SUN-828 Navigating Endocrine Toxicities In Immunotherapy: A Case Of Pembrolizumab-induced Endocrinopathy

Abstract Disclosure: T.M. Abugoukh: None. N. Sardarova: None. S. Yousuf: None. M. Hammoude: None. Background: Pembrolizumab is a monoclonal antibody targeting programmed death-1 (PD-1) receptors on T-cells. It was approved by the FDA in 2014 and has become an essential therapeutic agent for multiple malignancies in various combined therapies. While these revolutionary drugs have been highly effective, they are increasingly associated with immune-related adverse events (irAEs), including endocrine adverse events that can cause permanent impairments in glandular function. Clinical Case: A 79-year-old male with a history of high-grade urothelial bladder cancer (status post transurethral resection), HFpEF, atrial fibrillation, CKD, and hypertension, presented to the emergency department with complaints of severe fatigue, generalized weakness, loss of appetite for six weeks, and self-reported episodes of hypoglycemia in the 50s. Notably, he had recently completed cycle 7 of pembrolizumab two weeks prior. On the physical exam, he appeared very lethargic but alert, with stable vital signs except for borderline hypotension. Laboratory workup revealed a markedly elevated TSH (99.2 mcunit/ml), suppressed free T4 (0.3 ng/dl), low ACTH (<3 pg/ml), and low morning cortisol (2.1 mcg/dl), consistent with severe primary hypothyroidism and secondary (central) adrenal insufficiency. Imaging, including renal ultrasound, showed no obstruction, and a recent cystoscopy with cytology confirmed recurrent high-grade disease. Brain MRI showed an incidental small pituitary adenoma and ruled out pituitary metastasis. Pembrolizumab was held. The patient was treated with stress-dose IV hydrocortisone and IV levothyroxine, and when the patient's health condition improved, he was transitioned to oral hydrocortisone and levothyroxine, and subsequent labs showed improvement in thyroid functions, and he was discharged in stable condition to follow up with Endocrinology. Discussion: This is a unique case due to the rare co-occurrence of primary hypothyroidism (elevated TSH) and central adrenal insufficiency (low ACTH). This unusual pattern suggests that pembrolizumab (Keytruda) may have triggered autoimmune effects at two levels: a pituitary impact affecting corticotrophs and direct damage to the thyroid gland. Aside from one case in 2023, such a combination of conditions has not been documented. This case emphasizes the importance of keeping a high level of suspicion for multiple endocrine irAEs and conducting routine endocrine function monitoring during and after immune checkpoint inhibitor therapy. Early detection of irAEs through scheduled thyroid and adrenal axis screenings can enable prompt management and prevent life-threatening complications, such as myxedema coma and adrenal crisis. Presentation: Sunday, July 13, 2025