MON-621 Capivasertib-induced DKA in a non-diabetic female.

Abstract Disclosure: H. Dave: None. F. Abdulle: None. S. Shah: None. H. Hussien: None. Capivasertib is an oral targeted therapy that inhibits the AKT serine/threonine kinase pathway, which plays a crucial role in regulating cell growth and survival. It is used in treating HER-/+ breast carcinoma. Hyperglycemia is a recognized side effect of Capivasertib; however, life-threatening hyperglycemia, such as diabetic ketoacidosis (DKA), is a rare complication, with an incidence of approximately 0.03%. Here, we present a case of a non-diabetic, 54-year-old female who developed DKA following Capivasertib. A 54-year-old female presented to the emergency department with altered mental status. Her past medical history included metastatic invasive lobular carcinoma of the left breast (ER/PR positive; HER-2 negative) and deep vein thrombosis. She was initiated on Capivasertib two weeks prior to presentation. On examination, blood pressure was 80/64 mmHg. Workup revealed a blood glucose level of 839 mg/dL, a pH of 7.126, potassium of 6.3 mmol/L, sodium of 120 mmol/L, anion gap of 35 mmol/L, bicarbonate of 5 mmol/L, beta-hydroxybutyrate of 8.98, urinalysis showing ketones and glucose, confirming the diagnosis of DKA. She was managed with fluid resuscitation, insulin drip and empiric antibiotics. She was intubated for airway protection and admitted to the medical intensive care unit. Despite aggressive treatment, she continued to have persistent hyperglycemia, requiring high doses of insulin (13.8 units/hr; body weight 57 kg), with concurrent hyperkalemia resistant to insulin treatment. A bicarbonate drip was initiated in response to her acidosis. Furthermore, she developed anuria, which prompted a discussion with family regarding the need for dialysis. They opted against this, and the patient was transitioned to comfort care. She went into asystole and passed away. Blood cultures were negative. Capivasertib’s effects on glucose metabolism is attributed to its inhibition of the AKT pathway, which plays a crucial role in regulating insulin sensitivity. Inhibiting AKT activity may disrupt insulin-dependent glucose regulation and uptake in adipocytes. Our case demonstrates that persistent hyperglycemia, despite high doses of insulin, may lead to irreparable impairment in insulin sensitivity, resulting in fatal outcomes. This case highlights the potential for Capivasertib to induce new-onset diabetes mellitus and, subsequently, DKA in non-diabetic individuals. Literature contains limited case reports of patients developing DKA following Capivasertib therapy, highlighting the importance of healthcare providers being aware of this potentially lethal side effect. Although there are no established guidelines to mitigate the risk of this, regular glucose monitoring and the management of diabetic risk factors are essential prior to the initiation of treatment. Further research is imperative to better address this. Presentation: Monday, July 14, 2025