Congenital Adrenal Hyperplasia

Abstract

Congenital adrenal hyperplasia (CAH) describes a family of inherited disorders whose common feature is impaired cortisol synthesis. Cortisol is produced from cholesterol in the adrenal glands through a series of enzymatic reactions. A genetic mutation of the gene encoding one of these enzymes can lead to CAH. In some forms of CAH, a build up of steroid precursors to the defective enzyme leads to an overproduction of androgens, sex steroids, causing to virilization of a female foetus affected with CAH. Most cases of CAH are owed to a defect in the enzyme, 21‐hydroxylase. This family of disorders is treatable with oral glucocorticoids.

Key Concepts:

  • Congenital adrenal hyperplasia describes a group of autosomal recessive genetic defects in the enzymes of steroidogenesis.

  • The adrenal glands produce steroids including glucocorticoids, mineralocorticoids and sex steroids (androgens).

  • Deficiency of 21‐hydroxylase causes more than 90% of cases of CAH and is characterised by glucocorticoid and mineralocorticoid deficiency associated with virilization in females.

  • There are two forms of CAH: the classical form, which includes the salt‐wasting and the simple virilizing forms and the nonclassical form, which is associated with milder symptoms.

  • The main goals of medical therapy for CAH are to replace deficient cortisol with a suitable glucocorticoid, deficient aldosterone with mineralocorticoid replacement and sodium supplements, and to prevent excessive androgen secretion.

  • Prenatal dexamethasone treatment can prevent genital ambiguity in an affected female foetus with classical CAH. The presence of cell‐free foetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal testing of 21‐hydroxylase deficiency and other genetic steroid disorders.

Keywords: 21‐hydroxylase; ambiguous genitalia; cortisol; glucocorticoid; prenatal diagnosis and treatment

Figure 1.

Feedback in the hypothalamic–pituitary–adrenal axis of a normal individual.

Figure 2.

Simplified scheme of steroid hormone production in (a) a normal adrenal gland and (b) an adrenal gland in an individual with CAH. ACTH, adrenocorticotrophic hormone; CAH, congenital adrenal hyperplasia.

Figure 3.

Algorithm depicting prenatal management of pregnancy in families at risk for a foetus with 21‐hydroxylase deficiency. DNA, deoxyribonucleic acid; GA, gestational age; hCG, human chorionic gonadotrophin. Reproduced with permission from Mercado et al. (). © Endocrine Society.

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References

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Further Reading

Cabrera M, Vogiatzi M and New MI (2001) Long term outcome in adult males with congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism 86(7): 3070–3078.

Gmyrek GA, New MI, Sosa RE and Poppas DP (2002) Bilateral laparoscopic adrenalectomy as a treatment for classic congenital adrenal hyperplasia attributable to 21‐hydroxylase deficiency. Pediatrics 109(2): E28.

Meyer‐Bahlburg HFL, Gidwani S, Dittmann RW et al. (2000) Psychosexual quality of life in adult intersexuality: the example of congenital adrenal hyperplasia. In: Stabler B and Bercu BB (eds) Therapeutic Outcome of Endocrine Disorders: Efficacy, Innovation and Quality of Life, pp. 200–208. New York, NY: Springer.

Meyer‐Bahlburg HFL, Gruen RS, New MI et al. (1996) Gender change from female to male in classical congenital adrenal hyperplasia. Hormones and Behavior 30: 319–332.

Nass R, Heier L, Moshang T et al. (1997) Magnetic resonance imaging in the congenital adrenal hyperplasia population: increased frequency of white‐matter abnormalities and temporal lobe atrophy. Journal of Child Neurology 12: 181–186.

New MI (1994) Congenital adrenal hyperplasia. Frontiers in Endocrinology 7: 55–74.

New MI (1996) Infertility and androgen excess in nonclassical 21‐hydroxylase deficiency. Proceedings of Symposium on ‘The Ovary: Regulation, Dysfunction and Treatment’, Florida, 25–27 January 1996, Excerpta Medica International Congress Series, 1106: 195–198.

New MI, Carlson A, Obeid J et al. (2001) Update on prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies. Journal of Clinical Endocrinology and Metabolism 86(12): 5651–5657.

New MI, Crawford C and Wilson RC (1996) Genetic disorders of the adrenal gland. In: Rimoin DL, Connor JM and Pyeritz RE (eds) Principles and Practice of Medical Genetics, 3rd edn, pp. 1441–1476. New York, NY: Churchill Livingstone.

New MI and Josso N (1996) Disorders of sexual differentiation. In: Claude Bennett J and Plum F (eds) Cecil Textbook of Medicine, 20th edn, pp. 1284–1293. Philadelphia: WB Saunders.

New MI and Newfield RS (1997) Congenital adrenal hyperplasia. In: Bardin CW (ed.) Current Therapy in Endocrinology and Metabolism, 6th edn, pp. 179–187. Philadelphia: Mosby‐Year Book.

Quintos JBQ, Vogiatzi MG, Harbison MD and New MI (2001) Growth hormone therapy alone or in combination with GnRH analogue therapy to improve the height deficit in children with CAH. Journal of Clinical Endocrinology and Metabolism 86(4): 1511–1517.

Wajnrajch MP and New MI (1998) Disorders of the adrenal gland. In: Burg FD, Ingelfinger JR, Polin RA and Wald ER (eds) Current Pediatric Therapy, vol. 16, pp. 744–753. Philadelphia: WB Saunders.

Wajnrajch MP and New MI (2001) Defects of adrenal steroidogenesis. In: DeGroot LJ and Jameson JL (eds) Endocrinology, 4th edn, pp. 1721–1739. Philadelphia: WB Saunders.

Wilson RC and New MI (1998) Congenital adrenal hyperplasia. In: Jameson JL (ed.) Principles of Molecular Medicine, pp. 481–493. Totowa: Humana Press.

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Yau, Mabel, Pina, Christian, Khattab, Ahmed, and New, Maria I(Oct 2014) Congenital Adrenal Hyperplasia. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002261.pub2]