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Test Code 21DOC 21-Deoxycortisol, Serum

Useful For

As an adjunct to measurement of 17-hydroxyprogesterone, androstenedione, and cortisol in the diagnosis of difficult cases of suspected 21-hydroxylase (CYP21A2) deficiency

 

Identifying heterozygote CYP21A2 deficiency carriers

 

As an adjunct to measurements of 17-hydroxyprogesterone, androstenedione, testosterone, and, in females, estradiol in the follow-up of children with CYP21A2 deficiency

Testing Algorithm

See Steroid Pathways in Special Instructions.

Special Instructions

Method Name

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

Reporting Name

21-Deoxycortisol, S

Specimen Type

Serum


Specimen Required


Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 0.5 mL

Collection Instructions: Morning (8 a.m.) specimen is preferred.


Specimen Minimum Volume

0.4 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 21 days
  Frozen  21 days
  Ambient  14 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

Mild OK; Gross OK

Other

NA

Reference Values

<5.0 ng/dL

Reference values apply to all ages.

Interpretation

In untreated 21-hydroxylase (CYP21A2) deficiency, 21-deoxycortisol serum concentrations on average exceed the upper limit of the reference range 30-fold to 40-fold.

 

21-Hydroxycortisol measurements are particularly useful in equivocal cases of suspected 21-hydroxylase deficiency. Most untreated patients with 21-hydroxylase deficiency have serum 17-hydroxyprogesterone concentrations well in excess of 1,000 ng/dL. For the few patients with levels in the range of greater than 630 ng/dL (upper limit of reference range for newborns) to 2,000 ng/dL or 3,000 ng/dL, it might be prudent to consider 11-hydroxylase deficiency as an alternative diagnosis. This is particularly true if serum androstenedione concentrations are also only mildly-to-modestly elevated, and if the phenotype is not salt wasting but either simple virilizing (female) or normal (female or male). 11-Hydroxylase deficiency, in particular if it affects 11 beta-hydroxylase 1 (CYP11B1), can be associated with modest elevations in serum 17-hydroxyprogesterone concentrations. In these cases testing for CYP11B1 deficiency and 11 beta-hydroxylase 2 (CYP11B2) deficiency should be considered and interpreted as described above. Alternatively, measurement of 21-deoxycortisol might be useful in such cases. This minor pathway metabolite accumulates in CYP21A2 deficiency, as it requires 21-hydroxylation to be converted to cortisol, but is usually not elevated in CYP11B1 deficiency, since its synthesis requires via 11-hydroxylation of 17-hydroxyprogesterone.

 

For genetic counseling purposes, identification of asymptomatic carriers of CYP21A2 mutations and deletions is sometimes required. The gold-standard is full DNA sequencing of CYP21A2, its pseudogene CYP21A1P, and, if possible, recombinants of gene and pseudogene, along with deletion detection. Such a procedure is costly and complex, and often has a slow turnaround time. Therefore, many laboratories perform less complex, but also less complete, mutation and deletion assessments, which may miss a significant minority of heterozygote carriers. Biochemical testing using adrenocorticotropic hormone (ACTH) ACTH1-24 adrenal stimulation represents an alternative. However, for 17-hydroxyprogesterone and androstenedione measurements there is significant overlap between poststimulation results in normals and in heterozygote carriers. By contrast, poststimulation 21-deoxycortisol concentrations of 55 ng/dL identify virtually all heterozygote carriers, with minimal overlap with normal subjects.

 

The goal of congenital adrenal hyperplasia (CAH) treatment is normalization of cortisol levels and ideally also of sex steroid levels. Serum 17-hydroxyprogesterone, androstenedione, and testosterone should be measured and used to guide treatment modifications. Normal prepubertal androgen 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. 17-Hydroxyprogesterone levels should not significantly exceed the normal reference range at any time of the day. However, during puberty, the changing levels of sex steroid production may make 17-hydroxyprogesterone measurements less reliable. Since 21-deoxycortisol is not a sex-steroid precursor, its levels appear more reliable during the pubertal period, again, the aim being not to exceed the reference range significantly.

Day(s) and Time(s) Performed

Tuesday; 10 a.m.

Analytic Time

3 days

Specimen Retention Time

14 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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 U.S. Food and Drug Administration.

CPT Code Information

82542

LOINC Code Information

Test ID Test Order Name Order LOINC Value
21DOC 21-Deoxycortisol, S 74872-3

 

Result ID Test Result Name Result LOINC Value
89477 21-Deoxycortisol, S 74872-3