Presenting a case of alpelisib induced diabetic-ketoacidosis and status-epilepticus.

Alpelisib is a reversible Phosphoinositide-3-kinase α (PI3KCA) inhibitor,approved for management of hormone receptor-positive,human epidermal growth factor receptor-2(Her2) negative,PI3KCA mutated breast cancer in combination with fulvestrant.Alpelisib is known to causing a dose-dependent increase in the plasma glucose,insulin,and C-peptide levels, PI3K playing critical role in insulin signaling pathway. 

A 60-year-old Caucasian female with history of breast cancer with metastasis to brain, bone,and thyroid, was admitted following syncope.She was taking alpelisib with fulvestrant as the tumor was ER/PR positive, HER-2/neu negative, and PIK3CA mutation-positive.Her disease had progressed on previous endocrine therapy.She was on metformin for prediabetes.

On admission, she was afebrile, hemodynamically stable, and had no neurological deficits.MRI brain showed focal extra-axial density along the right anterior frontal lobe and mottled appearance of  skull representing known multifocal bony metastases(figures 1& 2).

During hospitalization, she developed DKA- glucose 513mg/dL, bicarbonate14, anion gap21, and pH7.3 resulting in status epilepticus with generalized tonic-clinic seizures, requiring intravenous levetiracetam and lorazepam.She was intubated for airway protection.Subsequent electroencephalogram showed prolonged study with presence of burst suppression activity and phase reversals in right temporal region. After correction of DKA, she did not have further epileptic activity.She was discharged on antiepileptics and close follow-up.

PI3KCA inhibitors are promising drugs in patients with metastatic breast cancer who have not responded to previous treatment;the SOLAR-1 trial showed 35% risk reduction in cancer progression and death.However, these patients are at risk of metabolic derangement with hyperglycemia and DKA, a potential limiting side-effect.The optimal management of hyperglycemia-induced by alpelisib warrants further research.