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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


Specimen Required


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 Special Container
Serum Refrigerated (preferred) 21 days
  Frozen  21 days
  Ambient  14 days

Reject Due To

Gross hemolysis Reject
Gross lipemia OK
Gross icterus OK

Clinical Information

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

<5.0 ng/dL

Reference values apply to all ages.

Day(s) and Time(s) Performed

Tuesday; 10 a.m.

Analytic Time

3 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


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

NY State Approved