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Test Code DOCS 11-Deoxycorticosterone, Serum

Useful For

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

See Steroid Pathways in Special Instructions.

Special Instructions

Method Name

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

Reporting Name

11-Deoxycorticosterone, 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  7 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

Mild OK; Gross OK

Other

NA

Reference Values

≤18 years: <30 ng/dL

>18 years: <10 ng/dL

Interpretation

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 1,000 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 2,000 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 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.

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

82633

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DOCS 11-Deoxycorticosterone, S In Process

 

Result ID Test Result Name Result LOINC Value
46922 11-Deoxycorticosterone, S 1656-8