SAT-432 Checkpoint Inhibitor Therapy and Adrenal Insufficiency: The Critical Role of ACTH Measurement

Abstract Disclosure: A. Fantasia-Davis: None. S. Reyes: None. T. Vedere: None. Introduction: The growing use of immune checkpoint inhibitors (ICI) for the treatment of various malignancies has resulted in increased attention to immune related adverse events (irAE). The incidence of adrenal insufficiency (AI) while on ICI is less than 1% when on single therapy and between 4-8% when used in combination (1). Of those patients, 33% develop primary AI and 20% exhibit secondary AI (1). Diagnosis of AI is then difficult due to the nonspecific symptoms that require a high degree of clinical suspicion.Clinical Case:A 52-year-old female was admitted due to a serum sodium of 116 mmol/L. She had a history of cervical adenocarcinoma treated with carboplatin/paclitaxel/bevacizumab plus pembrolizumab for 11 months. She had developed multiple irAE including hypothyroidism and elected to discontinue therapy. Shortly after, she experienced fatigue and weight loss. She presented to the hospital 6 months later with a benign exam. On admission, sodium was 116 mmol/L with potassium of 4.7 mmol/L. Thyroid function was normal. Morning serum cortisol was 6.4 ug/dL. Peak cortisol after cosyntropin 7.3 ug/dL. She was started on hydrocortisone and later fludrocortisone due to potassium on the higher end of normal. Her sodium and symptoms improved. A CT abdomen showed bilateral enlarged adrenal glands.Later, ACTH resulted as 296 pg/mL, aldosterone <3 ng/dL, and renin 2.2 ng/mL/hr. Her 21-hydroxylase antibody was negative.Records prior to admission showed a normal morning cortisol level but the concurrent ACTH of 252 pg/mL was unfortunately missed. At this time her sodium level was 127 mmol/L. Clinical Conclusions: The adverse events associated with ICI is unpredictable. The diagnosis of AI is challenging in these patients because nonspecific symptoms can be attributed to side effects from chemo or immunotherapy. Our patient presented with common features of primary AI. Early primary AI can be especially challenging to diagnose, but our case demonstrates the utility of checking an ACTH level when there is a clinical suspicion. Especially when a patient has already developed an irAE, the most common being hypothyroidism (2). Current ACSO guidelines recommend routine monitoring of thyroid function but do not recommend the same for the adrenal gland. Early monitoring of ACTH in patients on ICI therapy has the potential to diagnose and treat patients’ months before experiencing severe symptoms.References(1): Shi, Y., Shen, M., Zheng, X., & Yang, T. (2020). Immune checkpoint inhibitor-induced adrenalitis and primary adrenal insufficiency: Systematic review and Optimal Management. Endocr Pract, 27(2), 165-169. (2): Fujimiya, T., Azuma, K., Togashi, Y., Kuwata, K., Unezaki, S., & Takeuchi, H. (2024). Pembrolizumab-induced secondary adrenal insufficiency due to adrenocorticotrophic hormone deficiency in a patient with non-small-cell lung carcinoma: A case report. J Pharm Health Care Sci, 10(1). Presentation: Saturday, July 12, 2025