Congenital Adrenal Hyperplasia

CAH is the commonest inherited (AR) disorder of cortisol biosynthesis.

 

Cortisol deficiency increases secretion of ACTH which causes adrenocortical hyperplasia and over production of intermediate metabolites and could cause aldosterone deficiency.

 

The commonest cause of CAH in the UK is 21-Hydroxylase enzyme deficiency, which accounts for 90-95% of cases. There are two major clinical presentations:

 

Classical CAH manifests as:

Salt losing form/ Classical severe form– with Cortisol & Aldosterone deficiency(in approximately 75%); leading to salt and water loss.

 

Simple virilising form– able to synthesize adequate amounts of aldosterone but have elevated levels of androgens of adrenal origin. In female infants both these forms are associated with ambiguous genitalia

 

Presenting symptoms & signs: Poor feeding, vomiting, lethargy, poor weight gain, ambiguous genitalia, increased pigmentation of areolae and genital skin; and enlargement of penis.

 

Acutely unwell presentation within 2 weeks of age, with dehydration, hypotension, hypoglycemia, hyponatremia & hyperkalemia.

 

Non-Classical CAH-may be asymptomatic or have varying symptoms of androgen excess manifesting in late childhood or during adult life.

 

Initial investigations

– Serum U&Es, look for hyponatraemia / hyperkalaemia

– Blood Glucose, look for hypoglycemia

– Blood gas, look for metabolic acidosis if hypovolemic

 

Further tests to confirm diagnosis:

– Serum 17-OHP level is markedly elevated 

– Serum Cortisol –is low but not generally useful

– Androstenedione and testosterone are elevated in the affected female

– ACTH & Renin levels are elevated, but Aldosterone is inappropriately low

– Urinary steroid profile – 17-ketosteroid and pregnanetriol are elevated

– Karyotype

– USS Abdomen to evaluate adrenal glands and renal tract

 

Management

1. Resuscitate the newly diagnosed infant with CAH if in hypovolemic shock
2. Decrease excessive androgen secretion by replacing deficient hormones and achieve normal growth and development
3. Monitor glucose and electrolytes regularly; Sodium supplementation and treatment of symptomatic hyperkalemia with ECG changes
4. Ensure parents understand ‘sick day rules’ and have emergency plans if unwell

Glucocorticoid replacement- given as Hydrocortisone thrice a day; dose is doubled or tripled during periods of stress, such as infection or surgery

Mineralocorticoid replacement-Patients with salt wasting disease (aldosterone deficiency) require replacement with fludrocortisone