Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Congenital adrenal hyperplasia

Last updated: August 19, 2021

Summarytoggle arrow icon

Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive defects in the enzymes that are responsible for cortisol, aldosterone, and, in very rare cases, androgen synthesis. All forms of CAH are characterized by low levels of cortisol, high levels of ACTH, and adrenal hyperplasia. The exact clinical manifestations depend on the enzyme defect. The most common form of CAH is caused by a deficiency of 21β-hydroxylase and manifests with hypotension, ambiguous genitalia, virilization (in the female genotype), and/or precocious puberty (in both males and females). All newborn infants in the US are screened for 21β-hydroxylase deficiency by measuring 17-hydroxyprogesterone in a blood sample obtained from a heel prick. CAH treatment involves lifelong glucocorticoid and fludrocortisone replacement therapy. Certain rare forms of CAH (e.g., 11β-hydroxylase and 17α-hydroxylase deficiencies) manifest with symptoms of mineralocorticoid excess (e.g., hypertension) and therefore require spironolactone (aldosterone receptor inhibitor) in addition to glucocorticoid replacement. Individuals with a virilizing form of CAH have an increased likelihood of experiencing gender dysphoria. Intersex medical interventions may be considered in cases of ambiguous genitalia. Complications of CAH include severe hypoglycemia, adrenal insufficiency, and failure to thrive.

A deficiency in both 17α-hydroxylase and 11β-hydroxylase tends to result in overproduction of mineralocorticoids like DOC and underproduction of aldosterone.“1 DOC:” If the deficient enzyme starts with 1 (11β-, 17‑), there is increased DOC.
“AND 1:” If the deficient enzyme ends with 1 (21-, 11β‑), androgens are increased.

References:[1][2][3][4][5]

Blood pressure XX (female) genotype XY (male) genotype

21β-hydroxylase

11β-hydroxylase

17α-hydroxylase

Infants with 21β-hydroxylase deficiency can present with shock within the first few weeks of life because of severe dehydration due to an adrenal crisis and salt-wasting due to hypoaldosteronism.

Different types of mutations on the CYP21A2 gene (which codes for 21β-hydroxylase) are associated with different levels of disease severity.

Classic CAH Nonclassic CAH
21β-hydroxylase deficiency
  • Severe
  • Mild
Detection by neonatal screening
  • Yes
  • No
Prevalence
  • Less common
  • More common
Onset of symptoms
  • Early onset (during the neonatal period or early infancy)
  • Late onset (manifests during late childhood, adolescence, or adulthood)
Clinical manifestations
Ethnic predisposition
  • Inuit and Alaska native populations

Individuals with a virilizing form of CAH have an increased likelihood of experiencing gender dysphoria.

References:[3][4][5][6][7][8][9][10]

The differential diagnoses listed here are not exhaustive.

Laboratory findings Adrenal enzyme deficiencies
21β-hydroxylase 11β-hydroxylase 17α-hydroxylase
17-Hydroxyprogesterone
  • ↑↑
11-Deoxycorticosterone (DOC)
  • ↑↑
Corticosterone
  • ↑↑
Sodium
Potassium
Acid-base disorders

All newborns in the US are screened for CAH by measuring changes in 17-hydroxyprogesterone levels from a heel prick blood sample.References:[2][9][11][12]

The dose of glucocorticoids must be increased during severe infection, critical illness, and perioperatively to meet increased demands to prevent adrenal crisis.

References:[4][7][9][13]

  1. Becker KL, Bilezikian JP, Bremner WJ, et al . Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins ; 2001
  2. Auchus RJ, Arlt W. Uncommon Congenital Adrenal Hyperplasias. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/uncommon-congenital-adrenal-hyperplasias.Last updated: May 5, 2017. Accessed: May 10, 2017.
  3. Merke DP. Genetics and Clinical Presentation of Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/genetics-and-clinical-presentation-of-classic-congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency.Last updated: March 18, 2015. Accessed: May 10, 2017.
  4. Wilson TA. Congenital Adrenal Hyperplasia. In: Bowden SA, Congenital Adrenal Hyperplasia. New York, NY: WebMD. http://emedicine.medscape.com/article/919218. Updated: February 17, 2017. Accessed: May 10, 2017.
  5. Frindik JP. 17-Hydroxylase Deficiency Syndrome. In: Kemp S, 17-Hydroxylase Deficiency Syndrome. New York, NY: WebMD. http://emedicine.medscape.com/article/920532. Updated: December 18, 2015. Accessed: May 10, 2017.
  6. Kliegman R, Stanton B, St. Geme J, Schor N. Nelson Textbook of Pediatrics. Elsevier ; 2015
  7. Uwaifo GI. C-11 Hydroxylase Deficiency. In: Griffing GT, C-11 Hydroxylase Deficiency. New York, NY: WebMD. http://emedicine.medscape.com/article/117012. Updated: January 10, 2017. Accessed: May 10, 2017.
  8. Nieman LK. Genetics and Clinical Presentation of Nonclassic (Late-Onset) Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/genetics-and-clinical-presentation-of-nonclassic-late-onset-congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency.Last updated: August 5, 2016. Accessed: May 10, 2017.
  9. Uwaifo GI. C-17 Hydroxylase Deficiency. C-17 Hydroxylase Deficiency. New York, NY: WebMD. http://emedicine.medscape.com/article/117140-overview. Updated: December 16, 2014. Accessed: May 10, 2017.
  10. Dessens AB et al.. Gender Dysphoria and Gender Change in Chromosomal Females with Congenital Adrenal Hyperplasia. Arch Sex Behav. 2005; 34 (4): p.389-397. doi: 10.1007/s10508-005-4338-5 . | Open in Read by QxMD
  11. Fischer C. Master the Boards USMLE Step 3. Kaplan Publishing ; 2015
  12. Nieman LK, Merke DP. Diagnosis and Treatment of Nonclassic (Late-Onset) Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diagnosis-and-treatment-of-nonclassic-late-onset-congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency.Last updated: November 7, 2017. Accessed: November 27, 2017.
  13. Padidela R, Hindmarsh PC. Mineralocorticoid deficiency and treatment in congenital adrenal hyperplasia. J Pediatr Endocrinol. 2010; 2010 . doi: 10.1155/2010/656925 . | Open in Read by QxMD