SAT313 Therapeutic Dosing Of Steroids In Patients On Mitotane

Abstract

Abstract Disclosure: C. Pham: None. S.M. Cannon: None. J.S. Lopresti: None. Introduction: Mitotane is a known inhibitor of steroidogenesis with some patients requiring supraphysiologic dosing for steroid replacement. Clinical Case: A 43-year-old female with a history of adrenal cell carcinoma (ACC) on multiagent chemotherapy and mitotane presents with a pruritic rash. Three weeks prior, she had received her first dose of pembrolizumab. Her other home medications included mitotane 500mg QID and hydrocortisone 180mg (40mg-40mg-30mg -20mg QID). Labs on admission were notable for an ALT of 458 (ref 10-35 U/L), AST of 272 (ref 10-35 U/L), and normal alkaline phosphatase and bilirubin with otherwise normal electrolytes. Due to the temporal relation of her transaminitis and rash to recent pembrolizumab infusion with an otherwise negative work-up, the patient was diagnosed with immune-mediated liver injury from checkpoint inhibitors (ILICI). Per National Comprehensive Cancer Network (NCCN) guidelines, high dose methylprednisolone was initiated (1mg/kg) equivalent to approximately 525 mg hydrocortisone total daily. Over five days, the patient’s transaminases continued to rise and methylprednisolone was increased to 3mg/kg/day to account for the known effects of mitotane on steroid metabolism. The patient’s rash subsequently resolved followed by slow improvement of her transaminitis with steroid taper. Mitotane level obtained one week after discontinuation of mitotane was noted to be 21mcg/mL demonstrating persistent therapeutic levels (14-20mcg/mL). Mitotane has a profound inhibitory effect on steroidogenesis through multiple mechanisms, inhibiting glucocorticoid production by the adrenal and increasing hepatic disposal of glucocorticoids leading to subtherapeutic doses1, Furthermore, mitotane can persist in the body for a prolonged period, with a half-life between 18-154 days. As such, patients who develop adrenal insufficiency on mitotane typically require higher doses for physiologic replacement up to three times standard physiologic dose1. In this case, only when the patient’s methylprednisolone dose was tripled did her ILICI begin to improve. Conclusion: This is one of the first cases to describe ILICI in a patient with ACC highlighting unique clinical considerations in management. Higher doses of corticosteroids may be required to overcome the effects of mitotane on steroid metabolism in patients with adverse effects from immune checkpoint inhibitor therapy. 1.)Puglisi, S., Calabrese, A., Basile, V., Pia, A., Reimondo, G., Perotti, P., & Terzolo, M. (2020). New perspectives for mitotane treatment of adrenocortical carcinoma. Best Practice & Research Clinical Endocrinology & Metabolism, 34(3), 101415. https://doi.org/10.1016/j.beem.2020.101415 Presentation: Saturday, June 17, 2023