Clinical evaluation Female infants with classic<unk>  have ambiguous genitalia due to exposure to high concentrations of androgens in utero.<unk>  due to 21-hydroxylase deficiency is the most common cause of ambiguous genitalia in genotypically normal female infants (46XX). Less severely affected females may present with early pubarche. Young women may present with symptoms of polycystic ovarian syndrome (oligomenorrhea, polycystic ovaries, hirsutism). Males with classic<unk>  generally have no signs of<unk>  at birth. Some may present with hyperpigmentation, due to co-secretion with melanocyte-stimulating hormone, and possible penile enlargement. Age of diagnosis of males with<unk>  varies and depends on the severity of aldosterone deficiency. Boys with salt-wasting disease present early with symptoms of hyponatremia and hypovolemia. Boys with non-salt-wasting disease present later with signs of virilization. In rarer forms of<unk> , males are undermasculinized and females generally have no signs or symptoms at birth. Laboratory studies Genetic analysis can be helpful to confirm a diagnosis of<unk> , but it is not necessary if classic clinical and laboratory findings are present. In classic 21-hydroxylase deficiency, laboratory studies will show: :*Hypoglycemia (due to hypocortisolism) - One of cortisol's many functions is to increase blood glucose levels. This occurs via a combination of several mechanisms, including (a) the stimulation of gluconeogesis (i.e. the creation of new glucose) in the liver, (b) the promotion of glycogenolysis (i.e. the breakdown of glycogen into glucose), and (c) the prevention of glucose leaving the bloodstream via the downregulation of GLUT-4 receptors (which normally promote movement of glucose from the bloodstream into adipose and muscle tissues). Therefore, when cortisol is deficient, these processes (effectively) occur in the reverse direction. Although there are compensatory mechanisms that mitigate the impact of hypocortisolism, they are limited in their extent and the net effect is still hypoglycemia. :*Hyponatremia (due to hypoaldosteronism) - Aldosterone is the end product of the renin-angiotensin-aldosterone system that regulates blood pressure via blood pressure surveillance in the Kidney Juxtaglomerular apparatus. Aldosterone normally functions to increase sodium retention (which brings water as well) in exchange for potassium. Thus, lack of aldosterone causes hyperkalemia and hyponatremia. In fact, this is a distinguishing point from 11-hydroxylase deficiency, in which one of the increased products is 11-deoxycorticosterone that has weak mineralocorticoid activity. In 11-hydroxylase deficiency, 11-deoxycorticosterone is produced in such excess that it acts to retain sodium at the expense of potassium. It is this reason that patients with 11-hydroxylase deficiency do not show salt wasting (although sometimes they do in infancy), and instead have hypertension/water retention and sometimes hypokalemia. :*Hyperkalemia (due to hypoaldosteronism) :* Elevated 17α-hydroxyprogesterone Classic 21-hydroxylase deficiency typically causes 17α-hydroxyprogesterone blood levels >242 nmol/L. (For comparison, a full-term infant at three days of age should have Progesterone→ 11-DeoxycortisolDOC ↓ ↑ 11β-Hydroxylase<unk>  5% P450c11β 8q21-22 11-Deoxycortisol→DOC→ CortisolCorticosterone ↑ ↑ 3β-HSD<unk>  Very rare 3βHSD2 1p13 Pregnenolone→17-OH-Pregnenolone→DHEA→ Progesterone17-OH-ProgesteroneAndrostenedione ↓ ↓ 17α-Hydroxylase<unk>  Very rare CYP17A1 10q24.3 Pregnenolone→Progesterone→17-OH-Pregnenolone→ 17-OH-Pregnenolone17-OH-ProgesteroneDHEA ↑ ↓ Lipoid<unk> (20,22-desmolase) Very rare StARP450scc 8p11.215q23-q24 Transport of cholesterolCholesterol→ Into mitochondriaPregnenolone ↓ ↓
Congenital adrenal hyperplasia
Polycystic ovary syndrome
Lipoid congenital adrenal hyperplasia
Late onset congenital adrenal hyperplasia
Persistent adrenarche syndrome
Congenital iodine deficiency syndrome
Congenital hypothyroidism
Congenital hyperinsulinism