Advertisement

Journal of Inherited Metabolic Disease

, Volume 30, Issue 4, pp 563–575 | Cite as

Congenital adrenal hyperplasia: Diagnostic advances

  • T. Torresani
  • Anna Biason-Lauber
Newborn Screening

Summary

Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90% of cases. Much has been learned about the genetics of the various clinical forms of 21-hydroxylase deficiency, and correlations between the genotype and the phenotype have been studied extensively. Gene-specific diagnosis is now feasible and neonatal screening and prenatal treatment have been widely implemented. This discussion will be limited to the most common form of congenital adrenal hyperplasia, with focus on the diagnostic advances in this disease.

Keywords

Congenital Adrenal Hyperplasia Newborn Screening Neonatal Screening Androgen Excess Ligase Detection Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Balsamo A, Cacciari E, Piazzi S, et al (1996) Congenital adrenal hyperplasia: neonatal mass screening compared with clinical diagnosis only in the Emilia-Romagna region of Italy 1980–1995. Pediatrics 98: 362–367.PubMedGoogle Scholar
  2. Barnes RB, Rosenfield RL, Ehrmann DA, et al (1994) Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J Clin Endocrinol Metab 79: 1328–1333.PubMedCrossRefGoogle Scholar
  3. Cabrera MS, Vogiatzi MG, New MI (2001) Long term outcome in adult males with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab 86: 3070–3078.PubMedCrossRefGoogle Scholar
  4. Day DJ, Speiser PW, White PC, Barany F (1995) Detection of steroid 21-hydroxylase alleles using gene-specific PCR and a multiplexed ligation detection reaction. Genomics 29: 152-162.Google Scholar
  5. Deneux C, Tardy V, Dib A, et al (2001) Phenotype–genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 86: 207–213.PubMedCrossRefGoogle Scholar
  6. Fitness J, Dixit N, Webster D, et al (1999) Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 84: 960–966.PubMedCrossRefGoogle Scholar
  7. Hingre RV, Gross SJ, Hingre KS, Mayes DM, Richman RA (1994) Adrenal steroidogenesis in very low birth weight preterm infants. J Clin Endocrinol Metab 78: 266–270.PubMedCrossRefGoogle Scholar
  8. Honour JW, Torresani T (2001) Evaluation of neonatal screening for congenital adrenal hyperplasia. Horm Res 55: 206–211.PubMedCrossRefGoogle Scholar
  9. Hughes IA (1998) Congenital adrenal hyperplasia—a continuum of disorders. Lancet 352: 752–754.PubMedCrossRefGoogle Scholar
  10. Janzen N, Peter M, Sander S, et al (2007) Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 92: 2581–2589.Google Scholar
  11. Knochenhauer ES, Cortet-Rudelli C, Cunnigham RD, Conway-Myers BA, Dewailly D, Azziz R (1997) Carriers of 21-hydroxylase deficiency are not at increased risk for hyperandrogenism. J Clin Endocrinol Metab 82: 479–485.PubMedCrossRefGoogle Scholar
  12. Krone N, Braun A, Weinert S, et al (2002) Multiplex minisequencing of the 21-hydroxylase gene as a rapid strategy to confirm congenital adrenal hyperplasia. Clinical Chemistry 48: 818–825.Google Scholar
  13. Lamberts SW, Bruining HA, de Jong FH (1997) Corticosteroid therapy in severe illness. N Engl J Med 337: 1285–1292.PubMedCrossRefGoogle Scholar
  14. Lo JC, Grumbach MM (2001) Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia. Endocrinol Metab Clin North Am 30: 207–329.PubMedGoogle Scholar
  15. Merke DP, Chrousos GP, Eisenhofer G, et al (2000) Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency. N Engl J Med 343: 1362–1368.PubMedCrossRefGoogle Scholar
  16. Miller WL (1994) Clinical review 54: Genetics, diagnosis, and management of 21-hydroxylase deficiency. J Clin Endocrinol Metab 78: 241–246.PubMedCrossRefGoogle Scholar
  17. Miller WL, Levine LS (1987) Molecular and clinical advances in congenital adrenal hyperplasia. J Pediatr 111: 1–17.PubMedCrossRefGoogle Scholar
  18. Minutti C, Lacey J, Magera M, et al (2004) Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 89: 3687–3693.PubMedCrossRefGoogle Scholar
