In 1958, Nelson and colleagues (110) reported the rapid enlargement of ACTH-secreting pituitary adenomas after bilateral adrenalectomy. Historically, these patients develop hyperpigmentation by excessive ACTH elevation (the ACTH molecule contains a-MSH) and radiologic demonstration of pituitary enlargement (129). Although the incidence of Nelson's syndrome has been reported to be as high as 38% in patients with CD who underwent bilateral adrenalectomy (109,130133), it is encountered only rarely these days, because bilateral adrenalectomy is now reserved for patients who did not respond to pituitary surgery and/or radiotherapy. Because many ACTH-secreting pituitary adenomas respond to CRH stimulation, it is conceivable that, in analogy to some patients with severe hypothyroidism (TSH >100 U/mL, TRH elevation unknown) and subsequent pituitary enlargement, in patients after bilateral adrenalectomy the CRH stimulus causes enlargement of some but not all ACTH-secreting adenomas, with a subset having a more aggressive potential (those that might have recurred anyway, if pituitary surgery had been performed as first-line therapy).
Children with CD who underwent bilateral adrenalectomy as first-line treatment have a higher incidence of Nelson's syndrome than do adults, because they have more years of life to live and thus a longer follow-up period (134,135).
Whether pituitary irradiation before adrenalectomy can prevent the development of Nelson's syndrome is unknown (109,136). ACTH levels in patients with Nelson's syndrome frequently exceed 1000 pg/mL. Headaches and visual field defects may be present (131). The majority of Nelson's syndrome tumors are macroadenomas and invasive.
If possible, patients with Nelson's syndrome in whom vision is threatened should undergo pituitary surgery to remove or debulk the tumor. Pituitary irradiation is the only currently available second-line therapy, because medical treatment does not have a significant role in treating Nelson's syndrome (106,133,138,139).
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