9] Congenital adrenal hyperplasia represents a group of autosomal recessive inherited, metabolic errors, each characterized by decency or total lack of a particular enzyme involved in the biosynthesis of cortical steroids, Steroidogenesis is then channelled into other pathways leading to increased production of androgens, which accounts for virilization. Simultaneously, the decency of cortisol results in increased secretion of ACTH resulting in adrenal hyperplasia. Following enzymes are implicated in the congenital adrenal hyperplasia 21 α hydroxylase decency (partial or complete) 17 α hydroxylase deficiency 11β hydroxylase deficiency 21 α hydroxylase deficiency • Two forms of this deficiency include - A. Salt-wasting adrenogenital ism B. Simple Virilizing adrenogenital ism A) Salt-wasting syndrome (complete lack) The salt wasting syndrome results from complete lack of 21 hydroxylases. There is no synthesis of mineralocorticoids and glucocorticoids in the adrenal cortex. Decreased mineralocorticoids causes marked sodium loss in the urine, resulting in hyponatremia, hyperkalemia, acidosis and hypotension. Because of the enzyme block, there is increased formation of 17 - hydroxyprogesterone, which is then shunted into the production of testosterone. This may cause virilism (pseudo-hermaphroditism) in female infants. That is (XX) Female with 21 hydroxylase deficiency develops ovaries, female ductal structures and external male genitalia. But in the male child, the effect of increased testosterone will not be manifested at the time of birth. The complete21 hydroxylase deficiency or salt wasting syndrome usually comes to light only after the birth because in utero the electrolytes and uids can be maintained by maternal kidneys. Males with this disorder comes to clinical attention 5 to 15 days later because of salt losing crisis while females come to attention soon after the birth because of the virilization. B) Simple Virilizing adrenogenital syndrome (Partial deficiency) Occurs in individuals with partial deficiency of 21 hydroxylases Less severe deficiency of mineralocorticoid, is sufficient for salt reabsorption, but the lowered glucocorticoid fails to cause feedback inhibition of ACTH secretion. Thus level of aldosterone is mildly reduced, testosterone is increased and ACTH elevated with resultant adrenal hyperplasia. 11B hydroxylase deficiency-. Rare Leads to decreased cortisol and increased ACTH. This, in turn, leads to the accumulation of DOC (deoxycorticosterone) and 11 deoxycortisol both of which are strong mineralocorticoids. This results in increased sodium retention by the kidneys and hypertension, hypokalemia. Patients also develop virilization due to androgen excess. 17 α hydroxylase deficiency - Patients with deficiency of 17 hydroxylases also have impaired cortisol production, increased ACTH and secondary increased DOC. These patients, however, cannot synthesize normal amount of androgens and estrogens. This is because the gene that codes for 17 α hydroxylase is the same for the enzyme in the adrenal cortex and the gonads and the decency is same in both organs. Because of decreased sex hormones, genotypic females develop primary amenorrhoea and fail to develop secondary sex characteristics while genotypic males will present as pseudohermaphrodite. 3 β hydroxylase deficiency 3-β hydroxylase deficiency is a rare genetic disorder of steroid biosynthesis that results in decreased production of all three groups of adrenal steroids which include mineralocorticoid, glucocorticoid and sex steroids. Decreased mineralocorticoid secretion results in varying degrees of salt wasting in both males and females. Decent androgen production results in ambiguous genitalia in males The usual presentation is a male child with ambiguous genitalia and severe salt wasting. Sometimes it may also occur in females