CAH

Congenital Adrenal Hyperplasia (CAH)

Congenital Adrenal Hyperplasia (CAH) is a group of inherited autosomal recessive disorders that disrupt the adrenal gland’s production of cortisol. The most common cause in the UK is a deficiency of the 21-hydroxylase enzyme, which accounts for over 90% of cases. The condition is now included in the newborn screening programme to allow for early detection and management.

 

Pathophysiology

Cortisol deficiency leads to a lack of negative feedback on the pituitary gland, which causes an overproduction of adrenocorticotropic hormone (ACTH). The high ACTH levels stimulate the adrenal cortex to produce excessive amounts of intermediate metabolites. In 21-hydroxylase deficiency, these metabolites are diverted into the androgen pathway, leading to an overproduction of androgens. In the most severe form, there is also a deficiency of the mineralocorticoid, aldosterone.

 

Clinical Presentation

  • Classical CAH: This is the most severe form and is often detected in the newborn period.

    • Salt-wasting form: This affects approximately 75% of those with classical CAH. It presents acutely within the first two weeks of life with a hypovolemic crisis due to combined cortisol and aldosterone deficiency. Infants present with poor feeding, vomiting, dehydration, hypotension, hyponatraemia, and hyperkalaemia.

    • Simple virilising form: These infants have enough aldosterone to prevent a salt-wasting crisis but have an excess of androgens.

  • Non-Classical CAH: A milder form that can be asymptomatic or present later in childhood or adulthood with signs of androgen excess, such as premature pubic hair, hirsutism, or irregular periods.

 

Diagnosis

Early diagnosis is crucial to prevent a life-threatening adrenal crisis.

  • Newborn Screening: All UK newborn blood spot screening includes a test for CAH by measuring 17-hydroxyprogesterone (17-OHP), which is markedly elevated in 21-hydroxylase deficiency.

  • Initial Investigations: If an infant presents with a suspected adrenal crisis, immediate tests include:

    • U&Es: To check for hyponatraemia and hyperkalaemia.

    • Blood Glucose: To check for hypoglycaemia.

    • Blood Gas: To check for metabolic acidosis.

  • Confirmatory Tests: Serum 17-OHP, androstenedione, and testosterone levels will be elevated. A karyotype is essential to determine the child’s genetic sex, especially in the presence of ambiguous genitalia.

 

Management

  • Acute Adrenal Crisis: This is a medical emergency.

    • Resuscitation: The infant should be resuscitated with IV fluids to correct hypovolaemic shock.

    • Hormone Replacement: Give stress doses of hydrocortisone immediately, followed by mineralocorticoid replacement.

  • Long-Term Management:

    • Glucocorticoid Replacement: This is the cornerstone of management. Hydrocortisone is given 3 times a day. The dose must be increased during periods of stress, such as fever, surgery, or other illnesses.

    • Mineralocorticoid Replacement: Patients with the salt-wasting form require a mineralocorticoid, fludrocortisone, to maintain electrolyte balance.

    • Parental Education: Parents must be educated on the “sick day rules” and have an emergency plan in place to prevent an adrenal crisis.