Congenital Adrenal Hyperplasia - CAH

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

Laboratory Testing

  • Initial test – 17-hydroxyprogesterone (17-OHP)
    • If elevated, perform ACTH stimulation (cosyntropin); however, this is often unnecessary when there is marked elevation of 17-OHP
      • 17-OHP remains elevated after stimulation in classic CAH
    • If nonclassic form is suspected in adult female, obtain 17-OHP at 0800 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
  • Infants – karyotype 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
  • Adrenal steroid quantitative panel if ACTH stimulation is abnormal or if a marked elevation of 17-OHP is noted
    • 21-hydroxylase deficiency
      • Markedly elevated plasma 17-OHP
    • 11-beta-hydroxylase deficiency
      • Elevated 11-deoxycorticosterone and 11-deoxycortisol levels
    • 17-hydroxylase (17-OH) deficiency
      • Elevated pregnenolone, 11-deoxycorticosterone, corticosterone
      • Decreased 17-hydroxypregnenolone (17-OH-pregnenolone)
    • 3 beta-HSD deficiency
      • Elevated pregnenolone, 17-OH pregnenolone, DHEA and DHEAS

Differential Diagnosis

  • 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 (tend to have elevated 17-OHP)
      • Markedly elevated 17-OHP – disease confirmed
        • Follow up positive results with ACTH stimulation in all infants
    • False negative may occur if maternal glucocorticoids are administered
  • Prenatal diagnosis – via chorionic villus sampling or amniocentesis, 90-95% sensitive
    • Allows for prenatal treatment of disease through administration of maternal glucocorticoid
  • For assessment of glucocorticoid replacement
    • 17-OHP, androstenedione and testosterone
      • Every 3 months during infancy and every 3-6 months thereafter
  • For assessment of mineralocorticoid replacement
    • Blood pressure measurement
    • Plasma renin/renin activity
    • Aldosterone and potassium levels may also be helpful

Congenital adrenal hyperplasia (CAH) is an uncommon group of autosomal recessive disorders caused by several distinct enzymatic defects, usually with subsequent virilization.


  • Incidence
    • Most common adrenal disorder of infancy and childhood (1/3,000-5,000)
    • 1/10,000-20,000 (Endocrine Society, 2010)
  • Sex – M>F
  • Ethnicity
    • Ashkenazi Jews
      • 1-2% affected with nonclassical forms (11-beta-hydroxylase, late onset 21-hydroxylase deficiency)
    • Remote geographic location populations (eg, Alaskan Yupiks, French island of LaRéunion)

Risk Factors

  • Genetic
    • Autosomal recessive inheritance
    • Enzymatic defects include the following
      • 21-hydroxylase (CYP21A2 mutation) – most common defect (>90%)
      • 11-beta-hydroxylase (CYP11B1 mutation)
      • CYP17A1 deficiencies (CYP17A1 mutation)
      • 17,20-lyase deficiencies
      • 3 beta-hydroxysteroid dehydrogenase (HSD3B2 mutation)
      • Cytochrome P450 oxidoreductase deficiency
      • Hexose-6-phosphate dehydrogenase deficiency (H6PD mutation)
      • PAPSS2 deficiency (PAPSS2 mutation)
      • Congenital lipoid adrenal hyperplasia (StAR mutations)
      • P450scc side chain cleavage enzyme deficiency (CYP11A1 mutation)


  • Mutations cause a block in adrenal glucocorticoid and mineralocorticoid synthesis pathways
  • 21-hydroxylase deficiency
    • Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol
    • Blocked steroid synthesis causes adrenal insufficiency and compensatory elevation of adrenocorticotropic hormone (ACTH)
    • ACTH elevation causes adrenal hyperplasia and additional precursor synthesis
    • Precursor excess is shunted into the androgen synthesis pathway, causing virilization in females, premature sexual development in males, and adrenal insufficiency
  • 11-beta-hydroxylase deficiency
    • Impaired conversion of 11-deoxycortisol to cortisol
    • Accumulation of 11-deoxycorticosterone (a potent mineralocorticoid) leads to mineralocorticoid excess with possible hypertension
  • 17-alpha-hydroxylase/17,20-lyase deficiency
    • Usually combined deficiency
    • Decreased cortisol production and shunting of precursors into mineralocorticoid pathways
    • Minimal testosterone or estrogen produced
  • 3-beta-hydroxysteroid dehydrogenase deficiency
  • Synthesis of all active steroid hormones is impaired

