Work

SUN-053 Paradoxical Steroid Use in Ectopic ACTH Syndrome: Navigating Complications of Small Cell Lung Cancer and Chemotherapy-Related Immune Hepatitis

Year: 2025

Type: article

Abstract: Disclosure: A. Javaid: None. D. Deyar: None. M. Sabri: None. D. Bondarenko: None. A. Rasheed: None. C. O'Sullivan: None. Introduction: Cushing syndrome from ectopic ACTH production occurs in ∼1-5% of SCLC cases, posing diagnostic and therapeutic challenges. This case highlights the complex relationship between ectopic ACTH, hyperglycemia, hepatic dysfunction, and oncologic treatment complications, including the paradoxical use of exogenous steroids. Presentation: A 56-year-old man with poorly controlled type 2 diabetes presented with worsening hyperglycemia, leg swelling, and cough. Initial HbA1c was 11.6% (n <5.7%), reflecting chronic poor glycemic control despite metformin and insulin. Imaging revealed a lung mass confirmed as SCLC. Evaluation showed hypertension, hypokalemia (K+ 2.5 mmol/L, n 3.5-5.0 mmol/L), elevated transaminases (ALT 98 U/L, n 7-56 U/L; AST 110 U/L, n 10-40 U/L), and refractory hyperglycemia. Labs demonstrated elevated ACTH (210 pg/mL, n 10-50 pg/mL) and serum cortisol (44 μg/dL, n 6-23 μg/dL), consistent with ectopic ACTH production. Management: Treatment began with ketoconazole, later switched to metyrapone and mifepristone due to poor tolerance and drug interactions. His SCLC was treated with cisplatin/etoposide followed by maintenance atezolizumab. Early improvements in glycemic control and BP were noted, However, persistent transaminitis (ALT: 120 U/L; AST: 130 U/L) raised concerns for chemotherapy-induced immune-mediated hepatitis, a known complication of atezolizumab. Liver biopsy was deferred due to the patient’s clinical stability and the high likelihood of drug-induced liver injury (DILI). In a paradoxical therapeutic maneuver, exogenous corticosteroids (prednisone 40 mg daily) were initiated to mitigate the immune-mediated hepatotoxicity. This decision was particularly unconventional given the patient’s underlying hypercortisolism. Close monitoring of cortisol levels, liver enzymes, and glycemic control was maintained throughout this period. Remarkably, the patient’s transaminitis improved significantly within two weeks of steroid initiation, without exacerbation of his hypercortisolism symptoms. Conclusion: This case highlights the complexities of managing severe metabolic derangements, including hyperglycemia, hypokalemia, and hepatic dysfunction, in the setting of oncologic treatment. The paradoxical use of exogenous steroids to address chemotherapy-induced liver injury underscores the need for innovative and individualized therapeutic approaches. Further investigation is warranted to establish guidelines for the safe and effective use of corticosteroids in patients with hypercortisolism and concurrent immune-mediated complications. Presentation: Sunday, July 13, 2025

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvaf149.1638

Authors: Aheed Javaid, Dylan Deyar, Muhammad S Sabri, Darya Bondarenko, Ahsan Rasheed, Conor O'Sullivan

Institution: Thomas Jefferson University Hospital

Language: English

Topic: Adrenal Hormones and Disorders

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,255