What to Know About Congenital Adrenal Hyperplasia
Cortisol has many essential functions in the body. It affects energy and blood sugar levels, blood pressure, and stress and injury response. Aldosterone, on the other hand, manages the amount of salt in our body, which affects blood pressure.
Starting treatment for CAH soon after birth can minimize the chance of potentially life threatening consequences.
This article highlights the symptoms, causes, and treatment options related to CAH.
Sex and gender exist on spectrums. This article uses the terms “female” and “male” to refer to sex that was assigned at birth.
CAH is a group of genetic disorders that affect the adrenal glands. The human body contains two adrenal glands, one atop each kidney. These small glands regulate hormone production. CAH leads to hormone imbalances and typically causes enlarged adrenal glands (adrenal hyperplasia).
Classic and nonclassic CAH
Doctors classify all cases of CAH into one of two categories:
- Classic CAH: Classic CAH symptoms appear in infancy and are life threatening without treatment.
- Nonclassic CAH: Nonclassic CAH is sometimes referred to as late onset CAH. People born with this form start showing symptoms in their early teenage years or adulthood. This form is usually not life threatening, and it is milder than classic CAH.
Subtypes of classic CAH include:
- Salt-wasting CAH: In this form of classic 21-hydroxylase deficiency, the adrenal glands cannot make cortisol or aldosterone. This makes the body unable to retain enough salt. It also means that androgens, or “male hormones,” build up. Female infants born with salt-wasting CAH may have genitalia that appears ambiguous. This condition can be life threatening to newborns if doctors do not detect it early and start treatment.
- Virilizing: The virilizing form of classic 21-hydroxylase deficiency is a less severe aldosterone deficiency. However, it may also lead to ambiguous genitalia in female infants.
According to the National Organization for Rare Disorders (NORD), about 1 in 10,000 to 1 in 15,000 people in the United States and Europe are born with 21-hydroxylase deficiency.
Some research indicates that frequency varies among different ethnic groups. For example, the prevalence of the salt-wasting form of classic CAH may be 1 in 282 among Yupik people.
Signs and symptoms differ by the type of CAH.
Classic CAH signs and symptoms
The salt-wasting and virilizing forms of classic CAH may present with:
- an enlarged penis in males
- sexually ambiguous external genitalia but typical internal reproductive organs in females
In classic CAH, infants with aldosterone deficiency cannot maintain proper sodium and water levels. Symptoms of salt-wasting classic CAH appear shortly after birth and require immediate medical care. These symptoms may include:
- very low sodium levels
- low blood pressure
- an irregular heartbeat
- acidic blood
- weight loss
- poor feeding
Salt-wasting classic CAH can also cause an adrenal crisis, which is a condition wherein the body cannot supply adequate blood to the brain and other organs. Symptoms include irritability, a rapid heart rate, and coma.
Get tips for talking with your doctor about adrenal insufficiency.
Nonclassic CAH signs and symptoms
Nonclassic CAH symptoms may begin in early adulthood and include:
- irregular menstrual periods in females
- excess facial and body hair in females
- male pattern baldness
- rapid growth during childhood but a shorter final height
- an enlarged penis and small testicles in males
- early onset of puberty
CAH treatment involves receiving medications to balance hormones and possibly undergoing surgery. Treatment for classic CAH begins soon after birth. An infant will likely have a team of healthcare professionals caring for them, including a pediatric endocrinologist.
People with classic CAH receive hydrocortisone or other synthetic hormones to replace cortisol. For the salt-wasting form, fludrocortisone is necessary to replace aldosterone. Infants with the salt-wasting form of CAH may need salt supplements. For older children and adults, eating extra salty foods may be an option.
People with classic CAH continue steroid medications for life. The National Institutes of Health (NIH) suggests that people with the condition wear a medical alert identification bracelet or necklace to notify medical professionals of their adrenal insufficiency in case of emergency.
People with nonclassic CAH may not need hormone replacement therapy.
Genital reconstructive surgery may be an option for people with ambiguous external genitalia.
If a medical professional detects CAH in a fetus, they may discuss prenatal treatment with the birthing parent. For example, taking the oral drug dexamethasone during pregnancy may lessen the development of traditionally male characteristics in female fetuses.
However, this is an experimental treatment. The position of the Endocrine Society is to avoid prenatal dexamethasone treatment unless it is part of an “ethically approved protocol.”
CAH is the result of gene mutations. CYP21A2 gene mutations can cause 21-hydroxylase deficiency, and CYP11B1 gene mutations can cause 11-hydroxylase deficiency. These enzymes are necessary to make cortisol and aldosterone. Changes in other genes can cause additional rare forms of CAH.
There is currently no known way to prevent CAH. If you or your partner has a family history of the condition and you might want to start a family, consider talking with a doctor about genetic counseling.
According to NORD, CAH is inherited in an autosomal recessive pattern. This means that both copies of the gene in every cell must have the mutation for the person to have CAH.
This can happen when both biological parents have one copy of the mutated gene and one copy of the normal gene. The parents themselves do not show signs or symptoms of CAH. Instead, they are “carriers” of the mutation.
Doctors in all 50 U.S. states screen all newborns for classic CAH as a routine practice, regardless of family history. They typically conduct the test by drawing a small blood sample from the newborn’s heel using a needle prick.
Medical professionals do not usually detect nonclassic CAH as early as classic CAH, even though the condition is present at birth. They may order blood tests if a person displays any symptoms, such as irregular periods. These tests look at hormone and adrenal steroid levels. Diagnostic imaging of the adrenal glands may be necessary.
While people with CAH may live long lives with treatment, an adrenal crisis can be fatal.
The results of a survey of pediatric endocrinologists in Germany, published in 2018, led researchers to conclude that newborn screening (established in 1999 in Germany) and appropriate treatment of classic CAH has reduced fatalities. The researchers note older studies from various countries where 1 in 12 to 1 in 80 people with CAH died in childhood.
Mild, nonclassic CAH may have minimal impact on the person’s day-to-day life. However, both forms of CAH can affect a person’s fertility.
Steroid medications may present complications. The body’s cortisol needs fluctuate throughout life, so sometimes, a person may need more or less medication.
For example, adults and children with classic CAH may require extra steroid medications during high stress periods or while healing from an injury. However, taking too much of a steroid can cause Cushing’s syndrome. Symptoms of Cushing’s syndrome include:
Here are some other questions that people often ask about CAH.
Is CAH life threatening?
Without treatment, classic CAH can lead to an adrenal crisis. This sends the body into shock and is life threatening. An older study from 2014 found that adrenal crisis was the leading cause of death in males with classic CAH. Close medical supervision of people with CAH can increase the chance of a positive outcome.
What is the life expectancy of someone with CAH?
Although CAH is a chronic condition, people who undergo treatment have a typical life expectancy, according to the Texas Department of State Health Services.
Are people with CAH intersex?
“Intersex” is an old and outdated term for differences in sex development. It occurs in 1 in 20,000 to 1 in 36,000 people born with CAH. It happens when a fetus with two X chromosomes has high levels of androgens, such as testosterone. A fetus with this condition may develop with an enlarged clitoris that looks like a penis, or they may have a labia that resembles a scrotum.
CAH is a group of genetic disorders that affect the adrenal glands and cause low levels of cortisol and aldosterone and excess androgens. Infants begin showing symptoms of classic CAH quickly after birth. People with nonclassic CAH may begin showing mild symptoms during their teenage or adult years.
Doctors can diagnose CAH with a blood test. Treatment involves steroid replacement. People who receive lifelong treatment for classic CAH have a typical life expectancy. Treatment may not be necessary for nonclassic CAH.