Congenital adrenal hyperplasia (CAH): symptoms, causes and treatment

Congenital adrenal hyperplasia (CAH) is a group of inherited conditions that are present at birth (congenital), in which the adrenal glands are larger than usual (hyperplasia). Great Ormond Street Hospital (GOSH) explains that in CAH the body is missing an enzyme that stimulates the adrenal glands to release cortisol. Lacking cortisol means the body is less able to cope with physical stress, which can be life threatening, and androgen (male hormone) levels increase.

The adrenal glands sit on top of the kidneys. GOSH describes their outer part, the cortex, as releasing aldosterone (which helps regulate blood pressure by controlling how much salt is retained), cortisol (the body's natural steroid, which helps control blood sugar, deal with stress and control blood pressure) and androgen.

The NHS Genomics Education Programme says CAH is caused by single gene defects in enzymes involved in cortisol production, most commonly 21-hydroxylase. There are two forms of 21-hydroxylase deficient CAH, classical and non-classical.

GOSH says the symptoms and the age at which they appear depend on the degree of cortisol and/or aldosterone deficiency. Boys with severe CAH show symptoms soon after birth, when a baby may develop heart rhythm abnormalities, dehydration and vomiting, with low salt levels (hyponatraemia) and low blood sugar (hypoglycaemia). Girls with severe CAH are born with virilised genitalia, and have similar mineral imbalances.

Children with mild CAH may not have the same mineral imbalances. Later, symptoms from the extra androgen develop. GOSH lists abnormal or absent periods, a deep voice, early puberty and facial hair in girls, and an enlarged penis, small testicles, early puberty, acne and a deep voice in boys. Both may appear tall for their age but usually end up short as adults if the diagnosis is not made quickly and treatment started.

Symptoms in a baby who is vomiting, dehydrated, limp or not feeding are an emergency. Call 999 or go to A&E.

GOSH explains that CAH is an inherited disorder passed from parent to child. Most types are autosomal recessive, meaning both parents are carriers. Healthy carriers each have one faulty copy of the gene, and each pregnancy carries a 25 per cent chance of the child being affected and a 75 per cent chance of the child not being affected. In a small proportion of people, CAH is caused by a gene mutation that happens by chance.

The Genomics Education Programme adds that, ideally, management in pregnancy starts with preconception education and genomic counselling. GOSH notes that genetic counselling may be helpful.

GOSH says most cases are diagnosed soon after birth or in early childhood, but less severe CAH may not become apparent until a child does not start puberty at the expected age. CAH can also be diagnosed before birth now that the affected gene has been identified.

Blood and urine tests are used to work out the levels of minerals and hormones in the body so they can be replaced. If a baby is born with ambiguous genitalia, blood tests are usually used to determine genetic sex. X-rays to look at bone age may be suggested, and genetic testing may identify the specific type and gene change.

The Genomics Education Programme says that, based on the last UK National Screening Committee review (November 2021), newborn screening for CAH is not currently recommended.

GOSH says children with CAH are usually cared for by a multidisciplinary team including endocrinologists (hormone specialists) and urologists. Initially children may need to be stabilised with intravenous fluids to restore their electrolyte levels. Once stable, cortisol and/or aldosterone replacement therapy can start, with repeated blood tests to monitor hormone levels so the most effective dose can be prescribed.

Children with CAH will need to take replacement cortisol and aldosterone every day for the rest of their lives. If precocious puberty occurs, further hormone treatment may be required. Long-term follow-up monitoring is essential, with regular blood tests and adjustments of steroid doses.

The Genomics Education Programme says individuals with ambiguous genitalia need to be seen by a multidisciplinary team, with input from paediatric endocrinology, paediatric urology or surgery, clinical genetics and clinical psychology, and that the community midwife, health visitor and GP should be informed of care and treatment.

GOSH says that if a person with cortisol deficiency becomes unwell, they cannot increase production of cortisol to help the body cope, and this could be life threatening. Cambridge University Hospitals explains the same in its leaflet on steroid replacement for adrenal insufficiency: normally, if we are sick or injured the body immediately produces more cortisol, but because the adrenal glands cannot do this reliably, you will need extra steroid medication.

That leaflet describes general adult guidelines for extra cover, which include doubling the steroid dose during illness with a fever, taking an extra dose and seeking urgent help if vomiting persists, and ensuring the team treating you knows you are at risk of adrenal crisis, using the NHS Steroid Emergency Card. It says an adrenal crisis is a medical emergency, with signs that can include severe dizziness with serious vomiting or diarrhoea, sudden confusion, extreme weakness, headache, chills or fever. Exact doses depend on age, weight and medicine, so follow the plan from your own endocrine team rather than a general leaflet.

The Genomics Education Programme advises that people with CAH should wear or carry medical alert identification specifying adrenal insufficiency.

GOSH says men usually have normal fertility provided they have been optimally treated, but some women with CAH may have problems conceiving and may need additional help. Once pregnant, women with CAH should carry the baby to term but may need a caesarean section to deliver.

The Genomics Education Programme says that for most forms of the condition, health, fertility and lifespan can be restored to normal with appropriate hormone replacement therapy. Cambridge University Hospitals advises contacting the endocrine team if you become pregnant to discuss any changes to steroid replacement and arrange follow-up during pregnancy.

The Genomics Education Programme notes that prenatal dexamethasone treatment is controversial and that the 2018 Endocrine Society guidelines recommend that clinicians continue to regard prenatal therapy as experimental. Anyone considering this should discuss it with a specialist team.

On the NHS, CAH is usually diagnosed and managed by paediatric endocrinology teams, then by adult endocrinology after transition. Because treatment is lifelong and doses need regular adjustment, continuity with a specialist team matters. Some adults choose a private endocrinology opinion, and in either setting a written emergency plan and steroid emergency card should be kept up to date.