Congenital adrenal hyperplasia (CAH) is caused by an adrenal gland disorder whereby synthesis of cortisol is affected by an enzyme defect. This defect leads to an accumulation of androgen precursors in the blood, with results varying between salt-wasting, high blood pressure (hypertensive), virilising, or feminising.
CAH is caused by a mutation in a gene, and most defects result in either excessive or deficient sex hormone production, affecting the development of primary or secondary sex characteristics in babies, children or adults.
CAH is considered a cause of Differences (or Disorders) of Sexual Development (DSD).
This leaves an infant with salt-wasting that can lead to dehydration and death.
Too much of these sex hormones, and you end up with a functional and average-sized penis, but no sperm; ambiguous genitalia usually in females, so it is difficult to determine gender; early pubic hair and fast growth in childhood; precocious puberty, or in fact the complete failure of puberty; excessive facial hair, virilisation, and/or menstrual irregularity in teen years; infertility (caused by lack of ovulation); and an enlarged clitoris (clitoromegaly) and a shallow or closed-ended vagina (vaginal atresia).
How CAH works
Normal endocrine function is set about by cortisol production, with production starting in the second month in the womb. Most CAH is characterised by low cortisol production, which results in high levels of ACTH. This increase leads to hyperplasia – overgrowth – and overactivity of steroid-producing cells in the adrenal cortex, with this being present at birth (congenital).
CAH is caused by a recessive gene, meaning that both the mother and the father of a baby must be recessive carriers for the child to carry CAH genes. Couples with the gene can use various fertility and genetic testing to avoid the gene in their offspring. Every child in most western countries is screened for CAH at birth, and if detected early enough, the child can live a reasonably normal life with early intervention.
How CAH affects an individual
Each person will have their own version of CAH and it will affect each individual differently. The cortisol deficiency is likely to not be the worst problem affecting those with CAH, with production of androgens and oestrogens posing a greater set of issues.
The very mildest form affects ovulation and fertility in adults, but the worst types are associated with multiple enzymatic inefficiencies that cause foetal changes and issues in the womb and shortly after.
Treatment for CAH
Since it is a genetic issue, CAH treatment focuses on treating the symptoms and trying to re-regulate or mimic normal hormone systems. Some treatments may include all or any of the following:
- Supplementation with glucocorticoid to reduce hyperplasia (overgrowth) and overproduction of androgens and mineralocorticoids.
- Replacing mineralocorticoid and salt if deficient.
- Replacing hormones (testosterone, oestrogen) at puberty if deficient.
- Different hormone therapies to optimise growth (delay puberty or delaying bone maturation).
This condition has forced a lot of difficult discussions, including extensive debates over genital reconstructive surgery, gender assignment of severely affected XX infants, and how to treat this condition before birth.