Pregnenolone

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Point-of-Care Testing

At a Glance

Why Get Tested?

To help detect and monitor treatment for rare types of genetic conditions that affect production of steroid hormones; some of these are called congenital adrenal hyperplasia (CAH). In addition, pregnenolone tests may be ordered by healthcare practitioners to help rule out other conditions.

When To Get Tested?

When an infant has external sex organs that are not clearly male or female (ambiguous genitalia) and/or has low or high blood pressure, 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

Sample Required?

A blood sample drawn from a vein

Test Preparation Needed?

The healthcare practitioner may or may not request a morning sample and may or may not give an injection such as ACTH to stimulate steroid hormone release.

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You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

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
  • 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 and 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 (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 step is deficient or defective, 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, along with tests for other precursors, may be used to help establish a diagnosis of 3-beta-hydrosteroid dehydrogenase or 17-alpha-hydroxylase or StAR deficiency.

 

Common Questions

How is the test 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.

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 pregnenolone tests may be ordered among others to detect the rare forms as the cause of a person’s symptoms.

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 low or high blood pressure. It is usually ordered following testing for 17-OHP.

This test is primarily ordered when a healthcare 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.

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.

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 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.

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 healthcare 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?

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

If I have CAH, or my child does, should my family members be tested?

You should talk to your healthcare provider or a genetic counselor about this. Since CAH is caused by an autosomal recessive genetic mutation, both parents must have an altered gene in order for a child to have the condition. If both parents are carriers then each child has a 25% chance of having the condition.

How long will it take for pregnenolone results?

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?

Chromosome analysis (karyotyping) can be performed to identify whether the baby has XX (female) or XY (male) sex chromosomes.

Is this test used for other purposes?

Yes, sometimes it may be used to diagnose or follow treatment of neurological and memory issues. Pregnenolone, pregnenolone sulfate, and allopregnanolone have been implicated as neurosteroids largely through studies in rodents. There is limited and conflicting evidence for enhancement of memory in humans when pregnenolone is given as a supplement or drug. A placebo-controlled clinical trial was conducted, which demonstrated some efficacy improving functional capacity in participants with schizophrenia but did not improve cognitive symptoms. Pregnenolone is converted to pregnenolone sulfate and allopregnanolone, which may be the effective steroid to stimulate or suppress activity in various areas of the brain.

Related Content

On This Site

Elsewhere on the Web

View Sources

Sources Used in Current Review

2019 review performed by Donald Walt Chandler, PhD, Endocrinology Discipline Director, LabCorp and Endocrine Sciences.

Manna PR, Stetson CL, Slominski AT, Pruitt K. Role of the steroidogenic acute regulatory protein in health and disease. Endocrine. 2016 Jan;51(1):7-21. doi:10.1007/s12020-015-0715-6. Epub 2015 Aug 14. Review. PubMed PMID: 26271515; PubMed Central PMCID: PMC4707056.

Miller WL. Steroid hormone synthesis in mitochondria. Mol Cell Endocrinol. 2013 Oct 15;379(1-2):62-73. doi: 10.1016/j.mce.2013.04.014. Epub 2013 Apr 28. PubMed PMID: 23628605.

Katsumata N. Genetic defects in pregnenolone synthesis. Pediatr Endocrinol Rev. 2012 Oct;10 Suppl 1:98-109. Review. PubMed PMID: 23330251.

Weng JH, Chung BC. Nongenomic actions of neurosteroid pregnenolone and its metabolites. Steroids. 2016 Jul;111:54-59. doi: 10.1016/j.steroids.2016.01.017. Epub 2016 Feb 1. Review. PubMed PMID: 26844377.

Marx CE, Lee J, Subramaniam M, Rapisarda A, Bautista DC, Chan E, Kilts JD, Buchanan RW, Wai EP, Verma S, Sim K, Hariram J, Jacob R, Keefe RS, Chong SA. Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. Psychopharmacology (Berl). 2014 Sep;231(17):3647-62. doi: 10.1007/s00213-014-3673-4. Epub 2014 Jul 17. PubMed PMID: 25030803.

Sripada RK, Marx CE, King AP, Rampton JC, Ho SS, Liberzon I. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol Psychiatry. 2013 Jun 1;73(11):1045-53. doi: 10.1016/j.biopsych.2012.12.008. Epub 2013 Jan 21. PubMed PMID: 23348009; PubMed Central PMCID: PMC3648625.

Sources Used in Previous Reviews

Frindik, J. P. (Updated 2012 May 10). 17-Hydroxylase Deficiency Syndrome. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/920532-overview. Accessed June 2013.

(© 1995–2013). Pregnenolone, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/88645. Accessed June 2013.

Morley, J. (Revised 2013 February). Endocrine Disorders. Merck Manual for Healthcare Professionals [On-line information]. Available online through http://www.merckmanuals.com. Accessed June 2013.

Meikle, A. W. (2011 May). Adrenal Steroids Panel: High Specificity Lc-Ms/Ms Test For 11-Deoxycortisol, 17-Hydroxyprogesterone, 17-Hydroxypregnenolone, And Pregnenolone In Serum. ARUP Technical Information [On-line information]. Available online at http://www.aruplab.com/guides/ug/tests/iconpdf_25.pdf. Accessed June 2013.

Meikle, A. W. (Updated 2013 January). Congenital Adrenal Hyperplasia – CAH. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/CAH.html?client_ID=LTD. Accessed June 2013.

Wilson, T. (Updated 2013 June 13). Congenital Adrenal Hyperplasia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/919218-overview. Accessed May 2013.

Frindik, J. P. (Updated 2012 May 30). 3-Beta-Hydroxysteroid Dehydrogenase Deficiency. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/920621-overview. Accessed June 2013.

(Reviewed 2010 February). 3-beta-hydroxysteroid dehydrogenase deficiency. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency. Accessed June 2013.

Miller, W. (2012 January). The Syndrome of 17,20 Lyase Deficiency. J Clin Endocrinol Metab v 97(1):59–67. [On-line information]. Available online at http://jcem.endojournals.org/content/97/1/59.full.pdf. Accessed June 2013.

A.D.A.M. Health Solutions (Updated 2012 May 8). Congenital Adrenal Hyperplasia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000411.htm. Accessed June 2013.

Scott, H. et. al. (2009 December 1). Steroidogenesis in the Fetal Testis and Its Susceptibility to Disruption by Exogenous Compounds. Endocrine Reviews v 30 (7) 883-925 [On-line information]. Available online at http://edrv.endojournals.org/content/30/7/883.full. Accessed June 2013.

Kushnir, M. et. al. (2006 August) Development and Performance Evaluation of a Tandem Mass Spectrometry Assay for 4 Adrenal Steroids. Clinical Chemistry v 52 (8) 1559-1567 [On-line information]. Available online at http://www.clinchem.org/content/52/8/1559.full.pdf+html?sid=9d621d7c-9a8b-42c2-85f5-a0df3a464b7a. Accessed June 2013.

Strushkevich, N. et. al. (2011 June 21). Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci U S A. v 108 (25): 10139–10143. [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121847/. Accessed June 2013.

Haider, S. (2007 June 1). Leydig Cell Steroidogenesis: Unmasking the Functional Importance of Mitochondria. Endocrinology v 148 (6) 2581-2582 http://endo.endojournals.org/content/148/6/2581.full. Accessed June 2013.

 

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