Congenital Adrenal Hyperplasia (CAH)

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.
    1. Classic
      1. 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.
      2. 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.
    2. Non-Classic- will often present later on in childhood with signs and symptoms of androgen excess.


Physical Diagnosis

Evaluation Overview:


The physical exam should identify the urethral meatus and should include careful palpation for gonads in the inguinal canals and labia and scrotum.  A pelvic ultraosund should be performed to determine the presence or absence of internal female genetalia. 

Determining degree of virilizations


Figures-  TOP: External genitalia virilization spectrum. BOTTOM: Internal GU tract in relation to external genitalia virilization. Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Endocr Rev. 2000 Jun 1;21(3):245–91


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.



  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.

Treatment Algorithm


Flowchart for decisions pertaining to newborn screening for 21-hydroxylase deficiency. ACTH stim 17-OHP, 17-Hydroxyprogesterone level after cosyntropin stimulation; ′lytes, electrolytes. From Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Endocr Rev. 2000 Jun 1;21(3):245–91.


Corrective Surgery

The timing of corrective surgery is currently under debate with one camp endorsing neonatal correction according to the genetic/gonadal sex while the opposing camp proposes postponement of surgery until the patient is mature enough to make an informed decision. However, most experts agree that preserving reproductive function and assigning female external genitalia is warranted in 46XX patients with normal internal reproductive organs. The issue with cases that are not as straight forward is determining whether or not families are equipped to raise a child of indeterminate gender until he/she can make an informed decision. The psychosocial issues of growing up with an ambiguous gender identity for both the patient and family must be weighed when determining the timing of gender assignment surgery. However, experts argue that waiting for the patient to determine gender assignment is reasonable in societies where cultural pressures cause families to favor males.

Due to the complex ethical and social issues involved with determining the appropriate treatment plan for any given patient; it is crucial that a multidisciplinary team comprised of pediatricians, surgeons, psychiatrists, social workers, and ethicists work in concert to provide the best possible care for the patients and their families.


Patient Resources

From the Illinois Department of Public Health:

1)    Newborn Screening Guide for Parents  - Click Here 

2)    Congenital Adrenal Hyperplasia Fact Sheet - Click here 


Patient & Family Support Groups in Illinois

1)    CAH Research, Education, and Support (CARES) Foundation Coordinator

Cathy Layton
(708) 935-7535


2)    Support Group Leaders by Specialized Topic - Click Here



  1. AAP Section on Endocrinology (2000). Technical report: congenital adrenal hyperplasiaPediatrics, 106(6), 1511-1518
  2. Antal, Z. and Zhou, P. (2009). Congenital adrenal hyperplasia: diagnosis, evaluation, and managementPediatrics in Review, 30(7), 49-57. 
  3. Speiser, P.W., et. al. (2010). Congential adrenal hyperplasia due to sterois 21-hydroxylase deficiency: an endocrine society clinical practice guidelineJ Clin Endocrinol Metab, 95(9), 4133-4160.