Overview
Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive conditions characterised by impaired cortisol synthesis. The most common form is due to a deficiency in 21-hydroxylase, which consists of cortisol deficiency, and androgen excess with or without aldosterone deficiency.
To help make sense of this chapter, it may be helpful to refer to Endocrine and Metabolic Physiology.
Pathophysiology
In summary, 21-hydroxylase is necessary for the synthesis of glucocorticoids and aldosterone from progesterone. A deficiency in 21-hydroxylase leads to a surplus of progesterone which is converted to extra testosterone to reduce its levels. This leads to an increased level of androgens, and a cortisol and aldosterone deficiency.
Epidemiology
- 21-hydroxylase deficiency is the most common cause
- Clinical presentation is most commonly seen in the 1st year of life
- Boys are more likely to have more severe manifestations, such as a salt-wasting crisis
Risk Factors
- Family history
- Genetic predisposition
Presentation
Girls
The severity of CAH depends on the degree of 21-hydroxylase deficiency. In severe cases, it can lead to salt loss (hyponatraemia and hyperkalaemia). Features in girls may be:
- Features of virilisation (development of male physical traits) due to increased androgens:
- Ambiguous genitalia
- Male-pattern hair growth
- Early puberty and early menarche
- Adolescents/young adults may have oligo-/amenorrhoea
Boys
- Subtle hyperpigmentation:
- Due to increased ACTH secretion secondary to reduced cortisol
- Salt-loss crises often happen within the first 2 weeks of life and are characterised by:
- Lethargy
- Dehydration
- Shock
- Hyponatraemia
- Hyperkalaemia
Differential Diagnoses
Addison’s disease
- Features of hyperandrogenism are not present (e.g. virilisation of girls, early puberty etc.)
- Addison’s disease tends to have muscle weakness, CAH does not
- A short synacthen test shows a poor/absent cortisol response in Addison’s disease
Investigations
- U&Es:
- May show hyponatraemia and hyperkalaemia due to adrenal insufficiency
- Serum 17–hydroxyprogesterone:
- Raised in 21-hydroxylase deficiency
- Pelvic ultrasound:
- To assess pelvic organs in cases of ambiguous genitalia (e.g. looking for the absence of a uterus)
- Karyotyping:
- Establishing patient’s chromosomal sex if they have ambiguous genitalia
Management
Overview
Treatment involves glucocorticoids and fludrocortisone to account for the adrenal insufficiency
Complications
- Obesity and insulin resistance – worse in women due to hyperandrogenism
- Height limitation – excess androgens promote closure of the growth plates
- Precocious puberty
- Increased incidence of polycystic ovarian syndrome
- Infertility
