Year: 2024
Type: article
Study design: Case Report
Abstract: Disclosure: P. Aron: None. B. Connell: None. R. Longo: None. J. Upadhyay: None. This is a case of severe hyperglycemia with the use of Enfortumab Vedotin (EV) in the setting of advanced urothelial cancer. EV is a nectin-4-directed antibody-drug conjugate with a microtubule inhibitor approved for treating advanced/recurrent disease. It is the first of its class that is an antibody-drug conjugate (ADC), targeting nectin, but not the first ADC to cause hyperglycemia. Here we present a case of severe insulin resistance requiring insulin infusion at 50 units/hour in addition to subcutaneous insulin all in the setting of EV use.74 year old male with BMI of 28 and HbA1c of 7.5%, managed only with diet was started on EV for metastatic urothelial cancer. Patient received one cycle (3 doses) of EV (on days 1, 8, 15) and thereafter noticed worsening of hyperglycemia with blood glucose of 533 mg/dL, requiring subcutaneous insulin. Patient’s blood glucose readings remained elevated and he was admitted to the hospital as he was found to be in DKA with a pH of 7.2, bicarbonate 14 mmol/L, anion gap of 16 mmol/L and a glucose of 558 mg/dL. The patient was started on intravenous insulin (IV) infusion using insulin infusion protocol titrated up to 14 units an hour with an additional 30 units of glargine. Patients’ clinical condition continued to worsen and he was in septic shock with pressors and on insulin infusion exceeding 55 units/hour, NPH at 50 units, and regular insulin 30 units with glucose persistently above 400 mg/dL. Patient was started on hydrocortisone 50mg every 6h and his blood glucose readings eventually normalized over a span of 1 week. Patient eventually was able to be discharged to rehabilitation with just a correctional humalog insulin. Our case demonstrates DKA as a consequence of severe insulin resistance seen as a side effect of EV. Hyperglycemia is seen in 8% of patients using this medication, but severe cases are mostly seen with high BMI and uncontrolled diabetes. This case illustrates the fact that one needs to be cautious in ALL patients with diabetes when using this drug and warrants screening for DKA/severe insulin resistance if blood glucose is running >250mg/dL. The exact mechanism for hyperglycemia is unknown but it is likely immunomodulatory and therefore treatment with pulse dose steroids may help with overcoming insulin resistance in this setting like in our patient. More research needs to be done to understand mechanisms and establish treatment guidelines for severe insulin resistance and hyperglycemia caused by this medication. Presentation: 6/1/2024
Source: Journal of the Endocrine Society
Institutions: Lahey Hospital and Medical Center, Lahey Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,418
OpenAlex ID: W4403152818