Congenital Adrenal Hyperplasia
Screening
Tested By
17-OHP is measured by Fluoroimmunoassay. Abnormalities on the first assay trigger a second-tier test using the liquid chromatography, followed by tandem mass spectrometry (LC-MS/MS). Second-tier tests significantly increase the specificity and sensitivity of CAH screening. Because 17-OHP levels are affected by birth weight and gestational age and can be elevated in sick infants, the normal range must be adjusted in those circumstances.Overview
CAH comprises a group of autosomal recessive disorders caused by deficient adrenal corticosteroid enzyme, leading to inadequate synthesis of cortisol in the adrenal gland. Newborn screening programs screen for the most common form, 21-hydroxylase deficiency, which accounts for ~95% of CAH. 21-hydroxylase deficiency leads to impaired production of cortisol and aldosterone and resultant excess production of adrenocorticotropic hormone (ACTH). This leads to chronic stimulation of the adrenal gland without normal production of cortisol but with overproduction of androgens. 21-Hydroxylase deficiency causes two types of CAH:- The "classic" form has severe enzyme deficiency and prenatal onset and has two subtypes: simple virilizing and salt wasting. Both types can be life-threatening in infancy due to cortisol deficiency.
- The “non-classic” form is milder and presents later with variable degrees of postnatal androgen excess.
Incidence
The incidence of CAH ranges from 1:10,000 to 1:20,000 births, but it is more prevalent in small, genetically isolated groups. [Speiser: 2018]Prenatal Testing
Though routine genetic screening is not an option, following the birth of a child with CAH, genetic testing of that child and the parents can identify the specific genetic mutation in the family. Families should be encouraged to explore available options before another pregnancy. Use of molecular genetic testing, chorionic villus sampling (CVS) testing, or DNA analysis varies by trimester. Genetic counseling for couples with an affected child is recommended to discuss options for prenatal treatment or IVF options.Clinical Characteristics
A cardinal feature of classic CAH in newborn females is virilization (enlarged clitoris, posterior labial fusion, and rugation of the labia and urogenital sinus formation). Female infants are frequently diagnosed at birth with ambiguous genitalia.With treatment with gluco- and mineralocorticoid replacement, 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.
If not recognized early and treated, initial symptoms may include:
- Virilization in female infants (ambiguous genitalia)
- Vomiting
- Lethargy
- Poor feeding
- Pallor
- Shock
- Lab findings including:
- Metabolic acidosis
- Hyponatremia
- Hyperkalemia
- Hypoglycemia
Follow-up Testing after Positive Screen
A positive screen is an emergency; the family should be contacted immediately and additional testing performed: serum 17-OHP; serum electrolytes (high potassium, low sodium, low bicarbonate); blood glucose (low)Primary Care Management
Upon Notification of the + Screen
- Contact the family immediately and evaluate the infant for poor feeding, lethargy, vomiting; perform serum electrolytes and 17-OHP.
- Provide emergency treatment/referral for symptoms of
vomiting or evidence of electrolyte imbalance.
- If the infant is ill, regardless of electrolyte results, admit to the hospital for further evaluation and fluid management.
- If the infant appears well and the electrolytes are abnormal, admit to the hospital for further observation and management.
- If the infant appears well and the electrolytes are normal, observe and await the 17-OHP results.
- To confirm the diagnosis, work with the following service(s): Newborn Screening Services (see NW providers [1]).
- Contact Pediatric Endocrinology as soon as possible for assistance with evaluation and ongoing collaborative management, including possible gender assignment issues: see
- Pediatric Endocrinology (see NW providers [1]).
If the Diagnosis is Confirmed
- See Endocrine Society Clinical Practice Guideline [Speiser: 2018].
- Immediate referral to a pediatric endocrinologist for initiation of treatment and further evaluation, which may include: urologic surgery consultation Educate the family regarding signs and symptoms of salt wasting and adrenal crisis.
- Initiate and support maintenance of glucocorticoid and mineralocorticoid replacement therapy as indicated.
- Electrolytes, hormone levels, and renin should be monitored.
Specialty Care Collaboration
Initial consultation and ongoing collaboration with the Endocrine Clinic for management and monitoring of replacement therapy, growth, and puberty. Pediatric urology may be involved for the virilized female, as well as psychology. Genetic counseling for the family should be considered.Resources
Information & Support
For Professionals
Congenital Adrenal Hyperplasia (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular
pathogenesis; from the University of Washington and the National Library of Medicine.
Congenital Adrenal Hyperplasia (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
For Parents and Patients
Facts about CAH (NIHCC) (
313 KB)
Patient education material from the National Institutes of Health Clinical Center
Congenital Adrenal Hyperplasia: A Guide for Families (PES) ( 138 KB)
Fact sheet for families from the Pediatric Endocrine Society
21-hydroxylase deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
Congenital Adrenal Hyperplasia Research, Education & Support (CARES) Foundation
Information for parents and providers with treatment suggestions, links to research and support groups, new about conferences,
and parent-to-parent tips.
Tools
ACT Sheet for Congenital Adrenal Hyperplasia (ACMG) ( 348 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Services for Patients & Families Nationwide (NW)
| Service Categories | # of providers* in: | NW | Partner states (6) (show) | | ID | MT | NM | NV | RI | UT | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Newborn Screening Services | 1 | 22 | 4 | 1 | 2 | 1 | 3 | ||||
| Pediatric Endocrinology | 1 | 2 | 14 | 1 | 6 | 13 | 3 | ||||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Studies
Congenital Adrenal Hyperplasia (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.
I-CAH Registry
The International Congenital Adrenal Hyperplasia Registry, funded by the United Kingdom Medical Research Council, was developed
to support research and improvement in clinical care of patients with congenital adrenal hyperplasia.
Page Bibliography
Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, Meyer-Bahlburg HFL, Miller WL, Murad MH, Oberfield SE, White
PC.
Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline.
J Clin Endocrinol Metab.
2018;103(11):4043-4088.
PubMed abstract / Full Text
Comprehensive guideline addressing aspects of CAH from newborn screening through long-term management.