Congenital virilizing hyperplasia of the adrenal cortex
Congenital virilizing hyperplasia of the adrenal cortex is a disease caused by a congenital disorder of the biological synthesis of hormones in the adrenal cortex, resulting in excessive production of androgens. The disease is rare. In women, it occurs about 4-5 times more often than in men.
Historical data. The disease was first described in 1865, Crechio. Treatment of congenital virilizing hyperplasia of the adrenal cortex in cortisone in 1950 was suggested by Wilkins et al.
Etiology. The cause of the disease is a congenital, genetically determined inferiority of enzyme systems involved in normal steroidogenesis in the adrenal cortex, resulting from the inheritance of a mutant (autosomal recessive) gene.
Pathogenesis. The lack of enzymes (and first of all, 21-hydroxylases) involved in the biosynthesis of corticosteroids leads to a decrease in cortisol production, as a result of which ACTH pituitary production is compensatory (Fig. 58). The reduction in the formation of cortisol is accompanied by the accumulation in the blood of the precursors of its metabolism (17-hydroxyprogesterone, progesterone and pregnenolone) with an increased release of their meta-pains (pregnandiol, pregnantriol, pregnantriolone, dehydro-epiandrosterone and etoicholanolone) with urine.
As a result of the constant enhanced stimulation of the adrenal cortex ACTH, on the one hand, hyperplasia of its reticular zone occurs, and on the other, excessive production of androgens. This in turn leads to virilization (masculinization) of the child’s body. In children with a female genotype, an excess of androgens leads to the development of female pseudohermaphroditism (clitoral hypertrophy, formation of the urogenital sinus — the vagina and urethra open with one hole, underdevelopment of the vagina, uterus, mammary glands, excessive development of musculature, hypertrophy, coarsening of the voice, lack of menstruation etc.). In children with a male genotype, an excess of androgens leads to an accelerated growth, an increase in the penis, the emergence of secondary sexual characteristics, sexual desire, and erections.
With a deep deficiency of the enzyme 21-hydroxylase, along with low formation of cortisol, there is also a sharp decrease in the biosynthesis of aldosterone, as a result of which the salt-loss syndrome develops. The emergence of the latter is also associated with an increase in the number of precursors of cortisol,
with antialdosterone activity. Increased urine excretion of sodium and chlorides leads to dehydration and hypotension.
With a deficiency of the enzyme 11-hydroxylase, along with a violation of the synthesis of cortisol and aldosterone, it is believed that the formation of a precursor of cortisol, 11-deoxycorticosterone, with pronounced mineral-corticoid activity occurs. An excess of 11-deoxycorticosterone causes arterial hypertension, but without disrupting the electrolyte balance of the body.