Chriscopedia

Congenital adrenal hyperplasia (CAH) refers to the histiologic change in the adrenal gland that occus from a group of autosomal recessive disorders of adrenal steriodogenesis. Deficient activity of one of the 5 enzymes necessary fro cortisol synthesis results in inadequate cortisol production, a compensatory rise in ACTH and an accumulation of precursor steroids proximal to the defect. Each defect produces characteristic alteration in the levels of adrenal steroids, abnormality of fetal genital development, and metabolic disturbances.

Treatment Glucocorticoid replacement. Mineralcorticoid replacement in severe salt wasting. Sex assignment in a baby with ambigous genatalia requiring:

Karytyping

Pelvic Ultrasound

Hormonal evaluation

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21-Hydroxylase Deficiency

The most common form of CAH, accounting for more than 90% of cases. A deficiency in the fasiculata results in deficient cortisol production and a compensatory rise in ACTH. Precursors 17 hydroxypregesterone and Δ5-17 hydroxyprognenolone are channeled to androgen pathways.

Findings - In the female, excess androgens in the first trimester of pregnancy results in genital ambiguity ranging in degree from clitomegaly with or without partial or complete fusion of the labialscrotal folds with the appearance of a male urethra. In newborn males, the genitals are not ambiguous and are not "overvirilized". If left undiagnosed and untreated, symptoms of androgen excess would continue in both sexes: masculine habitus, acne, oily skin, increased growth velocity, rapid epiphyseal maturation, advanced bone age (and ultimatley short stature), and abnormal puberty with hirsuitism and polycystic ovarian disease.

The increase in pituitary ACTH release is associated with an increase in pigmentation of the mucous membranes and the intertringinal sites (palmar creases, knuckles, knees, elbows). In infants, there is hyperpigmentaion of the labia and scrotum.

Most also have a deficiency in the glomerulosa as well, thus causing an aldosterone deficiency. This can cause a salt-wasting variant of 21-hydroxylase deficiency resulting in natriuresis, water loss, and potassium retention with resultant hyponatremia, hyperkalemia and hypovolumia. This may present at one week to three months oof life with failure to thrive, poor weight gain, poor feeding, vomiting, irritability, lethargy and eventually coma.

Dx and treatment

Amniocentesis (at 16 weeks gestation)

Chorionic Vilus Sampling (at 7-9 weeks gestation)

Prenatal treatment - Maternal treatment with dexmethasone beginning early in the first trimester

Newborn screening - screening for CAH dues to 21-hydroxylase def is possible by measurement of 17OH progesterone

3-β-Hyroxysteroid Dehydrogenase Deficiency

Autosomal recessive deficiency of 3-β-Hyroxysteroid Dehydrogenase. It occurs in the adrenals and gonads, thus both adrenal and gonadal pruduction of androgens is deficienct.

In males, this results in undervirilization and ambiguous genatalia. In females, there is some clitoromegaly from the androgeneic effecs of elevated DHEA.

Findings = Elevated ratio of Δ5 to Δ4 steroids. the Δ5 steroids are elevated in the serum (17-hydroxypregnalone and DHEA). Urinary metabolites are also elevated (pregnenetriol and 16-pregnenetriol)

Deficient aldosterone production and salt wasting syndrome similar to 21-hydroxylase deficiency can be seen in some patients.

11-β-Hydroxylase Deficiency

Hypertensive CAH Autosomal recessive disorder in the fasiculata. Results in elevated serum deoxycortisol and deoxycorticosterone (DOC) and in their urinary metabolites. DOC is a mineralcorticoid and thus causes retension of sodium and water in the distal convuluted tubule. This results in hypertension.

Their is virilization of the female and males appear normal. Untreated, both sexes will become virilized.

17-α-Hydroxylase Deficiency

Hypertensive CAH Defect in the adrenals and gonads, with dimished corisol and sex hormones. Genetalia appear female in both sexes. Accumulation of DOC results in sodium and water retention, hypervolumiam hypokalemic alkalosis, volume overload and eventual hypetension. Plasma renin is uppressed and aldosterone production is low.

Females present with primary amenorrhea and lack of development of secondary sex characteristics because of the inability to egnerate androgens and estrogens. Males typically appear female.

Lipoid Adrenal Hyperplasia

Cholesterol accumulation occurs within the adrenal gland as there is a defect in the production of pregnenalone. This results in the deficiency of all steroids in the gonads and adrenals. Mineralcorticoid deficiency leads to salt wasting and severe electrolyte and fluid disterbances. Most patients do not survive infancy.

Nonclassic CAH

Of any of the above deficiencies as presenting in later childhood, puberty or adult life.

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