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Congenital Adrenal Hyperplasia
Test Guide

The diagnostic algorithms presented herein are intended to help the clinician select appropriate laboratory tests when congenital adrenal hyperplasia (CAH) is suspected. The work-up is complex owing to the various enzymatic defects (Figure 1) and clinical presentations and must include the patient’s family history as well as clinical and laboratory findings. Protocols for the work-up vary with treatment centers. The testing options presented in this test guide are based on accepted diagnostic standards1-10 and have been reviewed by Medical Directors at Quest Diagnostics Nichols Institute.
Figure 1. Pathways of Adrenal Steroid Synthesis
Figure 2. Test Algorithm for Abnormal Newborn Screen with
No CAH Symptoms
Figure 3. Test Algorithm for Individuals with CAH Symptoms

Table. CAH Panelsa and Genetic Assays

Test Code

Test Name

Analytes

15269X

CAH Panel 1 (21-Hydroxylase vs 11Beta-Hydroxylase Deficiency)

17-OH-progesterone, LC/MS/MS

11-deoxycortisol, LC/MS/MS

17-OH progesterone/11-deoxycortisol ratio

Total cortisol

11-deoxycortisol/cortisol ratio

Androstenedione, LC/MS/MS

Total testosterone, LC/MS/MS

15273X

CAH Panel 3 (Aldosterone Synthase Deficiency)

17-OH progesterone, LC/MS/MS

11-deoxycortisol, LC/MS/MS

17-OH progesterone/11-deoxycortisol ratio

18-OH corticosterone

Serum aldosterone, LC/MS/MS

18-OH corticosterone/aldosterone ratio

15274X

CAH Panel 4 (17-OH Deficiency in Females)

Progesterone, LC/MS/MS

17-OH progesterone, LC/MS/MS

Progesterone/17-OH progesterone ratio

Corticosterone, LC/MS/MS

Total cortisol

Serum aldosterone

Estradiol, LC/MS/MS

15276X

 CAH Panel 6 (StAR Deficiency)

Pregnenolone

DHEA

Cortisol

Aldosterone

10299X

CAH Panel 6b (Comprehensive Screen)

Androstenedione, LC/MS/MS

11-deoxycortisol, LC/MS/MS

Total cortisol

DHEA

Deoxycorticosterone

17-OH pregnenolone

Progesterone, LC/MS/MS

17-OH progesterone, LC/MS/MS

Total testosterone, LC/MS/MS

15277X

CAH Panel 7 (21-Hydroxylase Deficiency Therapeutic Monitoring)

Androstenedione, LC/MS/MS

Total testosterone, LC/MS/MS

17-OH progesterone, LC/MS/MS

15279X

CAH Panel 8 (17-Hydroxylase Deficiency in
Males)

Progesterone

17-OH progesterone, LC/MS/MS

Progesterone/17-OH progesterone ratio

Corticosterone, LC/MS/MS

Total cortisol

Aldosterone

Total testosterone, LC/MS/MS

15280X

CAH Panel 9 (3-Beta-Hydroxysteroid Dehydrogenase Deficiency )

17-OH pregnenolone

17-OH progesterone, LC/MS/MS

17-OH pregnenolone/17-OH progesterone

ratio

DHEA, LC/MS/MS

Androstenedione, LC/MS/MS

DHEA/androstenedione ratio

Total cortisol

10046X

CAH Panel 11 (Neonatal Random Urine)

34 steroid analytes and 11 ratios

14755Xb,c

CAH (21-Hydroxylase Deficiency) Common
Mutations

P30L, In2G, G110del8, I172N, exon 6 cluster mutation (1236N, V237E, M239K), V281L, F306+1nt, Q318X, R356W, and P453S mutations; the observed patterns can be used to deduce deletions and recombination events between CYP21A2 and its pseudogene

16072Xb,d

CAH (21-Hydroxylase Deficiency) Rare Mutations

Complete sequencing of the CYP21A2 gene

StAR, steroid acute regulatory protein; DHEA, dihydroepiandrostenedione.
a Panel components may be ordered individually; also available: Plasma Renin Activity (10537X).
b This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.
c This test is performed pursuant to a license agreement with Roche Molecular Systems, Inc, and Orchid Biosciences, Inc.
d This test is performed pursuant to a license agreement with Roche Molecular Systems, Inc.

References

  1. Orth DN, Kovacs WJ. The adrenal cortex. In: Wilson, Foster, Kronenberg, et al. eds. Williams Textbook of Endocrinology. 9th ed. Philadephia, PA: W.B. Saunders Company; 1998:598-607.

  2. Wajnrajch MP, New MI. Defects of adrenal steroidogenesis. In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia, PA: W.B. Saunders Company; 2001:1721-1739.

  3. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349:776-788.

  4. Speiser PW. Prenatal treatment of congenital adrenal hyperplasia. J Urol. 1999;162:534-5536.

  5. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21:245-291.

  6. White PC, Curnow KM, Pascoe L. Disorders of steroid 11β-hydroxlase isozymes. Endocr Rev. 1994;15:421-438.

  7. Santos M, Kater CE, Auchus RJ, et al. Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency. J Clin Endocrinol Metab. 2004;89:49-60.

  8. Arlt W, Walker EA, Draper N, et al. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet. 2004;363:2128-2135.

  9. Fukami M, Horikawa R, Nagai T, et al. Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. J Clin Endocrinol Metab. 2005;90:414-423.

  10. Caulfield MP, Lynn TL, Gottschalk ME, et al. The diagnosis of congenital adrenal hyperplasia in the newborn by gas chromatography/mass spectrometry analysis of random urine specimens. J Clin Endocrinol Metab. 2002;87:3682-3690.
     
     

Content reviewed 11/2009
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