Revisiting the Nelson’s Syndrome: Corticotroph Tumor Progression After Bilateral Adrenalectomy in Cushing’s Disease

Abstract

Since Don Nelson's first description in 1958 of a pituitary macroadenoma occurring after adrenalectomy in a patient with Cushing's disease, the ``Nelson's syndrome{''} has long been feared. However, major medical advances, such as pituitary imaging with MRI, surgery by the transsphenoidal route, and safe radiotherapy, have changed the way corticotroph tumor progression (CTP) can be monitored and treated. Rather than ``wait{''} for the late occurrence of Nelson's syndrome, as defined originally with the complications of macroadenomas, we can now detect, early and precisely, the possible occurrence of CTP long before the classical features of Nelson's syndrome have developed. In a recent study of 53 patients followed by MRI after bilateral adrenalectomy, we showed that 3 years after adrenalectomy, the proportion of patients showing evidence of CTP reached 39%; this number tended to plateau at 47% after 7 years. Thus, ca. 50% of the patients showed no evidence of CTP under this time period. Factors that were found to be significantly associated with a higher risk to develop CTP were duration of Cushing's disease, baseline ACTH plasma level in the year following adrenalectomy, and the rate of increase in ACTH plasma levels after adrenalectomy. If necessary, pituitary surgery and/or radiotherapy can control the CTP in a majority of situations. The CTP does not seem accelerated during the pregnancy. There is no question that pituitary surgery remains the first-line treatment in most patients with Cushing's disease. Yet, when complete removal of a corticotroph tumor is not achievable, total bilateral adrenalectomy can be considered among the various therapeutic options in Cushing's disease. The CTP is not constant and is manageable in most cases. There is a definite need for new pharmacologic agent directed against corticotroph tumors.