Nelson Syndrome Differential Diagnoses

Updated: Mar 25, 2021
  • Author: Thomas A Wilson, MD; Chief Editor: Robert P Hoffman, MD  more...
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DDx

Diagnostic Considerations

Diagnosis of Nelson syndrome is based on the clinical triad of elevated plasma adrenocorticotropic hormone (ACTH) levels, hyperpigmentation, and tumor progression. [11] Other conditions to consider include nonpituitary tumors, nonfunctioning pituitary adenomas, and ectopic ACTH syndrome.

Symptoms of associated endocrine conditions (including diabetes, thyroid disease, and vitiligo) should be sought. Very long chain fatty acids should be measured in males presenting with adrenal failure to evaluate for the possible diagnosis of X-linked adrenoleukodystrophy. Adrenal failure may precede the onset of neurologic symptoms in this condition.

Ectopic secretion of ACTH should be considered in pigmented patients with features of Cushing syndrome. This is a rare disorder in children that is frequently associated with very high levels of ACTH and other proopiomelanocortin (POMC) derivatives. The source of ACTH is commonly either a carcinoid, or neuroendocrine tumor. These may be found in embryologic derivatives of the foregut, including the lungs, pancreas, and proximal GI tract. Rarely, pheochromocytomas arising in the adrenal medulla may also secrete ACTH. See Glucocorticoid Therapy and Cushing Syndrome.

Other causes of hyperpigmentation may be considered, including hemochromatosis (see Hemochromatosis) and inherited disorders of skin pigmentation, such as Fanconi anemia.

Differential Diagnoses