Test Catalog

Test Id : DOCS

11-Deoxycorticosterone, Serum

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

Diagnosis of suspected 11-hydroxylase deficiency, including the differential diagnosis of 11 beta-hydroxylase 1 (CYP11B1) versus 11 beta-hydroxylase 2 (CYP11B2) deficiency

 

Diagnosis of glucocorticoid-responsive hyperaldosteronism

 

Evaluating congenital adrenal hyperplasia newborn screen-positive children, when elevations of 17-hydroxyprogesterone are only moderate, suggesting possible 11-hydroxylase 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

11-Deoxycorticosterone, S

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

DOCS

DOC

11-deoxycorticosterone

Deoxycorticosterone

21-hydroxyprogesterone

Desoxycortone

INN

Deoxycortone

BAN

Cortexone

Substance Q

desoxy compound B

21-Hydroxy-4-pregnene-3,20-dione

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 7 days

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

Diagnosis of suspected 11-hydroxylase deficiency, including the differential diagnosis of 11 beta-hydroxylase 1 (CYP11B1) versus 11 beta-hydroxylase 2 (CYP11B2) deficiency

 

Diagnosis of glucocorticoid-responsive hyperaldosteronism

 

Evaluating congenital adrenal hyperplasia newborn screen-positive children, when elevations of 17-hydroxyprogesterone are only moderate, suggesting possible 11-hydroxylase 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).

 

11-Deoxycorticosterone represents the last intermediate in the mineral corticoid pathway that has negligible mineral corticoid activity. It is converted by 11-beta-hydroxylase 2 (CYP11B2) or by 11-beta-hydroxylase 1 (CYP11B1) to the first mineral corticoids with significant activity, corticosterone. Corticosterone is in turn converted to 18-hydroxycorticosterone and finally to aldosterone, the most active mineral corticoid. Both of these reactions are catalyzed by CYP11B2, which, unlike its sister enzyme CYP11B1, also possesses 18-hydroxylase and 18-methyloxidase activity.

 

The major diagnostic utility of measurement of steroid synthesis intermediates is in diagnosing 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 cases 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 11-deoxycorticosterone and its glucocorticoid pendant, 11-deoxycortisol (also known as compound S), is aimed at diagnosing:

-CYP11B1 deficiency (associated with cortisol deficiency)

-The rarer CYP11B2 deficiency (no cortisol deficiency) 

-The yet less common glucocorticoid-responsive hyperaldosteronism (where expression of the gene CYP11B2 is driven by the CYP11B1 promoter, thus making it responsive to adrenocorticotrophic hormone: ACTH rather than renin)

 

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

-11-Hydroxylase deficiency:

- DOC / 11-Deoxycortisol, Serum

- CORTC / Corticosterone, Serum

- HYD18 / Hydroxycorticosterone, 18

- PRA / Renin Activity, Plasma

- ALDS / Aldosterone, Serum

 

-3-Beta-steroid-dehydrogenase deficiency:

- 17PRN / Pregnenolone and 17-Hydroxypregnenolone, Serum

 

-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.

 

In the diagnosis of suspected 11-hydroxylae deficiency and glucocorticoid-responsive hyperaldosteronism, this test should be used in conjunction with measurements of 11-deoxycortisol, corticosterone, 18-hydroxycorticosterone, cortisol, renin, and aldosterone.

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.

< or =18 years: <30 ng/dL

>18 years: <10 ng/dL

Interpretation
Provides information to assist in interpretation of the test results

In 11 beta-hydroxylase 1 (CYP11B1) deficiency, serum concentrations of cortisol will be low (usually <7 microgram/dL for a morning draw). 11-Deoxycortisol and 11-deoxycorticosterone are elevated, usually to at least 2 to 3 times (more typically 20-300 times) the upper limit of the normal reference range on a morning blood draw. Elevations in 11-deoxycortisol are usually relatively greater than those of 11-deoxycorticosterone, because of the presence of intact 11 beta-hydroxylase 2 (CYP11B2). For this reason, serum concentrations of all potent mineral corticoids (corticosterone, 18-hydroxycorticosterone, and aldosterone) are typically increased above the normal reference range. Plasma renin activity is correspondingly low or completely suppressed. Caution needs to be exercised in interpreting the mineral corticoid results in infants younger than 7 days; mineral corticoid levels are often substantially elevated in healthy newborns in the first few hours of life and only decline to near-adult levels by week 1.

