Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency

INTRODUCTION

Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol accounts for more than 90 percent of cases of congenital adrenal hyperplasia [1-3]. This conversion is mediated by 21-hydroxylase, or in current terminology, CYP21A2.

The most severely affected individuals with classic congenital adrenal hyperplasia due to CYP21A2 deficiency present during the neonatal period and early infancy with adrenal insufficiency with or without salt wasting, or later, with virilization. Females have genital ambiguity.

"Nonclassic," or late-onset CYP21A2 deficiency, does not manifest with neonatal genital ambiguity; rather, it presents later in life with signs of androgen excess. Clinical features in late childhood include premature pubarche, acne, and accelerated bone age; adolescent and adult females present with acne, hirsutism, and menstrual irregularity [4-10].

The diagnosis and treatment of late-onset congenital adrenal hyperplasia due to CYP21A2 deficiency are reviewed here. The genetics and clinical manifestations of the nonclassic form of CYP21A2 deficiency, and the classic form of CYP21A2 deficiency are reviewed separately. (See "Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults".)

DIAGNOSIS

Classic CYP21A2 deficiency — The characteristic biochemical abnormality in patients with CYP21A2 deficiency is a high serum concentration of 17-hydroxyprogesterone, the normal substrate for CYP21A2. Most affected neonates (with the classic form) have concentrations greater than 3500 ng/dL (105 nmol/L) [1], with most exceeding 10,000 ng/dL (300 nmol/L), whereas the levels in normal newborns are below 100 ng/dL (3 nmol/L) [2]. Patients with this disorder also have an exaggerated serum 17-hydroxyprogesterone response to ACTH stimulation with values more than 10,000 ng/dL (300 nmol/L), providing good diagnostic separation from patients with nonclassic CYP21A2 deficiency [3,4].

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Jan 31, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Witchel SF, Nayak S, Suda-Hartman M, Lee PA. Newborn screening for 21-hydroxylase deficiency: results of CYP21 molecular genetic analysis. J Pediatr 1997; 131:328.
  2. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003; 349:776.
  3. White PC, New MI, Dupont B. Congenital adrenal hyperplasia. (1). N Engl J Med 1987; 316:1519.
  4. New MI, Lorenzen F, Lerner AJ, et al. Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol Metab 1983; 57:320.
  5. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000; 21:245.
  6. Azziz R, Dewailly D, Owerbach D. Clinical review 56: Nonclassic adrenal hyperplasia: current concepts. J Clin Endocrinol Metab 1994; 78:810.
  7. Gutai JP, Kowarski AA, Migeon CJ. The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia. J Pediatr 1977; 90:924.
  8. Fiet J, Gueux B, Gourmelen M, et al. Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia. J Clin Endocrinol Metab 1988; 66:659.
  9. Bachega TA, Brenlha EM, Billerbeck AE, et al. Variable ACTH-stimulated 17-hydroxyprogesterone values in 21-hydroxylase deficiency carriers are not related to the different CYP21 gene mutations. J Clin Endocrinol Metab 2002; 87:786.
  10. Admoni O, Israel S, Lavi I, et al. Hyperandrogenism in carriers of CYP21 mutations: the role of genotype. Clin Endocrinol (Oxf) 2006; 64:645.
  11. Bidet M, Bellanné-Chantelot C, Galand-Portier MB, et al. Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members. J Clin Endocrinol Metab 2009; 94:1570.
  12. Dolzan V, Prezelj J, Vidan-Jeras B, Breskvar K. Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status. Eur J Endocrinol 1999; 141:132.
  13. Glintborg D, Hermann AP, Brusgaard K, et al. Significantly higher adrenocorticotropin-stimulated cortisol and 17-hydroxyprogesterone levels in 337 consecutive, premenopausal, caucasian, hirsute patients compared with healthy controls. J Clin Endocrinol Metab 2005; 90:1347.
  14. Knochenhauer ES, Cortet-Rudelli C, Cunnigham RD, et al. Carriers of 21-hydroxylase deficiency are not at increased risk for hyperandrogenism. J Clin Endocrinol Metab 1997; 82:479.
  15. Moran C, Azziz R, Weintrob N, et al. Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia. J Clin Endocrinol Metab 2006; 91:3451.
  16. Joint LWPES/ESPE CAH Working Group.. Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. J Clin Endocrinol Metab 2002; 87:4048.
  17. Spritzer P, Billaud L, Thalabard JC, et al. Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia. J Clin Endocrinol Metab 1990; 70:642.
  18. Fern M, Rose DP, Fern EB. Effect of oral contraceptives on plasma androgenic steroids and their precursors. Obstet Gynecol 1978; 51:541.
  19. Wiebe RH, Morris CV. Effect of an oral contraceptive on adrenal and ovarian androgenic steroids. Obstet Gynecol 1984; 63:12.
  20. Wild RA, Umstot ES, Andersen RN, Givens JR. Adrenal function in hirsutism. II. Effect of an oral contraceptive. J Clin Endocrinol Metab 1982; 54:676.
  21. Carr BR, Parker CR Jr, Madden JD, et al. Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment. J Clin Endocrinol Metab 1979; 49:346.
  22. Birnbaum MD, Rose LI. The partial adrenocortical hydroxylase deficiency syndrome in infertile women. Fertil Steril 1979; 32:536.
  23. Lo JC, Grumbach MM. Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia. Endocrinol Metab Clin North Am 2001; 30:207.
  24. Bonaccorsi AC, Adler I, Figueiredo JG. Male infertility due to congenital adrenal hyperplasia: testicular biopsy findings, hormonal evaluation, and therapeutic results in three patients. Fertil Steril 1987; 47:664.
  25. Cutfield RG, Bateman JM, Odell WD. Infertility caused by bilateral testicular masses secondary to congenital adrenal hyperplasia (21-hydroxylase deficiency). Fertil Steril 1983; 40:809.
  26. Cunnah D, Perry L, Dacie JA, et al. Bilateral testicular tumours in congenital adrenal hyperplasia: a continuing diagnostic and therapeutic dilemma. Clin Endocrinol (Oxf) 1989; 30:141.
  27. Claahsen-van der Grinten HL, Otten BJ, Takahashi S, et al. Testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia: evaluation of pituitary-gonadal function before and after successful testis-sparing surgery in eight patients. J Clin Endocrinol Metab 2007; 92:612.
  28. Horrocks PM, London DR. Effects of long term dexamethasone treatment in adult patients with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 1987; 27:635.
  29. Speiser PW. Nonclassic adrenal hyperplasia. Rev Endocr Metab Disord 2009; 10:77.