eMedicine Specialties > Endocrinology > Adrenal Gland

C-11 Hydroxylase Deficiency: Follow-up

Author: Gabriel I Uwaifo, MBBS, Clinical and Research Attending, Assistant Professor of Medicine and Endocrinology, MedStar Clinical Research Center, MedStar Research Institute and Washington Hospital Center
Contributor Information and Disclosures

Updated: Dec 30, 2008

Follow-up

Complications

  • Complications result from inadequate or excess glucocorticoid therapy.
  • Inadequate glucocorticoid therapy in patients with 11-beta-hydroxylase deficiency could result in exacerbation of the symptomatology associated with the disease, including virilization in females, hyperpigmentation, and accelerated growth in early childhood (with consequent early epiphysial fusion and, thus, short adult stature).

    • For males, inadequate treatment could encourage the growth of adrenal rest tumors that, when present in the testicles, are known to be associated with oligospermia and consequently infertility.
    • The problems of virilization and precocious puberty associated with poorly treated cases also result in myriad adjustment, self-image, identity, and mood disorders that often require long-term treatment and counseling by mental health professionals.
    • Patients with a poorly controlled condition may also have poorly controlled hypertension and the well-known cardiovascular sequelae.
  • Excessive glucocorticoid therapy is also associated with a litany of potential medical problems, as typified in patients with Cushing syndrome. Among the major conditions that must be carefully looked for are truncal obesity, poor wound healing, osteoporosis, chronic insomnia, and an increased risk for diabetes, dyspeptic ulcer disease with bleeding, and glaucoma

Patient Education

  • Patients should wear medic alert bracelets stating the potential for adrenal insufficiency.
  • Patients should have emergency intramuscular hydrocortisone at home. The patient and family members should be properly educated in its administration in case oral intake is not possible.
  • Patients should know the features of glucocorticoid excess and glucocorticoid deficiency and should receive education in the early detection of these conditions.

Miscellaneous

Medicolegal Pitfalls

  • Prenatal treatment with dexamethasone is an option for fetuses known to be at risk for classic 11-beta-hydroxylase deficiency.9,10
    • The only setting in which this therapy should be considered is that in which both parents are known carriers of virilizing congenital adrenal hyperplasia.
    • Prenatal therapy is controversial, because the long-term effects on the child are unknown.
    • Surgical intervention aimed at correcting genital anomalies is the subject of continuing debate.
    • Some adult patients with intersex conditions have advocated postponing genital surgery until the affected individual is able to provide informed consent. This option should be presented to parents. However, raising a child with ambiguous genitalia is a complex psychosocial issue, and it is unclear if children and their families would accept this alternative.

Special Concerns

  • Fertility and pregnancy16
    • Many women with congenital adrenal hyperplasia (CAH) wish to have children.
    • Reduced fertility may be caused by inadequately suppressed adrenal androgen production.17
    • Polycystic ovarian syndrome (PCOS) may develop secondary to adrenal hyperandrogenism.
    • The effect of ovarian exposure to adrenal androgens prenatally and during childhood is unknown, but it may predispose women with CAH to PCOS.
    • Other reasons for reduced fertility may include an inadequate vaginal vault for coitus and psychological factors leading to reduced sexual activity.17
    • Whether the increase in adrenal androgens associated with pregnancy requires increased glucocorticoid therapy is unclear. Placental aromatase appears to have a large reserve and is able to convert large amounts of ambient androgen to estrogen. This may prevent virilization of the fetus, even in cases of poorly controlled CAH in the mother.
    • Prednisone is the ideal glucocorticoid for use during pregnancy in patients with 11-hydroxylase deficiency and other CAH variants.
    • Dexamethasone or any other semisynthetic glucocorticoid crosses the placenta and suppresses the fetal hypothalamic-pituitary-adrenal (HPA) axis. This treatment should be used only when there is a high risk that a fetus will have virilizing CAH. In such a case, suppression of the fetal HPA axis is desirable.
    • During pregnancy, closely monitor glucocorticoid dosages and hormone levels.
  • Routine prenatal screening for CAH presently is available only for the 21-hydroxylase variety.
  • PCOS
    • PCOS is one of the most important differential diagnoses of late-onset (nonclassic) variants of virilizing CAH.
    • PCOS is characterized by hirsutism, virilism, hyperandrogenism, menstrual irregularities, chronic anovulation, obesity, insulin resistance, acanthosis nigricans, multiple ovarian cysts, and an elevated ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH).
    • The elevated LH-to-FSH ratio and significant insulin resistance are useful discriminant laboratory findings.
    • CAH is far less common than PCOS.
    • The best means of distinguishing CAH from PCOS is by measuring the levels of the appropriate metabolite after 250 mcg of ACTH (11-deoxycortisol in 11-beta-hydroxylase deficiency).
 
