In patients suffering from the adrenogenital syndrome, deficient corticosteroid release by the adrenal glands gives rise to an increased production of adrenocorticotropic hormone by the pituitary gland, which, in turn, causes an overproduction of sex steroids. The vast majority of cases is provoked by an inherited deficiency of 21-hydroxylase, an enzyme required for the biosynthesis of aldosterone, cortisol, and corticosterone.
The disease is related to the following processes: congenital and has an incidence of about 0 / 100.000.
The adrenal glands comprise distinct cell populations producing different hormones. In detail:
Adrenal hormone release is primarily controlled by superior centers like pituitary gland and hypothalamus and negative feedback loops assure the preservation of an equilibrium between demands and hormone synthesis. First and foremost, adrenal corticosteroids inhibit adrenocorticotropic hormone (ACTH) release by the pituitary gland. In the case of insufficient corticosteroid synthesis, the pituitary gland releases excess amounts of ACTH, which, in turn, stimulates the production of hormones by functional adrenal tissues . Moreover, any disturbance of aldosterone production interferes with electrolyte balance. In patients suffering from adrenogenital syndrome (AS), both aldosterone and corticosteroid synthesis may be impaired, most commonly due to an inherited 21-hydroxylase deficiency . Accordingly, AS is often referred to as congenital adrenal hyperplasia. The latter term, however, does not consider rare cases of acquired AS. These may be triggered by adrenal or gonadal neoplasms.
Of note, aldosterone release by zona glomerulosa cells is regulated by the renin-angiotensin system and is not part of the hypothalamic-pituitary-adrenal hormone axis .
Besides 21-hydroxylase deficiency, other enzyme defects may account for AS. All forms known to date are inherited as an autosomal recessive trait.
The clinical manifestation of the disease is largely dependent on the type and degree of enzyme deficiency . As has been indicated above, the majority of cases results from mutations of the gene encoding for 21-hydroxylase . This enzyme is required for corticosteroid and aldosterone synthesis, and affected individuals present with combined deficiencies. In contrast, CYP11B1 defects causing the 11β-hydroxylase deficiency, an uncommon form of AS, are related to decreased levels of corticosteroids while the release of aldosterone is largely unaltered . Accordingly, 21-hydroxylase deficiency is related to the so-called salt-losing form of AS, whereas reduced activity of 11β-hydroxylase provokes the simple virilizing form of the disease. Less common, non-classical forms of AS are associated with disturbances of sex steroid production.
About two-thirds of AS patients are classified as "salt wasters" . These individuals usually present with symptoms of adrenal insufficiency shortly after birth or within the first month of life . Lethargy, feeding difficulties, vomiting, and weight loss are common symptoms . Further examinations may reveal dehydration, hyponatremia, and hyperkalemia. If left untreated, life-threatening metabolic decompensation and shock may occur. Moreover, female neonates typically have ambiguous genitalia comprising an enlarged clitoris, partly fused labia majora, and a common urogenital sinus instead of separated urethra and vagina . Boys may show penile enlargement and hyperpigmentation.
Simple virilizing AS is less severe than salt-losing disease and may not manifest until puberty. In young women, the disease is associated with early pubarche, hirsutism, amenorrhea, and polycystic ovaries . Acne is commonly observed. Simple virilizing AS may cause precocious puberty in boys, who are also more prone to develop testicular tumors  . Adult patients are usually of short stature. In the long term, enhanced concentrations of sex steroids may cause hypogonadotropic hypogonadism  .