Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency.

Background: Glucocorticoids are essential for the normal development and fu nctioning of the adrenal medulla. Whether adrenomedullary structure and fun ction are normal in patients with congenital adrenal hyperplasia is not kno wn. Methods: We measured plasma and urinary catecholamines and plasma metanephr ines in 38 children with congenital adrenal hyperplasia due to 21-hydroxyla se deficiency (25 children with the salt-wasting form and 13 with the simpl e virilizing form), 39 age-matched normal subjects, and 20 patients who had undergone bilateral adrenalectomy. Adrenal specimens obtained from three o ther patients with 21-hydroxylase deficiency who had undergone bilateral ad renalectomy and specimens obtained at autopsy from eight other patients wer e examined histologically. Results: Plasma epinephrine and metanephrine concentrations and urinary epi nephrine excretion were 40 to 80 percent lower in the patients with congeni tal adrenal hyperplasia than in the normal subjects (P<0.05), and the value s were lowest in the patients with the most severe deficits in cortisol pro duction. Urinary epinephrine excretion and plasma epinephrine concentration s were at or below the limit of detection of the assay in 8 (21 percent) of the patients with congenital adrenal hyperplasia and in 19 (95 percent) of the patients who had undergone adrenalectomy. In the group of patients wit h congenital adrenal hyperplasia, plasma epinephrine and metanephrine conce ntrations and urinary epinephrine excretion were approximately 50 percent l ower in those who had been hospitalized for adrenal crises than in those wh o had not. In three patients with congenital adrenal hyperplasia who had un dergone bilateral adrenalectomy, the formation of the adrenal medulla was i ncomplete, and electron-microscopical studies revealed a depletion of secre tory vesicles in chromaffin cells. Conclusions: Congenital adrenal hyperplasia compromises both the developmen t and the functioning of the adrenomedullary system. (N Engl J Med 2000;343 :1362-8.) (C) 2000, Massachusetts Medical Society.