Also Known As
CAH
21-hydroxylase Deficiency
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This article waslast modified on January 5, 2018.

What is congenital adrenal hyperplasia?

Congenital adrenal hyperplasia (CAH) is a group of inherited disorders of the adrenal gland, small triangular organs located on top of the kidneys that secrete hormones. CAH is associated with deficiencies in the enzymes required for the production of the steroid hormones cortisol and/or aldosterone.

In the adrenal gland, cholesterol is turned into a precursor called pregnenolone and then several enzymes complete the production of aldosterone, cortisol, and androgens. If one or more of these enzymes is deficient or dysfunctional, then inadequate amounts of the final products are produced. Because low levels of cortisol cause levels of a pituitary hormone that stimulates adrenal growth and hormone production (adrenocorticotropic hormone, or ACTH) to become elevated, the adrenal gland increases in size (CAH). However, the increased size and activity cannot overcome the block in cortisol production. Other substances (such as 17-hydroxyprogesterone) that do not need the defective enzyme will be produced in excess. The vast majority of CAH cases are due to a deficiency in the enzyme 21-hydroxylase, so this type will be the main focus of this article.

With CAH, the enzyme deficiency can cause a decrease in cortisol and/or aldosterone and, in some cases, an increase in androgens, a group of "male hormones." Excess androgens can result in the development of male sexual characteristics in females (virilization), which is often noticed at birth. A baby girl's external sex organs may be ambiguous: her genitals may resemble a boy's anatomy or be somewhere in between a boy's and a girl's anatomy. While it is a rare disorder, CAH is the most common cause of ambiguous external sex organs (genitals) in newborns.

Males with this condition will appear normal at birth but may start to develop sexual characteristics of puberty in early childhood. Females may develop excess hair on the face and body (hirsutism) and other male secondary sexual characteristic during childhood and adolescence and have irregular menstruation. CAH may also lead to infertility in adults.

CAH enzyme deficiencies are due to mutations in specific genes. They are autosomal recessive, which means that it takes two copies of the gene mutation, one inherited from each parent, before a person will be affected by CAH. A person with one copy will be a carrier but will not typically have any symptoms.

About 90% of CAH cases are due to a 21-hydroxylase deficiency, which is caused by a mutation in the CYP21A2 gene. Those affected may have a classic (more severe) or nonclassic (less severe) type. About 75% of those with a classic deficiency will have a "salt-wasting" form that includes decreased aldosterone and leads to an excess loss of fluids, low sodium, and high potassium that, when severe, can be life-threatening.

The National Institute of Child Health and Human Development estimates that classic CAH affects about one in 15,000 babies worldwide, while nonclassic CAH affects about one in 1,000 people. CAH can occur in people of all ethnicities but is more common among Ashkenazi Jews, Yupik Eskimos, and those of Hispanic, Slavic, or Italian descent.

Several other rare inherited enzyme deficiencies can also cause CAH. Of these, 11-beta-hydroxylase deficiency is the most common, accounting for about 5-8% of CAH cases, and 17-alpha-hydroxylase and 3 beta-hydroxysteroid dehydrogenase occur to a lesser degree. The signs and symptoms that are experienced by males and females with CAH will depend upon which enzymes are deficient and the severity of the deficiencies. 

Accordion Title
About Congenital Adrenal Hyperplasia
  • Signs and Symptoms

    Symptoms associated with congenital adrenal hyperplasia (CAH) depend upon the type of enzyme deficiency and the amounts of cortisol, aldosterone, and androgens that are produced. Symptoms may vary over time and can worsen with illness and stress.

    Those associated with the form of classic 21-hydroxylase deficiency CAH that causes excess loss of fluids and salt ("salt-wasting") can lead to a life-threatening adrenal crisis.

