CAH

Question 1

A 46,XY baby will show under-development of the testes if

• SRY is ____expressed
• DAX1 is _____expressed
• WNT4 is _____expressed
• WT1 is _____ expressed
• SOX9 is _____ expressed
• NR5A1 is ______expressed

Answer 1

A 46,XY baby will show under-development of the testes if

• SRY is underexpressed
• DAX1 is overexpressed
• WNT4 is overexpressed
• WT1 is underexpressed
• SOX9 is underexpressed
• NR5A1 is underexpressed

Question 2

Describe development in androgen insensitivity syndrome

Answer 2

1. Baby is 46, XY, so testes develop
2. Androgens (testosterone) is produced by testes, but body cannot respond
   
   • So, Wolffian ducts regress
3. Anti-Mullerian Hormone is produced by Sertoli cells, so Mullerian ducts regress too
4. External genitals are female due to perceived lack of DHT

Question 3

Describe the gonads, internal genitalia, and external genitalia seen in Androgen Insensitivity Syndrome

Answer 3

• Gonads: testicles
• Internal genitalia: N/A
• External genitals: female (labia, clitoris, vagina) with scant axillary or pubic hair

Question 4

Describe the inheritance and defect in 5-alpha reductase deficiency.

Answer 4

• Autosomal recessive defect in 5-alpha reductase
• Testosterone isn’t converted into DHT
• External genitals are thus under-virulized
• Internal genitals and testes are fine (although testes may be undescended)

Question 5

What occurs to 5alpha-reductase deficient people at puberty?

Answer 5

• The overwhelming amount of testosterone is able to produce masculinization of external genitalia

Question 6

Describe the levels of testosterone, LH, and estrogen in androgen insensitivity syndrome

Answer 6

• High LH
• High testosterone
• High estrogen

Question 7

Describe the levels of testosterone, LH, and estrogen in 5alpha-reductase deficiency

Answer 7

• Normal testosterone, estrogen
• LH is normal or high

Question 8

What is the most common defect in congenital adrenal hyperplasia?

Answer 8

21-hydroxylase deficiency

(11beta-hydroxylase deficiency is much rarer)

Question 9

Describe levels of aldo, cortisol, and androgens in 21-hydroxylase deficient CAH

Answer 9

• 21-hydroxylase is needed for aldosterone and cortisol synthesis
• With this defect, excess hormone precursors get shunted into androgen synthesis
• Low aldosterone, low cortisol, high androgens

Question 10

Describe which enzymes are need for production of cortisol, aldosterone, and androgens

Answer 10

• Dessert always (desmolase is needed for all these hormones)
• Sex at 17 (17-hydroxylase needed for androgen synthesis)
• Salt on Thanksgiving (aldosterone synthesis requires 11beta and 21 hydroxylase)
• Sugar on everything (cortisol requires all these enzymes)

Question 11

Describe 4 symptoms of 21-hydroxylase deficient CAH

Answer 11

• Virilization of a 46,XX baby
• Hyperpigmentation (due to high ACTH)
• Hypotension with hyperkalemia, hyponatremia (due to low aldosterone)
• Hypoglycemia (due to low cortisol)

Question 12

How is 21-hydroxylase deficient CAH diagnosed?

Answer 12

Elevated 17-OH Progesterone

Question 13

What is the treatment for 21-hydroxylase deficient CAH?

Answer 13

Replace hormones with Hydrocortisone (for cortisol) and Fludrocortisone (for aldo)

Question 14

Compare the blood pressure, K, and renin levels in 11beta-hydroxylase deficiency and 21 hydroxylase deficiency

Answer 14

• 11beta hydroxylase deficiency: Hypertension (b/c defect is later in pathway and precursor acts as mineralocorticoid)
  
  • Low renin
  • Low K
• 21 hydroxylase deficiency: Hypotension
  
  • High renin
  • High K