(13.11) Successful Treatment of Hypothalamic Obesity with Tirzepatide: A Case Report

Introduction : Hypothalamic obesity (HO) occurs when there is hypothalamic damage resulting in hyperphagia and decreased energy expenditure. It is a rare form of obesity and can be caused by tumors, most commonly craniopharyngioma (CP). About, 75% of patients treated for CP will develop HO. HO is difficult to treat and diet, physical activity, and behavioral interventions are usually ineffective. There is limited data on the use of anti-obesity medications for HO, showing limited effectiveness for most agents. Bariatric surgery has also been attempted with variable results. In this study, we present a case in which tirzepatide was used successfully to treat HO. 

Case(s) Description : A 21-year-old male without any previous medical history presented with a 7-month history of headaches. Brain MRI revealed a large 4.7 cm multicystic lobulated sellar mass with suprasellar extension. Physical exam was notable for a BMI of 37kg/m² and baseline pituitary hormones were normal except for a mildly elevated prolactin attributed to stalk effect. He underwent transsphenoidal resection and pathology revealed adamantinomatous CP. Following  surgery, he developed panhypopituitarism with central diabetes insipidus and was started on desmopressin, levothyroxine, hydrocortisone, and testosterone. Postoperatively, he reported hyperphagia and  rapid weight gain of 40 lb to a BMI of 41kg/m². He was started on tirzepatide in the setting of hyperglycemia with gradual weight loss of 19 lb and  subsequent reduction of BMI to 38kg/m² over  4-months. He continues to lose weight as the tirzepatide dose is gradually uptitrated.

Discussion : We report the first known case of successful treatment of HO with tirzepatide. The pathophysiology of HO is complex involving  a decrease in sympathetic activity and energy expenditure, central insulin and leptin resistance, and increased energy storage in adipose tissue. 
Tirzepatide, which simultaneously stimulates GIP and GLP-1 receptors, increases insulin sensitivity, improves glycemic control, simultaneously targets multiple redundant weight regulatory pathways, and thus results in greater weight loss when compared to selective GLP-1-RAs. The effects on GLP-1 receptors cause weight loss via intact hindbrain signaling pathways and by modulating  the balance of sympathetic/parasympathetic tone, potentially counteracting abnormalities seen in HO. Marked anti-obesity effects occur when combined with a GIP agonist which regulates energy balance through cell surface receptor signaling in adipose tissue and the CNS.