When an infant has external sex organs that are not clearly male or female (ambiguous genitalia) and/or has high blood pressure (hypertension), low blood potassium (hypokalemia), or signs of excess loss of salt (salt wasting); when the most common cause for CAH, a 21-hydroxylase deficiency, has been ruled out; when a teen fails to develop secondary sexual characteristics and/or has delayed puberty
A blood sample drawn from a vein in your arm
Pregnenolone is a chemical substance that is a precursor to all steroid hormones. This test measures the amount of pregnenolone in the blood in order to help detect rare forms of congenital adrenal hyperplasia (CAH).
CAH is a group of inherited disorders associated with deficiencies in the enzymes required for the production of the steroid hormones. CAH may be due to:
- 21-hydroxylase deficiency, the most common cause of CAH (about 90% of cases)
- 11-beta-hydroxylase deficiency (about 5-8% of cases)
- 3-beta-hydroxysteroid dehydrogenase and 17-alpha-hydroxylase deficiencies, two rare forms of the disease
- Cortisol, which helps metabolize proteins, lipids, and carbohydrates, maintain blood pressure, and regulate the immune system
- Aldosterone, which maintains normal sodium and potassium levels in the blood and helps control blood volume and pressure
- Sex steroid hormones – including androgens, the "male hormones" such as testosterone, and "female" hormones including estrogen and progesterone, which are responsible for the development and maintenance of male and female secondary sexual characteristics
In congenital adrenal hyperplasia, one or more of the enzymes is deficient or dysfunctional and inadequate amounts of one or more final products are produced. Because a low level of cortisol causes the level of a pituitary hormone that stimulates adrenal growth and hormone production (adrenocorticotropic hormone, or ACTH) to become elevated, the adrenal gland increases in size. However, the increased size and activity cannot overcome the block in cortisol production. Other substances (such as pregnenolone) that do not need the defective enzyme will be produced in excess.
With CAH, the enzyme deficiency can cause a decrease in cortisol and/or aldosterone and, in some cases, an increase or decrease in androgens. Deficient androgens can cause male newborns to be born with external sex organs that are not clearly male or female (ambiguous genitalia) and can affect the development of secondary sexual characteristics of both males and females at puberty.
Pregnenolone, several of the intermediate precursors, and one or more of the steroid hormones can be measured by laboratory tests to determine which enzyme is deficient or defective, based upon which products have been produced and how much.
If both 21- and 11-hydroxylase deficiencies have been ruled out (the most common forms of CAH), then analysis of pregnenolone, along with tests for other precursors, may be used to help establish a diagnosis of 3-beta-hydrosteroid dehydrogenase or 17-alpha-hydroxylase deficiency.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
Pregnenolone is typically ordered as part of a panel of tests that are used to help diagnose, monitor and/or rule out two of the more rare forms of congenital adrenal hyperplasia (CAH). The test is typically used after the more common causes of CAH have been ruled out.
- 21-hydroxylase deficiency (about 90% of CAH cases)
- 11-beta-hydroxylase deficiency (about 5-8% of cases)
Two rare forms of CAH include:
- 3-beta-hydroxysteroid dehydrogenase deficiency
- 17-alpha-hydroxylase deficiency
All newborns are screened for the most common cause of CAH using a test that measures 17-hydroxyprogesterone (17-OHP). If this testing is abnormal, it may be followed by ACTH testing and then by groups or panels of precursors and hormones to determine which enzyme deficiencies are present. This includes 11-deoxycorticosterone and 11-deoxycortisol testing to help detect 11-beta-hydroxylase deficiency.
If the two common forms of CAH are ruled out, especially if a baby has external sex organs that are not clearly male or female (ambiguous genitalia), then the following tests may be ordered to detect the rare forms as the cause of a person's symptoms:
- DHEA, DHEAS
When is it ordered?
Pregnenolone is ordered when an infant has external sex organs that are not clearly male or female (ambiguous genitalia) and/or has signs of adrenal insufficiency, excess loss of sodium and fluids ("salt wasting"), or high blood pressure (hypertension). It is usually ordered following testing for 17-OHP.
This test is primarily ordered when a health practitioner suspects that symptoms may be due to a CAH other than 21-hydroxylase deficiency or 11-beta-hydroxylase deficiency and/or wants to rule it out. An affected person may have signs and symptoms that include:
With 3-beta-hydroxysteroid dehydrogenase deficiency
Both males and females may have signs of adrenal insufficiency and "salt wasting."
- Male infants may have sex organs that are not clearly male or female and/or may have an opening of the urethra on the underside of the penis instead of the tip (hypospadias).
- Teen boys may have poor and/or delayed development of secondary sexual characteristics, such as facial hair or deep voice.
- Males may have breast enlargement (gynecomastia).
- Female infants usually appear normal but may have some degree of abnormal enlargement of the clitoris.
- Girls may have acne and accelerated growth.
- Teen girls may have excess hair on their body and face (hirsutism) and may have ovaries with numerous fluid-filled cysts (polycystic ovaries).
With 17-alpha-hydroxylase deficiency
Both males and females may have high blood pressure (hypertension).
- Male infants may have entirely female external sex organs and be mistaken for a female, or they may have sex organs that are not clearly male or female
- Teen boys will have symptoms of delayed puberty, with a lack of development of secondary sexual characteristics.
- Female infants will appear normal.
- Teen girls will have symptoms of delayed puberty, with a lack of development of secondary sexual characteristics and no menstrual periods (amenorrhea).
In a person who has been diagnosed with one of these types of CAH, pregnenolone may be ordered periodically to monitor the condition and treatment.
What does the test result mean?
In general, if there is an enzyme deficiency somewhere in the steroid hormone production process, then there is likely to be a mild to significant increase in pregnenolone. The degree of increase depends upon the enzyme that is deficient and the severity of the deficiency. Results of pregnenolone need to be interpreted along with other precursor and hormone results.
With 3-beta-hydroxysteroid dehydrogenase deficiency, pregnenolone, 17-hydroxypregnenolone, and DHEA are typically elevated, and 17-OHP may be elevated. If they are measured, cortisol and aldosterone levels are likely to be low.
With 17-alpha-hydroxylase deficiency, pregnenolone and progesterone may be elevated, along with 11-deoxycorticosterone. Other precursors and hormones, if measured, may be low, including:
Is there anything else I should know?
Since deficiencies in 3-beta-hydroxysteroid dehydrogenase and 17-hydroxylase are rare causes of CAH, pregnenolone is much less commonly ordered than 17-OHP, the primary test for 21-hydroxylase deficiency CAH.
Excess facial and body hair in females and the delayed development of sexual characteristics in males and/or females may be due to a number of causes other than CAH. People should consult with their health care provider if they have concerns about their child's, or their own, symptoms or development.
Should I tell all of my doctors if I have CAH?
If I have CAH, or my child does, should my family members be tested?
Can pregnenolone be tested at my doctor's office?
No, this testing requires specialized equipment and is not offered by every laboratory. It may be necessary to send your blood sample to a reference laboratory and it may be several days to weeks for results to be available.
How can the doctor determine the sex of a baby with sex organs that are not clearly male or female?
On This Site
Elsewhere On The Web
MedlinePlus Medical Encyclopedia: Ambiguous genitalia
MedlinePlus Medical Encyclopedia: Congenital adrenal hyperplasia
The Magic Foundation: Congenital Adrenal Hyperplasia
National Adrenal Diseases Foundation
Genetics Home Reference: 3-beta-hydroxysteroid dehydrogenase deficiency
TeensHealth from Nemours: Delayed Puberty