SUN-085 - Acquired Hypothalamic Obesity after Craniopharyngioma Resection with Significant Weight Loss Following Tirzepatide Therapy

Introduction:
Craniopharyngiomas are rare sellar and suprasellar tumors that can cause hypothalamic and pituitary injury, leading to long-term endocrine and metabolic complications despite surgical resection. Acquired hypothalamic obesity is a severe sequela characterized by rapid, treatment-resistant weight gain. Injury to hypothalamic proopiomelanocortin (POMC) neurons and downstream melanocortin signaling results in impaired satiety and hyperphagia. We present a case of acquired hypothalamic obesity following craniopharyngioma resection with significant weight loss after initiation of tirzepatide.

Case:
A 58-year-old male with a history of craniopharyngioma diagnosed in September 2024 underwent aggressive subtotal resection followed by proton beam radiation. He was followed by endocrinology for multiple pituitary deficiencies, including secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, and central diabetes insipidus. Approximately one year postoperatively, he experienced over 40 lb weight gain despite adherence to hormone replacement therapy and normal laboratory values. The patient reported severe hyperphagia with frequent episodes of nausea and vomiting due to excessive intake. Tirzepatide therapy was initiated, resulting in a 20 lb weight loss within two months, with marked improvement in hyperphagia and resolution of binge-related symptoms.

Discussion:
Acquired hypothalamic obesity after craniopharyngioma resection is a debilitating and treatment-resistant condition caused by disruption of hypothalamic nuclei and POMC-mediated satiety signaling. Conventional lifestyle and pharmacologic interventions are often ineffective. GLP-1 receptor agonists, particularly tirzepatide with its dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) activity, may partially bypass impaired melanocortin pathways and restore appetite regulation. Emerging evidence supports the use of GLP-1–based therapies in hypothalamic obesity, with meaningful weight loss and metabolic improvement reported.
Teaching Points:
- Acquired hypothalamic obesity following craniopharyngioma resection is driven by POMC pathway disruption and is often resistant to standard therapies.
- Tirzepatide may offer an effective pharmacologic option by bypassing damaged hypothalamic satiety pathways, leading to significant weight loss.

References:
1. van Iersel, L., Brokke, K. E., Adan, R. A. H., & van der Klaauw, A. A. (2019). Pharmacological treatment of hypothalamic obesity: Current perspectives. Obesity Reviews, 20(6), 806–821. https://doi.org/10.1111/obr.1282
2. Roth, C. L., Eslamy, H., & Werny, D. (2011). Hypothalamic obesity in patients with craniopharyngioma: Pathophysiology, diagnosis, and treatment. Frontiers in Endocrinology, 2, 60. https://doi.org/10.3389/fendo.2011.00060

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