FRI341 Nothing Great Comes Without Its Risks; A Rare Case Of Pembrolizumab Induced Hypophysitis

Abstract

Abstract Disclosure: A.K. Fernando: None. R. Cheema: None. Introduction: Immune checkpoints are proteins expressed by immune cells and are crucial for maintaining self-tolerance. Immune checkpoint inhibitors (ICIs) are antibodies that inhibit these checkpoints and enhances T-cell activation and antitumor activity. This emerged as a powerful tool in treating cancer, however its use is jeopardized by various immune related adverse events (IRAEs). Secondary hypophysitis, although rare, is associated with immunotherapy. The incidence of hypophysitis is considerably lower with PD-1 inhibitors such as pembrolizumab (0.5-1.5%) than with CTLA-4 inhibitors. We present a case of hypophysitis following initiation of pembrolizumab for NSCLC. Case: A 64-year-old Caucasian male was seen in Endocrinology for evaluation of abnormal TFTs with nonspecific symptoms of fatigue and malaise. He was recently diagnosed with poorly differentiated lung carcinoma with metastasis to brain. After completing XRT, he was started on pembrolizumab/trastuzumab. TFTs prior to initiation of treatment were unremarkable. He developed a mild rash and fatigue post treatment but otherwise treatment was well tolerated. TFTs at week 8 after starting ICIs showed TSH 0.09 uIU/mL (0.27-4.2), T4 0.8 ng/dL (0.9-1.7) and T3 2.2 pg/mL (2.5-4.3). MRI Sella showed enlargement of the pituitary gland and stalk suggestive of hypophysitis. Pembrolizumab was discontinued. Additional studies showed low total testosterone 19.5 ng/dL (193-740) and free testosterone 4.5 pg/mL (35-130) with inappropriately normal gonadotropins suggestive of central hypogonadism. Other pituitary axis were intact. Cosyntropin stimulation test confirmed intact HP Adrenal axis. He was started on levothyroxine and hydrocortisone (20 mg AM and 10 mg PM) for hypophysitis. His symptoms improved. He is closely being monitored with plan to repeat MRI Sella in 3 months and to re-evaluate his HP adrenal prior to weaning off steroids. Discussion: IRAEs from ICIs typically present within 6 to 12 weeks but can present several months to years later. The non-specific nature of symptoms in patients on PD-1 inhibitors can delay clinical recognition with dire consequences. Treatment involves hormone replacement and stopping immunotherapy. Though benefit of GC in patients with grades 1-2 hypophysitis is unclear, low dose corticosteroids have been used to mitigate pituitary inflammation. High dose GC although commonly used in patients with critical illness (grades 3-4), its use remains controversial as they have not shown to significantly alter overall survival. Some degree of pituitary function may recover 4-12 weeks following withdrawal of ICIs. Given the increase in use of ICIs and the serious nature of IRAEs, it is critical to be aware of clinical manifestations, diagnosis, and management of this entity. Presentation: Friday, June 16, 2023