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Test Code CAH21 Congenital Adrenal Hyperplasia (CAH) Profile for 21-Hydroxylase Deficiency, Serum

Reporting Name

CAH 21-Hydroxylase Profile

Useful For

Preferred screening test for congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency

 

Part of a battery of tests to evaluate women with hirsutism or infertility, which can result from adult-onset CAH

Profile Information

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

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Serum Red


Ordering Guidance


This profile provides the simultaneous determination of 17-hydroxyprogesterone, androstenedione, and cortisol. These steroids can also be ordered individually: OHPG / 17-Hydroxyprogesterone, Serum; ANST / Androstenedione, Serum; and CINP / Cortisol, Mass Spectrometry, Serum.



Specimen Required


Collection Container/Tube: Red top (serum gel/SST are not acceptable)

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 collection.

3. Centrifuge and aliquot serum into a plastic vial.

Additional Information: If multiple specimens are collected, send separate order for each specimen.


Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 14 days
  Frozen  28 days
  Ambient  7 days

Reference Values

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 Scand. 1981;70(3):341-345

 

ANDROSTENEDIONE

PEDIATRICS*

Premature infants

26-28 weeks, day 4: 92-282 ng/dL

31-35 weeks, day 4: 80-446 ng/dL

Full-term infants

1-7 days: 20-290 ng/dL

1 month-1 year: <69 ng/dL

 

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

*Soldin SJ, Brugnara C, Wong EC. Androstenedione. In: Pediatric Reference Ranges. 4th ed. AACC Press; 2003:32-34

 

ADULTS

Males: 40-150 ng/dL

Females: 30-200 ng/dL

 

17-HYDROXYPROGESTERONE

Children

Preterm infants: Preterm infants may exceed 630 ng/dL, however, it is uncommon to see levels reach 1,000 ng/dL.

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, Tractenberg RE, Hilakivi-Clarke L, Soldin SJ. Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry. Fertil Steril. 2005;84(3):701-710

Day(s) Performed

Monday through Friday

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

82157

82533

83498

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CAH21 CAH 21-Hydroxylase Profile 79221-8

 

Result ID Test Result Name Result LOINC Value
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

Clinical Information

The cause of congenital adrenal hyperplasia (CAH) is an inherited genetic defect that results in decreased formation of one of the many enzymes that are involved in the production of cortisol. The enzyme defect results in reduced glucocorticoids and mineralocorticoids and elevated 17-hydroxyprogesterone (OHPG) and androgens. The resulting hormone imbalances can lead to life-threatening, salt-wasting crises in the newborn period and incorrect gender assignment of virilized female patients. Adult-onset CAH may result in hirsutism or infertility in women.

 

The adrenal glands, ovaries, testes, and placenta produce OHPG. It is hydroxylated at the 11 and 21 positions to produce cortisol. Deficiency of either 11- or 21-hydroxylase results in decreased cortisol synthesis, and the feedback inhibition of adrenocorticotropic hormone (ACTH) secretion is lost. Consequently, increased pituitary release of ACTH increases production of OHPG. In contrast, if 17-alpha-hydroxylase (which allows formation of OHPG from progesterone) or 3-beta-ol-dehydrogenase (which allows formation of 17-hydroxyprogesterone formation from 17-hydroxypregnenolone) are deficient, OHPG levels are low with possible increase in progesterone or pregnenolone, respectively.

 

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 (DOCS / 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.

Interpretation

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) variants 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 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.

 

Also less common is 3-beta hydroxysteroid dehydrogenase (HSD) type 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 StAR (steroidogenic acute regulatory) protein deficiency, all steroid hormone levels are low and cholesterol is elevated.

 

In the 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, of sex-steroid levels also. 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.

Cautions

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.

Report Available

2 to 5 days

Reject Due To

Gross hemolysis OK
Gross lipemia Reject
Gross icterus OK

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Portions of this test are covered by patents held by Quest Diagnostics

Forms

If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.