7 Key Signs and Symptoms of Congenital Adrenal Hyperplasia You Should Know

Congenital adrenal hyperplasia (CAH) is a group of inherited genetic disorders that affect the adrenal glands. These small glands located above the kidneys are responsible for producing essential hormones including cortisol, aldosterone, and androgens. When someone has CAH, their body cannot produce enough of certain hormones, which leads to a variety of symptoms that can range from mild to severe. Understanding the signs and symptoms of this condition is crucial for early detection and proper management.

CAH occurs when there is a deficiency in one of the enzymes needed to make these hormones. The most common form, accounting for about 95% of cases, is caused by 21-hydroxylase deficiency. This condition can affect both males and females, though the symptoms may present differently depending on the severity of the enzyme deficiency and the age at which symptoms appear.

1. Ambiguous Genitalia in Newborn Females

One of the most noticeable signs of classic CAH in newborn females is ambiguous genitalia. This occurs because the fetus is exposed to high levels of male hormones (androgens) in the womb due to the enzyme deficiency.

The characteristics may include:

• An enlarged clitoris that may resemble a small penis
• Fusion of the labia, giving a more masculine appearance
• A urogenital opening that is not clearly identifiable as typical female anatomy
• Normal internal reproductive organs (uterus and ovaries)

This presentation often leads to early diagnosis in females, as it is typically noticed immediately at birth during the newborn examination. The degree of virilization can vary from mild to severe depending on the level of androgen exposure during fetal development.

2. Salt-Wasting Crisis in Infants

Approximately 75% of individuals with classic CAH experience what is known as the salt-wasting form of the condition. This is a potentially life-threatening complication that typically manifests within the first few weeks of life.

The symptoms of a salt-wasting crisis include:

• Poor feeding and lack of appetite
• Vomiting and diarrhea
• Dehydration with decreased urine output
• Weight loss or failure to gain weight
• Lethargy and weakness
• Rapid heart rate
• Low blood pressure
• Shock in severe cases

This crisis occurs because the body cannot produce enough aldosterone, a hormone that helps regulate sodium and potassium levels. Without adequate aldosterone, the body loses too much salt and water through the kidneys, leading to severe dehydration and electrolyte imbalances. This is a medical emergency that requires immediate attention.

3. Early or Rapid Puberty in Children

Children with non-classic CAH or those with classic CAH that isn’t properly managed may experience precocious puberty or accelerated growth patterns. The excess androgens in the body trigger premature development of secondary sexual characteristics.

Signs of early puberty include:

• Appearance of pubic or underarm hair before age 8 in girls or age 9 in boys
• Rapid growth spurts in early childhood
• Early development of acne
• Deepening of the voice at a young age
• Increased muscle mass for age
• Advanced bone age compared to chronological age

While children with CAH may initially be taller than their peers, they often stop growing earlier than expected, resulting in shorter-than-average adult height. This occurs because the excess androgens cause the growth plates in bones to close prematurely.

4. Irregular Menstrual Periods and Fertility Issues in Women

CAH in women, particularly the non-classic form, often presents with reproductive and menstrual irregularities. The hormonal imbalance caused by excess androgens can significantly impact the menstrual cycle and fertility.

Common reproductive symptoms include:

• Irregular, infrequent, or absent menstrual periods
• Difficulty conceiving or infertility
• Polycystic ovaries (similar to PCOS)
• Anovulation (lack of ovulation)
• Shortened luteal phase

Many women with non-classic CAH are not diagnosed until they seek medical help for irregular periods or fertility problems. The symptoms can be quite similar to polycystic ovary syndrome (PCOS), which is why proper testing is essential for accurate diagnosis. With appropriate management, many women with CAH can achieve successful pregnancies.

5. Excessive Hair Growth and Acne

Hirsutism, or excessive hair growth in typically male-pattern areas, is a common symptom of CAH in women and can also affect males. This occurs due to elevated androgen levels in the body.

