Successful Treatment of Hypothalamic Obesity with Tirzepatide

Hypothalamic obesity (HO) is a rare but severe form of obesity characterized by hypothalamic damage resulting in hyperphagia and decreased energy expenditure. Tumors involving the hypothalamus, most commonly craniopharyngiomas, frequently result in HO. Treatment is typically refractory to standard antiobesity treatment modalities. Herein, we describe a young man with HO due to surgical resection of a large craniopharyngioma who was successfully treated with tirzepatide, a novel treatment for obesity and type 2 diabetes.

A 21-year-old man presented with headaches for 7 months. His physical examination revealed a body weight of 125 kg (body mass index [BMI], 35 kg/m²). Brain magnetic resonance imaging revealed a 5-cm multicystic lobulated sellar mass with suprasellar extension. He underwent transsphenoidal resection, and pathology revealed craniopharyngioma. Postoperatively, he developed hyperphagia and rapid weight gain of 15 kg over 3 months (weight, 140 kg; BMI, 40 kg/m²). He was started on tirzepatide, which was gradually up titrated to 10 mg in the first 4 months, during which time he lost 9 kg (weight, 131 kg; BMI, 37 kg/m²).

The pathophysiology of HO is complex, involving decreased sympathetic activity and energy expenditure, central insulin and leptin resistance, and increased energy storage in adipose tissue. By modulating sympathetic/parasympathetic tone and regulating energy balance, tirzepatide appears to be a promising agent to address the complex pathophysiology of HO.

This case report highlights the novel use of tirzepatide in the treatment of HO. This case informs clinicians of the potential benefits of considering tirzepatide in the management of HO and encourages further exploration of its use in this context.