Congenital adrenal hyperplasia (CAH)

What are the adrenal glands?

The adrenal glands, also called the suprarenal glands, regulate the production of hormones necessary for the body’s function.

The hormones produced by the adrenal gland cortex are divided into three types: hormones related to the reproductive system and development of the genitals, hormones related to the body’s reaction to stress and to blood sugar levels (cortisol), and hormones related to the body’s salt and water balance that regulate the levels of sodium and potassium (mineralocorticoids – mainly aldosterone).

Each of these hormones is regulated differently. Regulation of the sex hormones and of stress reaction hormones is conducted through the secretion of other hormones from the brain which encourage the activity of the adrenal glands. Hormones produced in the adrenal cortex are synthesized from cholesterol and as such are steroid compounds.

In addition, the medulla (the inner part of the adrenal gland) produces the hormones adrenaline (epinephrine) and norepinephrine.


What is CAH?

Congenital adrenal hyperplasia (or CAH) is a genetic disorder that has a higher prevalence in people of Ashkenazi Jewish, Mediterranean, Yup’ik, and Yugoslav ancestry.

CAH causes a deficiency in one of the enzymes that produces cortisol, and occasionally aldosterone.  This deficiency results in repeated reactions in the brain that encourage the development of gland cells and a production of excess sex hormones. Babies with this disease are born with enlarged adrenal glands (hence the name of this condition – hyperplasia refers to an enlargement of an organ caused by increased cell reproduction).


Signs and symptoms

Symptoms of CAH are all linked to an excess of sex hormones and a cortisol deficiency. Around 75% of children with this condition also have an aldosterone deficiency. Cortisol regulates blood sugar levels and is also responsible for salt regulation. 

Infants with this disease appear healthy during the first days after their birth, after several days to several weeks they begin to develop symptoms associated with a severe cortisol deficiency – vomiting, diarrhea, low glucose levels, and low blood pressure that may be life threatening. Aldosterone deficiency causes low levels of sodium and high levels of potassium in the blood (due to the deficiency of this hormone in the kidneys).

The excess in sex hormones presents mostly in girls – since they were exposed to high levels in utero, their external genitalia will appear masculine. These girls will be assigned male at birth, until the disease is diagnosed. This excess in sex hormones is less prominent in boys and will result only in a larger penis.

A rarer form of this disease has a less prominent expression and can manifest at a much later age, usually during adolescence or young adulthood. This is known as late onset CAH.


Genetic basis

CAH is caused by a mutation to a specific protein in the hormone synthesis chain. The mutation makes this protein inactive. In most cases, the deficient enzyme is known as 21-hydroxylase. Over 95% of cases are caused by this gene mutation.

Rarer cases are caused by deficiencies in other enzymes, such as 21 beta-hydroxylase. Deficiencies in other enzymes can lead to a different phenotype, such as high blood pressure, no excess in sex hormones, etc.

This disease is inherited in an autosomal recessive pattern. Carriers of one mutated gene do not develop the disease, only children who inherit one mutated gene from each parent will develop the disease. The chances for a child with two carrier parents to develop this condition are 25 percent.



The first step toward a diagnosis is a 17a-hydroxylase level test. This substance accumulates in the blood due to the enzyme deficiency; high levels of this substance indicate CAH.

The diagnosis can later be confirmed through molecular genetic testing, while optimally characterizing the specific mutation causing the disease.


Prenatal diagnosis and newborn screening

Newborn screening for CAH is offered in many countries worldwide. These tests help detect the disease in infants before symptoms develop.

Parents who are carriers of this disease are recommended prenatal genetic counseling. Genetic screening tests are also recommended in families with a child born with CAH. Prenatal diagnosis is based on sequencing the mutated genes linked to hormone synthesis in the adrenal glands. In the past, diagnosis was based on measuring 17a-hydroxylase levels through amniocentesis



Treatment of CAH includes steroid replacement therapy that replaces the deficient hormones in the body (cortisol and aldosterone) and suppresses the brain feedback causing the excess in sex hormones. 

In most cases, this hormone therapy allows patients to live normal lives. Treatment becomes lifesaving in infants with a severe deficiency in steroids, known as an Addisonian crisis.

When people with CAH suffer from infectious diseases or need to undergo surgery, they must take increased doses of hormone therapy to imitate the body’s reaction to upcoming stress.

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