Pregnenolone

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.

CAH is a group of inherited disorders associated with a deficiency in one of the enzymes required for the production of the steroid hormones. Two of the most common causes of CAH are:

• 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:

• Pregnenolone
• 11-deoxycorticosterone
• Corticosterone
• 17-hydroxypregnenolone
• DHEA, DHEAS

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."

Males

• 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).

Females

• 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).

Males

• 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.

Females

• 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.

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:

• 17-OHP
• 17-hydroxypregnenolone
• 11-deoxycortisol
• DHEA
• Androstenedione
• Cortisol
• Testosterone
• Estrogens
• Aldosterone

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.

Yes, this is an important thing for all of your health care providers to know. Most people with CAH will require the regular replacement of one or more hormones and will need to be monitored.