Acknowledgments

Deborah P Merke, MD, Chief of Pediatric Services, Pediatric and Reproductive Endocrinology Branch, Warren Grant Magnuson Clinical Center; Clinical Investigator, National Institute of Child Health and Human Development, contributed to this article.



More on C-11 Hydroxylase Deficiency

Overview: C-11 Hydroxylase Deficiency
Differential Diagnoses & Workup: C-11 Hydroxylase Deficiency
Treatment & Medication: C-11 Hydroxylase Deficiency
Follow-up: C-11 Hydroxylase Deficiency
Multimedia: C-11 Hydroxylase Deficiency
References
Further Reading
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References

  1. Mornet E, Dupont J, Vitek A. Characterization of two genes encoding human steroid 11 beta- hydroxylase (P-450(11) beta). J Biol Chem. Dec 15 1989;264(35):20961-7. [Medline]. [Full Text].

  2. Joehrer K, Geley S, Strasser-Wozak EM. CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Hum Mol Genet. Oct 1997;6(11):1829-34. [Medline]. [Full Text].

  3. Zhu YS, Cordero JJ, Can S, et al. Mutations in CYP11B1 gene: phenotype-genotype correlations. Am J Med Genet A. Oct 15 2003;122(3):193-200. [Medline].

  4. Pascoe L, Curnow KM, Slutsker L. Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency. Proc Natl Acad Sci U S A. Jun 1 1992;89(11):4996-5000. [Medline]. [Full Text].

  5. Davies E, Mackenzie SM, Freel EM, et al. Altered corticosteroid biosynthesis in essential hypertension: a digenic phenomenon. Mol Cell Endocrinol. Sep 19 2008;[Medline].

  6. Rosler A, Leiberman E, Cohen T. High frequency of congenital adrenal hyperplasia (classic 11 beta-hydroxylase deficiency) among Jews from Morocco. Am J Med Genet. Apr 1 1992;42(6):827-34. [Medline].

  7. Storr HL, Barwick TD, Snodgrass GA, et al. Hyperplasia of adrenal rest tissue causing a retroperitoneal mass in a child with 11 beta-hydroxylase deficiency. Horm Res. 2003;60(2):99-102. [Medline].

  8. Peter M, Janzen N, Sander S, et al. A case of 11beta-hydroxylase deficiency detected in a newborn screening program by second-tier LC-MS/MS. Horm Res. 2008;69(4):253-6. [Medline].

  9. Carlson AD, Obeid JS, Kanellopoulou N. Congenital adrenal hyperplasia: update on prenatal diagnosis and treatment. J Steroid Biochem Mol Biol. Apr-Jun 1999;69(1-6):19-29. [Medline].

  10. Cerame BI, Newfield RS, Pascoe L, et al. Prenatal diagnosis and treatment of 11beta-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia. J Clin Endocrinol Metab. Sep 1999;84(9):3129-34. [Medline]. [Full Text].

  11. Rosler A, Leiberman E, Rosenmann A, et al. Prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. Oct 1979;49(4):546-51. [Medline].

  12. Van Vliet G, Polak M, Ritzén EM. Treating fetal thyroid and adrenal disorders through the mother. Nat Clin Pract Endocrinol Metab. Dec 2008;4(12):675-82. [Medline].

  13. German A, Suraiya S, Tenenbaum-Rakover Y, et al. Control of childhood congenital adrenal hyperplasia and sleep activity and quality with morning or evening glucocorticoid therapy. J Clin Endocrinol Metab. Dec 2008;93(12):4707-10. [Medline].

  14. Mantero F, Opocher G, Rocco S. Long-term treatment of mineralocorticoid excess syndromes. Steroids. Jan 1995;60(1):81-6. [Medline].

  15. Burgu B, Duffy PG, Cuckow P, et al. Long-term outcome of vaginal reconstruction: comparing techniques and timing. J Pediatr Urol. Aug 2007;3(4):316-20. [Medline].

  16. Garner PR. Congenital adrenal hyperplasia in pregnancy. Semin Perinatol. Dec 1998;22(6):446-56. [Medline].

  17. Meyer-Bahlburg HF. What causes low rates of child-bearing in congenital adrenal hyperplasia?. J Clin Endocrinol Metab. Jun 1999;84(6):1844-7. [Medline]. [Full Text].

  18. Azziz R. Nonclassic adrenal hyperplasia. In: Bardin CW, ed. Current Therapy in Endocrinology and Metabolism. 6th ed. St Louis, Mo: Mosby-Yearbook; 1997:175-8.

  19. Azziz R, Boots LR, Parker CR Jr. 11 beta-hydroxylase deficiency in hyperandrogenism. Fertil Steril. Apr 1991;55(4):733-41. [Medline].

  20. Cathelineau G, Brerault JL, Fiet J, et al. Adrenocortical 11 beta-hydroxylation defect in adult women with postmenarchial onset of symptoms. J Clin Endocrinol Metab. Aug 1980;51(2):287-91. [Medline].

