SUN-444 Hydrocortisone Absorption While on Tirzepatide

Abstract Disclosure: S. Reyes: None. G. Gupta: None. H. Aftab: None. Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have evolved into a staple in the management of diabetes. One of its mechanisms of action is a delayed gastric emptying and small bowel transit (2). As a result, the use of GLP-1 RAs has been noted to slow the absorption of oral drugs which can be challenging to recognize. We present a case of adrenal insufficiency (AI) on hydrocortisone (HC) and fludrocortisone while on GLP-1 RA. Case: A 63 yo female with DM II, ACTH-dependent Cushing’s disease s/p hypophysectomy with recurrent cyclic Cushing’s disease s/p bilateral adrenalectomy on chronic HC was admitted for an adrenal crisis. She had doubled her usual HC dose for the past 2 weeks and administered IM HC prior to admission but was hypotensive on arrival. Serum sodium wnl, potassium 3.2 mEq/L, TSH 7.52 uIU/mL, fT4 1.35 ng/dL. She was treated with IV HC and IV antibiotics. She was discharged on her usual home PO HC and fludrocortisone. She continued to have BP on the lower end of normal, weight gain, worsening glucose control, hyperpigmentation, and nausea. Her HC dose was appropriate for her weight and her symptoms raised the possibility of HC malabsorption. She tried prednisone but symptoms were unchanged. Labs sodium 132 mmol/L, potassium 5.4 mmol/L, cortisol 6.2 ug/dL, ACTH 74 pg/mL, and renin activity 2.1 ng/mL/hr. She had been on tirzepatide for 2 years and decision was made to discontinue tirzepatide for 1 month. Repeat sodium 136 mmol/L, potassium 4.4 mmol/L, cortisol 11.1 ug/dL, ACTH 60.9 pg/mL and renin activity of 0.1 ng/mL/hr. She was restarted on tirzepatide but at a lower dose. Discussion: The results were suggestive of AI despite maintaining consistent intake of HC and fludrocortisone. There is limited data on drug-drug interactions between GLP-1 RA and other oral medications but we considered the possibility of the use of high-dose tirzepatide impacting absorption of HC. This has previously been observed however the GLP-1 RA used was exenatide (1). It also has been reported that GLP-1 RA can delay the absorption of dexamethasone (2). Our patient had improvement of all of her labs after discontinuation. This case highlights the utility of discontinuing a GLP-1 RA when there is a clinical suspicion of AI. (1)Fujita Y, Kitamura T, Otsuki M, Tamada D, Tabuchi Y, Kozawa J, Yasuda T, Okita K, Imagawa A, Kaneto H, Funahashi T, Shimomura I. Exenatide alters absorption of hydrocortisone in a diabetic patient with panhypopituitarism: iatrogenic adrenal insufficiency. Diabetes Care. 2013 Jan;36(1):e8. doi: 10.2337/dc12-1499. (2) Nagai Y, Mukai K, Otsuki M, Kimura T, Kozawa J, Nishizawa H, Maeda N, Matsuoka TA, Iwahashi H, Imagawa A, Shimomura I. Suppression Failure of Cortisol Secretion by Dexamethasone May Occur in Glucagon-like Peptide-1 Receptor Agonist-treated Patients with Diabetic Autonomic Neuropathy. Intern Med. 2019 Apr 1;58(7):949-953. Epub 2018 Dec 18. Presentation: Sunday, July 13, 2025