    Salt-wasting CAH signs and symptoms may include:

    • Abnormal heart rhythm, rapid heart rate
    • Confusion
    • Dehydration
    • High potassium (hyperkalemia)
    • Irritability
    • Low blood glucose (hypoglycemia)
    • Low blood pressure
    • Low sodium (hyponatremia)
    • Vomiting


    Females with classic 21-hydroxylase deficiency may have external sex organs that are not clearly male or female (ambiguous external genitalia) but normal reproductive organs (uterus, fallopian tubes, and ovaries).

    Signs and symptoms associated with excess male hormones (androgens) in both males and females in childhood and early adolescence may include:

    • Accelerated skeletal growth (tall during childhood but short as adults)
    • Acne
    • Deep voice
    • Enlarged penis (males)
    • Enlargement of clitoris (females)
    • Excess hair on face and body (hirsutism) in females
    • Infertility or decreased fertility
    • Irregular menstruation (females)
    • Excess muscle growth
    • Early development of pubic and armpit hair
  • Tests

    Laboratory Tests
    The goals with congenital adrenal hyperplasia (CAH) testing are to:

    • Screen all newborns for 21-hydroxylase deficiency
    • Help confirm the condition in those with positive newborn screens
    • Help diagnose the condition in those with symptoms
    • Identify the carrier status of a person who has a family member with 21-hydroxylase deficiency
    • Determine the chromosomal sex (XX or XY) of a newborn with genitals that are not clearly male or female (ambiguous genitalia)
    • Monitor treatment for CAH and detect overtreatment
    • Evaluate and monitor the health status of a person with an adrenal crisis
    • Detect 21-hydroxylase deficiency during pregnancy (sometimes)
    • Identify and/or rule out other types of CAH besides 21-hydroxlase deficiency (sometimes)


    Testing may include:

    Screening


    Detect/Diagnose

    • 17-OHP – may be greatly elevated with 21-hydroxylase deficiency
    • ACTH stimulation – measures the level of cortisol in a person's blood before and after an injection of synthetic ACTH (Cortrosyn™, cosyntropin). If the adrenal glands are functional, cortisol levels will rise in response to the ACTH stimulation; not performed frequently.
    • Additional testing may be performed when 17-OHP is elevated; often ordered as panels, depending upon which deficiencies and accumulations of precursors are suspected; may include several of the following:
    • Aldosterone and renin – to determine if levels of these substances are normal
    • Chromosome analysis (karyotyping) – to determine a baby's sex by evaluating their chromosomes (XX (female) or XY (male))
    • Genetic testing – performed to detect gene mutations; not usually needed for diagnosis but may be used for prenatal diagnosis of 21-hydroxylase deficiency and for detecting gene mutation(s) in family members to help determine carrier status; will detect the most common mutations. If a specific mutation has been identified in a family, testing should include that mutation.


    Monitor treatment, every few months:

    • 17-OHP
    • Androstenedione
    • Testosterone


    Health status, during illness, and to monitor


    Non-Laboratory Tests

    • Blood pressure
    • Pelvic ultrasonography to evaluate internal reproductive organs in females
    • Hand X-ray or bone-age study to evaluate rate of skeletal growth
  • Treatment

    Treatment of congenital adrenal hyperplasia (CAH) includes replacement of the substances that are not being adequately produced by the body because of the enzyme deficiency and suppression of excess androgen production. This may include:

    • Glucocorticoid – a steroid such as hydrocortisone to replace cortisol and suppress ACTH secretion and excess androgen production
    • Mineralocorticoid – to replace aldosterone if someone has a salt-wasting form of CAH; salt supplementation may also be recommended for some infants.

    Doses of steroids must be adjusted to avoid overtreatment as this can cause symptoms associated with Cushing syndrome. People will frequently require additional amounts of steroids during periods of stress and illness.

    An adrenal crisis can be life-threatening and is typically treated with intravenous (IV) injections of glucocorticoids and large volumes of intravenous saline solution with the sugar dextrose. This treatment usually brings rapid improvement.

    Surgery is sometimes indicated to modify external sex organs. It may be performed on a young female and is also sometimes required as a young adult.

    Certain symptoms, such as excess facial hair and acne, may be addressed with specific treatments, but these should be in addition to, not instead of, CAH treatments.

    There are a range of other treatments that may also be prescribed, for example, to block the effects of androgens, control blood pressure, stimulate growth, suppress puberty, and slow bone growth. People should talk to their doctors and to specialists as needed to determine the right therapies for their child (or themselves) at different stages of their development and to learn more about CAH.

View Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

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

(Updated 2012 November 30) Congenital Adrenal Hyperplasia (CAH): Condition Information. National Institute of Child Health and Human Development [On-line information]. Available online at http://www.nichd.nih.gov/health/topics/cah/conditioninfo/Pages/default.aspx through http://www.nichd.nih.gov. Accessed May 2013.

Zieve, D. and Eltz, D. (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 May 2013.

Meikle, A. (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 through http://www.arupconsult.com. Accessed May 2013.

Mayo Clinic staff (2011 March 4). Congenital adrenal hyperplasia. Mayo Clinic [On-line information]. Available online at http://www.mayoclinic.com/print/congenital-adrenal-hyperplasia/DS00915/METHOD=print&DSECTION=all through http://www.mayoclinic.com. Accessed May 2013.

Hindmarsh, P. (2012). Endocrine Society Congenital Adrenal Hyperplasia Guidelines, Great Content But How to Deliver? Medscape Today News from Clin Endocrinol. v76 (4):465-466. [On-line information]. Available online at http://www.medscape.com/viewarticle/760936 through http://www.medscape.com. Accessed May 2013.

Abraham, M. (2012 April 20). Adrenal Disease and Pregnancy. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/127772-overview#aw2aab6b5 through http://emedicine.medscape.com. Accessed May 2013.

Diamond, D. (Reviewed 2011). Congenital adrenal hyperplasia. Boston Children's Hospital [On-line information]. Available online at http://www.childrenshospital.org/az/Site2190/mainpageS2190P0.html through http://www.childrenshospital.org. Accessed May 2013.

(2010 September). Patient Guide to Congenital Adrenal Hyperplasia. The Hormone Foundation [On-line information]. PDF available for download at http://www.hormone.org/Other/upload/congenital-adrenal-hyperplasia-patient-guide-083110.pdf through http://www.hormone.org. Accessed May 2013.

(Reviewed 2010 February). 21-hydroxylase deficiency. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition/21-hydroxylase-deficiency through http://ghr.nlm.nih.gov. Accessed May 2013.

(2009 November). Facts about CAH (Congenital Adrenal Hyperplasia). Clinical Center National Institutes of Health, Patient Education [On-line information]. PDF available for download at http://cc.nih.gov/ccc/patient_education/pepubs/cah.pdf through http://cc.nih.gov. Accessed May 2013.

Nimkarn, S. and New, M. (Revised 2010 August 24). 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia. GeneReviews [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/books/NBK1171/ through http://www.ncbi.nlm.nih.gov. Accessed May 2013.

(© 2007-2011) What is Congenital Adrenal Hyperplasia (CAH)? CARES Foundation [On-line information]. Available online at http://www.caresfoundation.org/productcart/pc/overview_cah.html through http://www.caresfoundation.org. Accessed May 2013.

Jospe, N. (Revised 2009 May). Congenital Adrenal Hyperplasia. Merck Manual for Healthcare Professionals [On-line information]. Available online through http://www.merckmanuals.com. Accessed May 2013.

Clarke, W., Editor (© 2011). Contemporary Practice in Clinical Chemistry 2nd Edition: AACC Press, Washington, DC. Pp 457, 459, 478.

STAR-G. Newborn Screening. Genetics Fact Sheet for Parents. Available online at http://www.newbornscreening.info/Parents/otherdisorders/CAH.html#13 through http://www.newbornscreening.info. Accessed July 2013.