Congenital adrenal hyperplasia encompasses several
autosomal recessive disorders with complete or partial deficiency of an
enzyme involved in the cortisol or aldosterone synthesis.
Adrenal Steroid Biosynthesis
Ambiguous genitalia in an infant with adrenogenital syndrome.
Clitoris hypertrophy in a female with adrenogenital syndrome.
Adrenal Virilism; Congenital Adrenal Hyperplasia.
Worldwide, the frequency of the classic form is
estimated to be 1:5000 to 1:15,000. However, in Yupik Eskimos of Alaska, the
disease occurs in up to 1:300 neonates.
Most often autosomal recessive inheritance.
Spontaneous mutations are possible.
The common finding in all of these cases is an
elevated ACTH level resulting from significantly decreased negative feedback
of cortisol on ACTH secretion in the pituitary gland. Congenital adrenal
hyperplasia (CAH), which to the histopathologic finding of adrenal cortical
hyperplasia, is the result of these elevated ACTH levels. Any of the steps
involved in adrenal steroidogenesis can be affected. The classic form, which
is responsible for more than 90% of all cases of CAH, is
characterized by absent or decreased activity of the enzyme 21-hydroxylase.
Whereas the classic form denotes the early diagnosed form of 21-hydroxylase
deficiency, the nonclassic form denotes the same enzyme defect with late
diagnosis (because of absent salt wasting and developmental abnormalities)
and signs of hyperandrogenism. From 5 to 8% of CAH cases are caused by
dysfunction of the enzyme 11-β-hydroxylase. In the remainder of
patients with CAH, the affected enzyme is either 17α-hydroxylase or
Depending on the affected enzyme, the symptoms can vary widely. Deficiency
of 21-hydroxylase, which
converts 17α-hydroxyprogesterone to 11-deoxycortisol,
results in accumulation of cortisol precursors that are metabolized to
adrenal androgens (dehydroepiandrostenedione [DHEA] and androstenedione)
instead. Absence of negative feedback on pituitary ACTH secretion, which is
caused by a lack of cortisol, potentiates the symptoms. Clinically, the
children may present in two forms: “simple virilization” or “salt
wasting.” At birth, female infants appear virilized with clitoral
enlargement, labial fusion, and/or urogenital sinus. Left untreated, these
signs can become even more prominent over time. Sexual development in male
infants usually is normal, but excessive androgen production can result in
sexual precocity. In up to 70% of all infants, “simple virilization” is
accompanied by salt wasting because of a mineralocorticoid deficiency with
hyponatremia, hyperkalemia, and hypotension (hypovolemia). Plasma renin
activity is elevated, and signs of hypoaldosteronism may occur in the first
weeks of life.
Deficiency in 11-β-hydroxylase, which is needed to convert 11-deoxycortisol and deoxycorticosterone (DOC)
to cortisol and corticosterone, also results in decreased cortisol levels
and increased ACTH levels. As a ...