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HelpTest ID: PREGN Pregnenolone, Serum
Reporting Name
Pregnenolone, SUseful For
An ancillary test for congenital adrenal hyperplasia, particularly in situations in which a diagnosis of both 21- and 11-hydroxylase deficiency have been ruled out
Confirming a diagnosis of 3-beta-hydroxy dehydrogenase deficiency
Clinical Information
Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. Deficiencies in several enzymes can 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-OHPG, 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.
For more information see Steroid Pathways.
Interpretation
The 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) variants 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 variant, cortisol, 17-OHPG, and progesterone levels will be decreased; 17-hydroxypregnenolone, pregnenolone, and dehydroepiandrosterone (DHEA) levels will be increased.
In the much less common CYP11A1 variant, androstenedione levels are elevated to a similar extent as in CYP21A2 variant, and cortisol is also low, but OHPG is only mildly, if at all, elevated.
In the 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 (particularly pregnenolone, 11-dexycorticosterone, corticosterone, and 18-hydroxycorticosterone) are increased.
For more information see Steroid Pathways.
Testing Algorithm
For more information see Steroid Pathways.
Special Instructions
Report Available
3 to 7 daysDay(s) Performed
Monday through Wednesday, Friday
Clinical Reference
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. Kushnir MA, Rockwood AL, Roberts WL, et al: Development and performance evaluation of a tandem mass spectrometry assay for 4 adrenal steroids. Clinical Chemistry 2006;52(8):1559-1567
6. Collett-Solberg PF. Congenital adrenal hyperplasia: from genetics and biochemistry to clinical practice, Part 1. Clin Pediatr (Phila). 2001:40(1):1-16
7. Chormanski D, Muzio MR. C 17 hydroxylase deficiency. In: StatPearls [Internet]. StatPearls Publishing; 2021. Updated January 3, 2023. Accessed May 29, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK546644/
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Specimen Type
SerumSpecimen Required
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Within 2 hours of collection, centrifuge the specimen and immediately aliquot serum into a plastic vial.
2. Freeze immediately.
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Frozen | 28 days |
Reference Values
CHILDREN/ADOLESCENTS*
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
*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
ADULTS
≥18 years: 33-248 ng/dL
To convert to nmol/L, multiply the value in ng/dL by 0.03159757.
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
84140
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| PREGN | Pregnenolone, S | 2837-3 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 88645 | Pregnenolone, S | 2837-3 |
mml-adrenal-gonad-pituitary