Congenital adrenal hyperplasia

What it is

Congenital adrenal hyperplasia is an adrenal cause of hirsutism, grouped with Cushing's syndrome and virilising tumours under the adrenal causes, as against the pituitary cause, acromegaly, and the ovarian causes, polycystic ovary syndrome and virilising tumours. It is a block in the steroid chain, which runs from cholesterol to pregnenolone, then by 3β-HSD to progesterone and 17-hydroxy progesterone, by 21-hydroxylase to deoxycorticosterone and 11-deoxycortisol, and by 11β-hydroxylase to corticosterone and cortisol, so that aldosterone is the mineralcorticoids, cortisol the glucocorticoids and testosterone the androgens.

The mode of inheritance is AR, and the two types that matter are 21 hydroxylase deficiency, about 95% of cases, and 11 beta hydroxylase deficiency.

How it presents

Three enzyme deficiencies are set out. In 21-hydroxylase deficiency 17-hydroxyprogesterone is raised while cortisol and aldosterone are low and testosterone is raised, giving ambiguous genitalia in girls and salt wasting with vomiting, hypotension, low Na+ and high K+; the likely diagnosis in a newborn female presenting with salt wasting and clitoromegaly is congenital adrenal hyperplasia due to 21-hydroxylase deficiency. In 11β-hydroxylase deficiency cortisol and aldosterone are low, testosterone is raised, and 11-deoxycorticosterone, a weak mineralocorticoid, and 11-deoxycortisol are raised, giving ambiguous genitalia in girls with fluid and salt retention and hypertension; the summary is hypertension with virilization and a high 17-OH-progesterone, girls virilized at birth and boys with early puberty, that is precocious pseudopuberty. In 17α-hydroxylase deficiency cortisol and testosterone are low while mineralocorticoids and corticosterone, a weak glucocorticoid, are raised, so all patients are phenotypically female with fluid and salt retention and hypertension; the summary is hypertension with sexual infantilism in both sexes, low 17-OH-progesterone and low androgens, girls with no secondary sex characteristics and boys undervirilized. Of the three, only the 21-hydroxylase type causes hypotension; the other two cause hypertension. Congenital adrenal hyperplasia is also one of the peripheral, gonadotrophin-independent causes of precocious puberty, alongside McCune-Albright syndrome, gonadal tumors, adrenal tumors, familial male limited precocious puberty and exogenous exposure to sex steroids.

Late treatment of CAH turns up on the other side of the same approach to precocious puberty. Under central precocious puberty, which is gonadotropin dependent, it is listed with McCune-Albright syndrome under prolonged exposure to elevated sex steroids, and it appears there for males and for females alike.

Hair is what it is followed by in the older child. Hirsutism is often used to describe androgen-dependent hair growth in women, with hypertrichosis being used for androgen-independent hair growth, and congenital adrenal hyperplasia may cause early pubic hair to develop and later excessive facial hair in adolescence. Polycystic ovarian syndrome is the most common cause of hirsutism; the other causes listed beside congenital adrenal hyperplasia are Cushing's syndrome, androgen therapy, obesity through peripheral conversion of oestrogens to androgens, an adrenal tumour, an androgen secreting ovarian tumour, and drugs, that is phenytoin. Lanugo hair is not this at all. It is generally found in newborn babies and those with chronic malnutrition, and it is an important sign to remember because it can be found in patients with anorexia nervosa. The hirsutism of polycystic ovarian syndrome differs from lanugo hair in that it tends to affect certain areas of the body such as the face, and tends to be thick and dark rather than fine and un-pigmented.