SAT-506 Rare Case of Durvalumab-Induced Thyroiditis, Transient Secondary Adrenal Insufficiency and Autoimmune Diabetes

Abstract

Introduction:Cancer Immunotherapy (CI) is rapidly advancing field with different immune check point inhibitors (ICPi) targeting different cancers, with Durvalumab being one of the recent ICPi. Durvalumab induced endocrinopathies are common, mostly irreversible and if managed appropriately do not require cessation. Here we are presenting a patient (pt) who developed 3 different endocrinopathies simultaneously.Case:A 69 year old female with type 2 diabetes mellitus (T2DM), Stage III lung cancer was started on Durvalumab for unresectable cancer. 2 months later, presented to Emergency Department with fatigue, poor appetite, dizziness, palpitations, heat intolerance, polydipsia, polyuria. Labs suggestive of Thyrotoxicosis, blood glucose of 600mg/dl, AM Cortisol & ACTH consistent with central adrenal insufficiency (AI). Her previously well controlled T2DM (A1C 6.1%), suddenly became uncontrolled (A1C 9.5%), Antibodies were positive suggesting superimposition of autoimmune diabetes (AID). Pt was discharged on Methimazole (MMI), hydrocortisone (HC) and modified Insulin regimen.After discharge patient stopped MMI and HC. TFT’s 2 weeks after stopping MMI were suggestive of hypothyroidism. AM Cortisol 10 days after stopping HC was normal, her subsequent AM cortisol remained normal. Her clinical picture with rapid conversion of thyrotoxicosis to hypothyroidism is suggestive of Thyroiditis from Durvalumab.Discussion:Durvalumab an ICPi is a programmed death-ligand 1(PD-L1) blocking antibody, initially approved for urothelial cancer, but was later shown to be effective in other solid tumors. Immune-related adverse events (irAE) due to Durvalumab therapy are mostly thyroid-related, AID and AI rarely reported. Pathogenesis of AID is likely related to PD-L1 blockage on autoreactive T cells that target islet cells. Ansari et al showed the development of autoimmune antibodies in a mouse model, later demonstrated in few human studies. irAE can affect more than one endocrine gland, typically occur in 10-11 weeks, can happen at same time or in succession. ICPi-induced hypophysitis should be considered prior to committing to diagnosis of primary AI. American Society of Clinical Oncology (ASCO) recommends screening for endocrine irAE with TSH/FT4 every 4-6 weeks, checking BG at baseline, every cycle for 12 weeks and then every 3 to 6 weeks. In patients with suspected type 1 DM, ASCO recommends checking antibodies, insulin, and, C-peptide levels. For AI, routine diagnostic work-up not recommended if asymptomatic.Conclusion:Our pt with T2DM developed AID, thyroiditis which progressed to hypothyroidism, central AI. This is a rare case where pt developed all 3 endocrinopathies secondary to durvalumab and also a rare case where AI self-resolved when pt still on durvalumab.