Intro to CAH Flashcards
Congenital adrenal hyperplasia
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
CAH clinical presentations
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
Salt losing crisis presentation
History of progressive failure-to-thrive Lethargy Vomiting Dehydrated, may present with shock Arrhythmias secondary to hyperkalemia Hypoglycemia
Salt losing crisis acute management
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
Where are steroids produced in the cell?
Mitochondria
What protein does the steroid use to get into the mitochondria?
StAR protein
Steroids can go into paths that result in what 3 hormones
Aldosterone
Cortisol
Androstenedione
What is the most common enzyme block?
21-hydroxylase
What are the 3 most common enzyme blocks?
21-hydroxylase
11B-hydroxylase
3BHSD2
The presence of what 2 hormones causes male differentiation?
AMH
Testosterone
Wolffian system causes the development of what 4 things
Epidiymis
Vas deferens
Seminal vesicles
Ejaculatory ducts
Mullerian ducts cause the development of what 3 things
Fallopian tubes
Uterus
Upper vagina
When does external genitalia
- Begin differentiating
- Become recognizable
- 8 weeks
2. 3 months
Function of DHT
Causes fusion of the urethral and labioscrotal folds, growth of the genital tubercle, and prostate
Inhibits growth of the vesicovaginal septum (vagina)
Androgen exposure after 12 weeks
Vagina has formed
After 12 weeks androgen exposure cannot cause fusion of the labioscrotal and urethra folds
Classic 21-hydroxylase deficiency clinical presentation
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
Simple virilizing 21-hydroxylase deficiency presentation
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
Late onset 21-hydroxylase deficiency presentation
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
21-hydroxylase deficiency diagnostic tests
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
21-hydroxylase deficiency treatment
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
11-hydroxylase deficiency clinical features
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)
3B-hydroxysteroid dehydrogenase deficiency
Deficiency in cortisol and aldosterone
Excessive DHEA
Inadequate amounts of androstenedione or testosterone
Female infants have clitoromegaly
Male infants have incomplete virilization
3B-hydroxysteroid dehydrogenase deficiency treatment
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
