Provider News

Congenital Adrenal Hyperplasia (CAH): Q&A With Dr. Patricia Y. Fechner

June 1, 2022

June Is Congenital Adrenal Hyperplasia (CAH) Month

Dr. Fechner is the medical director of the Seattle Children’s CAH Center of Excellence, a Level 1 Comprehensive Care Center for CAH designated by the CARES Foundation. She is also the Washington State Department of Health Newborn Screening Program pediatric endocrinology consultant.

Q: How common is CAH?

Congenital adrenal hyperplasia, or CAH, is a disorder where the adrenal gland is unable to produce cortisol from cholesterol. The production of cortisol from cholesterol requires several enzymes, and thus a defect in any of the genes encoding one of the enzymes required to produce cortisol can lead to CAH. CAH is an autosomal recessive condition, which means that both alleles encoding the enzyme need to be affected.  The most common enzyme deficiency is 21-hydroxylase deficiency, which accounts for about 90 to 95% of the cases of CAH. The carrier frequency for CAH is 1 in 60. In the state of Washington, about 1 in every 16,000 babies are born with CAH due to 21-hydroxylase deficiency.

Q: What percent of CAH is picked up by state newborn screening?

All babies born with CAH have been identified by the Washington state newborn screening program. All states screen for CAH. The purpose of newborn screening is to identify infants with a serious condition that if missed could have dire consequences but with the initiation of early therapy could have improved outcomes. Prior to the use of newborn screening for CAH, male infants born with CAH were usually not diagnosed in a timely manner, and most died in the first month of life due to unrecognized salt wasting adrenal crisis.

In the United States, all babies are screened for CAH, but newborns born at home have an increased risk of not being screened. In 2021, 228 infants in Washington screened positive for CAH out of about 85,000 but only 6 were confirmed to have CAH.

Q: Does the timing of the newborn screening test impact the results?

The newborn screen uses the hormone 17-hydroxyprogesterone to screen for 21-hydroxylase deficiency CAH.  17-hydroxyprogesterone levels are quite elevated at birth but begin to fall by 24 hours. Thus, infants screened in the first 24 hours of life will have higher values than those screened after 24 hours, which can make interpreting the results of the newborn screen more difficult if the screen occurs shortly after birth. 

Q: Are two newborn screening tests better than one for making the diagnosis of CAH?

Yes, two newborn screening tests are better than one for making the diagnosis of CAH. We are very fortunate in Washington to have a second newborn screen, as it can eliminate infants who may have had higher 17-OH progesterone levels based on age of initial testing, gestational age (results are based on birthweight) or stress, all of which can lead to higher 17-hydroxyprogesterone levels at the time of the first newborn screen. In addition, the second screen may pick up infants whose adrenal glands were suppressed due to the use of maternal glucocorticoids such as dexamethasone. In 2021, 148 infants screened abnormal for CAH on their first screen, 57 infants screened abnormal on their second and 23 screened abnormal on their third or later screens.

Q: How common are false-positive and false-negative results?

The goal of the newborn screen is to not miss any infant with classic CAH due to 21-hydroxylase deficiency. The goal is not to pick up infants with non-classic CAH, which is not life threatening and can be identified in childhood by findings on physical exam and review of growth charts.  For those infants that have final classifications, there were 181 false-positive screens for CAH in 2021. At this time, we are not aware of any false-negative screens for CAH in 2021.

Q: What confirmatory testing should be ordered?

The newborn screen is a screening test to identify infants at risk for CAH. The more definitive test is to obtain a blood test for 17-hydroxyprogesterone in order to confirm or rule out CAH. If the 17-hydroxyprogesterone level is elevated, then an urgent referral to a pediatric endocrinologist is required.

Q: What treatment should be initiated for newborns with positive newborn screening for CAH?

Not all babies with a positive screen have CAH. A confirmatory blood test for 17-hydroxyprogesterone is needed. Though if the screening 17-hydroxyprogesterone is sufficiently high, treatment may be initiated prior to the results of the confirmatory 17-hydroxyprogesterone. It should be noted that the newborn screen 17-hydroxyprogesterone is reported in ng/mL and the Seattle Children’s lab and most other labs use ng/dL. Therefore, the number provided by the newborn screen needs to be multiplied by 100 in order to get the more familiar units of ng/dL. In other words, a newborn screen of 150 ng/mL is 15,000 ng/dL. If there is concern that the screen is a true positive, a pediatric endocrinologist can be consulted by phone for the next steps. The Washington Department of Health Newborn Screening Program does an excellent job of contacting providers by phone for the next steps based on the level of the screening result. If treatment is needed, hydrocortisone and fludrocortisone would be recommended by a pediatric endocrinologist.

