80-85% cases of Cushings disease show bilateral adrenal hyperplasia due to excess stimulation by adrenocorticotrophic hormone (ACTH). There is a failure of the negative feedback mechanism at the level of the pituitary and so ACTH is produced in an unregulated fashion. This is thought to occur due to a functional chromophobe cell (Produces ACTH and MSH) neoplasia, although visible macroadenomas are only found in 10-15% cases with this aetiology. Most cases are therefore thought to be microadenomas and may be visualised by histopathological staining of the pituitary.
Grossly the adrenals have an irregular surface with protruding nodules of cortical tissue; the hyperplased zona fasciculata cells.