Preferred screening test for congenital adrenal hyperplasia (CAH) that is caused by 21-hydroxylase deficiency
Part of a battery of tests to evaluate females with hirsutism or infertility, which can result from adult-onset CAH
Preferred screening test for congenital adrenal hyperplasia (CAH) that is caused by 21-hydroxylase deficiency. Also useful as part of a battery of tests to evaluate females with hirsutism or infertility, which can result from adult-onset CAH.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CORTI | Cortisol, S | Yes, (order CINP) | Yes |
ANDRO | Androstenedione, S | Yes, (order ANST) | Yes |
H17 | 17-Hydroxyprogesterone, S | Yes, (order OHPG) | Yes |
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Portions of this test are covered by patent(s) held by Quest Diagnostics
17-OHP (17-Hydroxyprogesterone)
21 Hydroxylase Deficiency
Androstenedione
CA21H
CAH (Congenital Adrenal hyperplasia)
Corticosteroids
Cortisol
CYP21
Delta-4-Androstenedione
17-Alpha Hydroxyprogesterone (17-OHP)
Progesterone, 17-Alpha Hydroxy
Serum Red
Question ID | Description | Answers |
---|---|---|
COLT1 | Collection Time in Military Time |
Collection Container/Tube: Red top
Specimen Volume: 0.6 mL
Submission Container/Tube: Plastic vial
Collection Instructions:
1. Morning (8 a.m.) and afternoon (4 p.m.) specimens are preferred.
2. Include time of draw.
3. Centrifuge and aliquot serum into a plastic vial.
Additional Information: If multiple specimens are collected, send separate order for each specimen.
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
0.25 mL
Gross hemolysis | Reject |
Gross lipemia | Reject |
Gross icterus | OK |
Other | Serum gel tube |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum Red | Refrigerated (preferred) | 14 days | |
Frozen | 28 days | ||
Ambient | 7 days |
Preferred screening test for congenital adrenal hyperplasia (CAH) that is caused by 21-hydroxylase deficiency
Part of a battery of tests to evaluate females with hirsutism or infertility, which can result from adult-onset CAH
Preferred screening test for congenital adrenal hyperplasia (CAH) that is caused by 21-hydroxylase deficiency. Also useful as part of a battery of tests to evaluate females with hirsutism or infertility, which can result from adult-onset CAH.
The cause of congenital adrenal hyperplasia (CAH) is an inherited
The adrenal glands, ovaries, testes, and placenta produce OHPG. It
Most (90%) cases of CAH are due to mutations in the 21-hydroxylase gene (CYP21A2). CAH due to 21-hydroxylase deficiency is diagnosed by confirming elevations of OHPG and androstenedione with decreased cortisol. By contrast, in 2 less common forms of CAH, due to 17-hydroxylase or 11-hydroxylase deficiency, OHPG and androstenedione levels are not significantly elevated and measurement of progesterone (PGSN / Progesterone, Serum) and deoxycorticosterone (DCRN / 11-Deoxycorticosterone, Serum), respectively, are necessary for diagnosis.
OHPG is bound to both transcortin and albumin, and total OHPG is measured in this assay. OHPG is converted to pregnanetriol, which is conjugated and excreted in the urine. In all instances, more specific tests than pregnanetriol measurement are available to diagnose disorders of steroid metabolism.
The CAH profile allows the simultaneous determination of OHPG, androstenedione, and cortisol. These steroids can also be ordered individually (OHPG / 17-Hydroxyprogesterone, Serum; ANST / Androstenedione, Serum; CINP / Cortisol, Serum, LC-MS/MS).
CORTISOL
5-25 mcg/dL (a.m.)
2-14 mcg/dL (p.m.)
Pediatric reference ranges are the same as adults, as confirmed by peer-reviewed literature.
Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr
ANDROSTENEDIONE
PEDIATRICS*
Males*
Tanner Stages | Age (Years) | Reference Range (ng/dL) |
Stage I (prepubertal) | <9.8 | <51 |
Stage II | 9.8-14.5 | 31-65 |
Stage III | 10.7-15.4 | 50-100 |
Stage IV | 11.8-16.2 | 48-140 |
Stage V | 12.8-17.3 | 65-210 |
Females*
Tanner Stages | Age (Years) | Reference Range (ng/dL) |
Stage I (prepubertal) | <9.2 | <51 |
Stage II | 9.2-13.7 | 42-100 |
Stage III | 10.0-14.4 | 80-190 |
Stage IV | 10.7-15.6 | 77-225 |
Stage V | 11.8-18.6 | 80-240 |
*Source: Androstenedione. In Pediatric Reference Ranges. Fourth Edition. Edited by SJ Soldin, C Brugnara, EC Wong. Washington, DC, AACC Press, 2003, pp 32-34
ADULTS
17-HYDROXYPROGESTERONE
Preterm infants:
Term infants
0-28 days: <630 ng/dL
Levels fall from newborn (<630 ng/dL) to prepubertal gradually within 6 months.
