Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis

BackgroundHypophysitis is a well-recognized immune-related adverse event in patients treated with immune checkpoint inhibitors for cancer. Some anterior pituitary hormones may recover; however, secondary adrenal insufficiency is usually permanent.Case presentationA 26-year old male with metastatic clear cell renal cell carcinoma was started on treatment with the anti-programmed cell death-1 monoclonal antibody (anti-PD-1 mAb) nivolumab, followed by combined nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb, ipilimumab. After starting nivolumab monotherapy the patient developed thyroiditis, which resolved without treatment. Prior to commencing combined ICI therapy, a random serum cortisol drawn at 1:30pm and was 15.0 mu g/dL (414nmol/L). Three weeks after starting combined ICI therapy he developed sudden onset of severe fatigue and 1pm serum cortisol was 2.0 mu g/dL (55.2nmol/L), adrenocorticotropic hormone (ACTH) was 16pg/mL (3.52pmol/L). A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1mg/kg. His symptoms resolved rapidly, and he continued immune checkpoint inhibitor therapy. He was noted to also have low gonadotropic hormones and testosterone (nadir testosterone 81.19ng/dL). The prednisone was tapered slowly over the next six weeks to a maintenance dose of 5mg daily. Four months after the initial presentation his cortisol remained low, but his testosterone level had increased to 973.43ng/dL. After five months his random serum cortisol (1pm) increased to 11.0 mu g/dL (303.6nmol/L). The prednisone was cautiously discontinued with close monitoring. Two months off glucocorticoid replacement he remained asymptomatic with an ACTH of 24.1pg/mL (5.3pmol/L), and cortisol of 13.0 mu g/dL (358.8nmol/L).ConclusionsThis case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypophysitis from immune checkpoint inhibitor therapy. Repeated pituitary hormone testing every three months for the first year after the development of hypophysitis may identify more patients with hypothalamic-pituitary-adrenal axis recovery.