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FeedbackCongenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by several distinct enzymatic defects that result in changes in steroidogenesis. These disruptions cause irregular genital and sexual characteristics, and interfere with electrolyte balance. Newborn screening detects elevations in 17-hydroxyprogesterone (17-OHP). Other forms of CAH without significant 17-OHP increases are often not identified until later in life due to their more subtle clinical presentations. Initial testing generally involves 17-OHP testing and, if 17-OHP is increased, adrenocorticotropic hormone (ACTH) testing.
Diagnosis
Indications for Testing
- Ambiguous genitalia or unexplainable electrolyte results in infancy
- Premature sexual development in older children
- Hirsutism and irregular menses in adult females
Laboratory Testing
- Initial testing
- 17-OHP
- If elevated, perform ACTH stimulation (cosyntropin)
- Often unnecessary when there is marked elevation of 17-OHP
- 17-OHP remains increased after stimulation in classic CAH
- If nonclassic form is suspected in adult female, obtain 17-OHP at 0800 hours and during follicular phase of menstrual cycle
- Further evaluation should include assessment of salt wasting
- Serum sodium, potassium, and renin activity: expect hyponatremia, hyperkalemia, and increased renin in classic 21-hydroxylase deficiency CAH
- If elevated, perform ACTH stimulation (cosyntropin)
- 17-OHP
- Secondary testing
- Adrenal steroid quantitative panel: if ACTH stimulation is abnormal or if a marked elevation of 17-OHP is noted
- 21-hydroxylase deficiency
- Characterized by markedly elevated plasma 17-OHP
- 11-beta-hydroxylase deficiency
- Indicated by increased 11-deoxycorticosterone and 11-deoxycortisol levels
- 17-hydroxylase (17-OH) deficiency
- Characterized by increased pregnenolone, 11-deoxycorticosterone, and corticosterone, and decreased 17-hydroxypregnenolone (17-OH-pregnenolone)
- 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency
- Indicated by increased pregnenolone, 17-OH pregnenolone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS)
- 21-hydroxylase deficiency
- Adrenal steroid quantitative panel: if ACTH stimulation is abnormal or if a marked elevation of 17-OHP is noted
- Testing in infants
- Karyotyping to rule out chromosomal disorder
- Pelvic ultrasonography to assess internal genital organs in females
- Assess glucose, electrolytes, liver function, and blood gases in infants suspected of acute adrenal insufficiency
Screening
- Newborn screening for CAH in most states: 17-OHP
- Threshold for positive tests is set relatively low to prevent missing true positives
- False positives common in premature infants, who tend to have increased 17-OHP
- Markedly increased 17-OHP confirms disease
- Follow up positive results with ACTH stimulation in all infants
- Markedly increased 17-OHP confirms disease
- False negative may occur if maternal glucocorticoids are administered
- Prenatal diagnosis
- Chorionic villus sampling or amniocentesis, 90-95% sensitive
- Allows for prenatal treatment of disease through administration of maternal glucocorticoid
Monitoring
- For assessment of glucocorticoid replacement
- 17-OHP, androstenedione, and testosterone
- Every 3 months during infancy and every 3-6 months thereafter
- 17-OHP, androstenedione, and testosterone
- For assessment of mineralocorticoid replacement
- Blood pressure measurement
- Plasma renin/renin activity
- Aldosterone and potassium levels may also be helpful
ARUP Laboratory Tests
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Components include androstenedione; 17-OHP; testosterone; 11-deoxycortisol, quantitative by LC/MS-MS; and dehydroepiandrosterone
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Components include 11-deoxycortisol, quantitative; 17-OHP, quantitative by MS/MS; 17-hydroxypregnenolone, quantitative by MS/MS; and pregnenolone by MS/MS
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Components include androstenedione; 17-OHP, quantitative by LC-MS/MS; and testosterone, females or children
Quantitative Enzymatic Assay
Quantitative Ion-Selective Electrode/Enzymatic Assay
Quantitative Enzyme-Linked Immunosorbent Assay
Quantitative Enzymatic Assay/Quantitative Spectrophotometry
Panel includes albumin; alkaline phosphatase; aspartate aminotransferase; alanine aminotransferase; bilirubin, direct; protein, total; and bilirubin, total
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
References
19570920
Antal Z, Zhou P. Congenital adrenal hyperplasia: diagnosis, evaluation, and management. Pediatr Rev. 2009;30(7):e49-57.
19500762
Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009;23(2):181-192.
20569798
Lambert SM, Vilain EJ, Kolon TF. A practical approach to ambiguous genitalia in the newborn period. Urol Clin North Am. 2010;37(2):195-205.
20392211
Nimkarn S, New MI. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A paradigm for prenatal diagnosis and treatment. Ann N Y Acad Sci. 2010;1192:5-11.
17452967
Nimkarn S, New MI. Prenatal diagnosis and treatment of congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Nat Clin Pract Endocrinol Metab. 2007;3(5):405-413.
20823466
Speiser PW, Azziz R, Baskin LS , et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(9):4133-4160.
19499408
Trakakis E, Basios G, Trompoukis P , et al. An update to 21-hydroxylase deficient congenital adrenal hyperplasia. Gynecol Endocrinol. 2010;26(1):63-71.
28450075
Witchel SF. Congenital adrenal hyperplasia. J Pediatr Adolesc Gynecol. 2017;30(5):520-534.
22499220
Witchel SF. Nonclassic congenital adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes. 2012;19(3):151-158.
Medical Experts
Straseski
Components include androstenedione; 17-OHP; 17-hydroxypregnenolone, quantitative by LC-MS/MS; and dehydroepiandrosterone