NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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. 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.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See Steroid Pathways in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 1 mL
Collection Instructions: Morning (8 a.m.) specimen is preferred.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Mild reject; Gross reject
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Serum||Refrigerated (preferred)||7 days|
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:
- DOC/8547 11-Deoxycortisol, Serum
- CORTC/88221 Corticosterone, Serum
- PRA/8060 Renin Activity, Plasma
- ALDS/8557 Aldosterone, Serum
- 17PRN/88646 Pregnenolone and 17-Hydroxypregnenolone
-17-Hydroxylase deficiency or 17-lyase deficiency (CYP17A1 has both activities):
- PREGN/88645 Pregnenolone, Serum
- 17OHP/81151 17-Hydroxypregnenolone
- PGSN/8141 Progesterone, Serum
- OHPG/9231 17-Hydroxyprogesterone, Serum
- DHEA_/81405 Dehydroepiandrosterone (DHEA), Serum
- ANST/9709 Androstenedione, Serum
Cortisol should be measured in all cases of suspected CAH.
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.
Reference values apply to all ages.
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 >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 post stimulation results in normals and in heterozygote carriers. By contrast, post stimulation 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/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 Provides recommendations for further 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
Method Description Describes how the test is performed and provides a method-specific reference
A deuterated stable isotope 21-deoxycortisol-d8 is added to a 0.1-mL serum sample as internal standard and assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analyte is further purified via online turbulent flow extraction. Analyte and internal standard are monitored in electrospray ionization mode (ESI) and are detected by multiple-reaction monitoring (MRM).(Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Tuesday; 2 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|89477||21-Deoxycortisol, S||In Process|