Pathophysiology

The production of cortisol occurs in the zona fasciculata of the adrenal cortex
through 5 enzymatic steps.

Scheme of adrenal corticosteroid synthesis

Deficiency of 21-hydroxylase enzyme causes insufficient cortisol production,

stimulating increased production of corticotrophin-releasing hormone and
ACTH. High ACTH levels lead to adrenal hyperplasia and production of excess
androgens (e.g., delta-4-androstenedione), which do not require 21-
hydroxylation for synthesis. Symptoms of excessive androgens are found in
varied degrees in classical and non-classical forms of 21-hydroxylase deficiency
and are attributable to the severity of the enzyme defect.

The internal female reproductive tract remains normal, as the ovaries do not
produce anti-Mullerian hormone. Postnatal virilisation includes rapid growth,
premature development of pubic hair, and advanced epiphyseal maturation
leading to secondary precocious puberty, early epiphysis fusion, and short final
adult height. Short stature may be the combined result of elevated adrenal
androgens causing advanced epiphyseal maturation and premature epiphyseal
fusion. Glucocorticoid over treatment leads to growth suppression and short
stature. Gonadal dysfunction usually occurs, as the excess adrenal androgens
suppress pituitary gonadotrophins and thus impair gonadal growth and function.

When the loss of 21-hydroxylase function is severe, adrenal aldosterone

secretion is insufficient to stimulate sodium reabsorption by the distal renal
tubules, resulting in salt-wasting as well as cortisol deficiency, in addition to
androgen excess.

(http://bestpractice.bmj.com/best-
practice/monograph/699/basics/pathophysiology.html)