Clinical Presentation

  • 21-hydroxylase deficiency
  • 11-beta-hydroxylase deficiency
    • Hypertension, hypokalemia, and premature sexual development in males, ambiguous genitalia in females
  • 17-alpha-hydroxylase deficiency
    • Hypertension, hypokalemia, hypogonadism, lack of secondary sexual characteristics in females and males
    • Isolated 17,20-lyase deficiency – males with under virilization, females with delayed pubarche
  • 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency
    • Feminized males, partial virilization of females
    • Cortisol and aldosterone deficiency signs and symptoms – feeding difficulty, vomiting, hyponatremia, hyperkalimia
  • P450
    • Oxidoreductase deficiency
    • Severe virilization in females, severe under virilization in males
    • No mineralocorticoid deficiency
    • Craniofacial abnormalities
  • P450scc
    • May be lethal due to potential insufficiency
    • Defective synthesis of all adrenal hormones
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Congenital Adrenal Hyperplasia Panel, 21-Hydroxylase Deficiency 2002283
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Congenital Adrenal Hyperplasia Panel, 11-Beta Hydroxylase Deficiency 2002282
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Congenital Adrenal Hyperplasia Treatment Panel 2002029
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Adrenal Steroid Quantitative Panel by HPLC-MS/MS, Serum or Plasma 0092330
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry


Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC, Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95(9): 4133-60. PubMed

General References

Antal Z, Zhou P. Congenital adrenal hyperplasia: diagnosis, evaluation, and management. Pediatr Rev. 2009; 30(7): e49-57. PubMed

Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009; 23(2): 181-92. PubMed

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. PubMed

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. PubMed

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): 405-13. PubMed

Trakakis E, Basios G, Trompoukis P, Labos G, Grammatikakis I, Kassanos D. An update to 21-hydroxylase deficient congenital adrenal hyperplasia. Gynecol Endocrinol. 2010; 26(1): 63-71. PubMed

Witchel SF. Nonclassic congenital adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes. 2012; 19(3): 151-8. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Kushnir MM, Neilson R, Roberts WL, Rockwood AL. Cortisol and cortisone analysis in serum and plasma by atmospheric pressure photoionization tandem mass spectrometry. Clin Biochem. 2004; 37(5): 357-62. PubMed

Kushnir MM, Rockwood AL, Roberts WL, Pattison EG, Owen WE, Bunker AM, Meikle W. Development and performance evaluation of a tandem mass spectrometry assay for 4 adrenal steroids. Clin Chem. 2006; 52(8): 1559-67. PubMed

Mao R, McDonald J, Cantwell M, Tang W, Ward K. The implication of de novo 21-hydroxylase mutation in clinical and prenatal molecular diagnoses. Genet Test. 2005; 9(2): 121-5. PubMed

Rogers MA, Liu J, Kushnir MM, Bryleva E, Rockwood AL, Meikle W, Shapiro D, Vaisman BL, Remaley AT, C Y Chang C, Chang T. Cellular pregnenolone esterification by acyl-CoA:cholesterol acyltransferase. J Biol Chem. 2012; 287(21): 17483-92. PubMed

Schwarz E, Liu A, Randall H, Haslip C, Keune F, Murray M, Longo N, Pasquali M. Use of steroid profiling by UPLC-MS/MS as a second tier test in newborn screening for congenital adrenal hyperplasia: the Utah experience. Pediatr Res. 2009; 66(2): 230-5. PubMed

Medical Reviewers

Last Update: August 2016