 

Mild cases of CYP11B1 deficiency might require adrenocorticotrophic hormone (ACTH)1-24 stimulation testing for definitive diagnosis. In affected individuals, the observed serum 11-deoxycortisol concentration 60 minutes after intravenous or intramuscular administration of 250 microgram of ACTH1-24 will usually exceed 20 ng/mL, or demonstrate at least a 4-fold rise. Such increments are rarely, if ever, observed in unaffected individuals. The corresponding cortisol response will be blunted (<18 ng/mL peak).

 

In CYP11B2 deficiency, serum cortisol concentrations are usually normal, including a normal response to ACTH1-24. 11-Deoxycorticosterone will be elevated, often more profoundly than in CYP11B1 deficiency, while 11-deoxycortisol may or may not be significantly elevated. Serum corticosterone concentrations can be low, normal, or slightly elevated, while serum 18-hydroxycorticosterone and aldosterone concentrations will be low in the majority of cases. However, if the underlying genetic defect has selectively affected 18-hydroxylase activity, corticosterone concentrations will be substantially elevated. Conversely, if the deficit affects aldosterone synthase function primarily, 18-hydroxycorticosterone concentrations will be very high.

 

Expression of the CYP11B2 gene is normally regulated by renin and not ACTH. In glucocorticoid-responsive hyperaldosteronism, the ACTH-responsive promoter of CYP11B1 exerts aberrant control over CYP11B2 gene expression. Consequently, corticosterone, 18-hydroxycorticosterone, and aldosterone are significantly elevated in these patients and their levels follow a diurnal pattern, governed by the rhythm of ACTH secretion. In addition, the high levels of CYP11B2 lead to 18-hydroxylation of 11-deoxycortisol (an event that is ordinarily rare, as CYP11B1, which has much greater activity in 11-deoxycortisol conversion than CYP11B2, lacks 18-hydroxylation activity). Consequently, significant levels of 18-hydroxycortisol, which normally is only present in trace amounts, might be detected in these patients. Ultimate diagnostic confirmation comes from showing direct responsiveness of mineral corticoid production to ACTH1-24 injection. Normally, this has little if any effect on corticosterone, 18-hydroxycorticosterone, and aldosterone levels. This testing may then be further supplemented by showing that mineral corticoid levels fall after administration of dexamethasone. Sex steroid levels are moderately to significantly elevated in CYP11B1 deficiency and much less, or minimally, pronounced in CYP11B2 deficiency. Sex steroid levels in glucocorticoid-responsive hyperaldosteronism are usually normal.

 

Most untreated patients with 21-hydroxylase deficiency have serum 17-hydroxyprogesterone concentrations well in excess of 1000 ng/dL. For the few patients with levels in the range of higher than 630 ng/dL (upper limit of reference range for newborns) to 2000 or 3000 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 CYP11B1, can be associated with modest elevations in serum 17-hydroxyprogesterone concentrations. In these cases, testing for CYP11B1 deficiency and CYB11B2 deficiency should be considered and interpreted as described above. Alternatively, measurement of 21-deoxycortisol might be useful. This minor pathway metabolite accumulates in CYP21A2 deficiency, as it requires 21-hydroxylaion to be converted to cortisol, but is usually not elevated in CYP11B1 deficiency, since its synthesis requires via 11-hydroxylation of 17-hydroxyprogesterone.

Cautions

At birth, the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis are activated and all adrenal steroids are high, including mineral corticoids and sex steroids and their precursors. In preterm infants, 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.

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 are high, including mineral corticoids and sex steroids and their precursors. In preterm infants, 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, Ribeiro-Neto LM, Verreschi JTN, Kater CE: Serum 21-deoxycortisol, 17-hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11 beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2006;91:2179-2184

6. Lashanske G, Sainger P, Fishman K, et al: Normative data for adrenal steroidogenesis in a healthy pediatric population: age-and sex-related changes after adrenocorticotropin stimulation. J Clin Endocrinol Metab. 1991;73:674-686

7. Holst JP, Soldin SJ, Tractenberg RE, et al: Use of steroid profiles in determining the cause of adrenal insufficiency. Steroids. 2007;72:71-84

8. Berneis K, Staub JJ, Gessler A, Meier C, Girard J, Muller B: Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function. J Clin Endocrinol Metab. 2002;87(12):5470-5475

9. Sciarra F, Tosti-Croce C, Toscano V: Androgen-secreting adrenal tumors. Minerva Endocrinol. 1995;20:63-68

10. Speiser PW, Arlt W, Auchus RJ, et al: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 Nov;103(11):4043-4088. doi: 10.1210/jc.2018-01865 Correction in: J Clin Endocrinol Metab. 2019 Jan;104(1):39–40

11. Khattab A, Haider S, Kumar A, et al: Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1933–E1940 doi: 10.1073/pnas.1621082114

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
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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.

82633

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