Congenital Adrenal Hyperplasia

Cholesterol is the main ingredient that the adrenals use to manufacture cortisol, aldosterone, and androgen. In the human body, the production of each hormone is like the division of flow, pictured as pipes above. This is achieved by very specific chemicals called enzymes, that act like traffic coordinators. This regulatory system is present to ensure that the specific hormones are produced in the correct amount in response to the required body chemistry. This delicate system involves the pituitary gland which detects the level of adrenal hormones in the blood, and secretes the corresponding amount of Adrenocorticotrophic Hormone, ACTH.

In Congenital Adrenal Hyperplasia (CAH), the adrenal glands are unable to produce the required adrenal hormones, which can lead to very serious consequences. Without proper medical treatment, people with this condition, especially newborns, infants, and children, can die.

Congenital Adrenal Hyperplasia is a congenital disorder, that is, the condition is present at birth. It is a genetic disorder arising from a deficiency of one of several enzymes responsible for the production of corticosteroids and its subsequent formation of Glucocorticoids, Mineralocorticoids, and Adrenal Androgens (Sex Hormones).

The most common enzyme deficiency is 21-Hydroxylase deficiency, which is believed to account for 90 percent of all cases of CAH. As such, the term CAH in this website will refer to 21-Hydroxylase
deficiency.

CAH is caused by a missing or defective enzyme that controls the production of both the stress hormone cortisol, and the salt retaining hormone aldosterone. The missing or defective enzyme reduces, or completely blocks, the production of cortisol and aldosterone. The body would then signal (wrongly) to the pituitary gland that not enough cortisol is being produced.

The pituitary gland would then instruct the adrenals to produce more cortisol and aldosterone by delivering more cholesterol. However, the pipes remained blocked, as shown in the picture above, and the accumulated cholesterol metabolites are channelled into unblocked pathways through the androgenic limb.If this cycle is allowed to continue, the body will have insufficient cortisol and aldosterone, leading to an Adrenal Crisis.

Congenital Adrenal Hyperplasia can present itself in three levels of severity. These are:

1) The severe salt-wasting form.
2) The  non salt-wasting form.
3) A milder form.

Because of low salt levels from a deficiency of glucocorticoids and mineralocorticoids, newborns with the salt-wasting CAH can have any or all of the following symptoms within the first few weeks of life: vomiting, poor feeding, poor weight gain, drowsiness, diarrhea, and dehydration. The infant may even go into shock and without proper treatment, the infant will die from an adrenal crisis.

In relation to increased adrenal androgen exposure, female newborns with the salt-wasting CAH willl have ambiguous external genitalia, which make the female infant appear like a male. The clitoris may be enlarged and looks like a penis, while the labial folds may be joined together and wrinkled to look like a scrotum. In male newborns with the salt-wasting CAH, the external genitals appear normal. However, in all children with CAH, the rise in ACTH results in increased pigmentation (darkening) of the skin, mouth, lips, nipples and scrotum.

Infants with non salt-losing CAH are usually healthy, but girls may also develop genital abnormalities resulting from an excess of adrenal androgen. Boys with non salt-losing CAH may present later in
childhood with early virilisation from an increase of adrenal androgens. They can experience a growth spurt, and precocious (early onset) puberty.

In much milder forms, adult females usually develop excess body hair, acne, menstrual irregularity, and sometimes infertility. Infertility among males with the milder form of CAH is also possible but not common.