Severe Cushing Syndrome From Ectopic Adrenocorticotropin Secretion In Metastatic Prostate Cancer Treated With...

Treatment of severe hypercortisolism from Cushing syndrome due to ectopic adrenocorticotropin (ACTH) secretion (EAS) can lead to therapeutic challenges, particularly in the context of high doses of medication needed to normalize cortisol levels and other patient comorbidities. We present a case of a 64-year-old man with known metastatic prostate cancer for several years, whose disease had recently progressed despite androgen deprivation and chemotherapy, who presented with polyuria and generalized weakness. Initial evaluation revealed diabetic ketoacidosis, hypothyroidism, markedly elevated cortisol levels, along with elevated ACTH. He was suspected to have ectopic ACTH-secreting Cushing syndrome with plans to start outpatient treatment with osilodrostat. In the interim, he developed severe hypokalemia and proximal muscle weakness and was readmitted for potassium repletion and initiation of therapy with osilodrostat in combination with prednisone as part of a block-and-replace strategy. His serum cortisol and 24-hour urine cortisol levels progressively decreased with increasing doses of osilodrostat.