Adrenal Hyperplasia

What the adrenal glands do

The two adrenal glands sit on top of the kidneys. Their outer layer (cortex) makes three groups of hormones:

• Cortisol: helps the body handle stress, illness and blood sugar
• Aldosterone: controls salt, water and blood pressure
• Androgens: male-type hormones such as DHEA

The pituitary gland controls cortisol production with a hormone called ACTH. When the glands are pushed to work harder, or are stimulated abnormally, their cells multiply and the glands enlarge. That enlargement is called hyperplasia.

Types of adrenal hyperplasia

Congenital adrenal hyperplasia (CAH)

Congenital adrenal hyperplasia is a group of inherited conditions passed on when both parents carry a gene change. More than 90 percent of cases are caused by 21-hydroxylase deficiency. The body cannot make enough cortisol, so the pituitary releases more ACTH, which overstimulates the glands. The blocked pathway diverts building blocks into androgen production.

Classic CAH affects roughly 1 in 15,000 to 20,000 newborns. Nonclassic CAH is much more common, especially in some populations such as Ashkenazi Jewish, Hispanic and Mediterranean people.

Symptoms of CAH

• Newborns with salt-wasting CAH: vomiting, poor feeding, weight loss, dehydration, low blood pressure and low sodium within the first 1 to 3 weeks. Without treatment this adrenal crisis can be fatal
• Girls with classic CAH: genitalia that may look more male-typical at birth, such as an enlarged clitoris or fused labia, with normal internal female organs
• Children: early pubic hair, body odor, acne, rapid growth and advanced bone age, but shorter final adult height if untreated
• Teenagers and women with nonclassic CAH: hirsutism (excess facial and body hair), acne, irregular or absent periods and reduced fertility. It can look very similar to polycystic ovary syndrome
• Men: may have few symptoms, sometimes reduced fertility from adrenal tissue in the testicles

Acquired adrenal hyperplasia in adults

• Bilateral adrenal hyperplasia: a common cause of primary aldosteronism. Excess aldosterone causes high blood pressure that is often resistant to treatment, sometimes with low potassium, muscle cramps and weakness
• ACTH-driven hyperplasia: a pituitary tumor (Cushing's disease) or, rarely, a tumor elsewhere producing ACTH, leading to Cushing's syndrome with weight gain around the middle, a round face, purple stretch marks, easy bruising, high blood sugar and high blood pressure
• Incidental finding: enlarged adrenals are sometimes seen on CT scans done for other reasons and need hormone testing

Diagnosis

• Newborn screening: all US states screen for CAH with a heel-prick test measuring 17-hydroxyprogesterone (17-OHP)
• Blood tests: 17-OHP (often after an ACTH stimulation test for nonclassic CAH), cortisol, ACTH, sodium, potassium, renin and androgens
• Genetic testing of the CYP21A2 gene confirms CAH and helps with family planning
• For suspected aldosteronism: the aldosterone-to-renin ratio, confirmatory tests, CT scan and adrenal vein sampling to decide whether one or both glands are overactive
• For suspected Cushing's: overnight dexamethasone suppression test, late-night salivary cortisol or 24-hour urine cortisol
• Pelvic ultrasound and karyotype for a newborn with atypical genitalia

Treatment

Congenital adrenal hyperplasia

• Glucocorticoid replacement: hydrocortisone in children, and hydrocortisone or longer-acting steroids in adults, to replace cortisol and suppress excess ACTH and androgens
• Mineralocorticoid replacement: fludrocortisone, often with salt supplements in infancy, for salt-wasting CAH
• Stress dosing: extra steroid during illness, fever, surgery or injury, and an emergency hydrocortisone injection kit at home
• Monitoring of growth, bone age, blood pressure and hormone levels
• Newer medicines such as crinecerfont, which lowers ACTH and androgens and can allow lower steroid doses
• Surgery for atypical genitalia is a complex decision made with specialist teams and families, increasingly delayed until the person can take part
• Nonclassic CAH often needs treatment only for symptoms, such as birth control pills or anti-androgens for excess hair, or steroids to help with fertility

Acquired hyperplasia

• Bilateral aldosteronism: mineralocorticoid receptor blockers such as spironolactone or eplerenone, which control blood pressure and potassium. Surgery is not usually used because both glands are affected
• ACTH-driven Cushing's: surgery to remove the pituitary or other tumor, with medicines or adrenal surgery if needed

Living with CAH

People with classic CAH need lifelong treatment and should:

• wear a medical alert bracelet
• carry a steroid emergency card
• know their sick-day rules for doubling or tripling steroid doses during illness
• have a hydrocortisone injection available at home and know how to use it

With careful treatment, most people with CAH lead full, active lives. Many women with CAH can become pregnant, often with specialist support.

Frequently asked questions

What is adrenal hyperplasia?

It is enlargement of the adrenal glands caused by an increased number of cells, usually with abnormal hormone production. The most common form is congenital adrenal hyperplasia, an inherited condition. In adults, acquired hyperplasia can cause high blood pressure from excess aldosterone or Cushing's syndrome.

What are the symptoms of congenital adrenal hyperplasia?

Newborns with severe CAH can have vomiting, dehydration and collapse in the first weeks, and girls may have atypical genitalia. Children may have early pubic hair and rapid growth. Milder nonclassic CAH causes excess hair, acne and irregular periods in teens and women.

Is adrenal hyperplasia dangerous?

Classic salt-wasting CAH is life-threatening without treatment, because of adrenal crisis. With steroid replacement and sick-day rules, it is well controlled. Nonclassic CAH is not dangerous but can affect fertility and appearance. Acquired hyperplasia raises cardiovascular risk through high blood pressure.

Is congenital adrenal hyperplasia genetic?

Yes. It is inherited in an autosomal recessive pattern, meaning a child is affected when they inherit a changed gene from both parents. When both parents are carriers, each pregnancy has a 1 in 4 chance of CAH. Genetic counseling is offered to affected families.

Can nonclassic CAH be mistaken for PCOS?

Yes. Both cause irregular periods, acne and excess hair. A 17-hydroxyprogesterone blood test, ideally taken early in the morning in the first days of the cycle, helps tell them apart, and an ACTH stimulation test confirms nonclassic CAH.