Congenital Adrenal Hyperplasia Flashcards
How does ACTH receptor work?
GPCR: increases cAMP–>StAR protein and cholesterol transport into mitochondria
StAR Protein function
Steroidogenic acute regulatory: cholesterol translocation from cytoplasm to mitochondria
21-Hydroxylase defect
Glucocorticoid and mineralocorticoid deficiency Leads to build-up of CAH
11-ß-OH defect
Leads to buildup of cortisol precursors–>CAH
Function of Adrenal Androgens
Pubic hair development in males/females
What are symptoms of adrenal insufficiency
Nausea/vomiting, Fatigue, Hyperpigmentation, Hypoglycemia, Hyponatremia/hyperkalemia, Muscle weakness, poor weight gain, anorexia
Presentation of classic CAH: 21-hydroxylase deficiency
GC and MC deficiency
Adrenal androgen excess
Ambiguous genitalia in females/postnatal virlization in males
Diagnosis
Symptoms
Steroid profile
Treatment for Adrenal insufficiency
GC replacement: Hydrocortisone with increased coverage for stress, illness
MC replacement: fludrocortisone (florinef)
CAH: Severe “Salt wasting” Presentation (males vs. females)
Adrenal crisis in first 2 weeks
Males: no physical signs or penile enlargement
Female: postnatal virilization, ambiguous genitalia
Treatment of Salt Wasting CAH
Glucocorticoids
Mineralocorticoids
What are symptoms of simple virilizing?
Pubic/axillary/pubic hair Penile/clitoral enlargement GU anomalies BO Growth acceleration with bone age advancement
Treatment for Simple virilizing
Hydrocortisone
Non-classical CAH Presentation (4)
Early pubic hair development
Growth acceleration
Women: hirsutism, abnormal menses, acne (like PCOS)
Infertility (13% patients)
How do heterozygotes of CAH present?
No hyperandrogenism
No treatment indicated
How do you diagnosis CAH? (3)
Elevated 17-OH-progesterone (substrate of 21-hydroxylase)
Cosyntropin stimulation test– see lots of 17-OHP, no cortisol
Genotype
How is most CAH detected?
Detect salt-wasters via statewide newborn screening of 17-OHP
What is presentation of 11-ß-hydroxylase deficiency? (2)
Hypertension due to increased precursors with mineralocorticoid activity (HTN key)
Genital abnormalities similar to 21-hydroxylase
How can you distinguish 21-hydroxylase deficiency from 11-ß-hydroxylase deficiency?
Hypertension (11-ß; mineralocorticoid activity) vs. hypotension (21-OH)
Diagnosis of 11ßhydroxylase deficiency
High 11-DOC, high androgens
Treatment of 11ßhydroxylase deficiency (2)
Glucocorticoids and antihypertensive
3ß-hydroxysteroid dehydrogenase deficiency: Presentation (1) + males vs. females
Symptoms of glucocorticoid and mineralocorticoid deficiency
Females: mild virilization due to high DHEA
Males: ambiguous genitalia
3ß-hydroxysteroid dehydrogenase deficiency: Treatment (3)
Glucorticoid replacement
Mineralocorticoid replacement
Testosterone
17 hydroxylase: presentation
Decreased cortisol, increased ACTH
17,20 lyase deficiency: presentation
Decreased DHEA, androstenedione
StAR Deficiency: Presentation (3)
Salt wasting adrenal crisis within 1st month
Female phenotype regardless of genotype
High mortality