Manifestations include:

• Facial hair growth, including on the upper lip, chin, and sideburns
• Excessive hair on the chest, back, and abdomen
• Hair growth on the arms and legs that is darker and coarser than typical
• Severe or persistent acne that may not respond well to typical treatments
• Oily skin
• Male-pattern baldness or thinning hair on the scalp

These symptoms can have significant psychological and emotional impacts, particularly on adolescent girls and women. The severity of hirsutism can vary widely among individuals with CAH, ranging from mild to severe. The acne associated with CAH tends to be more persistent and may appear on the face, chest, and back.

6. Masculine Features in Females

Beyond hirsutism, women with CAH may develop other virilizing features due to chronic exposure to excess androgens. These changes can develop gradually over time, particularly if the condition is not diagnosed or not well-controlled.

Virilization symptoms may include:

• Deepening of the voice
• Increased muscle mass and a more muscular build
• Decreased breast size
• Enlarged clitoris (clitoromegaly)
• Male-pattern body shape with increased muscle definition
• Increased aggression or changes in behavior
• Decreased feminine body curves

The extent of virilization depends on the severity of the enzyme deficiency and how long the condition has gone untreated. Early diagnosis and appropriate management can help prevent or minimize these features.

7. Fatigue and Low Blood Pressure

Individuals with CAH often experience chronic fatigue and symptoms related to low cortisol and aldosterone production. These symptoms may be subtle and develop gradually, making them easy to overlook or attribute to other causes.

Common symptoms include:

• Persistent tiredness and low energy levels
• Weakness and decreased stamina
• Dizziness, especially when standing up quickly
• Low blood pressure (hypotension)
• Salt cravings
• Difficulty handling stress or illness
• Nausea and loss of appetite
• Hypoglycemia (low blood sugar)

During times of physical stress, such as illness, surgery, or injury, people with CAH may experience adrenal crisis if their bodies cannot produce enough cortisol to meet increased demands. This is a serious medical emergency that requires immediate treatment. Symptoms of adrenal crisis include severe weakness, confusion, abdominal pain, severe vomiting, and loss of consciousness.

Main Causes of Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia is caused by genetic mutations that are inherited from parents. Understanding the underlying causes can help families better comprehend this condition.

Genetic Inheritance Pattern:

CAH is inherited in an autosomal recessive pattern. This means that a child must inherit two copies of the defective gene (one from each parent) to develop the condition. Parents who carry one copy of the gene mutation typically do not show symptoms but are carriers who can pass the gene to their children.

• If both parents are carriers, there is a 25% chance with each pregnancy that the child will have CAH
• There is a 50% chance the child will be a carrier like the parents
• There is a 25% chance the child will neither have CAH nor be a carrier

Enzyme Deficiencies:

The specific cause of CAH is a deficiency in one of the enzymes needed for cortisol production:

• 21-hydroxylase deficiency: Accounts for about 90-95% of all CAH cases. This enzyme is crucial for producing both cortisol and aldosterone.
• 11-beta-hydroxylase deficiency: Accounts for about 5-8% of cases and leads to cortisol deficiency and excess androgens.
• 3-beta-hydroxysteroid dehydrogenase deficiency: A rare form that affects the production of all steroid hormones.
• 17-alpha-hydroxylase deficiency: Another rare form that results in low cortisol and sex hormones but excess aldosterone.

Types of CAH:

The severity of symptoms depends on the type of CAH:

• Classic CAH: The severe form with very low enzyme activity, presenting with symptoms at birth or in early infancy
• Non-classic CAH: A milder form with partial enzyme deficiency, often not diagnosed until later childhood, adolescence, or adulthood

Prevention Strategies

Since congenital adrenal hyperplasia is a genetic condition, it cannot be prevented entirely. However, there are important strategies for early detection and management that can prevent complications.

