Adrenocorticotropin-secreting pituitary macroadenomas: expanding the clinical spectrum

Cushing disease (CD) secondary to adrenocorticotropin (ACTH)-secreting pituitary macroadenomas is uncommon, accounting for 10% to 15% of cases. We describe 3 patients from South Africa who presented with overt clinical features of hypercortisolism and considerable systemic complications, including hypertension, diabetes mellitus, and osteoporosis. Biochemical testing confirmed ACTH-dependent hypercortisolism with hypopituitarism and mild hyperprolactinemia consistent with stalk effect. Magnetic resonance imaging demonstrated pituitary macroadenomas, measuring 10 mm or greater, with parasellar extension. Mass effect was observed in 1 patient resulting in cranial nerve III palsy, while the others had visual field deficits secondary to optic chiasm compression. All patients underwent endoscopic transsphenoidal surgery, with 1 achieving remission and 2 developing recurrence. These cases highlight that ACTH-secreting macroadenomas can present with severe systemic disease and significant mass effect, and emphasize the importance of lifelong follow-up.