MON-361 Isolated ACTH Deficiency after Treatment with Immune-Checkpoint Inhibitors

Abstract

Background: Immune-checkpoint inhibitors targeting PDI or CTLA-4 are promising therapies in metastatic malignancies, including metastatic melanoma, and their usage has been increasing over the last few years. As more patients are treated with these agents, there will likely be an increased incidence of the relatively rare endocrine adverse events. Clinical Case: A 58-year-old New Orleans rock musician with metastatic melanoma underwent chemotherapy in 2015 with an anti-CTLA-4 checkpoint inhibitor (Ipilimumab at 3 mg/kg IV every 3 weeks for 4 cycles, given over 3 months). He later had progression of disease on imaging so was switched to an anti-PD1 checkpoint inhibitor (Pembrolizumab at 2 mg/kg IV every 3 weeks). Within 6 weeks of starting Pembrolizumab, he developed fatigue, weakness, nausea, and a loss of appetite. Within 10 months of starting immune checkpoint inhibitor therapy, he had lost 40 lbs - 28.6% of his pre-checkpoint inhibitor body weight - and he was too weak to continue his career as a rock musician. In response to his failure to thrive, the Endocrinology service consulted on his case. His endocrine evaluation revealed a severe ACTH deficiency (8 am ACTH <1.1 pg/mL, normal 7-69) and a failed response to Cosyntropin stimulation - after a 0.25 mg IV cosyntropin injection, his cortisol level increased from <0.4 micrograms/dL to 1.2 micrograms/dL at 30 minutes and to 1.4 micrograms/dL at 60 minutes. Other pituitary hormone levels drawn at 3pm (when he would awaken from sleep) revealed normal LH (6.2 mIU/mL, normal 2.0-12.0), FSH (13.8 mIU/mL, normal 1.5-15), testosterone (577 ng/dL, normal 175-781), prolactin (4.1 ng/mL, normal 1.0-18.0), IGF-1 (118 ng/mL, normal 68-245), TSH (4.45 uIU/mL, normal 0.5-5.0), and free T4 (0.71, normal 0.60-1.15). He was started on a stress dose of IV hydrocortisone then transitioned to an oral maintenance dose of 20 mg hydrocortisone daily. He has gained back the weight he lost and has returned to a successful career as a rock musician. Conclusion: This report presents a case of isolated ACTH deficiency after treatment with immune checkpoint inhibitors targeting CTLA-4 and PD1. It is a unique case due to the rare finding of an isolated ACTH deficiency. The prolonged illness and weight loss that the patient experienced as a consequence of secondary adrenal insufficiency emphasizes the importance of selective case screening of patients on immune checkpoint inhibitors for endocrinopathies.