Current topics in neuropathology. Cushing's disease.

The application of modern investigative techniques, particularly electron microscopy and immunohistochemistry, to the pituitary gland in Cushing's disease have confirmed that in the majority of cases (up to 90% in some series) the disease is due to a corticotroph microadenoma. It has also been shown that the tumours may produce not only ACTH, but also other peptides derived from the same precursor molecule, pro-opiomelanocortin and, in a small minority of cases, other pituitary hormones (e.g. prolactin). Since these peptides are known to have physiological actions they may account for some of the varied symptoms and signs of Cushing's disease. Because of the high incidence of single tumours the treatment of choice in many centres has become selective adenomectomy by the transsphenoidal route. However, a minority of cases appear to be the result of primary hypothalamic or central abnormalities and this may account for the identification of a normal pituitary gland or of corticotroph hyperplasia (with or without tumour formation). It is not possible at the present to identify these groups of patients on the basis of biochemical testing. It is hoped that detailed prospective studies correlating hormone secretion, responses to biochemical testing and detailed investigation of pathological tissue will provide further insight into the pathogenesis of particular variants of the disease.