6576 Nivolumab and Ipilimumab Induced Hypophysitis and Adrenal Crisis
Authors: Ripa Rashelle , Kainth Kashish , Nasuti Danielle , Von Gizycki Christian 
Published: October 2024

Abstract
Disclosure: R. Ripa: None. K. Kainth: None. D. Nasuti: None. C. Von Gizycki: None.
Introduction: Over the years, immunotherapy has evolved to become the new standard of treatment due to its favorable clinic outcomes over the conventional regimens. Immunotherapies have been designed to elicit an immune response through various ways, one of which includes immune checkpoint inhibitors (ICIs). Although ICIs have shown significant impact on boosting the immune system against cancer cells, they have also shown unwarranted systemic inflammatory side effects. Endocrinopathies are the most seen in these cases, yet many may not be life threating, hypophysitis can potentially be life- threating and requires a timely diagnosis and management. Case: This is a gentleman in his 70s with medical history notable for metastatic melanoma to the lungs and brain status post craniotomy on Nivolumab and Ipilimumab, with most recent cycle one week prior to admission, who presented with weakness and encephalopathy. He was found to have a multi-drug-resistant E. coli urinary tract infection, treated with meropenem. Despite antibiotics, the patient became significantly more altered and hemodynamically unstable, requiring oxygen and vasopressors with little improvement. Lumbar puncture was unable to be performed given his brain masses. CT head without contrast showed post-surgical changes and parenchymal volume loss and nonspecific white matter changes. Thyroid function tests showed low TSH, free T3, free T4, and the patient had no signs of myxedema coma. Random cortisol was 3.9 mcg/dL, consistent with acute adrenal crisis. He was diagnosed with hypothyroidism and adrenal insufficiency secondary due to his immunotherapy which was exacerbated by an acute infection leading to adrenal crisis. He was given stress-dose hydrocortisone followed by levothyroxine, with a drastic improvement in his clinical course and blood pressures. His final cycle of immunotherapy was canceled with plans to change his treatment plan for his next course of therapy. Discussion: Immunotherapy-induced hypophysitis occurs in up to 22% of patients. The risk is higher with anti-CTLA-4 antibody, likely because of the expression of CTLA-4 in the pituitary cells. Immunotherapy-induced hypophysitis usually occurs within 1 month of combined immunotherapy and at diagnosis, roughly 80% of patients present with TSH, ACTH and LH/FSH deficiency. Therefore, it is important to evaluate pre- immunotherapy laboratory testing including plasma sodium, TSH, free T4, cortisol, and LH/FSH. The workup is crucial, as hypophysitis may cause deficiency of several hormones, and a missed ACTH abnormality due to adrenal insufficiency can lead to a fatal case. Evaluation should also include a dedicated pituitary MRI and any corticotroph deficiency should be systematically treated with hydrocortisone. The presence of hyophysitis secondary to a first immunotherapy should not be considered a contraindication for maintaining immunotherapy.
Presentation: 6/2/2024