Congenital Adrenal Hyperplasia

Excerpt

Congenital Adrenal Hyperplasia (CAH) is a term used to describe a group of genetically determined disorders of defective steroidogenesis that result in variable deficiency of the end products cortisol and/or aldosterone and their deleterious, including life-threatening, effects on metabolism and electrolytes with simultaneous diversion to the accumulation of androgens and their virilizing effects. Although we discuss the various enzymatic defects that are involved, we focus on the most common enzyme deficiency, 21-hydroxylase. Depending on the residual enzymatic activity governed by the genetic mutation, 21-hydroxylase deficiency CAH is classified as either classical (salt wasting or simple virilizing) or non-classical. In classical 21-hydroxylase deficiency CAH, there is an accumulation of 17-hydroxyprogesterone which is shunted into the intact androgen pathway and may lead to prenatally virilized external genitalia in females as early as 9 weeks of gestation. Inadequately treated patients may develop progressive penile or clitoral enlargement, premature adrenarche, precocious puberty, rapid linear growth accompanied by premature epiphysis maturation leading to compromised final adult height and impaired fertility. Moreover, inadequately treated salt loss increases the risk for adrenal crises. In contrast, over treatment with cortisol results in “Cushingoid” effects including retarded bone development. We describe the various defects, their manifestations and goals for therapy, and emerging newer therapies for CAH to both correct the deficiency in cortisol and aldosterone secretion while suppressing overproduction of ACTH. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.