2 Diabetes is a very serious side-effect of obesity.

Dr. Zeitler stated in an article published by BBC news this week, that “probably the biggest recommendation changes are much more aggressive treatment of kids. The default position has been, “Well, you know, they’re kids, we shouldn’t be exposing them to lots of medications and we should take our time.’ And I think what we’ve learned is that that’s the exact opposite of what we should be doing.”

In Summary

Well, children with hypothalamic obesity are just as likely if not more likely to develop Type 2 Diabetes and thus, I assert that kids with HO deserve to receive more aggressive treatment as well. Unfortunately, the reality is that in order to get most doctors on board, more studies will need to establish the safety and efficacy of medications that treat hypothalamic obesity.

This blog post is based on an article that I wrote for Healthcare Professionals on EndocrineWeb in 2019, Would You Recognize and Know How to Treat Hypothalamic Obesity?- Marci Serota, RDN (7).

Sources

1. 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 Journal. 2018; 26(11): 1727-1732.
2. Hsu EA, Miller JL, Perez FA, et al. Oxytocin and naltrexone successfully treat hypothalamic obesity in a boy post-craniopharyngioma resection. J Clin Endocrinol Metab. 2018;103(2):370-375.
3. Miller, JL, Tamura, R, Butler, MG, et al. Oxytocin treatment in children with Prader–Willi syndrome: A double‐blind, placebo‐controlled, crossover study. Am J Med Genet Part A. 2017; 173A: 1243– 1250. https://doi.org/10.1002/ajmg.a.38160
4. Dykens EM, Miller J, Angulo M, et al. Intranasal carbetocin reduces hyperphagia in individuals with prader-willi syndrome. JCI Insight. 2018.3(12):98333.
5. Sadia Ashraf, Prashant Nadkarni, Nidhi Bansal, and Susan E. Stred (2018) Liraglutide for the treatment of hypothalamic obesity. AACE Clinical Case Reports: July/August 2018, Vol. 4, No. 4, pp. e342-e345.
6. Serota, Marci. Hungry for Solutions, A Mother’s Quest to Defeat Hypothalamic and Childhood Obesity. Brown Books Publishing Group, 2018.
7. Serota, Marci. “Would You Recognize and Know How to Treat Hypothalamic Obesity.” EndocrineWeb, Remedy Health Media, LLC , July 16, 2019. https://www.endocrineweb.com/professional/obesity/would-you-recognize-know-how-treat-hypothalamic-obesity