Classification
Cortisol is an adrenal steroid hormone required for normal endocrine function. Production begins in the second month of fetal life. Poor cortisol production is a hallmark of most forms of CAH. Inefficient cortisol production results in rising levels of ACTH, because cortisol feeds back to inhibit ACTH production, so loss of cortisol results in increased ACTH. This increased ACTH stimulation induces overgrowth (hyperplasia) and overactivity of the steroid-producing cells of the adrenal cortex. The defects causing adrenal hyperplasia are congenital (i.e. present at birth). Cortisol deficiency in CAH is usually partial, and not the most serious problem for an affected person. Synthesis of cortisol shares steps with synthesis of mineralocorticoids such as aldosterone, androgens such as testosterone, and estrogens such as estradiol. The resulting excessive or deficient production of these three classes of hormones produce the most important problems for people with CAH. Specific enzyme inefficiencies are associated with characteristic patterns of over- or underproduction of mineralocorticoids or sex steroids. Since the 1960s, most endocrinologists have referred to the forms of CAH by the traditional names in the left column, which generally correspond to the deficient enzyme activity. As exact structures and genes for the enzymes were identified in the 1980s, most of the enzymes were found to be cytochrome P450 oxidases and were renamed to reflect this. In some cases, more than one enzyme was found to participate in a reaction, and in other cases, a single enzyme mediated in more than one reaction. Variation in different tissues and mammalian species also was found.
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. Most of these disorders involve excessive or deficient production of hormones such as glucocorticoids, mineralocorticoids, or sex steroids, and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults. It is one of the most common autosomal recessive disorders in humans. Types
CAH can occur in various forms. The clinical presentation of each form is different and depends to a large extent on the underlying enzyme defect, its precursor retention, and deficient products. Classical forms appear in infancy, and nonclassical forms appear in late childhood. The presentation in patients with classic CAH can be further subdivided into two forms: salt-wasting and simple-virilizing, depending on whether mineralocorticoid deficiency presents or absents, respectively (you should put absents before presents to straight the meaning of respectively). This subtyping is often not clinically meaningful, though, because all patients lose salt to some degree, and clinical presentations may overlap. Classic
Salt-wasting
In 75% of cases of severe enzyme deficiency, insufficient aldosterone production can lead to salt wasting, failure to thrive, and potentially fatal hypovolemia and shock. A missed diagnosis of salt-loss CAH is related to the increased risk of early neonatal morbidity and death. Simple-virilizing
The main feature of CAH in newborn females is the abnormal development of the external genitalia, which has varying degrees of virilization.