[Congenital adrenal hyperplasia]

Congenital adrenal hyperplasia is generally considered to be a rare disease; however, the incidence of severe forms of CAH is probably greater than 1 in 10,000 people and the incidence of milder forms is probably 10 times higher. It is a group of autosomal recessive disorders of adrenal steroidogenesis caused by a genetic disorder in one of the steroidogenic enzymes. These disorders impair cortisol synthesis, resulting in stimulation of pituitary proopiomelanocortin and hypersecretion of adrenocorticotropin, which in turn causes adrenal growth. A genetic disorder in one of the steroidogenic enzymes interferes with normal steroid hormone synthesis. The sings and symptoms of the disease derive from a deficiency of the steroidal end product and from the effects of the accumulated steroidal precursors proximal to the disordered step. Because five enzymatic steps are involved in cortisol biosynthesis, there are five distinct CAH syndromes. CAH-SYNDROMES: 21-Hydroxylase deficiency is the most common variant of CAH, accounting for about 90% of all cases. The clinical syndrome is consequence of defective 21-hydroxylation of progesterone and 17-OH progesterone, with resulting deficient production of both cortisol and aldosterone. The disease occurs in a wide spectrum of clinical variants, including a severely affected form with defect in aldosterone biosynthesis ("salt-wasting" type), a form with apparently normal aldosterone biosynthesis ("simple virilizing" type) and a mild "nonclassic" form that may be asymptomatic or may be associated with symptoms of androgen excess developing during childhood or at puberty. In "classic" forms ("salt-wasting" and "simple virilizing") sings of androgen excess often are prominent. The key measurement for the diagnosis of 21-hydroxylase deficiency is basal plasma 17-OH progesterone. It will be elevated and will hyper-respond to ACTH stimulation. 11 beta-hydroxylase deficiency is the second most frequent cause of CAH. The abnormality is an inherited deficiency of 11 beta-hydroxylase enzyme of the adrenal cortex with consequences in impaired conversion of 11-deoxycortisol to cortisol and of deoxycorticosterone to corticosterone and aldosterone. About two thirds of patients with the severe, "classic" form have hypertension, often beginning within the first few years of life. Patients with mild ("late onset" or "nonclassic") form have normal or, at most, mildly elevated blood pressure. Signs of androgen excess are also often prominent. The diagnosis can be confirmed by demonstrating marked accumulation of deoxycorticosterone and 11-deoxycortisol in plasma and their tetrahydrometabolites in urine. 17 alpha-hydroxylase/17, 20 lyase deficiency is the second of two hypertensive forms of CAH. Deficient 17 alpha-hydroxylation of pregnenolone and progesterone result in decreased secretion of cortisol and sex steroids, but increased secretion of sodium-retaining corticoids (corticosterone and deoxycorticosterone). Females present with normal external genitalia but failure to develop secondary sex characteristics and primary amenorrhea. Males frequently fail to develop masculine external genitalia fully (male pseudohermaphroditism). Both sexes have hypertension, hypokalemic alkalosis, and failure to progress into puberty. The diagnosis can be established by the demonstration of elevated plasma deoxycorticosterone and corticosterone 3 beta-hydroxysteroid dehydrogenase is rare cause of CAH. Patients with this biosynthetic defect have deficient production of adrenal glucocorticoids, mineralocorticoids, and testicular testosterone. However, they have excessive production of 5-adrenal androgens. In "classic" form, affected newborns present with symptoms and sings of adrenal insufficiency of varying degree and ambiguous genitalia in both sexes. The "late onset" form is a mild type of disorder. It has been described in women with hirsutism and menstrual abnormalities and may be quite common. (ABSTRACT TRUN