However, this blockade can also lead to an unintended increase in autoimmune destruction of cells including pancreatic insulin producing beta cells

However, this blockade can also lead to an unintended increase in autoimmune destruction of cells including pancreatic insulin producing beta cells. This case is the first to describe type 1 diabetes mellitus (T1DM) secondary to Gingerol atezolizumab therapy developing in a patient previously diagnosed with type 2 diabetes mellitus (T2DM). Screening for T1DM in patients receiving PD-L1 inhibitors is critical when patients present with new Rabbit polyclonal to ANGPTL4 onset hyperglycaemia and in when patients with T2DM present with a decompensation in glucose control and/or diabetic ketoacidosis. Footnotes Twitter: @diabetes Contributors: KDS and WR participated in the care of the reported patient. has revolutionised cancer treatment and led to clinical improvements in outcomes for metastatic malignancies previously deemed incurable. Currently available drugs target molecules that regulate immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 or ligand 1 (PD-1 or PD-L1).1 2 Checkpoint immune inhibitors operate by manipulating the bodys own immune T cells to recognise cancer cells as foreign, thereby making the cancer cells vulnerable to immune attack.1C3 Checkpoint immune inhibitors lead to a bolstering of T-cell activity, which is responsible for both the desired antitumour response and also the unintended autoimmune side effects.4C6 Atezolizumab, an engineered humanised IgG1 isotype checkpoint inhibitor against PD-L1, is approved by the USA Food and Drug Administration for use in advanced urothelial,7 lung8 and breast9 cancers and is under investigation for other cancers including renal cell carcinoma.10 Associated autoimmune endocrine side effects are uncommon and include hypothyroidism (5%), hyperthyroidism (2%), adrenal insufficiency ( 1%) and type 1 diabetes mellitus (T1DM) with diabetic ketoacidosis (DKA) ( 1%).4 6 11C20 As a result of the success that this group of cancer chemotherapeutic agents, the number of reports of immune checkpoint inhibitor endocrinopathies is expected to grow. We present a case of glutamic acid decarboxylase (GAD) antibody-positive T1DM developing in a patient with a history of long-standing well-controlled type 2 diabetes mellitus (T2DM) following treatment with atezolizumab for metastatic renal cell carcinoma. Case presentation A 64-year-old man with a history of presumed T2DM, renal cell carcinoma with metastasis to liver, congestive heart failure and postablative hypothyroidism was admitted to the hospital after presenting to an outpatient oncology appointment with polyuria, polydipsia, blurred vision and hyperglycaemia (glucose 609?mg/dL). High-dose glucocorticoids Gingerol (prednisone 60?mg three doses over the 12?hours prior to imaging) taken for an intravenous contrast allergy in preparation for a CT scan were thought to contribute to the hyperglycaemia. Inpatient evaluation showed serum bicarbonate 16 mEq/dL and +2 urine ketones which were concerning for DKA (table 1). Table 1 Admission laboratory evaluation thead Serum values (range)Results /thead Plasma glucose (70C99?mg/dL)609?mg/dLAcetone, blood (ref: negative)Mildly elevatedAnion gap (4C16)22Serum bicarbonate (22C26?mmol/L)16?mmol/LUrine ketones (negative)2+Haemoglobin A1c (5.6%)8.3 %Venous pH (7.32C7.44)7.29Glutamic acid decarboxylase antibody-65 (0C5?IU/mL) 250?IU/mL Open in a separate window At the time of presentation, he had received eight cycles of combination immunotherapy with atezolizumab (PD-L1 inhibitor), interleukin-2 (IL-2) and bevacizumab (vascular endothelial growth factor-A inhibitor) over the course of the previous 3?months for metastatic renal cancer. Since developing capillary leak syndrome, a complication of IL-2 treatment, 2?months prior to admission, he was also treated with high-dose glucocorticoids (hydrocortisone 200?mg) every 2?weeks Gingerol before each chemotherapy cycle. The patient was originally diagnosed with T2DM by his primary care provider 5? years prior to presentation at our institution. He was presumed to have T2DM based on his initial clinical presentation which included obesity (body mass index 35.8?kg/m2) and other features of metabolic syndrome including hypertension and hyperlipidaemia, absence of DKA, good glucose control on oral medications and strong family history of T2DM. Glucose levels had been previously well controlled with haemoglobin A1c of 5.5% and he did not have evidence of microvascular or macrovascular complications. Three months prior to presentation, linagliptin and metformin were discontinued due to nausea with chemotherapy. Off of oral hypoglycaemic medications, glucose levels were initially 80C90 mg/dL on diet alone; however, glucose levels rose to 300C400 mg/dL over the month prior to admission (figure 1) despite no changes in diet or activity and included times when the patient was not receiving glucocorticoid therapy. Open in a separate window Figure 1 Serum glucose trend since initiation of atezolizumab. Investigations Because of the presentation with recent decompensation in glucose control, DKA and the prior use of atezolizumab, a PD-L1 inhibitor known to trigger the onset of autoimmune.