Nelson's syndrome after Cushing's disease in childhood: a continuing problem

Nelson's syndrome--progressive cutaneous hyperpigmentation with x-ray film evidence of an expanding pituitary tumor--is now a well-recognized sequela of bilateral adrenalectomy for Cushing's disease. It is estimated to occur in 8% to 38% of adults. Because Cushing's disease is rare in children, a higher incidence of Nelson's syndrome has not been suggested until recently. Although transsphenoidal operation is now the treatment of choice for Cushing's disease, children who have undergone bilateral adrenalectomy remain at risk for the development of Nelson's syndrome. A review of our experience and the literature indicates that the incidence of Nelson's syndrome after the treatment of Cushing's disease is higher in children than in adults. In our six children who underwent adrenalectomy between 8 and 17 years of age, four developed Nelson's syndrome at 2, 6, 10, and 12 years after adrenalectomy. Two of these patients remain well at 6 and 9 years after treatment with external irradiation. One patient treated with external irradiation developed recurrence at 5 years and required total hypophysectomy. The fourth patient required total hypophysectomy followed by external irradiation. Of the 37 patients reviewed and analyzed, the mean age at diagnosis of Cushing's disease was 12 years, with a mean interval of 8.4 years between adrenalectomy and Nelson's syndrome. Information regarding treatment for Nelson's syndrome was known in 24 patients and included pituitary irradiation (four patients), pituitary operation (11 patients), pituitary irradiation followed by operation (six patients), and pituitary operation followed by irradiation (three patients).