Nelson's syndrome
Nelson's syndrome is a rare condition which may follow bilateral adrenalectomy for Cushing's syndrome. It results from the loss of feedback control of serum cortisol which leads to the development of an enlarging pituitary adenoma in 15-20% of cases. The spectrum of clinical features observed relates to the local effects of the tumor on surrounding structures, the
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secondary loss of other pituitary hormones, and the effects of the high alpha-melanocyte–stimulating hormone (a-MSH), another derivative of proopiomelanocortin (POMC, the precursor peptide from which ACTH is derived) on the skin.
Nelson's syndrome is the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for Cushing's disease. Extremely high plasma ACTH levels and aggressive neoplastic growth might be explained by the lack of appropriate glucocorticoid negative feedback due to defective glucocorticoid signal transduction. Nelson's syndrome classically presents with a pronounced pigmentation of the skin due to high levels of ACTH and melanocyte stimulating hormone. This is associated with a large, invasively growing tumour of the pituitary that occurs in up to 20% of those who have had a bilateral adrenalectomy. Almost all cases of Nelson syndrome follow bilateral adrenalectomy in patients who have Cushing disease due to an ACTH-secreting pituitary adenoma. Small ACTH-secreting pituitary adenomas may evade detection with MRI, and diagnostic evaluation may be misleading. Most adenomatous corticotropes still retain their responsiveness to corticotropin-releasing hormone (CRH). Following bilateral adrenalectomy and normalization of cortisol levels that had suppressed hypothalamic CRH production, an increase in CRH occurs, which then has a trophic effect on the tumor, stimulating its growth. Regulatory gene mutations and mutations in the glucocorticoid receptor may also be important in determining tumor behavior. When the adrenal glands have been removed, there is very little cortisol circulating, hence there is less negative feedback to the pituitary gland. This causes an increased cleavage of Pro-Opiomelanocortin (POMC) to ACTH and melanocyte stimulating hormone (MSH), the latter responsible for increasing skin pigmentation. This is becoming rarer due to the decrease in adrenalectomies performed. External radiation immediately after surgery is thought to prevent Nelson's syndrome. |
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