Test Catalog

Test Id : 21DOC

21-Deoxycortisol, Serum

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

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
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Steroid Pathways in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

21-Deoxycortisol, S

Aliases
Lists additional common names for a test, as an aid in searching

21-Deoxycortisol

Deoxycortisol

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Steroid Pathways in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 0.5 mL

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.4 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

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

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
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Steroid Pathways in Special Instructions.

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

The adrenal glands, ovaries, testes, and placenta produce steroid hormones, which can be subdivided into 3 major groups: mineral corticoids, glucocorticoids, and sex steroids. Synthesis proceeds from cholesterol along 3 parallel pathways, corresponding to these 3 major groups of steroids, through successive side-chain cleavage and hydroxylation reactions. At various levels of each pathway, intermediate products can move into the respective adjacent pathways via additional, enzymatically catalyzed reactions (see Steroid Pathways in Special Instructions).

 

21-Deoxycortisol is an intermediate steroid in the glucocorticoid pathway. While the main substrate flow in glucocorticoid synthesis proceeds from 17-hydroxyprogesterone via 21-hydroxylation to 11-deoxycortisol and then, ultimately, to cortisol, a small proportion of 17-hydroxyprogesterone is also hydroxylated at carbon number 11 by 11-beta-hydroxylase 1 (CYP11B1), yielding 21-deoxycortisol. This in turn can also serve as a substrate for 21-hydroxylase (CYP21A2), resulting in formation of cortisol.

 

The major diagnostic utility of measurements of steroid synthesis intermediates lies in the diagnosis of disorders of steroid synthesis, in particular congenital adrenal hyperplasia (CAH). All types of CAH are associated with cortisol deficiency with the exception of CYP11B2 deficiency and isolated impairments of the 17-lyase activity of CYP17A1 (this enzyme also has 17-alpha-hydroxylase activity). In case of severe illness or trauma, CAH predisposes patients to poor recovery or death. Patients with the most common form of CAH (21-hydroxylase deficiency, >90% of cases), with the third most common form of CAH (3-beta-steroid dehydrogenase deficiency, <3% of cases) and those with the extremely rare StAR (steroidogenic acute regulatory protein) or 20,22 desmolase deficiencies, might also suffer mineral corticoid deficiency, as the enzyme blocks in these disorders are proximal to potent mineral corticoids. These patients might suffer salt-wasting crises in infancy. By contrast, patients with the second most common form of CAH, 11-hydroxylase deficiency (<5% of cases), are normotensive or hypertensive, as the block affects either CYP11B1 or CYP11B2, but rarely both, thus ensuring that at least corticosterone is still produced.

 

In addition, patients with all forms of CAH might suffer the effects of substrate accumulation proximal to the enzyme block. In the 3 most common forms of CAH the accumulating precursors spill over into the sex steroid pathway, resulting in virilization of females or, in milder cases, in hirsutism, polycystic ovarian syndrome or infertility, as well as in possible premature adrenarche and pubarche in both genders.

 

Measurement of the various precursors of mature mineral corticoids and glucocorticoids, in concert with the determination of sex steroid concentrations, allows diagnosis of CAH and its precise type, and serves as an aid in monitoring steroid replacement therapy and other therapeutic interventions.

 

Measurement of 21-deoxycortisol can supplement or confirm 17-hydroxyprogesterone and androstenedione measurements in the diagnosis of difficult cases of CAH presumed to be due to CYP21A2 deficiency. 11-Hydroxylation remains intact in such patients. However, since the CYP21A2 enzyme block prevents formation of 11-deoxycortisol, while simultaneously increasing the concentrations of the precursor, 17-hydroxyprogesterone, unoccupied CYP11B1 starts to 11-hydroxylate the abundant 17-hydroxyprogesterone substrate into 21-deoxycortisol. The 21-deoxycortisol accumulates, as the diminished or absent CYP21A2 activity slows or prevents its conversion into cortisol.

 

For other forms of CAH the following tests might be relevant:

 

-11-Hydroxylase deficiency:

 - DOC / 11-Deoxycortisol, Serum

 - CORTC / Corticosterone, Serum

 - PRA / Renin Activity, Plasma

 - ALDS / Aldosterone, Serum

 

-3-Beta-steroid-dehydrogenase deficiency:

 - 17PRN / Pregnenolone and 17-Hydroxypregnenolone

 

-17-Hydroxylase deficiency or 17-lyase deficiency (CYP17A1 has both activities):

 - PREGN / Pregnenolone, Serum

 - 17OHP / 17-Hydroxypregnenolone, Serum

 - PGSN / Progesterone, Serum

 - OHPG / 17-Hydroxyprogesterone, Serum

 - DHEA_ / Dehydroepiandrosterone (DHEA), Serum

 - ANST / Androstenedione, Serum

 

Cortisol should be measured in all cases of suspected CAH.

 

It has been suggested that in the pubertal patient with 21-hydroxylase deficiency, 21-deoxycortisol may be useful and better then 17-hydroxyprogesterone for therapeutic decisions.

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.

<5.0 ng/dL

Reference values apply to all ages.

Interpretation
Provides information to assist in interpretation of the test results

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.

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

At birth the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis are activated and all adrenal steroids, including mineral corticoids and sex steroids and their precursors are high. In preterm infants the elevations can be even more pronounced due to illness and stress. In doubtful cases, when the initial test was performed on a just-born baby, repeat testing a few days or weeks later is advised.

 

Adrenocorticotrophic hormone (ACTH)1-24 testing has a low, but definite risk of drug and allergic reactions and should, therefore, only be performed under the supervision of a physician in an environment that guarantees the patient's safety, typically an endocrine, or other centralized, testing center.

 

Interpretation of ACTH1-24 testing in the context of diagnosis of congenital adrenal hyperplasia (CAH) requires considerable experience, in particular for the less common variants of CAH, such as 11-hydroxylase deficiency, or 3-beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency, for which very few, if any, reliable normative data exist. For the even rarer enzyme defects, such as deficiencies of StAR (steroidogenic acute regulatory protein), 20,22 desmolase, 17a-hydroxylase/17-lyase, and 17-beta-hydroxysteroid dehydrogenase (17beta-HSD), there are only case reports. Expert opinion from a pediatric endocrinologist with experience in CAH should, therefore, be sought.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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

3. Collett-Solberg PF: Congenital adrenal hyperplasia: from genetics and biochemistry to clinical practice, part I. Clin Pediatr 2001;40:1-16

4. Forest MG: Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum Reprod Update 2004;10:469-485

5. Tonetto-Fernandes V, Lemos-Marini SH, Kuperman H, et al: Serum 21-deoxycortisol, 17-hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency. J Clin Endocrinol Metab 2006;91:2179-2184

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

The specimen and an internal standard are assayed by liquid chromatography-tandem mass spectrometry. The analyte is detected by multiple-reaction monitoring.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Tuesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 9 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82542

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
21DOC 21-Deoxycortisol, S 74872-3
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.
89477 21-Deoxycortisol, S 74872-3

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports