Congenital adrenal hyperplasia

Title

Other Names:

CAH

Summary Summary

Congenital adrenal hyperplasia (CAH) refers to a group of genetic conditions that affect the adrenal glands. These glands sit on top of the kidneys and are responsible for releasing various types of hormones that the body needs to function. Affected people lack an enzyme the adrenal glands need to make one or more of these hormones and often overproduce androgens (male hormones such as testosterone).^[1] The signs and symptoms present in each person depend on many factors including the type of CAH, the age of diagnosis, and the sex of the affected person. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems. Treatment for CAH varies but may include medication and/or surgery.^[2]^[3]

Last updated: 12/26/2014

Symptoms Symptoms

The signs and symptoms of congenital adrenal hyperplasia (CAH) vary based on many factors including the type of CAH, the age of diagnosis and the sex of the affected person. For example, girls with the severe form of CAH may be born with ambiguous genitalia, which often allows the condition to be diagnosed before other associated health problems such as poor feeding, vomiting, dehydration, and abnormal heart beat, can develop. Males typically appear unaffected at birth even when they have a severe form of CAH and without proper diagnosis, will develop associated health problems within 2-3 weeks after birth. Both genders can experience other symptoms such as early onset of puberty, fast body growth, and premature completion of growth leading to short stature, if they are not treated in early life.^[4]^[1]^[2]

People affected by milder forms may not have any signs and symptoms of CAH during childhood. In these cases, a diagnosis may not be made until adolescence or adulthood when the affected person experiences early signs of puberty or fertility problems. Females with this type may have excessive facial or body hair; irregular menstrual periods; and/or acne.^[4]^[1]^[2]

There are two main types of CAH: classic CAH, the more severe form, and a milder form called nonclassic CAH. For a detailed description of the signs and symptoms found in each type of CAH, please click here.^[3]

Last updated: 12/26/2014

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of metabolism/homeostasis	90%
Accelerated skeletal maturation	90%
Cryptorchidism	90%
Displacement of the external urethral meatus	90%
Female pseudohermaphroditism	90%
Hypercortisolism	90%
Abnormality of the thorax	-
Abnormality of the urinary system	-
Adrenal hyperplasia	-
Adrenogenital syndrome	-
Ambiguous genitalia, female	-
Autosomal recessive inheritance	-
Congenital adrenal hyperplasia	-
Decreased circulating aldosterone level	-
Decreased circulating renin level	-
Decreased testicular size	-
Fever	-
Growth abnormality	-
Gynecomastia	-
Hyperpigmentation of the skin	-
Hypertension	-
Hypoglycemia	-
Hypokalemia	-
Hypokalemic alkalosis	-
Hypoplasia of the uterus	-
Hypoplasia of the vagina	-
Hypospadias	-
Long penis	-
Male pseudohermaphroditism	-
Neonatal onset	-
obsolete Clitoromegaly	-
Precocious puberty in males	-
Primary amenorrhea	-
Renal salt wasting	-
Short stature	-

Last updated: 9/1/2016

Cause Cause

Congenital adrenal hyperplasia (CAH) is a group of genetic conditions that can be caused by a change (mutation) in several different genes:^[2]

21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene
3-beta-hydroxysteroid dehydrogenase deficiency is caused by mutations in the HSD3B2 gene
11-beta-hydroxylase deficiency is caused by mutations in the CYP11B1 gene
Cytochrome P450 oxidoreductase deficiency is caused by mutations in the POR gene
17-hydroxylase deficiency is caused by mutations in the CYP17A1 gene
Congenital lipoid adrenal hyperplasia is caused by mutations in the STAR gene

Most of these genes encode enzymes that the adrenal glands need to make one or more hormones. The adrenal glands are cone-shaped organs that sit on top of the kidneys and are responsible for releasing various types of hormones that the body needs to function. Mutations in these genes lead to deficient levels of enzymes which cause low levels of hormones such as cortisol and/or aldosterone and an overproduction of androgens (male hormones such as testosterone). Cortisol is a hormone that affects energy levels, blood sugar levels, blood pressure, and the body's response to stress, illness, and injury. Aldosterone helps the body maintain the proper level of sodium (salt) and water and helps maintain blood pressure. Irregular levels of these hormones lead to the signs and symptoms of CAH.^[3]^[4]

Last updated: 12/26/2014

Inheritance Inheritance

All forms of congenital adrenal hyperplasia (CAH) are inherited in an autosomal recessive manner.^[2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Last updated: 12/26/2014

Diagnosis Diagnosis

Yes, genetic testing is available for many of the genes known to cause congenital adrenal hyperplasia (CAH).^[5] Carrier testing for at-risk relatives and prenatal testing are possible if the disease-causing mutations in the family are known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Last updated: 12/27/2014

