MON-693 A Case of Hypothalamic Obesity Treated with Dual GLP-1/GIP Agonist and Stimulant Therapy

Abstract Disclosure: B. Lam: None. D. Fraser: None. M.M. Kristan: None. Background: The hypothalamus plays an important role in regulating energy metabolism and appetite. Damage to the hypothalamus, commonly through intracranial tumors or iatrogenic injury, often leads to rapid weight gain and hyperphagia known as hypothalamic obesity (HO). Historically, HO has been difficult to treat, and research on pharmacological options including stimulants and GLP1 agonists has been limited with variable efficacy1,2. Tirzepatide is a dual GLP1/GIP agonist that is effective in weight loss but has limited data for us in HO3. This case presents successful HO treatment using a regimen of combination tirzepatide and phentermine. Clinical CaseA 47 year old female with no pertinent past medical history presented with 4 months of headaches and 1 month of blurred vision. Symptoms began shortly after uncomplicated delivery of her 2nd child. Brain MRI revealed a 1.3 cm suprasellar mass arising from the pituitary infundibulum with compression of the optic chiasm. Weight at that time was 78.9 kg with normal pituitary function. Patient underwent surgical resection with no complications and biopsy revealed papillary craniopharyngioma. Post surgery, the patient developed panhypopituitarism including central diabetes insipidus, adrenal insufficiency, central hypogonadism, and central hypothyroidism requiring hormonal supplementation. Within 6 months of surgery, the patient gained around 10kgs (89kg) without reported hyperphagia or appetite changes. She was started on low dose semaglutide therapy with reduction in weight in 3 months (84.8kg); however, she had significant GI distress so was switched to a liraglutide and phentermine regimen. She experienced weight gain on liraglutide (94.8kg) so restarted semaglutide. Due to ongoing GI distress, the patient was on/off therapies for the next year leading to plateaued weight (92.5kg). She was transitioned to tirzepatide and low-dose phentermine which she tolerated well and led to weight loss (81kg) in 12 months. Clinical LessonThere have been limited studies with variable success on pharmacologic therapies for HO. GLP-1 agonists have become increasingly popular in HO and general weight loss; however, many patients are unable to tolerate the GI distress often associated with GLP1 agonists. This is the first reported case of successful treatment of HO using a regimen of tirzepatide and phentermine and offers an alternative treatment for HO. References: 1.Dimitri P. Treatment of Acquired Hypothalamic Obesity: Now and the Future. Front Endocrinol (Lausanne). 2022;13:846880. Published 2022 Apr 6.2.Paul Dimitri, Christian L Roth, Treatment of Hypothalamic Obesity With GLP-1 Analogs, Journal of the Endocrine Society, Volume 9, Issue 1, January 2025, bvae2003.Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. 2024;184(9):1056-1064 Presentation: Monday, July 14, 2025