  19. Moran C, Azziz R, Carmina E, et al (2000) 21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol 183: 1468–1474.PubMedCrossRefGoogle Scholar
  20. Mulaikal RM, Migeon CJ, Rock JA (1987) Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N Engl J Med 316: 178–182.PubMedCrossRefGoogle Scholar
  21. Murphy H, George C, de Kretser D, Judd S (2001) Successful treatment with ICSI of infertility caused by azoospermia associated with adrenal rests in the testes: case report. Hum Reprod 16: 263–267.PubMedCrossRefGoogle Scholar
  22. Nordenstrom A, Forest MG, Wedell A (2007) A case of 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) deficiency picked up by neonatal screening for 21-hydroxylase deficiency: difficulties and delay in etiologic diagnosis. Horm Res 68: 204–208.PubMedCrossRefGoogle Scholar
  23. Oelkers W (1996) Adrenal insufficiency. N Engl J Med 335: 1206–1212.PubMedCrossRefGoogle Scholar
  24. Pang S, Hotchkiss J, Drash AL, Levine LS, New MI (1977) Microfilter paper method for 17 alpha-hydroxyprogesterone radioimmunoassay: its application for rapid screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 45: 1003–1008.PubMedGoogle Scholar
  25. Premawardhana LD, Hughes IA, Read GF, Scanlon MF (1997) Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience. Clin Endocrinol (Oxf) 46: 327–332.CrossRefGoogle Scholar
  26. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30: e57.PubMedCrossRefGoogle Scholar
  27. Speiser PW, White PC (2003) Congenital adrenal hyperplasia. N Engl J Med 349: 776–788.PubMedCrossRefGoogle Scholar
  28. Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI (1985) High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet 37: 650–667.PubMedGoogle Scholar
  29. Speiser PW, Dupont J, Zhu D, et al (1992) Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest 90: 584–595.PubMedCrossRefGoogle Scholar
  30. Steigert M, Schoenle EJ, Biason-Lauber A, Torresani T (2002) High reliability of neonatal screening for congenital adrenal hyperplasia in Switzerland. J Clin Endocrinol Metab 87: 4106–4110.PubMedCrossRefGoogle Scholar
  31. Stikkelbroeck NM, Otten BJ, Pasic A, et al (2001) High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and Leydig cell failure in adolescent and adult males with congenital adrenal hyperplasia. J Clin Endocrinol Metab 86: 5721–5728.PubMedCrossRefGoogle Scholar
  32. Tajima T, Fujieda K, Nakae J, et al (1997) Molecular basis of nonclassical steroid 21-hydroxylase deficiency detected by neonatal mass screening in Japan. J Clin Endocrinol Metab 82: 2350–2356.PubMedCrossRefGoogle Scholar
  33. Therrell BL (2001) Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 30: 15–30.PubMedCrossRefGoogle Scholar
  34. Therrell BL Jr, Berenbaum SA, Manter-Kapanke V, et al (1998) Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics 101: 583–590.PubMedCrossRefGoogle Scholar
  35. Torresani T, Gruters A, Scherz R, Burckhardt JJ, Harras A, Zachmann M (1994) Improving the efficacy of newborn screening for congenital adrenal hyperplasia by adjusting the cut-off level of 17α-hydroxyprogesterone to gestational age. Screening 3: 77–84.Google Scholar
  36. Urban MD, Lee PA, Migeon CJ (1978) Adult height and fertility in men with congenital virilizing adrenal hyperplasia. N Engl J Med 299: 1392–1396.PubMedCrossRefGoogle Scholar
  37. van der Kamp H, Oudshoorn C, Elvers B, et al (2005) Cutoff levels of 17α-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight. J Clin Endocrinol Metab 90: 3904–3907.Google Scholar
  38. Walker BR, Skoog SJ, Winslow BH, Canning DA, Tank ES (1997) Testis sparing surgery for steroid unresponsive testicular tumors of the adrenogenital syndrome. J Urol 157: 1460–1463.PubMedCrossRefGoogle Scholar
  39. White PC, Speiser PW (2000) Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 21: 245–291.PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  1. 1.ZurichSwitzerland
  2. 2.Department of Endocrinology and DiabetologyUniversity Children’s HospitalsZurichSwitzerland

Personalised recommendations