  21. Deaton MA, Glorioso JE, McLean DB. Congenital adrenal hyperplasia: not really a zebra [published erratum appears in Am Fam Physician 1999 Sep 15;60(4):1107]. Am Fam Physician. Mar 1 1999;59(5):1190-6, 1172. [Medline]. [Full Text].

  22. Ghazi AA, Hadayegh F, Khakpour G, et al. Bilateral testicular enlargement due to adrenal remnant in a patient with C11 hydroxylase deficiency congenital adrenal hyperplasia. J Endocrinol Invest. Jan 2003;26(1):84-7. [Medline].

  23. Kalaitzoglou G, New MI. Congenital adrenal hyperplasia. Molecular insights learned from patients. Receptor. Fall 1993;3(3):211-22. [Medline].

  24. Lucky AW, Rosenfield RL, McGuire J, et al. Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche. J Clin Endocrinol Metab. May 1986;62(5):840-8. [Medline].

  25. Mantero F, Opocher G, Armanini D. 11 Beta-hydroxylase deficiency. J Endocrinol Invest. Jul-Aug 1995;18(7):545-9. [Medline].

  26. Merke DP, Tajima T, Chhabra A. Novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency. J Clin Endocrinol Metab. Jan 1998;83(1):270-3. [Medline]. [Full Text].

  27. Miller WL. Congenital adrenal hyperplasia in the adult patient. Adv Intern Med. 1999;44:155-73. [Medline].

  28. Miller WL. Early steps in androgen biosynthesis: from cholesterol to DHEA. Baillieres Clin Endocrinol Metab. Apr 1998;12(1):67-81. [Medline].

  29. Moran C, Knochenhauer ES, Azziz R. Non-classic adrenal hyperplasia in hyperandrogenism: a reappraisal. J Endocrinol Invest. Nov 1998;21(10):707-20. [Medline].

  30. New MI, Newfield RS. Congenital adrenal hyperplasia. In: Bardin CW, ed. Current Therapy in Endocrinology and Metabolism. 6th ed. St Louis, Mo: Mosby-Yearbook; 1997:179-187.

  31. Pang S. Congenital adrenal hyperplasia. Baillieres Clin Obstet Gynaecol. Jun 1997;11(2):281-306. [Medline].

  32. Pang S, Levine LS, Lorenzen F. Hormonal studies in obligate heterozygotes and siblings of patients with 11 beta-hydroxylase deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. Mar 1980;50(3):586-9. [Medline].

  33. Panitsa-Faflia C, Batrinos ML. Late-onset congenital adrenal hyperplasia. Ann N Y Acad Sci. Jun 17 1997;816:230-4. [Medline].

  34. Stratakis CA, Rennert OM. Congenital adrenal hyperplasia: molecular genetics and alternative approaches to treatment. Crit Rev Clin Lab Sci. Aug 1999;36(4):329-63. [Medline].

  35. White PC. Genetic diseases of steroid metabolism. Vitam Horm. 1994;49:131-95. [Medline].

  36. White PC. Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am. Mar 2001;30(1):61-79, vi. [Medline].

  37. White PC, Curnow KM, Pascoe L. Disorders of steroid 11 beta-hydroxylase isozymes. Endocr Rev. Aug 1994;15(4):421-38. [Medline].

  38. White PC, Obeid J, Agarwal AK. Genetic analysis of 11 beta-hydroxysteroid dehydrogenase. Steroids. Feb 1994;59(2):111-5. [Medline].

  39. White PC, Speiser PW. Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am. Jun 1994;23(2):325-39. [Medline].

  40. Zachmann M, Tassinari D, Prader A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients. J Clin Endocrinol Metab. Feb 1983;56(2):222-9. [Medline].

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Keywords

C-11 hydroxylase deficiency, adrenal, aldosterone, ACTH, adrenal glands, adrenal hyperplasia, congenital adrenal hyperplasia, adrenal insufficiency, congenital hyperplasia, glucocorticoid, glucocorticoids, mineralocorticoid, adrenocorticotropic hormone, congenital adrenal, hydroxylase deficiency, 11 hydroxylase deficiency, 11 beta hydroxylase, 11 beta hydroxylase deficiency, 11-beta-hydroxylase deficiency, CAH, cortisol biosynthesis, C-11 beta-hydroxylase deficiency, C-11–beta-hydroxylase deficiency, CYP11B2, aldosterone deficiency, mineralocorticoid deficiency

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Contributor Information and Disclosures

Author

Gabriel I Uwaifo, MBBS, Clinical and Research Attending, Assistant Professor of Medicine and Endocrinology, MedStar Clinical Research Center, MedStar Research Institute and Washington Hospital Center
Gabriel I Uwaifo, MBBS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Society of Hypertension, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Ghassem Pourmotabbed, MD†, Former Associate Professor, Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Tennessee School of Medicine and Health Science Center
Ghassem Pourmotabbed, MD† is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, and Endocrine Society
Disclosure: Nothing to disclose.

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Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
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Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
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Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
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