CAH is an autosomal recessive hereditary disease that occurs in about 1 in 16,000 infants born in North America. The disease is caused by an absence of various synthetic enzymes in the adrenal cortex involved in the production of cortisol and aldosterone. 21-hydroxylase deficiency accounts for the vast majority of cases (90%), while 11-hydroxylase (5%), cholesterol desmolase, 17-hydroxylase and 3-hydroxysteroid dehydrogenase deficiencies are much less common.

The absence of these enzymes lead to the increased production of ACTH in the pituitary and the increase production of steroids that do not require the missing enzyme. Steroids produced distal to the missing enzyme are deficient.

Clinical features

21- OH Deficiency

1. Presentation of CAH depends on which enzyme in cortisol synthesis is missing. 21-hydroxylase deficiency can be divided into classic deficiency with and without salt wasting (cortisol and aldosterone deficiencies) and non-classic type.

a. Classic

i. Virilizing syndrome- affected females are virilized in utero and present at birth with cliteromegaly, labial fusion, and normal internal organs. This is the most common cause of ambiguous genitalia in females. Gender assignment must be carefully evaluated in these patients.

ii. Salt losing 75% of 21-OH deficiency have salt losing because there is inadequate production of aldosterone. These neonates will fail to gain weight, vomit, have hyponatremia and hyperkalemia, hypoglycemia and be acidotic. They may appear septic.

b. Non-Classic- will often present later on in childhood with signs and symptoms of androgen excess.

Diagnosis

Newborn screening test for 21-hydroxylase deficiency in about 31 states. The aim is to catch potential salt-wasters early and to prevent virilization. The test actually measures a substrate for 21-hydroxylase, 17-hydroxyprogesterone, which will be elevated in patients who lack the enzyme. If the screen comes back positive, the newborn should be seen and examined, the test must be repeated, send serum electrolytes, and obtain an endocrinology consult.
 
 

Treatment

1. Correct fluid and electrolyte imbalances

2. Correct hypoglycemia

3. Provide glucocorticoids and mineralocorticoids if necessary

4. Maintain normal growth, development, and puberty, and sexual function.

5. Supply extra glucocorticoids in time of stress.

6. Emergency treatment- IV hydrocortisone 50-100mg/m2/day. At these high doses, there is mineralocorticoid activity.

References

1. Levine Lenore. Congenital Adrenal Hyperplasia. Pediatrics in Review. May 2000

2. Speiser Phyllis and White Perrin. Congenital Adrenal Hyperplasia. NEJM Vol 349(8) August 21, 2003

3. Shulman d. et al. Adrenal Insufficiency: Still a Cause of Morbidity and Death in Children.  Pediatrics Feb 2007