Congenital adrenal hyperplasia, Endocrine Disorder Screening -Infant

Congenital adrenal hyperplasia, Endocrine Disorder Screening -Infant

Congenital adrenal hyperplasia, Endocrine Disorder Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The congenital screening for Congenital adrenal hyperplasia  is recommended.

B

Congenital adrenal hyperplasia (CAH) is a group of rare inherited autosomal recessive disorders characterized by a deficiency of one of the enzymes needed to make specific hormones. CAH effects the adrenal glands located at the top of each kidney. 

OVERVIEW

Caused by a group of inherited disorders of biosynthesis of cortisol and aldosterone. 21-hydroxylase deficiency accounts for roughly 90% of CAH. "Classic" form has severe enzyme deficiency and prenatal onset, while nonclassic has moderate enzyme deficiency and later onset. Within the classic form are two types: simple virilizing (apparent in females and comprising approximately 25% of affected individuals) and salt wasting (>75%). Individuals with the nonclassic form present postnatally with evidence of hyperandrogenism and females are not virilized at birth. Most of those affected with the nonclassic form will be detected by newborn screening.

SCREENING

Finding

Elevated 17-Hydroxyprogesterone (17-OHP)

Tested By

Fluoroimmunoassay (high sensitivity, low specificity); with positives then tested by tandem mass spectrometry (low sensitivity, specificity: 99.5 to 99.8%)

PREVALENCE

Prevalence is about 1:15,000 live births; 1:5,000 in Saudi Arabi; 1:21,000 in Japan; 1:23,000 in New Zealand.

INHERITANCE

CAH is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

Use of molecular genetic testing, CVS testing, or DNA analysis varies by trimester. Prenatal therapy with dexamethasone can reduce female virilization.

CLINICAL CHARACTERISTICS

With treatment with gluco- and mineralocorticoid replacement, good prognosis and near-normal growth and life expectancy should result. Surgical management of virilization may be indicated in females. 

Without treatment, life-threatening salt-wasting crises may occur, even before the results of newborn screening are reported; hypoglycemia may also occur with stress.

Initial symptoms may include:

    • Poor feeding
    • Vomiting
    • Lethargy
    • Hypotonia
    • Heptomegaly
    • Cardiac insufficiency
    • Cardiomyopathy
    • Lab findings:
      1. Elevated liver function tests
      2. Elevated CK
      3. Metabolic acidosis
      4. Lactic acidosis
      5. Hypoglycemia

EARLY SIGNS

The signs of congenital adrenal hyperplasia (CAH) vary from person to person and by the form of CAH. There are three main forms of CAH: the “salt-wasting form," the “simple virilizing form," and non-classic CAH.

Salt-wasting classic CAH accounts for about 75% of classic CAH cases. This is the most severe form. Signs of salt-wasting CAH usually begin within the first few weeks of life. These signs include:

  • Poor feeding
  • Sleeping longer or more often
  • Tiredness
  • Vomiting
  • Diarrhea
  • Weight loss
  • Irritability
  • Rapid heart rate
  • Male-like genitals in females (described in detail below)

Simple virilizing classic CAH accounts for about 25% of classic CAH cases. This form is less severe than salt-wasting CAH, but more severe than non-classic CAH. Signs of simple virilizing CAH begin before birth. These signs differ between males and females, which usually become apparent during childhood due to early puberty.

Early signs of simple virilizing CAH include:

  • Enlarged clitoris (it may look like a small penis)
  • Labia that are fused together (they may resemble a scrotum)
  • Small testicles

While the majority of CAH cases are “classic,” some people are affected by non-classic CAH.

Non-classic CAH is much less severe than classic forms of CAH. Signs of non-classic CAH can begin in childhood, adolescence, or adulthood. Both males and females with non-classic CAH may show signs of early puberty. 

TREATMENT

Medications and Supplements

The main form of treatment for the classic forms of congenital adrenal hyperplasia (CAH) is hydrocortisone pills. These pills help replace the cortisol that your baby’s body cannot make naturally. An endocrinologist can help determine the appropriate dosage of hydrocortisone for your baby (see Accessing Care).  Patients with the salt-wasting form of CAH require additional treatment with fludrocortisone, which replaces aldosterone.

Your baby’s doctor might prescribe medications or human growth hormone supplements to help regulate your child’s growth. Children with CAH can experience delayed or rapid growth. X-rays can indicate if your child’s bones are growing too quickly. Talk to your baby’s doctor before starting this type of treatment.

Medications are also available to treat the early puberty that occurs during childhood in individuals with CAH. Your baby’s doctor can write a prescription for these hormone medications.

Surgery

The genital changes associated with CAH can be reversed with surgery. Genital surgery is a very complex decision. What may be the right choice for one family might not be best for another family. It is important to talk to your baby’s doctor about the risks and benefits of genital surgery in order to make an informed decision that is right for your child and family.

EXPECTED OUTCOMES

If congenital adrenal hyperplasia (CAH) is treated soon after birth, children can have healthy growth and development. This is why newborn screening is so important.

Early puberty is a common sign of CAH in childhood. Children who receive treatment may still have slightly early puberty. Adults with CAH may have shorter stature than other members of their family, even with treatment.

Babies who do not receive treatment for salt-wasting CAH are at risk for coma or death.

CAUSES

In our bodies, enzymes help make hormones. Hormones send messages throughout the body. These messages help control various functions of the body, including growth and development. The adrenal gland makes hormones including cortisol, aldosterone, and androgens.

Cortisol helps control how the body uses sugar for energy, protects the body during injury, and regulates immune response. Aldosterone helps the body recycle salt and water from urine. Androgens are sex hormones that influence sexual development by promoting the development of male-like features.

The enzyme 21-hydroxylase (21-OH) helps the adrenal glands make cortisol and aldosterone. In 95% of congenital adrenal hyperplasia (CAH) cases, the body does not make enough 21-OH enzymes. When 21-OH does not work correctly, the levels of cortisol, aldosterone, and androgen change. Different forms of CAH have different levels of 21-OH activity. More 21-OH activity leads to less severe CAH.

Individuals with salt-wasting classic CAH have very low levels of 21-OH activity. Their levels of cortisol and aldosterone are too low, while their androgen levels are too high. The low aldosterone levels cause low levels of sodium in the blood, high levels of acid in the blood, and dehydration. While it is normal to have certain acid and sodium levels in the blood, low levels of sodium and high levels of acid can be toxic. The low sodium levels give this form its “salt-wasting” name.

Individuals with simple virilizing classic CAH have intermediate levels of 21-OH activity. Their aldosterone levels are healthy, but their cortisol levels are too low. They also have too much androgen. These babies don’t have the salt-wasting qualities described above, but they do have genital changes and experience early puberty because high androgen levels cause rapid growth and sexual development, and they promote the development of male sexual features.

Individuals with non-classic CAH have healthy levels of cortisol and aldosterone, but they have high levels of androgens. The high levels of androgens cause early puberty as described above.

About 5% of CAH cases are not caused by 21-OH deficiency. Other causes of CAH may include:

  • Steroidogenic acute regulartory protein deficiency (STAR)
  • 3-beta-hydroxysteroid dehydrogenase deficiency (3B-HSD)
  • 17-alpha-hydroxylase deficiency
  • 11-beta-hydroxylase deficiency
  • Cytochrome P450 oxidoreductase deficiency

A geneticist or genetic counselor can help identify and explain these various causes of CAH.

CAH is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for CAH, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with CAH is rare, when both parents are carriers, they can have more than one child with the condition.