Congenital adrenal hyperplasia (CAH) is a group of inherited disorders that interfere with healthy adrenal function. Approximately 1 in 14,000 to 18,000 newborns show classic signs of CAH. This rare genetic disorder is usually present at birth (congenital). The salt-wasting form of congenital adrenal hyperplasia can be life-threatening if not treated immediately.
CAH is usually caused by a genetic mutation that prevents the adrenal glands, which are pyramid-shaped at the top of each kidney, from producing healthy amounts of cortisol and aldosterone. When these two hormones are not produced in sufficient quantities, the adrenal glands become larger than usual (hyperplastic) and produce excess androgens (male hormones).
This article explains how CAH is inherited, the differences between classic and non-classic congenital adrenal hyperplasia, the symptoms, when to seek treatment, and where to get support.
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Note on Terminology
In this article, the terms “male” and “female” are used to describe chromosomal, biological, or anatomical characteristics, not to describe an individual's gender identity or gender expression.
What causes congenital adrenal hyperplasia?
Congenital adrenal hyperplasia is caused by a genetic mutation. Most people with CAH are deficient in 21-hydroxylase. This deficiency leads to lower cortisol levels.
CAH affects the production of hormones, including:
- Cortisol: Glucocorticoids, commonly known as “stress hormones.”
- aldosterone: It is a mineralocorticoid that affects salt and water balance in the body.
- sex hormones: Hormones such as testosterone, androgens, and DHEA-S that are necessary for sexual growth and development regardless of gender.
- adrenaline: A fight-or-flight hormone secreted during times of extreme stress.
Without the necessary components to produce cortisol or aldosterone during healthy adrenal hormone synthesis, precursors of the adrenal biosynthetic pathway, such as 17-hydroxyprogesterone, accumulate. This results in overproduction of androgens, leading to masculinization.
Types of Congenital Adrenal Hyperplasia
There are two main types of congenital adrenal hyperplasia. classic CAH (more serious) and Non-classical CAH (more mild).
Classic CAH
Classical or classic CAH is usually discovered at birth or in early infancy. There are two subtypes of conventional CAH: Salt waste type and Simple masculinization type.
Salt wasting CAH is very dangerous and usually requires emergency treatment soon after birth. Simple virilizing CAH may cause girls to have large genitals at birth, but boys will not have these changes.
Nonclassic or late-onset CAH
Nonclassical or nonclassical CAH is also called late-onset CAH because it does not become apparent until adolescence or early adulthood. Typically, this is the mildest form of CAH, but it can still cause noticeable virilization (development of male sex characteristics) in women.
People can have varying degrees of nonclassical CAH, depending on the degree of 21-hydroxylase deficiency and increased androgen production. In some cases, nonclassic CAH is so mild that it causes no symptoms and does not require medical treatment.
rare form
More than 95% to 99% of CAH cases are caused by mutations in the CYP21A2 gene that cause steroid 21-hydroxylase deficiency (21-OHD). The second most common variant of CAH is 11 beta-hydroxylase deficiency (11-βOHD). It accounts for approximately 0.2% to 0.8% of all CAH cases. This extremely rare form occurs in approximately 1 in 100,000 to 200,000 live births.
Other uncommon forms of CAH include:
- 3 Beta-hydroxysteroid dehydrogenase/isomerase deficiency (3β-HSDD)
- P450-oxidoreductase deficiency (PORD)
- Lipid congenital adrenal hyperplasia (LCAH)
Congenital Adrenal Hyperplasia Symptoms
Symptoms of congenital adrenal hyperplasia vary depending on the type.
There are two subtypes of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: salt-wasting CAH and non-salt-wasting CAH (also known as simple virilizing CAH). Symptoms of simple virilizing CAH that do not waste salt are less likely to cause a life-or-death medical emergency.
“Traditional” CAH, which does not involve salt wasting, is associated with excess androgens and insufficient cortisol, but does not cause serious life-threatening symptoms in the newborn due to sodium deficiency due to salt wasting.
Simple virilization Newborn girls with CAH typically have ambiguous genitalia, and younger children (both boys and girls) show signs of virilization. There is a strong correlation between the degree to which a genetic mutation impairs the activity of hormone-producing enzymes in the adrenal glands and the clinical severity of CAH symptoms.
Classic CAH
Female infants with CAH may have external genitalia or a large clitoris, but male infants do not show any noticeable changes. Both aldersterone and cortisol deficiencies can cause symptoms such as:
- sickness
- fatigue
- loss of appetite
- Increased risk of adrenal crisis
Non-classical CAH
Non-traditional CAH symptoms may appear in childhood, adolescence, or adulthood. For some people, symptoms are so mild that they remain unaware that they have nonclassic CAH for their entire life.
