Search

ABSTRACT: Objective: Alpelisib-induced diabetic ketoacidosis (DKA) is a rare, but life-threatening, adverse event. There have been only 2 reported cases in the literature. We describe such a case, with emphasis on the importance of screening and achieving adequate glycemic control prior to and after initiation of therapy. Methods: A 49-year-old woman, known to have advanced breast cancer, presented with a 3-day history of nausea, vomiting, and diffuse abdominal pain. She had started alpelisib at 300 mg/day 2 months prior to presentation, after failing other options. She was diagnosed with DKA using her clinical and laboratory features, leading to treatment with hydration and intravenous insulin therapy. Results: Laboratory data showed high anion gap metabolic acidosis, hyperglycemia, and ketonemia with negative GAD-65 antibodies, leading to the diagnosis of alpelisib-associated DKA. Alpelisib was held, and she was treated with intravenous insulin and hydration. When DKA and hyperglycemia resolved, alpelisib was resumed at a lower dose (200 mg/day) and her blood glucose was managed using a regimen combining insulin and metformin. Conclusion: Phosphatidylinositol-3 kinase signaling is important for the metabolic actions of insulin, and alpelisib has been associated with severe hyperglycemia. Metformin is the first-line treatment, however when DKA is the presenting syndrome, insulin needs to be considered. Blood glucose and hemoglobin A1c should be checked prior to treatment initiation and monitored closely after drug initiation. DKA, albeit rare, must be considered in an acutely ill, alpelisib-treated patients presenting with metabolic acidosis, and if drug discontinuation is not an option, insulin treatment may be required to control glycemia. Abbreviations: DKA diabetic ketoacidosis HbA1c hemoglobin A1c PI3K phosphatidylinositol-3 kinase

ABSTRACT: Objective: To describe 2 spontaneous cerebrospinal fluid (CSF) leaks complicating treatment of macroprolactinoma (MPRL) with dopamine agonist (DA) therapy. Methods: We present the 2 cases of spontaneous, DA-related CSF leaks. Prolactin levels were used to assess hyperprolactinemia. Beta-2 transferrin was tested in rhinorrhea fluid, and magnetic resonance imaging was used to assess the sella. Results: Case 1 was a 45-year-old woman with a history of MPRL, recently started on bromocriptine at 15 mg/day, presented with clear rhinorrhea, headache, and nuchal rigidity. Magnetic resonance imaging showed a large sellar lesion extending into the cavernous sinuses, posterior sphenoid sinuses, and suprasellar cistern. Computed tomography revealed areas concerning for bony erosion, likely representing leak sites, and the rhinorrhea fluid was positive for beta-2 transferrin, confirming the CSF source. Empiric antibiotics for meningitis were given and she underwent urgent neuroendoscopic, transsphenoidal CSF leak repair and debulking of the pituitary mass. Case 2 was a 55-year-old man with a 10-year history of untreated MPRL who was started on bromocriptine at 5 mg/day 2 weeks prior to admission. He presented with clear rhinorrhea and a metallic taste in his mouth, worse with the Valsalva maneuver. Imaging confirmed clinical suspicion and he was taken for surgery. A high-flow CSF leak was encountered once the tumor was debulked. This was repaired with an abdominal fat pad graft. Both patients developed diabetes insipidus and required postoperative adjuvant DA therapy. Conclusion: Spontaneous CSF leaks can complicate medical therapy of large MPRL with underlying skull defects, typically within weeks of initiation of DA. This should prompt clinicians to educate patients about the symptoms of potential CSF rhinorrhea and encourage them to promptly report them.