Laboratory Studies
Male and female patients have no biochemical differences.
All steroids requiring 17-hydroxylase (17-OH) activity for their production are found in very low concentrations. 17-Hydroxypregnenolone (17-OH Preg), 17-hydroxyprogesterone (17-OH Prog; see 17-Hydroxyprogesterone, Serum and 17-Hydroxyprogesterone, Urine), 11-deoxycortisol (compound S), cortisol, dehydroepiandrosterone (DHEA), androstenedione, and testosterone are all decreased or absent. The urinary metabolites 17-hydroxylase corticosteroid and 17-ketosteroid also are decreased or absent.
Serum estrogens and urinary estrogens are low.
Pregnenolone and progesterone levels are somewhat elevated; diagnosis is confirmed by markedly elevated levels of 11-deoxycorticosterone (11-DOC) and corticosterone.
Aldosterone and plasma renin concentrations are usually low. DOC-mediated mineralocorticoid activity causes sodium retention and plasma volume expansion, with subsequent suppressed renin and aldosterone levels in most untreated patients.
Within the pituitary, adrenocorticotropic hormone (ACTH) levels are elevated due to lack of cortisol secretion. The gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are elevated secondary to deficient sex steroid production by the gonads.
Other Tests
17-Hydroxylase deficiency is inherited as an autosomal recessive trait similar to other forms of congenital adrenal hyperplasia (CAH). However, 17-hydroxylase is not linked to the human leukocyte antigen (HLA) system. Detection of heterozygote carriers is difficult and requires biochemical rather than genetic criteria.
Unstimulated levels of 11-deoxycorticosterone (11-DOC) and corticosterone may be somewhat elevated in heterozygotes, and these individuals may have an exaggerated response to ACTH stimulation.
Prenatal diagnosis of an affected infant is possible by measuring amniotic fluid concentrations of adrenal steroids or maternal urine steroid metabolite excretion. [33]
-
17-Hydroxylase Deficiency Syndrome. Normal adrenal steroid biosynthesis results in three products: mineralocorticoids (aldosterone), glucocorticoids (cortisol), and androgens (androstenedione). Cortisol production is regulated by feedback with adrenocorticotropic hormone (ACTH). ACTH stimulates the enzyme P-450scc (20,22 desmolase), with subsequently increased production of all adrenal steroids.
-
17-Hydroxylase Deficiency Syndrome. Representation of typical congenital adrenal hyperplasia (CAH). This example shows a deficiency in both the mineralocorticoid and glucocorticoid pathways. Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. Increased ACTH secretion causes overproduction of adrenal steroids preceding the missing enzyme as well as those not requiring the missing enzyme. The example depicts a deficiency of 21-hydroxylase, resulting in deficient mineralocorticoid and glucocorticoid production and excessive androgen production.
-
17-Hydroxylase Deficiency Syndrome. C-17α-hydroxylase is necessary to convert pregnenolone to 17-hydroxypregnenolone (17-OH Preg) and progesterone to 17-hydroxyprogesterone (17-OH Prog). Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production. Low levels of cortisol result in increased adrenocorticotropic hormone (ACTH) stimulation of steroids prior to the 17-hydroxylase step, resulting in increased accumulation and secretion of 17-deoxysteroids by the zona fasciculata, including pregnenolone, progesterone, deoxycorticosterone (DOC), and corticosterone.
-
17-Hydroxylase Deficiency Syndrome. Graphic illustration of deficiency. Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production.
