SUN-417 Recovery Of Central Adrenal Insufficiency In A Patient With Hypophysitis Secondary To Immune Checkpoint Inhibitors Therapy

Hypophysitis is a well-recognized immune-related adverse event that occurs in approximately 16% of patients treated with immune checkpoint inhibitors (ICIs), particularly the anti-cytotoxic T-lymphocyte associated antigen (CTLA4) monoclonal antibody, ipilimumab. While the synthesis and secretion of some anterior pituitary hormones may recover, central adrenal insufficiency is thought to be permanent. A 26-year old male with metastatic renal cell carcinoma was started on treatment with the anti-programmed cell death 1 (PD-1) monoclonal antibody nivolumab. His pre-treatment TSH was 3.27 (0.34-5.60 µIU/mL). Six weeks after his first dose of nivolumab he developed biochemical hyperthyroidism: TSH 0.04µIU/mL, FT4 2.1 (0.80-1.50 ng/dL), without symptoms. He continued treatment with nivolumab, and 11 weeks after the first dose he remained hyperthyroid (TSH undetectable, FT4 2.65 (0.80-1.50 ng/dL)). He was then started on ipilimumab in addition to nivolumab for 4 cycles. A baseline random serum cortisol drawn at 1:30pm was 15.0 (6.7 - 22.6 µg/dL). Five weeks after starting combined ICI therapy he developed sudden onset of severe fatigue, and reported feeling unable to get out of bed. Random serum cortisol was 2.0µg/dL at 1pm, and further pituitary hormone evaluation was performed: ACTH 16 (7.2-63.3 pg/mL), prolactin 47.2 (2.6-13.1ng/mL), LH 3.47 (1.2-8.6 mIU/mL), FSH 14.6 (1.3-19.3 mIU/mL), TSH 1.91, FT4 0.85, testosterone 545.46 (300-1080ng/dL). Thyroid autoantibodies (anti-TPO, thyroglobulin, TSH receptor) were normal. A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1mg/kg. A brain MRI reported no pituitary abnormalities. 48 hours after starting prednisone his symptoms resolved. He remained on prednisone 20mg daily for 4 weeks, and continued treatment with the ICI’s. His pituitary labs were repeated (3pm) - ACTH 5, cortisol 4.0, TSH 1.6, FT4 0.99, Testosterone 119, LH 3.63, FSH 18.4, IGF1 195 (155-432 ng/dL). His dose of prednisone was reduced to 5mg once daily. He continued to be monitored regularly by endocrinology with follow up testing of hormone levels. Four months after the initial presentation his testosterone level improved to 973.4, but his cortisol remained low. After five months his random serum cortisol (1pm) increased to 11.0, and testosterone was 901.5. The prednisone was cautiously discontinued with close monitoring for symptoms and hormone levels. He remained asymptomatic after discontinuation of prednisone, and after two months off glucocorticoid replacement his ACTH was 24.1 and cortisol was 13.0. This case demonstrates that central adrenal insufficiency can recover in patients who develop hypophysitis from ICI therapy. Close follow up and repeated measurement of pituitary hormones may identify more patients with hypothalamic-pituitary-adrenal axis recovery.