Pituitary Cushing's disease arising from a previously non-functional corticotrophic chromophobe adenoma

Severe pituitary Cushing's disease of sudden onset after 18 years of unsuccessful treatment for a previously non-functioning chromophobe adenoma is described in a middle-aged woman. Initial presentation with symptoms of optic nerve compression had been preceded by two years of amenorrhoea. Transfrontal resection of a chromophobe adenoma followed by radiotherapy, performed both at this time and again after a recurrence eight years later, failed to eradicate the tumour. Ten more years elapsed before she rapidly developed florid features of Cushing's syndrome. Plasma ACTH levels were markedly elevated and were only partially reduced by further transfrontal surgery, complete removal of the tumour proving impossible. Subsequent bilateral adrenalectomy was performed to control her hypercortisolism and a course of cytotoxic chemotherapy was administered in an attempt to treat the tumour recurrence. Immunocytochemical staining of tumour obtained at surgery demonstrated ACTH immunoreactivity both before and after the development of Cushing's disease. Although silent corticotrophic adenomas of the human pituitary, including chromophobic tumours, have been previously described, this is the first report of such a tumour becoming functional, sufficient to cause clinically evident Cushing's disease.