Classification
Cortisol is an adrenal steroid hormone that is 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, which in turn 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.
| Common medical term | % | OMIM | Enzyme(s) | Locus | Substrate(s) | Product(s) | Mineralocorticoids | Androgens |
|---|---|---|---|---|---|---|---|---|
| 21-hydroxylase CAH | 90-95% | 201910 | P450c21 | 6p21.3 | 17OH-progesterone→ progesterone→ |
11-deoxycortisol DOC |
↓ | ↑ |
| 11β-hydroxylase CAH | 5% | 202010 | P450c11β | 8q21-22 | 11-deoxycortisol→ DOC→ |
cortisol corticosterone |
↑ | ↑ |
| 3β-HSD CAH | very rare | 201810 | 3βHSD II | 1p13 | pregnenolone→ 17OH-pregnenolone→ DHEA→ |
progesterone 17OH-progesterone androstenedione |
↓ | ↓ |
| 17α-hydroxylase CAH | very rare | 202110 | P450c17 | 10q24.3 | pregnenolone→ progesterone→ 17OH-pregnenolone→ |
17OH-pregnenolone 17OH-progesterone DHEA |
↑ | ↓ |
| lipoid CAH (20,22-desmolase) |
very rare | 201710 | StAR P450scc |
8p11.2 15q23-q24 |
transport of cholesterol cholesterol→ |
into mitochondria pregnenolone |
↓ | ↓ |
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. There was also variation in different tissues and mammalian species.
In all its forms, congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for about 95% of diagnosed cases of CAH. Unless another specific enzyme is mentioned, "CAH" in nearly all contexts refers to 21-hydroxylase deficiency. (The terms "salt-wasting CAH", and "simple virilizing CAH" usually refer to subtypes of this condition.) CAH due to deficiencies of enzymes other than 21-hydroxylase present many of the same management challenges as 21-hydroxylase deficiency, but some involve mineralocorticoid excess or sex steroid deficiency.
Read more about this topic: Congenital Adrenal Hyperplasia