Fifty patients bilaterally adrenalectomized for Cushing's disease were followed for 1 to 22 (mean, 12) years. In 14 of them (28%) Nelson's syndrome appeared within 1.5 to 12 (mean, 4.8) years after adrenalectomy. All the patients were deeply pigmented, 12 had a radiologically demonstrable tumour and six had visual defects. Plasma ACTH levels ranged from 450 to 8000 ng/l. However in every case at least one estimation during circadian studies equalled 2000 ng/l. One patient with an anaplastic pituitary tumour died 3 years after the discovery of the tumour. Anaplasia was also diagnosed in another patient with recurrence of pituitary tumour after a transsphenoidal operation. Symptoms of tumour infarction occurred in two patients, followed by clinical remission of Nelson's syndrome. In the majority of cases the course was benign. We conclude that all cases, however, should be followed indefinitely because Nelson's tumours are not infrequently aggressive.
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