MON-423 Pembrolizumab induced hypothyroidism and autoimmune diabetes

Abstract Disclosure: G. Patel: None. P. Lekprasert: None. K.K. Win: None. Immune check point inhibitors (ICI) have become a novel treatment approach to several malignancies. Though they have revolutionized cancer treatment they have several adverse effects on the body, especially endocrinopathies. There are several reported endocrine disturbances related to ICIs including hypopituitarism, adrenal dysfunction, thyroid/parathyroid dysfunction, and autoimmune diabetes. We report a case of a patient treated with pembrolizumab who first developed hypothyroidism and later also developed autoimmune diabetes.The patient is a 55-year-old female with a history of cervical cancer. She had completed chemotherapy and was being maintained on pembrolizumab therapy. Prior to starting pembrolizumab, her baseline TSH was 1.19 mIU/mL with a free T4 of 0.76 ng/dL. Three months later, she had a low TSH of 0.01 mIU/mL and elevated free T4 of 1.81 ng/dL, believed to have been destructive thyroiditis. One month later TSH rose to 9.33 mIU/mL with a free T4 of 0.48 ng/dL, as expected in the hypothyroid phase of destructive thyroiditis. Just a few weeks after that thyroid function tests were rechecked to ensure return to baseline, but TSH was elevated to 86.0 mIU/mL with an undetectable free T4 and total T3. She was started on levothyroxine replacement requiring increasing doses over the next six months. Her final levothyroxine dose to maintain a euthyroid state was significantly higher than her weight-based dose. In addition, seven months after starting initial pembrolizumab therapy she was found to have hyperglycemia with a serum glucose of 244 mg/dL and an HbA1c of 8.0%. Autoimmune diabetes antibody panel returned positive for a GAD-65 antibody level of >120. She had a C-peptide level of 1.9 ng/mL with a serum blood glucose of 397 mg/dL. She was started on a basal bolus insulin regimen and diagnosed with pembrolizumab-induced autoimmune diabetes in addition to acquired hypothyroidism.Pembrolizumab is an ICI used in the treatment of lung, lymphoma, urothelial, renal cell, and head/neck cancers and more. It is an anti-programmed cell death-1 antibody commonly associated with thyroid dysfunction occurring in about 5-10% of patients. Patients on pembrolizumab therapy need frequent monitoring of the thyroid function, and prompt treatment when testing is positive. Autoimmune diabetes because of beta cell destruction from pembrolizumab therapy has also been reported, but it is much rarer occurring in only about 0.4% of patients. The beta cell defect is permanent, and patients require treatment with insulin. It is crucial to keep these endocrinopathies in mind when patients are being treated with an ICI, and screening and treatment should be completed when appropriate. ICI therapy is continued without interruption while endocrinopathies are being managed separately via a multidisciplinary team approach. Presentation: Monday, July 14, 2025