Genetic Counseling:

Families with a history of CAH should consider genetic counseling before planning a pregnancy. A genetic counselor can:

• Assess the risk of having a child with CAH
• Explain inheritance patterns
• Discuss carrier testing options for prospective parents
• Provide information about prenatal testing options
• Offer emotional support and resources

Newborn Screening:

Most developed countries include CAH in their newborn screening programs. This screening:

• Detects elevated levels of 17-hydroxyprogesterone, which indicates possible CAH
• Allows for early diagnosis before life-threatening symptoms develop
• Enables prompt treatment to prevent salt-wasting crises
• Helps prevent long-term complications

Prenatal Testing:

For families with known CAH history, prenatal testing options include:

• Chorionic villus sampling (CVS) at 10-13 weeks of pregnancy
• Amniocentesis at 15-20 weeks of pregnancy
• Preimplantation genetic diagnosis (PGD) for those using in vitro fertilization

Prevention of Complications:

For those diagnosed with CAH, preventing complications involves:

• Regular monitoring by an endocrinologist
• Adherence to prescribed treatment plans
• Wearing medical alert identification
• Having an emergency action plan for adrenal crisis
• Increasing medication during times of stress, illness, or surgery (under medical guidance)
• Regular bone density monitoring
• Periodic assessment of growth and development in children

Frequently Asked Questions

What is congenital adrenal hyperplasia?

Congenital adrenal hyperplasia (CAH) is a group of inherited genetic disorders affecting the adrenal glands. It prevents the body from producing adequate amounts of cortisol and sometimes aldosterone, while often causing excess androgen production. The condition is present from birth and requires lifelong management.

How is CAH diagnosed?

CAH is typically diagnosed through blood tests that measure hormone levels, particularly 17-hydroxyprogesterone. Newborn screening programs detect most cases of classic CAH shortly after birth. Additional tests may include measuring cortisol, aldosterone, androgens, electrolytes, and genetic testing to confirm the specific enzyme deficiency.

Can CAH be cured?

There is currently no cure for CAH as it is a genetic condition. However, it can be effectively managed with appropriate medical care throughout life. Treatment focuses on replacing deficient hormones and managing symptoms. With proper treatment, most people with CAH can lead healthy, normal lives.

Is CAH more common in males or females?

CAH affects males and females equally in terms of occurrence since it is an autosomal recessive genetic condition. However, it is often detected earlier in females because of the visible sign of ambiguous genitalia at birth. Males with the salt-wasting form may not be diagnosed until they experience a salt-wasting crisis.

What is the difference between classic and non-classic CAH?

Classic CAH is the severe form with very low enzyme activity, causing symptoms from birth or early infancy, including ambiguous genitalia in females and salt-wasting crisis. Non-classic CAH is a milder form with partial enzyme deficiency that may not cause noticeable symptoms until later childhood, adolescence, or adulthood, often presenting with hirsutism, acne, or fertility issues.

Can women with CAH have children?

Yes, many women with CAH can have children, although fertility may be reduced compared to the general population. With appropriate hormonal management and fertility support when needed, most women with CAH can achieve successful pregnancies. It’s important to work closely with healthcare providers, including endocrinologists and reproductive specialists, when planning a pregnancy.

What triggers an adrenal crisis in people with CAH?

An adrenal crisis in people with CAH can be triggered by physical stressors that increase the body’s demand for cortisol, such as severe infections, surgery, injuries, severe dehydration, prolonged vomiting or diarrhea, or suddenly stopping hormone replacement medication. People with CAH should have an emergency plan and may need to increase their medication during stressful events under medical guidance.

When should I see a doctor about CAH symptoms?

You should see a doctor immediately if you notice ambiguous genitalia in a newborn, signs of a salt-wasting crisis in an infant (poor feeding, vomiting, lethargy), or symptoms of adrenal crisis at any age. For non-emergency situations, consult a healthcare provider if you experience irregular periods, excessive hair growth, severe acne, difficulty conceiving, signs of early puberty in children, or persistent fatigue and low blood pressure.

References:

• Mayo Clinic – Congenital Adrenal Hyperplasia
• National Institute of Child Health and Human Development – CAH
• NHS – Congenital Adrenal Hyperplasia
• Johns Hopkins Medicine – Congenital Adrenal Hyperplasia
• CARES Foundation – Congenital Adrenal Hyperplasia Research, Education and Support