Congenital adrenal hyperplasia

Question 1

What kind of disease is congenital adrenal hyperplasia?

Answer 1

A rare inherited condition present at birth

Autosomal recessive

Question 2

What are risk factors for inheriting congenital adrenal hyperplasia?

Answer 2

Both parents are carriers

Certain ethnic groups eg. Ashkenazi Jews, Hispanics, Italians, Yugoslavians and Yupik inuits

Question 3

What are the types of congenital adrenal hyperplasia?

Answer 3

Classical and non-classical

Question 4

What is classical congenital adrenal hyperplasia?

Answer 4

More severe
Detected in newborn screening programme
2/3 salt-losing form
1/3 virilising form

Question 5

What are the main symptoms of classical congenital adrenal hyperplasia?

Answer 5

46 XX have genital ambiguity due to increased testosterone production
Ambiguous external genitalia
Normal internal sex organs

Question 6

What is the effect of loss of cortisol production?

Answer 6

Salt-losing form

Simple-virilising form

Question 7

What is the effect of loss of aldosterone production?

Answer 7

Salt-losing form

Question 8

What is the effect of excess male sex hormones?

Answer 8

Short height
Early puberty
Ambiguous genitalia

Question 9

What is adrenal crisis?

Answer 9

Caused by severely low levels of cortisol in the blood
Diarrhoea, vomiting, dehdydration, low blood glucose and shock
Life threatening
Requires immediate treatment
Hyperkalaemia
Does not occur in non-classical CAH

Question 10

What are ambiguous genitalia?

Answer 10

Enlarged clitoris, genitals look more male than female

Question 11

What is non-classical congenital adrenal hyperplasia?

Answer 11

Milder
Appears in childhood/ early adulthood
More common

Question 12

What are symptoms of non-classical congenital adrenal hyperplasia?

Answer 12

Irregular or absent menstrual periods
Masculine characteristics
Severe acne

Question 13

What is a common internal symptom of congenital adrenal hyperplasia?

Answer 13

Adrenomegaly

Question 14

How is congenital adrenal hyperplasia diagnosed?

Answer 14

Adrenomegaly
Increased androgen production
Lack of mineralocorticoids and/or glucocorticoids

Question 15

What tests can diagnose congenital adrenal hyperplasia?

Answer 15

Physical exam
Blood and urine tests
Genetic testing
CT scan

Question 16

How is congenital adrenal hyperplasia treated?

Answer 16

Not treatable but can treat the symptoms

Question 17

How is lack of aldosterone treated?

Answer 17

Give aldosterone

Treat to reduce sex hormones

Question 18

How is glucocorticoid deficiency treated?

Answer 18

Cortisol replaced

Must avoid iatrogenic Cushing’s

Question 19

What is the main cause of congenital adrenal hyperplasia?

Answer 19

95% cases

21-hydroxylase deficiency

Question 20

What is the mechanism of 21-hydroxylase deficiency?

Answer 20

Enzyme needed to produce cortisone and aldosterone
No negative feedback
Elevated ACTH
Adrenal hyperplasia in response
DHEA production increased
Cholesterol enters only androgen route
46 XX differential sexual differentiation

Question 21

What are the symptoms of 21 hydroxylase deficiency?

Answer 21

Decreased glucocorticoid and mineralocorticoid

Increased sex hormones

Question 22

What is the prevalence and what are the symptoms of aldosterone deficiency?

Answer 22

75% of classical congenital adrenal hyperplasia
Dehydration
Hypovolaemia
Hypotension

Question 23

What mutations other than 21 hydroxylase cause congenital hyperplasia?

Answer 23

17alpha hydroxylase
11beta hydroxylase
3beta hydroxylase

Question 24

What is congenital lipoid adrenal hyperplasia?

Answer 24

Mutations in CYP11A1 and StAR

Question 25

What is StAR?

Answer 25

Rate limiting step

Imports cholesterol from the outer to inner membrane of the mitochondria