Powered By
The adrenal glands are small organs that sit on top of the kidneys and act like tiny hormone factories. They make essential hormones like cortisol, aldosterone, and androgens. Cortisol helps manage stress, blood sugar, and inflammation. Aldosterone helps regulate the balance of salt, water, and blood pressure. Androgens — often called male sex hormones— are present in all bodies and affect growth and development.
In congenital adrenal hyperplasia (CAH), the adrenal glands don’t work properly due to an enzyme deficiency. Enzymes are proteins that help the body carry out chemical reactions. In CAH, the enzymes needed to make hormones like cortisol, aldosterone, and androgens are missing or don’t work correctly. As a result, the body can’t make the correct amounts of these steroid hormones.
Most cases of CAH are caused by variants (changes) in the CYP21A2 gene. This gene tells the body how to make the enzyme 21-hydroxylase. Most people with congenital adrenal hyperplasia have either classic or nonclassic CAH, but several rare types also exist. Read on to learn more about the different types of CAH.
Classic CAH is the most severe form. In the United States, all newborns are screened for classic CAH, and the diagnosis is usually confirmed shortly after birth.
Classic CAH is caused by significant 21-hydroxylase deficiency — a shortage or lack of 21-hydroxylase. This enzyme helps your adrenal glands make cortisol and aldosterone. There are two subtypes:
People with the salt-wasting form of CAH make almost no 21-hydroxylase, whereas people with the simple-virilizing form still have some enzyme activity.
The symptoms of classic CAH are related to changes in hormone levels.
If you can’t make enough cortisol, it’s difficult to maintain healthy blood pressure, blood sugar, and energy levels. Without treatment, people with classic CAH are at risk of a life-threatening condition called an adrenal crisis.
Low levels of aldosterone can cause:
High androgen levels can cause problems with how children grow and develop, including:
High androgen levels can also result in infertility, making it harder for women to get pregnant, according to Mayo Clinic. Men may also have fertility issues.
Nonclassic CAH is usually milder than the classic form. Because it typically isn’t detected through newborn screening tests, it may not be diagnosed until later in childhood or even adulthood — often when symptoms begin to appear.
The nonclassic form is also caused by 21-hydroxylase deficiency, but the enzyme still works a little, so cortisol levels are closer to normal. However, the adrenal glands make extra androgens.
Some people with nonclassic CAH have no symptoms. When symptoms do occur, they usually appear in late childhood or early adulthood. Symptoms are linked to an overproduction of androgen and may include:
Nonclassic CAH is more common — it affects up to 1 in every 100 to 200 people. Classic CAH affects about 1 in every 10,000 to 15,000 newborns in the U.S. and Europe.
A deficiency in the enzyme 11-beta-hydroxylase accounts for about 5 percent of all CAH cases. This form is more common in Jews of Moroccan ancestry, according to Wolters Kluwer UpToDate. Like 21-hydroxylase deficiency, 11-beta-hydroxylase deficiency can occur in both classic and nonclassic forms. The classic form is more common and typically more severe, often causing symptoms earlier in life.
A shortage of 11-beta-hydroxylase prevents the adrenal glands from making enough cortisol — or corticosterone, which is needed to produce aldosterone. Instead of being used to produce these hormones, the leftover building blocks are redirected into making excess androgens.
Symptoms often look similar to those of 21-hydroxylase deficiency:
Deficiency in 11-beta-hydroxylase can also cause hypertension (high blood pressure) and low levels of potassium in the blood.
Deficiency in the enzyme 17-hydroxylase makes up about 1 percent of all CAH cases. This form affects both the adrenal glands and the gonads (ovaries or testicles).
This form of CAH is caused by changes in the CYP17A1 gene, which provides instructions for producing 17-hydroxylase. This enzyme plays a key role in making cortisol and sex hormones like estrogen and testosterone. When 17-hydroxylase is missing or not working well, the body produces very little of these essential hormones.
A deficiency in 17-hydroxylase leads to hormone imbalances that can cause a range of symptoms. These may include:
People with 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) deficiency have difficulty making all steroid hormones. This form of CAH is very rare, with only about 60 people reported to have it. This condition comes in three forms: salt-wasting, non-salt-wasting, and nonclassic.
This form of CAH is caused by changes in 3-beta-HSD type 2, which is active in the adrenal glands and gonads. This enzyme helps the body make all major steroid hormones, including cortisol, aldosterone, and sex hormones such as testosterone and estrogen. When 3-beta-HSD type 2 is missing or not working well, hormone levels drop and precursors build up.
People with 3-beta-HSD deficiency may have the following symptoms:
Because it affects so many hormones, this deficiency can be life-threatening if not recognized and treated early.
P450 oxidoreductase deficiency (PORD) is a rare form of CAH, with about 100 reported cases worldwide. However, researchers believe the actual number may be higher because PORD is often misdiagnosed as other types of CAH. In some populations — including people in Korea and Japan — PORD may be the second most common cause of CAH.
PORD is caused by changes in the POR gene, which makes P450 oxidoreductase. This enzyme plays an important role in making steroid hormones.
The symptoms of PORD can range from mild to severe. Mild symptoms may include:
Moderate PORD symptoms include atypical genitalia and infertility.
Some people with severe PORD may also have features of Antley-Bixler syndrome, a condition that affects bone and physical development. These features can include:
Lipoid CAH is the rarest and most severe form of CAH. Many newborns with this condition experience a life-threatening adrenal crisis soon after birth.
Lipoid CAH is caused by a change in the STAR gene. This gene controls how cholesterol is transported into the mitochondria, where it’s converted into pregnenolone — the first step in making all steroid hormones. Without this process, the adrenal glands and gonads can’t produce enough cortisol, aldosterone, or sex hormones.
Newborns with lipoid CAH often develop:
Males may have female-appearing or atypical genitalia, according to the ThinkGenetic Foundation. Females usually have typical external genitalia.
Without treatment, lipoid CAH can be fatal. However, with early diagnosis and lifelong hormone replacement, many people with this condition can live into adulthood.
On CAHteam, people share their experiences with congenital adrenal hyperplasia, get advice, and find support from others who understand.
What type of CAH do you have? Are you living with a rare type of CAH? Let others know in the comments below.
Get updates directly to your inbox.
When Did You Start Noticing Symptoms, And How Did It Change Your Approach To Health?
Continue with Facebook
Sign up with your email
Become a member to get even more
Join
A CAHteam Visitor
I would love to learn more about people CAH non classical with 3 beta dex. Any women in your 40's. I would love to hear about your experiences with meds, facial hair, and high blood pressure.
We'd love to hear from you! Please share your name and email to post and read comments.
You'll also get the latest articles directly to your inbox.