SUN-871 - AKT Inhibitor-Associated Hyperglycemic Crisis Requiring Continuous Renal Replacement Therapy for Metabolic Control

Capivasertib is an oral AKT inhibitor used in advanced hormone receptor–positive/human epidermal growth factor-negative (HR+/HER2-) breast cancer, with a known side effect of hyperglycemia due to insulin signaling disruption. Life-threatening diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) with extreme insulin resistance are rarely reported.
A 60-year-old woman with recurrent metastatic HR+/HER2- breast adenocarcinoma on capivasertib plus letrozole and no prior diabetes (pre-treatment HbA1c 5.7%) presented to the emergency department with profound weakness, altered mental status, and hypotension requiring pressors. She had been treated with capivasertib for several months, with her dose increased 4 days prior to presentation from 200mg BID to 400mg BID. Her glucoses prior to dose escalation ranged from 86 – 136 mg/dL. Initial evaluation showed glucose 716 mg/dL, anion gap 28, beta-hydroxybutyrate 6.85 mmol/L, venous pH 7.24, creatinine 1.6 mg/dL (baseline 0.6), osmolality 343 mOsm/kg and potassium 6.0 mmol/L—consistent with combined DKA/HHS physiology.
Capivasertib was held. The patient was admitted to the ICU for treatment with insulin infusion. Severe hyperglycemia >600mg/dL and acidosis persisted despite insulin infusion rates reaching the protocol maximum of 200 units/hr (>2.5U/kg/hr), consistent with profound insulin resistance due to AKT inhibition. Fluid resuscitation was limited by systolic heart failure and volume overload. Given refractory hyperglycemia with shock and acute kidney injury, continuous renal replacement therapy (CRRT) was initiated. CRRT likely facilitated rapid glucose clearance and osmolar reduction independent of insulin-mediated uptake. After CRRT initiation, serum glucose became measurable and steadily declined, allowing for taper and eventual discontinuation of insulin infusion; acid–base status improved with anion gap normalization; and hemodynamics stabilized.
AKT inhibitor therapy can precipitate severe DKA/HHS by blocking insulin signaling and inducing extreme insulin resistance in previously normoglycemic patients, particularly after dose escalation. In refractory cases complicated by hemodynamic limitations, CRRT may be an effective adjunct to rapidly improve hyperosmolarity and acidosis and reduce insulin requirements. We propose routine early glucose surveillance after AKT-inhibitor dose escalation and consideration of CRRT for refractory hyperglycemic crisis, including cases with hemodynamic compromise.

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