CAH is inherited in an autosomal recessive pattern. Normally a person has two functional CYP21A2 genes. In people with CAH due to 21-hydroxylase deficiency, both genes have a mutation and cortisol is not produced in the adrenal gland. Each parent of a newborn with CAH typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of CAH do not typically have symptoms.
There are three types of 21-hydroxylase deficiency related CAH: simple virilizing classic form, salt wasting classic form and non-classic form. Adult height is usually shorter than other family members for all three types. Reduced fertility can also occur in all three types.
- Salt wasting classic form: Babies with this form of CAH are at risk for life threatening adrenal crisis if not treated. Sodium is lost in the urine and the low sodium causes poor feeding, dehydration and vomiting. In addition, females have ambiguous genitalia (not clearly male or female).
- Simple virilizing classic form: Virilizing is the development of male secondary sex characteristics. Females with this form of CAH have ambiguous genitalia (not clearly male or female), but are not at risk for adrenal crisis.
- Non-classic CAH: The symptoms of non-classic CAH are not present at birth and people with non-classic CAH are not at risk for adrenal crisis. Females have male pattern baldness, excessive growth of hair on the body (hirsutism) and irregular menstruation. Males have early beard growth and small testes.
- Incidence: The incidence of classic CAH is 1 in 15,000.
- New York State Method of Screening (First Tier): Screening for CAH due to 21-hydroxylase deficiency is accomplished by measuring 17-hydroxyprogesterone (17-OHP) by immunoassay. 21-hydroxylase deficiency leads to accumulation of the 17-OHP hormone and therefore elevated levels of 17-OHP could indicate CAH. The cut-off level for the test varies based on the baby’s birth weight and age.
- Second Tier Screening: None
- Testing can be affected by: Newborn screening cannot detect all cases of 21-hydroxylase deficiency related CAH. Prematurity and specimens collected at less than 24 hours of age can cause a false positive result. Infants with CAH may have a normal screen (false negative) if they are administered steroids prior to specimen collection. Steroids prescribed to the mother during pregnancy can also cause a false negative result. There have been reports of babies with classic, salt wasting CAH with a negative newborn screen, therefore the screening test is not 100% effective. If there is any clinical suspicion or family history of CAH, a diagnostic evaluation is indicated regardless of screening results. Newborn Screening will not detect the 5% of non-21-hydroxylase deficiency related CAH.
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for CAH are referred to an Endocrinology Specialty Care Center for evaluation by an Endocrinologist trained in the diagnosis and treatment of CAH.
Diagnostic testing may include 17-hydroxyprogesterone, plasma renin activity, serum electrolytes, steroid profile, adrenocorticotropic hormone (ACTH) stimulation testing and CYP21A2 DNA testing.
CAH is treated with oral glucocorticoid replacement therapy, usually hydrocortisone. A high dose of glucocorticoid may be needed during times of physical stress or illness. People with classic salt wasting CAH should carry an emergency letter regarding the need for glucocorticoids. The classic salt wasting form should also be treated with 9α-fludrohydrocortisone and sodium chloride. Some females with ambiguous genitalia undergo surgery.
On treatment, many of the symptoms can be prevented including the risk for salt wasting adrenal crises.
Congenital adrenal hyperplasia (CAH) is a group of inherited endocrine disorders of impaired steroid hormone production by the adrenal glands. The synthesis of cortisol in the adrenal gland requires the production of a number of different enzymes, the lack of which will result in CAH. In 95% of CAH cases, 21-hydroxylase deficiency causes CAH and therefore newborn screening tests for the deficiency in this enzyme. In 21-hydroxylase deficiency CAH, the adrenal glands produce too much male sex hormone (androgens) which cause many of the symptoms of CAH. Additionally, in severe forms of CAH, the resultant lack of cortisol and aldosterone can cause life threatening complications. Cortisol is important for the body’s stress response and for controlling blood sugar levels. Aldosterone is important for regulating sodium balance in the body.