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California Newborn Screening Program

Congenital Adrenal Hyperplasia (CAH)

The term “congenital adrenal hyperplasia” or “adrenogenital syndrome” refers to a group of disorders. The most common disorder is due to a 21-hydroxylase deficiency. Screening for 21-hydroxylase deficiency is included in the California Newborn Screening Program. The incidence of CAH due to 21-hydroxylase deficiency in California is approximately 1:12,000 live births. It is anticipated that each year between 40 and 50 newborns in California will be identified with classical CAH, through screening.

CAH is inherited as an autosomal recessive disorder. All forms of CAH are due to an inborn error of steroid hormone synthesis, which blocks the production of cortisol. By four to five months gestation cortisol production is diminished in the affected fetus. The low level of cortisol stimulates the production of ACTH, causing adrenal hyperplasia and increased secretion of steroid precursors.

Classical CAH Salt Wasting:

Two-thirds of the infants with classical CAH have the salt wasting form, which may include virilization of the female genitalia. In these cases the 21-hydroxylase deficiency causes reduced production of mineralocorticoids, leading to a hypotensive, hyperkalemic, and salt losing crisis with rapid onset of adrenocortical failure within 7-28 days of birth. Without treatment the disorder progresses rapidly to coma and death. Infants with ambiguous genitalia or virilization should be considered at risk for this disorder and should have electrolyte monitoring until the diagnosis is ruled out.

Every effort should be made to expedite confirmatory testing and treatment.

Classical CAH Simple Virilizing:

In one-third of classical cases, the infant has a “non salt losing” or “simple virilizing form”. In this less severe form of classical CAH, female external genitalia may be virilized, though ovaries and the uterus are unaffected. Male infants may be asymptomatic or have increased scrotal pigmentation. If untreated, these children may have mild postnatal virilization, rapid growth with advanced skeletal age, early puberty and short stature as adults. In adults, there may be hirsutism and acne. Women may have irregular menses and infertility

Non-Classical CAH:

The milder non-classical forms of CAH often present later in life. The body makes some cortisol, normal amounts of aldosterone, and too much androgen. These forms of Non-Classical (NCAH) are not specifically included in the California Newborn Screening Program. However, a small percent of newborns with NCAH may be detected through newborn screening.

Laboratory testing:

Screening for CAH consists of two-tier testing. The first tier measures 17-hydroxyprogesterone (17-OHP) using the AutoDelphia instrument (the same machine that measures TSH for primary congenital hypothyroidism screening). This is an immunofluorescence-assay (FIA). 17-OHP is elevated in newborns with classical CAH due to the pathway to cortisol being blocked by the absence of the enzyme, 21-hydroxylase. Newborns with very high first tier 17-OHP values, based upon four birth weight categories, will be referred immediately to a CCS-approved Endocrine Center for a diagnostic evaluation.

The second tier test will be performed if a newborn has values that are elevated but below the initial cut-offs for immediate reporting. The second test will be performed on the initial blood specimen via Tandem Mass Spectrometry. This test will measure 17-OHP, androstenedione and cortisol. Newborns with an elevated 17-OHP and a high ratio of 17-OHP and androstenedione to cortisol will be referred to a CCS-approved Endocrine Center or CCS-paneled pediatric endocrinologist for a diagnostic evaluation.

Newborns with non-classical congenital adrenal hyperplasia (NCAH) have only slightly elevated 17-OHP values and therefore, the test will only identify some of the newborns with NCAH.

Pre-term, low birth weight or sick infants have a relatively high incidence of false positives.

Referral and Treatment Considerations:

Infants with a positive result which can be indicative of any form of Classical CAH on either the first or second tier of CAH screening will be referred immediately by the Newborn Screening Program to a CCS approved Endocrine Special Care Center, or a pediatric endocrinologist, for a full work-up and the initiation of treatment when indicated.

The treatment for Classical CAH consists of the administration of hydrocortisone and mineralocorticoids. Those with ambiguous genitalia need chromosome analysis to confirm gender and determine a course of treatment.

Variant Forms of CAH:

There are variant forms of CAH which account for less than 10% of cases. Screening for these variants is not included in the California Newborn Screening program. All are autosomal recessive disorders in which there is a deficiency of one of the enzymes in the adrenal steroid synthetic pathway. Signs and symptoms depend on the specific enzyme deficiency.

These conditions include Lipoid CAH in which there is there is salt-wasting and ambiguous genitalia in males and 17 (alpha) hydroxylase deficiency which causes ambiguous genitalia in males and hypertension.

Two other forms have both classical and non-classic presentations. These are 3 B (beta)-OH-steroid dehydrogenase deficiency, which has salt-wasting as well as ambiguous genitalia in both males and females in classical cases, but not in non-classic cases and Classical 11 B(beta) hydroxylase deficiency which has ambiguous genitalia in females and hypertension but non-classic cases do not.

Regardless of the cause, adrenal insufficiency is life threatening in classical cases of CAH. It is strongly recommended that an infant presenting with any of these symptoms be referred for further diagnosis and treatment to a CCS approved Endocrine Special Care Center or a pediatric endocrinologist, regardless of newborn screening results. Treatment for these types of CAH consists of glucocorticoid and/or mineralocorticoid replacement.

Parents' Guide to Congenital Adrenal Hyperplasia (PDF, 1 MB, English)  ...Spanish (PDF, 1 MB)

 
 
Last modified on: 4/11/2014 3:52 PM