Intro to CAH

Question 1

Congenital adrenal hyperplasia

Answer 1

Autosomal recessive disorders involving the steroidogenic pathway
Most result in decreased cortisol secretion
POMC and ACTH are elevated (causes hyperpigmentation and adrenal hypertrophy)
The enzyme blocks can result in alterations of androgen production (leading to DSD)
Symptoms are related to deficiencies of end-products as well as accumulation of precursor steroids proximal to the block

Question 2

CAH clinical presentations

Answer 2

Salt-losing crisis
Disorder of sexual development
Peripheral precocious puberty
HTN in rare subtypes
Delayed or absent puberty in rare subtypes
An abnormal newborn screen

Question 3

Salt losing crisis presentation

Answer 3

History of progressive failure-to-thrive
Lethargy
Vomiting
Dehydrated, may present with shock
Arrhythmias secondary to hyperkalemia
Hypoglycemia

Question 4

Salt losing crisis acute management

Answer 4

Resuscitation with normal saline bolus, followed by an infusion of D10NS
Draw blood for 17-hydroxyprogesterone and electrolytes
Give a stat dose of HC IV
ECG monitoring if K is excessively high
In some cases, treatment with Kayexalate may be needed to decrease the K

Question 5

Where are steroids produced in the cell?

Answer 5

Mitochondria

Question 6

What protein does the steroid use to get into the mitochondria?

Answer 6

StAR protein

Question 7

Steroids can go into paths that result in what 3 hormones

Answer 7

Aldosterone
Cortisol
Androstenedione

Question 8

What is the most common enzyme block?

Answer 8

21-hydroxylase

Question 9

What are the 3 most common enzyme blocks?

Answer 9

21-hydroxylase
11B-hydroxylase
3BHSD2

Question 10

The presence of what 2 hormones causes male differentiation?

Answer 10

AMH

Testosterone

Question 11

Wolffian system causes the development of what 4 things

Answer 11

Epidiymis
Vas deferens
Seminal vesicles
Ejaculatory ducts

Question 12

Mullerian ducts cause the development of what 3 things

Answer 12

Fallopian tubes
Uterus
Upper vagina

Question 13

When does external genitalia

1. Begin differentiating
2. Become recognizable

Answer 13

1. 8 weeks

2. 3 months

Question 14

Function of DHT

Answer 14

Causes fusion of the urethral and labioscrotal folds, growth of the genital tubercle, and prostate
Inhibits growth of the vesicovaginal septum (vagina)

Question 15

Androgen exposure after 12 weeks

Answer 15

Vagina has formed

After 12 weeks androgen exposure cannot cause fusion of the labioscrotal and urethra folds

Question 16

Classic 21-hydroxylase deficiency clinical presentation

Answer 16

Females will present with genital ambiguity
Salt losing crises occur in the 2nd week of life
Infants are now picked up on the newborn screen

Question 17

Simple virilizing 21-hydroxylase deficiency presentation

Answer 17

Milder enzyme defect
They can make adequate amounts of aldosterone (no salt losing crisis)
Girls often have mild genital ambiguity
Both sexes present as a toddler with pubic hair development, growth acceleration, and an advanced bone age

Question 18

Late onset 21-hydroxylase deficiency presentation

Answer 18

Mild enzyme block
There is adequate cortisol and aldosterone production
There is excess adrenal androgen production
They may present with premature pubarche
Girls may have hirsutism
There may be irregular menses or a PCOS-like picture

Question 19

21-hydroxylase deficiency diagnostic tests

Answer 19

Measuring a 17-hydroxyprogesterone level at presentation is often diagnostic (but levels can be elevated in the 1st 48-72 hours after birth)
In some of the milder forms, ACTH-stimulated 17-OHP levels are required

Question 20

21-hydroxylase deficiency treatment

Answer 20

HC replacement
Will need stress dose HC at diagnosis, during illness, and surgeries
Classic form: fludrocortisone and salt supplementation
Girls with virilization may need gynae surgery
Psych support for families

Question 21

11-hydroxylase deficiency clinical features

Answer 21

Female infants present with genital ambiguity
Infants may have failure to thrive
Infants may present with an adrenal crisis
Enzyme block leads to increased levels of DOC which causes salt retention and HTN
Neonates are resisitant to mineralocorticoids (may have transient salt loss)

Question 22

3B-hydroxysteroid dehydrogenase deficiency

Answer 22

Deficiency in cortisol and aldosterone
Excessive DHEA
Inadequate amounts of androstenedione or testosterone
Female infants have clitoromegaly
Male infants have incomplete virilization

Question 23

3B-hydroxysteroid dehydrogenase deficiency treatment

Answer 23

HC replacement
Will need stress dosing at diagnosis and for illness
Fludrocortisone
Salt supplementation during infancy
Males will need test replacement in the neonatal period as well as at puberty
Girls often need estrogen replacement at puberty