Mobile Site ›
Print Friendly View

Test ID: PREGN    
Pregnenolone, Serum

‹ Back to Pediatric index

Useful For Suggests clinical disorders or settings where the test may be helpful

An ancillary test for congenital adrenal hyperplasia, 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 deficiency

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. Deficiencies in several enzymes cause CAH including 21-hydroxylase (CYP21A2 mutations; 90% of cases), 11-hydroxylase (CYP11A1 mutations; 5%-8%), 3-beta-hydroxy dehydrogenase (HSD3B2 mutations; <5%), and 17-alpha-hydroxylase (CYP17A1 mutations; 125 cases reported to date). The resulting hormone imbalances (reduced glucocorticoids and mineralocorticoids, and 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 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-hydroxy dehydrogenase [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, respectively, 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-Hydoxylase Deficiency allows the simultaneous determination of these 3 analytes. Alternately, these tests may be ordered individually: OHPG / 17-Hydroxyprogesterone, Serum; CINP / Cortisol, Serum, LC-MS/MS; 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.

 

See Steroid Pathways in Special Instructions.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

CHILDREN*

Males

0-6 years: not established

7-9 years: <206 ng/dL

10-12 years: <152 ng/dL

13-15 years: 18-197 ng/dL

16-17 years: 17-228 ng/dL

Tanner Stages

Stage I: <157 ng/dL

Stage II: <144 ng/dL

Stage III: <215 ng/dL

Stage IV-V: 19-201 ng/dL

 

Females

0-6 years: not established

7-9 years: <151 ng/dL

10-12 years: 19-220 ng/dL

13-15 years: 22-210 ng/dL

16-17 years: 22-229 ng/dL

Tanner Stages

Stage I: <172 ng/dL

Stage II: 22-229 ng/dL

Stage III: 34-215 ng/dL

Stage IV-V: 26-235 ng/dL

 

ADULTS

> or =18 years: 33-248 ng/dL

*Kushnir MM, Rockwood AL, Roberts WL, et al: Development and performance evaluation of a tandem mass spectrometry assay for 4 adrenal steroids. Clin Chem 2006;52(8):1559-1567

Interpretation Provides information to assist in interpretation of the test results

Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always require 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 levels will be increased.

 

In the much less common CYP11A1 mutation, androstenedione levels are elevated to a similar extent as seen in CYP21A2 mutation, and cortisol also is low, but 17-OHPG is only mildly, if at all, elevated.

 

In the also very rare 17-hydroxylase deficiency, androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, 17-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.

 

See Steroid Pathways in Special Instructions.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

No significant cautionary statements

Supportive Data

To convert to nmol/L, multiply the value in ng/dL by 0.03159757.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Wudy S A, Hartmann M, Svoboda M: Determination of 17-hydroxyprogesterone in plasma by stable isotope dilution/benchtop liquid chromatography-tandem mass spectrometry. Horm Res 2000;53(2):68-71

2. Therrell BL: Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001:30(1):15-30

3. Bachega TA, Billerbeck AE, Marcondes JA, et al: Influence of different genotypes on 17-hydroxyprogesterone levels in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol (Oxf) 2000:52(5):601-607

4. Kao P, Machacek DA, Magera MJ at al: Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass spectrometry. Ann Clin Lab Sci 2001;31(2):199-204

5. Sciarra F, Tosti-Croce C, Toscano V: Androgen-secreting adrenal tumors. Minerva Endocrinol 1995:20(1):63-68

6. Collett-Solberg PF: Congenital adrenal hyperplasia: from genetics and biochemistry to clinical practice, Part 1. Clin Pediatr (Phila) 2001:40(1):1-16

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test