As an ancillary test for congenital adrenal hyperplasia (CAH), particularly in situations in which a diagnosis of 21-hydroxylase and 11-hydroxylase deficiency have been ruled out.
Confirming a diagnosis of 3-beta-hydroxy dehydrogenase (3-beta-HSD) deficiency.
Analysis for 17-hydroxypregnenolone is also useful as part of a battery of tests to evaluate females with hirsutism or infertility; both can result from adult-onset CAH.
Centrifuge and aliquot serum into plastic vial.
At birth, the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary gonadal axis are activated and adrenal and sex steroid levels are high. In preterm infants, the elevations can be even more pronounced due to illness and stress. As a result, preterm infants may occasionally have 17-hydroxypregnenolone levels of up to 9,799 ng/dL. Term infants (0-28 days) will have levels <3,104 ng/dL. These then fall over the following 2 years to prepubertal levels of <277 ng/dL.
Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. Deficiencies in several enzymes cause CAH including 21-hydroxylase (CYP21A2 variants; 90% of cases), 11-hydroxylase (CYP11A1 variants; 5%-8%), 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) (HSD3B2 variants; <5%), and 17-alpha-hydroxylase (CYP17A1 variants; 125 cases reported to date). The resulting hormone imbalances (reduced glucocorticoids and mineralocorticoids; elevated steroid intermediates and androgens) can lead to life-threatening, salt-wasting crises in the newborn period and incorrect gender assignment of virilized females.
The adrenal glands, ovaries, testes, and placenta produce steroid intermediates, which are hydroxylated at the position 21 (by 21-hydroxylase) and position 11 (by 11-hydroxylase) to produce cortisol. Deficiency of either 21-hydroxylase or 11-hydroxylase results in decreased cortisol synthesis and loss of feedback inhibition of adrenocorticotropic hormone (ACTH) secretion. The consequent increased pituitary release of ACTH drives increased production of steroid intermediates.
The steroid intermediates are oxidized at position 3 (by 3-beta-HSD). The 3-beta-HSD enzyme allows formation of 17-hydroxyprogesterone (17-OHPG) from 17-hydroxypregnenolone and progesterone from pregnenolone. When 3-beta-HSD is deficient, cortisol is decreased, 17-hydroxypregnenolone and pregnenolone levels may increase, and 17-OHPG and progesterone levels are low. Dehydroepiandrosterone is also converted to androstenedione by 3-beta-HSD and may be elevated in patients affected with 3-beta-HSD deficiency.
The best screening test for CAH, most often caused by either 21- or 11-hydroxylase deficiency, is the analysis of 17-hydroxyprogesterone, along with cortisol and androstenedione. CAH21 / Congenital Adrenal Hyperplasia (CAH) Profile for 21-Hydroxylase Deficiency, Serum allows the simultaneous determination of these 3 analytes. Alternatively, these tests may be ordered individually: OHPG / 17-Hydroxyprogesterone, Serum; CINP / Cortisol, Mass Spectrometry, Serum; and ANST / Androstenedione, Serum.
If both 21- and 11-hydroxylase deficiency have been ruled out, analysis of 17-hydroxypregnenolone and pregnenolone may be used to confirm the diagnosis of 3-beta-HSD or 17-alpha-hydroxylase deficiency.
Premature (26-28 weeks): 1,219-9,799 ng/dL
Premature (29-36 weeks): 346-8,911 ng/dL
Full term (1-5 months): 229-3,104 ng/dL
6 months-364 days: 221-1,981 ng/dL
1-2 years: 35-712 ng/dL
3-6 years: <277 ng/dL
7-9 years: <188 ng/dL
10-12 years: <393 ng/dL
13-15 years: 35-465 ng/dL
16-17 years: 32-478 ng/dL
Stage I: <209 ng/dL
Stage II: <356 ng/dL
Stage III: <451 ng/dL
Stage IV-V: 35-478 ng/dL
7-9 years: <213 ng/dL
10-12 years: <399 ng/dL
13-15 years: <408 ng/dL
16-17 years: <424 ng/dL
Stage I: <236 ng/dL
Stage II: <368 ng/dL
Stage III: <431 ng/dL
Stage IV-V: <413 ng/dL
> or =18 years: 55-455 ng/dL
> or =18 years: 31-455 ng/dL
Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always requires the measurement of several steroids. Patients with CAH due to steroid 21-hydroxylase gene (CYP21A2) mutations usually have very high levels of androstenedione, often 5-fold to 10-fold elevations. 17-hydroxyprogesterone (17-OHPG) levels are usually even higher, while cortisol levels are low or undetectable. All 3 analytes should be tested.
For the HSD3B2 mutation, cortisol, 17-OHPG and progesterone levels will be will be decreased; 17-hydroxypregnenolone and pregnenolone and dehydroepiandrosterone (DHEA) levels will be increased.
In the much less common CYP11A1 mutation, androstenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol is also low, but OHPG is only mildly, if at all, elevated.
In the also very rare 17-alpha-hydroxylase deficiency, androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG, dehydroepiandrosterone sulfate), androgens (testosterone, estrone, estradiol), and cortisol are low, while production of mineral corticoid and its precursors (in particular pregnenolone, 11-dexycorticosterone, corticosterone, and 18-hydroxycorticosterone) are increased.