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.

Background Hypercholesterolemia (HC) in cholestatic liver disease commonly involves a high lipoprotein-X (LpX) and low LDL receptors. No evidence has been found to suggest the association of LpX with an increased risk of cardiovascular disease (CVD). Hence, lipid lowering therapy is unnecessary as HC improves with treatment of cholestasis, but plasmapheresis should be considered in markedly elevated LDL values given the uncertainty of short term complications. Clinical Case A 47-year-old man with HTN, DMT2, nephrotic syndrome secondary to DM glomerulosclerosis and CKD stage 3 was admitted for an NSTEMI and acute heart failure due to non-ischemic cardiomyopathy. On exam he had jaundice and hepatomegaly without xanthelasma or tendon xanthomas. Laboratory evaluation revealed elevated HDL 200 [35-75 mg/dl], LDL 2,182 [0-130 mg/dl] and triglyceride 326 [30-150 mg/dl] although his lipid panel four months ago was normal. He had no family history of HC or premature CAD. Interestingly, two months prior the patient was seen in GI clinic due to jaundice, pruritus, acholia and coluria. Work-up showed cholestasis with total bilirubin 5.2 [0.1-1.2 mg/dl], AST 148 [0-40 U/L], ALT 112 [5-25 U/L], alkaline phosphatase 1,874 [20-120 U/L] and GGT 2,307 [3-60 U/L]. Further evaluation was unrevealing with negative viral hepatitis serologies, antinuclear antibodies, anti-smooth muscle antibody, anti-mitochondrial antibody, ceruloplasmin, α-1antitrypsin. He underwent liver biopsy which demonstrated cholestatic hepatitis with advanced biliary fibrosis, lymphocytic cholangitis and perivenular infiltrate thought secondary to an atypical autoimmune cholangiopathy. Due to concern for hyperviscosity and potential CVD complications, two sessions of plasma exchange were performed with a rapid lowering of LDL to 661 mg/dL. He was given a dose of evolocumab and discharged on ursodeoxycholic acid with improvement in liver function and normalization of lipid panel within three weeks. His HC was presumed mainly from atypical autoimmune cholangiopathy. LpX was unlikely since his Apolipoprotein B was elevated at 239 [RR 52-109 mg/dl]. Once his liver function normalized, he was started on high intensity statin and ezetimibe due to an elevated CVD risk with a low ApoA 30 mg/dL [RR 94-176]. Conclusion This is a rare case of cholestatic liver disease causing markedly elevated LDL, successfully managed with plasma exchange and ursodeoxycholic acid with subsequent resolution of LDL abnormality. References 1. Cohen LB, Ambinder EP, Wolke AM, Field SP, Schaffner F. Role of plasmapheresis in primary biliary cirrhosis. Gut. 1985;26(3):291-4. 2. Suraweera D, Fanous C, Jimenez M, Tong MJ, Saab S. Risk of Cardiovascular Events in Patients with Primary Biliary Cholangitis - Systematic Review. J Clin Transl Hepatol. 2018;6(2):119-126.