Shortly after birth, all newborns in the United States are screened for a variety of conditions, including 21-hydroxylase deficiency. This is the most common cause of congenital adrenal hyperplasia (CAH) and accounts for 95% of classic CAH cases. Nonclassic CAH is not detected through newborn screening and is often not suspected until signs and symptoms of the condition begin to appear later in childhood or early adulthood. In these cases, a diagnosis of CAH is usually based on physical examination; blood and urine tests that measure hormone levels; and/or genetic testing. An X-ray may also be helpful in confirming the diagnosis in children since CAH can cause bones to grow and develop more quickly than usual (advanced bone age) .^[2]^[3]^[4]

Last updated: 12/27/2014

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
The Newborn Screening Coding and Terminology Guide created by the National Library of Medicine (NLM) at the National Institutes of Health (NIH) promotes and facilitates the use of electronic health data standards in recording and transmitting newborn screening test results. The Web site includes standard codes and terminology for newborn tests and conditions for which they screen, and links to related sites. Click on the links to below view details for this condition.
Congenital adrenal hyperplasia (due to 11-beta-hydroxylase deficiency)
Congenital adrenal hyperplasia (non-classical)
Congenital adrenal hyperplasia (salt-wasting)
Congenital adrenal hyperplasia (simple virilizing)
National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

Treatment Treatment

The best treatment options for congenital adrenal hyperplasia (CAH) depend on many factors including the type of CAH and the signs and symptoms present in each person. Many people with CAH require steroids to replace the low hormones. These medications will need to be taken daily throughout life or the symptoms of CAH may return. It is important that affected people on medications be closely followed by their healthcare provider because their dose may need to be adjusted at different times in life such as periods of high stress or illness.

Girls with severe CAH who are born with ambiguous genitalia may undergo surgery to ensure proper function and/or to make the genitals look more female.^[2]^[3]^[4]

For more information on the treatment of CAH, please click here.

Last updated: 12/27/2014

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Prognosis Prognosis

The long-term outlook (prognosis) for people with congenital adrenal hyperplasia (CAH) is usually good. With lifelong treatment, affected people typically have good health and normal lifespans.^[1] However, problems with psychological adjustment are common, particularly in people with genital abnormalities.^[4]

Last updated: 12/27/2014

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Congenital adrenal hyperplasia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Accord Alliance
531 Route 22 East #244
Whitehouse Station, NJ 08889
Telephone: 908-349-0534
Fax: 801-349-0534
E-mail: http://www.accordalliance.org/contact/email-us.html
Website: http://www.accordalliance.org/
CAH Support Group
2 Windrush Close
Flitwick
Bedfordshire
MK45 1PX
United Kingdom
Telephone: 01525 717536
E-mail: http://www.livingwithcah.com/contact.html
Website: http://www.livingwithcah.com
Congenital Adrenal Hyperplasia Research Education and Support (CARES) Foundation
2414 Morris Ave, Suite 110
Union, NJ 07083
Toll-free: 866-227-3737
E-mail: contact@caresfoundation.org
Website: http://www.caresfoundation.org
National Adrenal Diseases Foundation
505 Northern Boulevard
Great Neck, NY 11021
Telephone: 516-487-4992
E-mail: nadfsupport@nadf.us
Website: http://www.nadf.us/
The MAGIC Foundation
6645 West North Avenue
Oak Park, IL 60302
Toll-free: 800-362-4423
Telephone: 708-383-0808
Fax: 708-383-0899
E-mail: mary@magicfoundation.org
Website: http://magicfoundation.org

Do you know of an organization? Send us your suggestions.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides information related to the health of children, adults, and families. Click on the link to view information on this topic.
Genetics Home Reference (GHR) contains information on Congenital adrenal hyperplasia. This website is maintained by the National Library of Medicine.
21-hydroxylase deficiency
3-beta-hydroxysteroid dehydrogenase deficiency
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency
Cytochrome P450 oxidoreductase deficiency
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.
The MAGIC Foundation provides information on this condition. Click on the link to view the information.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
21-hydroxylase deficiency
17-hydroxylase deficiency
11-beta-hydroxylase deficiency
3-beta-hydroxysteroid dehydrogenase deficiency
Congenital lipoid adrenal hyperplasia
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital adrenal hyperplasia. Click on the link to view a sample search on this topic.

News & Events News & Events

News

GARD Information Navigator
May 10, 2016

NCATS Co-Sponsored Conferences

International Adrenal Cortex Conference “Adrenal 2010” Wednesday, June 16, 2010 - Friday, June 18, 2010
Location: San Diego, California
Description: This conference provided a forum for both new and established investigators to present their most recent work, highlighting new findings relevant to adrenal physiology, biochemistry and molecular biology, genetics, and medicine. It was anticipated that these discoveries would provide a framework for further understanding of the function of the adrenal gland and its contributions to health and disease.

Contact: Maria L. Dufau, M.D., Ph.D., dufaum@mail.nih.gov dufaum@mail.nih.gov

Co-funding Institute(s): National Institute of Child Health and Human Development, Office of Rare Diseases Research
- Agenda ( - 53KB)
- Report ( - 71KB)

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