Q: What is the timing of initiation of treatment?

Therapy is initiated as soon as the diagnosis is made or if screening results are highly likely to indicate CAH. Infants can be referred to the Seattle Children’s Emergency Department for urgent evaluation and initiation of therapy if a pediatric endocrinologist cannot evaluate the baby promptly.

Q: What are the common signs and symptoms of classic CAH in the newborn?

Most female infants will have evidence of androgenization of their external genitalia leading to ambiguous genitalia. Male infants usually do not have any signs of CAH, which is why they were not diagnosed prior to the initiation of newborn screening for CAH. Babies with the salt-wasting form of CAH, which occurs in about 75% of the cases of CAH, are at risk for rapid, uncontrolled loss of sodium and elevated potassium levels with low glucose levels that can be lethal. Other infants may present with emesis, dehydration, and failure to gain weight within the first few weeks of life. The goal of the newborn screening program is to identify infants with CAH so that they don’t have an adrenal crisis.

Q: What are the common signs and symptoms of non-classic CAH?

Infants with non-classic CAH do not have salt wasting or ambiguous genitalia. They may develop premature adrenarche-body odor, pubic/axillary hair and enlargement of the phallus without testicular enlargement. They may have an increased rate of growth.

Q: What tests should a PCP order if worried about non-classic CAH?

17-hydroxyprogesterone, androstenedione, testosterone, 11-deoxycortisol and dehydroepiandrosterone sulfate (DHEAS) can be checked. A bone age can also be checked.

Q: When should pediatric endocrinology be consulted?

Pediatric endocrinology should be consulted if recommended by the Department of Health Newborn Screening Program or if serum 17-hydroxyprogesterone is elevated.

Q: How quickly should newborns with classic CAH be evaluated in person by pediatric endocrinology?

The newborn should be seen within 24 to 48 hours. If it is not possible for the newborn to be seen in a timely manner or if there is concern that the newborn is having a salt-wasting adrenal crisis, the newborn should be evaluated immediately in a pediatric emergency department where labs, vital signs, physical exam and endocrine consult can be obtained.  

Q: What if there are no pediatric endocrinologists in the newborn’s community? 

The pediatrician can page the endocrinologist on call at Seattle Children’s for an educational consultation and, if necessary, the newborn can be transported to Seattle Children’s for care.

Q: Do you have tips for talking with parents about the diagnosis of CAH, especially sex assignment?

Parents should be told that while their newborn has a life-threatening condition, it can be managed successfully with medication so that their child can lead a normal life as long as the child takes the medication as prescribed. Close follow-up with a pediatric endocrinologist is crucial for normal growth and development. For females with CAH and ambiguous genitalia, sex assignment in the newborn is female. These female infants have a uterus and ovaries and have fertility. Seattle Children’s has a Comprehensive CAH Center of Excellence with pediatric urologists who are experts in restorative feminizing surgery if it is indicated.

The CARES Foundation website ( has a wealth of information for families, and monthly support group meetings for families with newborns diagnosed with CAH, as well as for parents of children with CAH and for teens with CAH.

Q: Is prenatal diagnosis possible/recommended?

Prenatal diagnosis of CAH in the fetus via chorionic villus sampling or amniocentesis is possible but not recommended unless it will make a difference in the outcome of the pregnancy. Prenatal treatment of a female fetus at risk for CAH by maternal treatment with dexamethasone must be initiated by six to seven weeks of the pregnancy to prevent androgenization of female fetal external genitalia, but it is considered experimental by the endocrine community and should only be done as part of a research study looking at long-term outcomes for any fetus exposed to dexamethasone.

Q: And for who? 

CAH is an autosomal recessive condition. If parents have had a child with CAH, then it is likely that they are both carriers for changes in the 21-hydroxylase gene. For each pregnancy, they would have a one in four chance of having a baby with CAH and a one in eight chance of having a female infant with CAH. If one parent has CAH and if the other parent is a known carrier for CAH (1 in 60 chance), then there is a 50% chance that each pregnancy will result in a child with CAH and a 25% chance that the child will be a female with CAH. If their child does not have CAH, he or she will be a carrier for CAH. If one parent has CAH and the other parent is not a carrier for CAH, then all offspring will be carriers for CAH. In order to perform prenatal genetic testing, it is important to know the genotypes of the 21-hydroxylase gene for each parent. This should be determined prior to conceiving if possible. Parents interested in a prenatal diagnosis for CAH, or if they are desiring more information regarding recurrence risk for CAH, should meet with a prenatal genetic counselor. The Seattle Children’s CAH Center of Excellence offers genetic counseling and genetic testing for patients with CAH who are seen there.

For more information on the CAH Center of Excellence, follow the link: