Congenital adrenal hyperplasia Flashcards
What is congenital adrenal hyperplasia (CAH)?
An inherited group of disorders caused by enzyme deficiencies that impair cortisol synthesis
What is the inheritance pattern of CAH?
Autosomal recessive
What is the most common enzyme deficiency in CAH?
21α-hydroxylase deficiency (90% of cases)
What happens to the adrenal glands in CAH?
They become enlarged at birth due to ACTH stimulation from cortisol deficiency
What is the main hormonal imbalance in 21α-hydroxylase deficiency?
↓ Aldosterone
↓ Cortisol
↑ Androgens (testosterone & dihydrotestosterone)
Why does CAH cause increased androgens?
The lack of 21α-hydroxylase prevents aldosterone and cortisol synthesis, shunting precursors into the androgen pathway
What are the main features of classic CAH?
(1) Genital ambiguity (virilisation) in females
(2) Adrenal failure
= collapse, hypotension, hypoglycaemia, poor weight gain
(3) Biochemical pattern similar to Addison’s disease
How does non-classic CAH present in females?
(1) Later onset (adolescence/adulthood)
(2) Precocious puberty
(3) Hirsutism
(4) Acne
(5) Oligomenorrhoea, infertility, or subfertility
What is the first-line biochemical test for CAH?
Basal (or stimulated) 17-OH progesterone
What hormone is overproduced in response to cortisol deficiency in CAH?
Adrenocorticotropic hormone (ACTH) from the anterior pituitary
Why does CAH lead to virilisation in female infants?
Elevated ACTH stimulates excessive adrenal androgen production, leading to ambiguous genitalia due to excess androgen exposure in utero
Why is CAH diagnosis often delayed in male infants?
Male infants appear phenotypically normal at birth, as their genitalia are already masculinised in utero
What is the first-line diagnostic test for CAH?
Serum 17-hydroxyprogesterone (17OHP) measurement
How is CAH confirmed?
ACTH stimulation test
What is the primary treatment for CAH?
Glucocorticoid replacement
= to reduce ACTH levels and limit adrenal androgen production
When is fludrocortisone needed in CAH?
In cases with mineralocorticoid deficiency (e.g., salt-wasting CAH) to maintain sodium and blood pressure levels
What is salt-wasting CAH?
A severe form of 21-hydroxylase deficiency causing
(1) aldosterone deficiency
(2) leading to dehydration
(3) hypotension
(4) hyponatraemia
(5) hyperkalaemia
A 3-week-old female infant is brought to the GP by her parents, who are concerned about ambiguous genitalia. The infant was born at full term with no complications during delivery. On examination, the infant has clitoromegaly and partial labial fusion. A blood test reveals elevated levels of 17-hydroxyprogesterone and hyponatraemia.
What is the most appropriate next step in confirming the diagnosis?
ACTH stimulation test
You are performing a newborn baby check and discover during your examination that the neonate has ambiguous genitalia. On discussing this with the baby’s parents, they understandably distressed and want to know what the reason for this is.
What is the most likely cause of the ambiguous genitalia in this case?
Ambiguous genitalia
= Congenital adrenal hyperplasia is the most common cause in newborns
How do excess androgens in congenital adrenal hyperplasia (CAH) affect females and males?
- excessive androgen production leads to virilisation (development of male characteristics) In males, the increased androgen exposure may cause early puberty.
- In females, this can cause masculinisation of the external genitalia, leading to ambiguous genitalia at birth (such as an enlarged clitoris or fused labia)
Why does low cortisol lead to increased ACTH and adrenal hyperplasia in congenital adrenal hyperplasia (CAH)?
Low cortisol triggers the pituitary to release more ACTH in an attempt to stimulate the adrenal glands.
This leads to hyperplasia (enlargement) of the adrenal glands and increased production of androgens (such as testosterone)