Symptoms of nonclassic CAH include:
- early signs of puberty
- They grow rapidly during childhood, but as adults they are shorter than their parents.
- acne
- male pattern hair loss
- Excessive facial or body hair (women)
- Irregular menstrual cycle (women)
- Infertility problems (women)
- Penis enlargement (male)
- Large clitoris (female)
- Small testicles (male)
When is CAH dangerous?
CAH is dangerous when it causes salt wasting. The salt-wasting form of CAH causes sodium levels in the blood to plummet. CSW can lead to life-threatening complications such as adrenal crisis, which requires immediate treatment.
Dangerous symptoms associated with salt wasting CAH include:
How is CAH diagnosed?
CAH is usually diagnosed through blood and urine tests that measure the hormones produced by the adrenal glands to ensure that cortisol, aldosterone, and androgen levels are within healthy standard ranges.
Blood and urine tests check electrolyte and sodium levels to determine if someone is experiencing salt wasting. Genetic testing may also be used to look for mutations associated with CAH. Early detection is important, especially when newborns may develop a salt-wasting form of CAH.
CAH Treatment Options
Treating CAH requires regular monitoring and follow-up care. It is important to work closely with a healthcare team that includes an endocrinologist with expertise in CAH so that prescriptions and dosages can be regularly adjusted to meet the ever-evolving medical needs of a CAH patient's life.
drug
People with classic CAH are unable to produce adequate amounts of cortisol (A). glucocorticoids) Hormone replacement medications containing glucocorticoids are needed daily. The two goals of glucocorticoid steroid drugs for classic CAH are to increase inappropriate cortisol levels and to reduce excessive androgen production. Depending on the severity of symptoms, patients with nonclassic CAH may or may not require drug treatment.
Salt-wasting CAH patients who do not produce enough aldosterone ( mineralocorticoids) Replacement hormonal medications containing mineralocorticoids, such as: fludrocortisoneThis increases sodium levels and offsets the risk of dangerous low blood pressure and adrenal crisis.
Glucocorticoid and mineralocorticoid replacement are standard treatments for CAH. Drug dosage requirements fluctuate depending on an individual's lifespan and timing of pain. Some people need less medication as they age. During periods of high anxiety or when someone is injured or sick, it may be necessary to increase the glucocorticoid dose to compensate for the body's increased need for cortisol.
surgery
For severely masculinized female CAH patients, genital reconstruction surgery, known as feminizing genioplasty, may be performed in infancy. It is important to find a surgeon who is knowledgeable and expert in this surgery.
Living with CAH
Living with CAH often requires managing your condition on a daily basis. The good news is that people with CAH can live long, healthy lives if their symptoms are treated effectively with medications and/or surgery.
For many people with CAH, in addition to receiving good medical care, emotional support is of utmost importance. Fortunately, there are numerous support groups and counseling services specifically designed to help people cope with CAH.
Here are some online resources that can help people affected by CAH connect with others in this community:
What are the prospects for CAH?
This hereditary genetic disorder is incurable, but with appropriate treatment and a strong support network, people with CAH can thrive and thrive in all aspects of their lives.
Prenatal Screening: Does My Baby Have CAH?
If your family has a history of CAH, it may be helpful to talk to a genetic counselor when making the difficult decision about using genetic testing before or during pregnancy to screen for congenital adrenal hyperplasia.
In the United States, all newborns are required to be tested for CAH in the hospital immediately after delivery using a 17-OHP test using a filter paper blood sample. If your newborn has salt-wasting CAH, treatment for this life-threatening type should be started immediately.
Can CAH be prevented in babies?
You can't prevent CAH in your baby, but you can test for genes linked to congenital adrenal hyperplasia. As with other autosomal recessive disorders, both parents must have the gene associated with CAH for one of their children to be born with this genetic disorder. A baby born to two parents who carry the CAH gene has a 1 in 4 (25%) chance of having CAH.
Advances in prenatal genetic testing and in vitro fertilization (IVF) have made it possible to use preimplantation genetic testing, such as PGT-M, to screen for genetic mutations that cause CAH, so that only unaffected embryos are implanted.
However, these preventive measures are complex, expensive, and may not be a feasible or justifiable option for everyone.
summary
Congenital adrenal hyperplasia (CAH) is a genetic disorder that affects the adrenal glands. People with CAH inherit genes from their parents that interfere with the ability of the adrenal glands to produce certain hormones. You can take medications to replace these missing hormones. CAH is an incurable but treatable disease. With proper treatment and support, people with CAH can live long, healthy lives.