Definition of the Disease

Beta Switch Program

Beta Switch Program

Get Instant Access

Congenital adrenal hyperplasia (CAH) is a group of diseases that result from reduced or absent activity of one of the five enzymes of cortisol synthesis in the adrenal cortex (Fig. 20.1). Each enzyme deficiency produces characteristic alterations in the concentrations of the particular steroid hormones that are substrates for, or products of, metabolism by the defective enzyme.1,2 Approximately 90% of cases of CAH are attributable to deficiency of 21-hydroxylase, a microsomal cytochrome P450 enzyme required in the pathways leading to cortisol and aldosterone but not required in the production of sex steroids. In the presence of a defect in 21-hydroxylase, the synthesis of cortisol is blocked. This leads to disruption of the normal feedback mechanisms and overproduction of ACTH. The result is adrenal hyperplasia, the oversecretion of

Adrenal Microsomal Cytochrome P450

Figure 20.1 Pathways of steroidogenesis within the adrenal gland. Enzyme nomenclature is given inside boxes; common names of steroid intermediates are listed. Steroid structures are shown for cholesterol (upper left), aldosterone, cortisol, testosterone, and estradiol (bottom of figure). Adrenal precursors hormones such as androstenedione are converted to sex steroids in the periphery by various additional enzyme pathways. There are alternative metabolic pathways within the adrenal gland as well.

Figure 20.1 Pathways of steroidogenesis within the adrenal gland. Enzyme nomenclature is given inside boxes; common names of steroid intermediates are listed. Steroid structures are shown for cholesterol (upper left), aldosterone, cortisol, testosterone, and estradiol (bottom of figure). Adrenal precursors hormones such as androstenedione are converted to sex steroids in the periphery by various additional enzyme pathways. There are alternative metabolic pathways within the adrenal gland as well.

precursors of potent androgens such as androstenedione, and pre- and postnatal virilization. Deficiency of 21-hydroxylase may also interfere with the synthesis of aldosterone, which leads to salt-wasting.

The disease has an autosomal recessive mode of inheritance. The gene (termed CYP21A2) encoding the active 21-hydroxylase enzyme and a highly homologous pseudogene are located on the short arm of the sixth chromosome in the midst of the HLA complex (chromosome 6p21.3). A combination of two severe mutations in each of the CYP21A2 alleles produces the classic form of the disease (e.g., deletion-deletion), whereas two milder mutations (exon 7 valine-281 to leucine-exon 7 valine-281 to leucine) or a combination of a severe and a mild deficiency allele produces mild or nonclassic CAH. Numerous other mutations, aside from these two mentioned, have been detected in patients with 21-hydroxylase deficiency. Heterozygotes have reduced enzymatic activity that is detectable only by the mildly elevated 17-hydroxyprogesterone concentration after ACTH stimulation.

Was this article helpful?

0 0
How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

Get My Free Ebook


Post a comment