Prepubertal males: <110 ng/dL
Prepubertal females: <100 ng/dL
Adults
Males: <220 ng/dL
Females
Follicular: <80 ng/dL
Luteal: <285 ng/dL
Postmenopausal: <51 ng/dL
Note: For pregnancy reference ranges, see: Soldin OP, Guo T, Weiderpass E, et al: Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry. Fertil Steril 2005 Sept;84(3):701-710
Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always requires the measurement of several steroids. Patients with CAH due to 21-hydroxylase gene (CYP21A2) mutations usually have very high levels of androstenedione, often 5- to 10-fold elevations. 17-Hydroxyprogesterone (OHPG) levels are usually even higher, while cortisol levels are low or undetectable. All 3 analytes should be tested.
In the much less common CYP11A 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.
Also less common is 3 beta-hydroxysteroid dehydrogenase type 2 (3 beta HSD-2) deficiency, characterized by low cortisol and substantial elevations in dehydroepiandrosterone sulfate (DHEA-S) and 17-alpha-hydroxypregnenolone, while androstenedione is either low, normal, or rarely, very mildly elevated (as a consequence of peripheral tissue androstenedione production by 3 beta HSD-1).
In the very rare steroidogenic acute regulatory protein deficiency, all steroid hormone levels are low and cholesterol is elevated.
In the also very rare 17-alpha-hydroxylase deficiency, androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG, DHEA-S), androgens (testosterone, estrone, estradiol), and cortisol are low, while production of mineral corticoid and its precursors, in particular progesterone, 11-deoxycorticosterone, corticosterone, and 18-hydroxycorticosterone, are increased.
The goal of CAH treatment is normalization of cortisol levels and, ideally, also of sex-steroid levels. OHPG is measured to guide treatment, but this test correlates only modestly with androgen levels. Therefore, androstenedione and testosterone should also be measured and used to guide treatment modifications. Normal prepubertal levels may be difficult to achieve, but if testosterone levels are within the reference range, androstenedione levels up to 100 ng/dL are usually regarded as acceptable.
Androstenedione and, to a lesser degree, dehydroepiandrosterone sulfate supplements can result in elevations of serum androstenedione level. With large androstenedione doses of 300 to 400 mg/day, serum androstenedione levels can almost double in some patients. Testosterone levels and, particularly in men, estrone and estradiol levels may also increase, but to a much lesser degree.
This test provides merely supplementary information and should, therefore, never be employed as the sole diagnostic tool.
1. Von Schnakenburg K, Bidlingmaier F, Knorr D: 17-hydroxyprogesterone, androstenedione, and testosterone in normal children and in prepubertal patients with congenital adrenal hyperplasia. Eur J Pediatr 1980;133(3):259-267
2. Sciarra F, Tosti-Croce C, Toscano V: Androgen-secreting adrenal tumors. Minerva Endocrinol 1995;20(1):63-68
3. Collett-Solberg PF: Congenital adrenal hyperplasia: from genetics and biochemistry to clinical practice, part I. Clin Pediatr 2001;40(1):1-16
4. Speiser PW, Azziz R, Baskin LS, et al: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2010;95(9):4133-4160
Deuterated stable isotopes (d4-cortisol, d7-androstenedione, d8-17-hydroxyprogesterone) are added to a 0.1-mL serum sample as internal standards. Cortisol, androstenedione, 17-hydroxyprogesterone, and the internal standards are extracted from specimens using a Strata X 30-mg cartridge and eluted from the cartridge with methanol. The extracts are then dried down under nitrogen, reconstituted with 75 mcL of 70/30 methanol/H2O containing 1 g/mL of estriol and analyzed by liquid chromatography-tandem mass spectrometry using multiple-reaction monitoring. A calibration curve is generated by spiking standards into a bovine serum albumin buffer and extracted with each batch of new working internal standard. Controls are extracted with each batch.(Unpublished Mayo method)
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
82157-Androstenedione
82533-Cortisol; total
83498-Hydroxyprogesterone, 17-d
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CAH21 | CAH 21-Hydroxylase Profile | 79221-8 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
30041 | Androstenedione, S | 1854-9 |
30042 | 17-Hydroxyprogesterone, S | 1668-3 |
30040 | Cortisol, S | 2143-6 |
30070 | AM Cortisol | 9813-7 |
30071 | PM Cortisol | 9812-9 |
Change Type | Effective Date |
---|---|
Test Status - Test Down | 2023-02-28 |
Test Status - Test Delay | 2023-02-21 |