About the Test
Pregnenolone tests are blood tests conducted on infants, usually as part of a panel of tests. It is used as a diagnostic tool to help find the underlying cause of CAH in infants. CAH is suspected when an infant has ambiguous external sex organs, signs of adrenal insufficiency, excess loss of sodium and fluids, or low or high blood pressure.
Purpose of the test
Pregnenolone tests are one diagnostic tool doctors use on newborns after the more common causes of CAH have been ruled out.
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 adrenocorticotropic hormone (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), pregnenolone tests may be ordered, among others, to detect the rare forms as the cause of the symptoms.
What does the test measure?
This test measures the amount of pregnenolone in the blood to help detect rare forms of CAH.
CAH is a group of inherited disorders associated with deficiencies in the enzymes required to produce steroid hormones. This 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
- Lipoid CAH, also very rare, is most often due to a defect in the StAR gene, which codes for the Steroidogenic acute regulatory protein, which, in turn, regulates the conversion of cholesterol to pregnenolone
For normal steroid hormone production, cholesterol is converted into pregnenolone in the adrenal glands. Then several enzymes complete the production of multiple hormones, including:
- 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
Because a low level of cortisol causes the level of a pituitary hormone that stimulates adrenal growth and hormone production (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). This can affect the development of secondary sexual characteristics of both males and females at puberty.
Laboratory tests can measure pregnenolone, several intermediate precursors, and one or more steroid hormones to determine which step is deficient or defective. This is based upon which products have been produced and how much, and which precursors are in excess.
If both 21- and 11-hydroxylase deficiencies have been ruled out (the most common forms of CAH), then analysis of pregnenolone and tests for other precursors may help establish a diagnosis of 3-beta-hydrosteroid dehydrogenase or 17-alpha-hydroxylase or StAR deficiency.
When should I get this test?
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 low or high blood pressure. It is usually ordered following testing for 17-OHP.
This test is primarily ordered when a health care practitioner suspects symptoms may be due to a CAH other than 21-hydroxylase deficiency or 11-beta-hydroxylase deficiency and/or wants to rule it out. If affected, the signs and symptoms 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.
- Female infants usually appear normal but may have some 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 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).
If a patient has been diagnosed with one of these types of CAH, pregnenolone may be ordered periodically to monitor the condition and treatment.
Some doctors may also use a pregnenolone test to help diagnose and determine the effectiveness of treatment for memory and neurologic illnesses. There is limited and conflicting evidence for memory enhancement in humans when pregnenolone is given as a supplement or drug.
A placebo-controlled clinical trial was conducted, which demonstrated some efficacy in improving functional capacity in participants with schizophrenia but did not improve cognitive symptoms. Pregnenolone is converted to pregnenolone sulfate and allopregnanolone, which may be an effective steroid to stimulate or suppress activity in various brain areas.
Finding a Pregnenolone Test
How can I get a pregnenolone test?
A pregnenolone test is almost always ordered by a doctor, whether it’s for an infant or someone with a memory or cognitive disease. Typically, it will be one of several tests performed. You can order a pregnenolone test from Testing.com and have your blood drawn at a local lab.
Can I take the test at home?
Pregnenolone tests are not available as at-home tests.
How much does the test cost?
Pregnenolone test costs may vary depending on your health insurance coverage, the reason for the test, and where the test is administered. With most plans, you will be at least partially covered, depending on if you have a copayment or deductible to pay. A pregnenolone test from Testing.com is $119.
Taking a Pregnenolone Test
A pregnenolone test is done by taking a blood sample from a vein. In adults, the blood draw is usually done in the arm, but blood is collected using a heel prick for infants.
Before the test
There are no particular instructions to follow before a pregnenolone test.
During the test
For infants, the health care provider will usually collect blood from the heel. The skin will first be warmed for one minute to dilate the capillaries and increase blood flow. Then, the heel will be sterilized with an alcohol pad. The phlebotomist will gently squeeze the heel and prick it with a lancet. Next, they will gently massage the foot and collect the drops of blood into a tube as they come out.
Adults taking this test will have a more traditional blood draw from a vein in their arm.
After the test
There are no side effects expected from taking this blood test other than possible minor bruising at the blood draw site.
Pregnenolone Test Results
Receiving test results
Your health care provider or laboratory should contact you with the results of the pregnenolone test within seven to 10 business days. You may also see results when available if you have access to an online patient portal.
Interpreting test results
In general, if there is an enzyme deficiency somewhere in the steroid hormone production process, there is likely to be a mild to significant increase or decrease in pregnenolone levels. The degree of increase or decrease 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 steroid hormones, if measured, may be low, including:
With Lipoid CAH, all the steroids tested would be low, but ACTH is expected to be elevated.
With complex testing like pregnenolone, it’s important to ask your doctor questions about the results. Some to consider include:
- What follow-up or repeat testing is needed to confirm a diagnosis?
- What is the prognosis and treatment if pregnenolone test results confirm CAH?
- Should I have my other children tested for CAH if one of them is diagnosed?