Congenital Adrenal Hyperplasia

Question 1

How does ACTH receptor work?

Answer 1

GPCR: increases cAMP–>StAR protein and cholesterol transport into mitochondria

Question 2

StAR Protein function

Answer 2

Steroidogenic acute regulatory: cholesterol translocation from cytoplasm to mitochondria

Question 3

21-Hydroxylase defect

Answer 3

Glucocorticoid and mineralocorticoid deficiency Leads to build-up of CAH

Question 4

11-ß-OH defect

Answer 4

Leads to buildup of cortisol precursors–>CAH

Question 5

Function of Adrenal Androgens

Answer 5

Pubic hair development in males/females

Question 6

What are symptoms of adrenal insufficiency

Answer 6

Nausea/vomiting, Fatigue, Hyperpigmentation, Hypoglycemia, Hyponatremia/hyperkalemia, Muscle weakness, poor weight gain, anorexia

Question 7

Presentation of classic CAH: 21-hydroxylase deficiency

Answer 7

GC and MC deficiency
Adrenal androgen excess
Ambiguous genitalia in females/postnatal virlization in males

Question 8

Diagnosis

Answer 8

Symptoms

Steroid profile

Question 9

Treatment for Adrenal insufficiency

Answer 9

GC replacement: Hydrocortisone with increased coverage for stress, illness
MC replacement: fludrocortisone (florinef)

Question 10

CAH: Severe “Salt wasting” Presentation (males vs. females)

Answer 10

Adrenal crisis in first 2 weeks

Males: no physical signs or penile enlargement
Female: postnatal virilization, ambiguous genitalia

Question 11

Treatment of Salt Wasting CAH

Answer 11

Glucocorticoids

Mineralocorticoids

Question 12

What are symptoms of simple virilizing?

Answer 12

Pubic/axillary/pubic hair
Penile/clitoral enlargement 
GU anomalies
BO
Growth acceleration with bone age advancement

Question 13

Treatment for Simple virilizing

Answer 13

Hydrocortisone

Question 14

Non-classical CAH Presentation (4)

Answer 14

Early pubic hair development
Growth acceleration
Women: hirsutism, abnormal menses, acne (like PCOS)
Infertility (13% patients)

Question 15

How do heterozygotes of CAH present?

Answer 15

No hyperandrogenism

No treatment indicated

Question 16

How do you diagnosis CAH? (3)

Answer 16

Elevated 17-OH-progesterone (substrate of 21-hydroxylase)
Cosyntropin stimulation test– see lots of 17-OHP, no cortisol
Genotype

Question 17

How is most CAH detected?

Answer 17

Detect salt-wasters via statewide newborn screening of 17-OHP

Question 18

What is presentation of 11-ß-hydroxylase deficiency? (2)

Answer 18

Hypertension due to increased precursors with mineralocorticoid activity (HTN key)
Genital abnormalities similar to 21-hydroxylase

Question 19

How can you distinguish 21-hydroxylase deficiency from 11-ß-hydroxylase deficiency?

Answer 19

Hypertension (11-ß; mineralocorticoid activity) vs. hypotension (21-OH)

Question 20

Diagnosis of 11ßhydroxylase deficiency

Answer 20

High 11-DOC, high androgens

Question 21

Treatment of 11ßhydroxylase deficiency (2)

Answer 21

Glucocorticoids and antihypertensive

Question 22

3ß-hydroxysteroid dehydrogenase deficiency: Presentation (1) + males vs. females

Answer 22

Symptoms of glucocorticoid and mineralocorticoid deficiency

Females: mild virilization due to high DHEA
Males: ambiguous genitalia

Question 23

3ß-hydroxysteroid dehydrogenase deficiency: Treatment (3)

Answer 23

Glucorticoid replacement
Mineralocorticoid replacement
Testosterone

Question 24

17 hydroxylase: presentation

Answer 24

Decreased cortisol, increased ACTH

Question 25

17,20 lyase deficiency: presentation

Answer 25

Decreased DHEA, androstenedione

Question 26

StAR Deficiency: Presentation (3)

Answer 26

Salt wasting adrenal crisis within 1st month
Female phenotype regardless of genotype
High mortality