Reference Range

The serum reference ranges of 11-deoxycortisol are as follows^{[1, 2, 3]}:

Persons aged 18 years or younger: < 344 ng/dL
Adults older than 18 years: 10-79 ng/dL
Ranges decrease with age after puberty
Serum reference range of 11-deoxycortisol after a single-dose overnight metapyrone test is >1700 ng/dL

Interpretation

In patients with suspected congenital adrenal hyperplasia (CAH), elevated 11-deoxycortisol levels indicate possible 11-beta-hydroxylase deficiency.

Pharmacologic blockade of 11-beta-hydroxylase with metyrapone normally stimulates a rise in 11-deoxycortisol levels. A subnormal rise in 11-deoxycortisol levels after a single-dose overnight metapyrone stimulation test is associated with causes of adrenal insufficiency, including the following:

Primary adrenal insufficiency: Addison disease, adrenal adenoma, CAH
Secondary adrenal insufficiency: Pituitary microadenoma, hypothalamic tumor, pituitary apoplexy, head trauma
Tertiary adrenal insufficiency: Hypothalamic disease with decrease in corticotropin-releasing factor (CRF)

Collection and Panels

Specifics for collection and panels of 11-deoxycortisol are as follows:

Specimen type: Blood serum
Container: Vacutainer, red top (see image below)

Vacutainer tube-red top
Collection method: Venipuncture
Specimen volume: 0.3 mL (minimum 0.25 mL)
Collection instructions: Morning (eg, 8 AM) collection desirable
Other instructions: For metapyrone test, indicate if drawn before or after metapyrone administration

Description

CAH is a general term for a group of inherited disorders in which a defect in cortisol biosynthesis results in overproduction of adrenocorticotropic hormone (ACTH), with secondary adrenal hyperplasia as a consequence. An enzymatic defect in 11-beta-hydroxylase, which converts 11-deoxycortisol to cortisol, is the second most common variant of CAH and accounts for approximately 5%-8% of cases. Patients present with features of androgen excess, such as ambiguous genitalia in female newborns and premature sexual development in male children. With the severe (classic) form of 11-beta-hydroxylase deficiency, hypertension develops in approximately two thirds of patients, often in the first few years of life.

The overnight metyrapone test is used to assess the functioning of the hypothalamic-pituitary-adrenal (HPA) axis; impairment of any component of the HPA-axis results in a subnormal rise in 11-deoxycortisol levels in response to metapyrone stimulation. The test is used mainly to diagnose secondary adrenal insufficiency.

Indications/Applications

Indications for testing of serum 11-deoxycortisol include the following:

Diagnostic workup of CAH for 11-beta-hydroxylase deficiency
Part of metapyrone testing to evaluate the HPA-axis in the workup of suspected secondary or tertiary adrenal insufficiency

Considerations

For the overnight metapyrone stimulation test, the patient is administered oral metapyrone at a weight-based dosage (30 mg /kg). Blood samples are collected before the time of dosage (eg, at midnight) and 8 hours after dosage (eg, at 8 AM).

A study by London et al suggested that statins reduce the level of certain precursors found in the steroidogenic pathway, including 11-deoxycortisol, a result which “may be of clinical relevance for individuals with underlying or subclinical adrenal insufficiency.” The investigators reported that 24 hours after a single dose of pitavastatin, individuals showed a significant decrease in 11-deoxycortisol, corticosterone, and cortisone. However, cortisol and aldosterone levels were not significantly changed.^[4]