Hypercortisolism with non-pigmented micronodular adrenal hyperplasia: transition from pituitary-dependent to...

We report on a female patient with Cushing's syndrome in whom we observed the transition from pituitary dependency to adrenal dependency. Basal ACTH and cortisol values, the CRH test, the dexamethasone suppression test as well as CT of the pituitary and the adrenal gland all reflected pituitary-dependent Cushing's disease in 1985. The patient refused treatment, but presented again five years later. At that time ACTH was suppressed before and after CRH injection. Plasma cortisol did not respond to CRH. After ketoconazole therapy, ACTH was within the high normal range. The patient underwent bilateral adrenalectomy. The adrenals exhibited a bilateral micronodular hyperplasia of the zona fasciculata. In vitro examination of adrenal cells revealed a maintained ACTH response. Some weeks postoperatively, the patient died from pneumonia. Histological examination later showed a chromophobe pituitary microadenoma; ACTH was demonstrated immunohistologically in the adenoma. We postulate that some cases of pituitary Cushing's disease initially exhibit a bilateral homogeneous adrenal hyperplasia which then develops into a nodular hyperplasia; in the next stage of the disease, single micronodules may become autonomous and elevated cortisol levels suppress ACTH secretion of the pituitary adenoma.