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Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children

Author
Deborah P Merke, MD, MS
Section Editor
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol accounts for more than 95 percent of cases of congenital adrenal hyperplasia [1,2]. This conversion is mediated by 21-hydroxylase, deficiency of which is caused by mutations in the CYP21A2 gene. (See "Adrenal steroid biosynthesis".)

The treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children is reviewed here. The pathophysiology, genetics, and clinical manifestations of 21-hydroxylase deficiency, the treatment of 21-hydroxylase deficiency in adults, and the clinical presentation and treatment of nonclassic (mild) congenital adrenal hyperplasia (CAH) are discussed separately. (See "Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults" and "Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency".)

OVERVIEW

Therapy of 21-hydroxylase deficiency is directed toward providing glucocorticoid in sufficient doses to reduce the associated excessive corticotropin-releasing hormone (CRH) and corticotropin (ACTH) secretion and hyperandrogenemia, so that growth, sexual maturation, and, later, reproductive function, are normal. In patients with the salt-losing form of the disorder, mineralocorticoid is given to restore serum electrolyte concentrations and extracellular fluid volume to normal. These goals can be difficult to achieve without overtreatment, and its attendant risk of growth retardation and other clinical manifestations of Cushing's syndrome [3]. (See "Epidemiology and clinical manifestations of Cushing's syndrome".)

An Endocrine Society Clinical Practice Guideline on the diagnosis and treatment of 21-hydroxylase deficiency in children and adults is available [2]. Guidelines regarding comprehensive care are also available based on a conference attended by pediatric endocrinologists, medical endocrinologists, reproductive endocrinologists, pediatric urologists/surgeons, endocrine nurses, psychologists and affected individuals and their families [4].

PRENATAL THERAPY

Prenatal diagnosis of 21-hydroxylase deficiency was originally undertaken to provide parents with information regarding the disease status of the fetus. Prenatal diagnosis also has been performed if prenatal therapy is contemplated. However, because adverse effects of prenatal therapy (on the fetus and mother) have been described and long-term risks are unknown, the decision to treat should only be considered in consultation with a highly experienced team in a research setting and after a detailed discussion with the pregnant couple [2]. (See "Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency", section on 'Prenatal diagnosis'.)

                      

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Literature review current through: Nov 2016. | This topic last updated: Thu Nov 03 00:00:00 GMT+00:00 2016.
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