Cushing Disease Mimicking Ectopic Adrenocorticotropic Hormone-Secreting Disease

We present the case of a patient whose initial biochemical results suggested an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor, with markedly increased serum ACTH levels, increased 24-hour urinary free cortisol levels, and hypokalemia. Although these features are more commonly associated with ectopic ACTH secretion, the patient was ultimately diagnosed with Cushing disease.

A 46-year-old man presented with recurrent headaches and progressive skin darkening. He had hypertension and a body mass index of 28.4 kg/m². Initial blood work revealed hypokalemia at 3.2 mEq/L (normal reference range, 3.5-5.1 mEq/L), and screening tests for Cushing syndrome were pathologic including a highly increased urinary free cortisol level (605 μg/24 h; normal reference range, 20.9-292 μg/24 h). The serum ACTH level was high (89 pg/mL; normal reference range, 0-45.4 pg/mL), and pituitary magnetic resonance imaging showed an 8-mm lesion in the pituitary gland. Transsphenoidal pituitary surgery was performed with subsequent postsurgical remission.

Higher urinary and plasma cortisol levels are typical of ectopic ACTH-secreting tumors and likely cause hypokalemia and hypertension, which are encountered more frequently in patients with ectopic ACTH-secreting tumors. In the absence of a pituitary mass 1 cm or more in size, further testing to differentiate Cushing disease from an ectopic source is required.

Highly increased serum ACTH and cortisol levels, hypokalemia, and hypertension occur more frequently in patients with ectopic ACTH-secreting tumors. However, we show that they may occur in Cushing disease, and therefore, it would be wrong to assume a diagnosis of an ectopic ACTH-secreting tumor based on these findings alone.