Congenital Adrenal Hyperplasia (CAH)

What happens in CAH

The adrenal glands, on top of the kidneys, make three main types of hormones:

• cortisol, which helps the body handle stress, illness and blood sugar
• aldosterone, which keeps salt and water balance and blood pressure
• androgens, such as testosterone precursors

Making cortisol and aldosterone requires a chain of enzymes. In CAH, one enzyme does not work, so the pathway is blocked. Low cortisol makes the pituitary gland release more ACTH, which overstimulates and enlarges (hyperplasia) the adrenal glands. The building blocks pile up and are diverted into androgen production.

CAH is inherited in an autosomal recessive pattern: a child must inherit a non-working gene from both parents. Parents who each carry one copy have a 1 in 4 chance with each pregnancy of having a child with CAH.

Types of CAH

Classic CAH affects about 1 in 15,000 births. Non-classic CAH is far more common and is particularly frequent in some groups, including Ashkenazi Jewish, Hispanic and Mediterranean populations. Rarer forms involve other enzymes, such as 11-beta-hydroxylase deficiency, which causes high blood pressure.

Symptoms

Newborns with classic CAH

• girls: atypical genitals, such as an enlarged clitoris and fused labia, with normal internal female organs
• boys: usually normal-appearing genitals, so salt-wasting may be the first sign
• salt-wasting crisis at 1 to 4 weeks: poor feeding, vomiting, weight loss, dehydration, low sodium, high potassium, low blood pressure and shock. This can be fatal without treatment

Children with untreated or under-treated CAH

• early pubic hair, body odor and acne
• rapid growth in childhood, but early closure of growth plates and short adult height
• enlarged penis in boys or clitoris in girls

Non-classic CAH

• early pubic hair in childhood (premature pubarche)
• severe acne
• excess facial and body hair (hirsutism)
• irregular or absent periods
• reduced fertility
• often mistaken for polycystic ovary syndrome
• many men have no symptoms

Adults with classic CAH

• risk of adrenal crisis during illness
• fertility problems in women and men (including testicular adrenal rest tumors in men)
• metabolic effects of long-term steroid treatment

Diagnosis

• Newborn screening: all US states screen for 21-hydroxylase deficiency using a heel-prick 17-hydroxyprogesterone (17-OHP) test. Premature or sick babies can have false positives.
• Confirmatory blood tests: 17-OHP, electrolytes, renin, and other adrenal hormones.
• ACTH stimulation test: the standard test for non-classic CAH, measuring 17-OHP after an injection of synthetic ACTH.
• Genetic testing of the CYP21A2 gene confirms the diagnosis and informs family planning.
• Pelvic ultrasound and karyotype in newborns with atypical genitals.

Treatment

Hormone replacement

• Glucocorticoids replace cortisol and suppress excess ACTH and androgens. Children take hydrocortisone, usually 3 times daily, to protect growth. Adults may use hydrocortisone, prednisolone or dexamethasone.
• Fludrocortisone replaces aldosterone in salt-wasting CAH.
• Salt supplements for infants with salt-wasting.
• Crinecerfont, approved in 2024 as an add-on, lowers ACTH and androgens so steroid doses can be reduced in classic CAH.
• Doses are adjusted to growth, puberty, hormone levels and side effects by a pediatric or adult endocrinologist.

Stress dosing and emergencies

People with classic CAH cannot raise cortisol during stress. They must:

• double or triple their steroid dose during fever or significant illness, following their sick-day plan
• use an emergency hydrocortisone injection if vomiting or unable to take tablets
• wear medical ID
• receive extra steroid cover for surgery

An adrenal crisis is life-threatening and needs IV hydrocortisone and fluids.

Non-classic CAH

Treatment is based on symptoms: oral contraceptives and anti-androgens for hirsutism and acne, low-dose glucocorticoids for fertility treatment or early puberty in children. Many adults need no treatment. Stress dosing is usually not required.

Genital surgery

Decisions about surgery for atypical genitals are made with families, specialist multidisciplinary teams and, increasingly, deferred until the person can take part. Psychological support is an important part of care.

Outlook

With early diagnosis and careful treatment, people with CAH lead full lives. Ongoing challenges include balancing steroid doses to avoid both androgen excess and steroid side effects (weight gain, bone thinning, high blood pressure), fertility, and preventing adrenal crises. Lifelong endocrinology follow-up is needed.

Frequently asked questions

What is congenital adrenal hyperplasia?

CAH is an inherited condition in which the adrenal glands lack an enzyme needed to make cortisol, and often aldosterone. The body makes too many androgens instead. It ranges from a severe newborn form that can cause dangerous salt loss to a mild form causing acne, excess hair and irregular periods.

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

Classic CAH is severe, present from birth, and causes low cortisol, sometimes salt-wasting crises, and atypical genitals in girls. Non-classic CAH is milder and more common, with enough cortisol for daily life, and shows up later as early pubic hair, acne, excess hair or irregular periods.

How is CAH detected in newborns?

In the US and many other countries, newborn screening measures 17-hydroxyprogesterone from a heel-prick blood sample. High levels prompt confirmatory blood tests and genetic testing. Early detection prevents life-threatening salt-wasting crises, especially in boys who look typical at birth.

How is CAH treated?

Classic CAH is treated with lifelong glucocorticoids to replace cortisol and reduce androgens, plus fludrocortisone and sometimes salt for salt-wasting forms. Doses are increased during illness. Non-classic CAH may need treatment only for symptoms such as acne, hirsutism or infertility.

Can women with CAH get pregnant?

Yes. Many women with non-classic CAH conceive naturally or with mild treatment. Women with classic CAH may have reduced fertility, but with good hormonal control and specialist care, many have successful pregnancies. Steroid doses are adjusted during pregnancy and delivery.