01-21 Hirsutism and CAH: Clinical and Molecular

Question 1

Hirsuitism vs. Hypertrichosis

Answer 1

Hirsuitism: vellous hair ∆ing to coarse, terminal hair in androgen-dependent (i.e. in areas w/ 5α-reductase) in ♀
—Occurs @ [T] just above ♀ ref range
—Dx: In white ♀ use Ferriman and Gallwey score

Hypertrichosis: peach fuzz all over body

Question 2

Presentation of CAH
—In ♀
—In ♂
—Labs for both

Answer 2

♀: in order of increasing [T]
—ambiguous genitalia at birth
—clitoromegaly, hirsuitism, acne, amenorrhea
—↑ SKM
—deeper voice, temporal balding

♂: precocious puberty, early growth spurt and then stops short, aggressive behavior

LABS for Both
—cortisol deficient
—aldo deficient

Question 3

Action of 5α-reductase

Answer 3

conversion of testosterone to dihydrotestosterone (DHT)

Question 4

DDx of Hirsuitism

Answer 4

85% is PCOS
—lesser degree, lesser elevation of T, insulin Res.
10% is idiopathic
3% is CAH
—Classic
—Adult onset = nonclassic
2% Other:
—Neoplasm: small ovarian; larger adrenal cortex
—Cushing's syndrome
—Exogenous androgen use

Question 5

What lab findings would exogenous androgen (not testosterone) use result in?

Answer 5

—LH low
—normal T
—mass spec to determine compound

Question 6

CAH: most common etiology?

Answer 6

21-hydroxylase (CYP21A2) deficiency
—progesterone —X→ → → aldost.
—17-OH-pro” —X→ → → cortisol
So.. ^^—→ ↑↑ androstenedione

Question 7

Hirsuitism + hypokalemia?

Answer 7

11β-hydroxylase deficiency (vanishingly rare)
—progesterone → —X→ → aldost.
—deoxycortisol has some cortisol effect

Question 8

Why is CYP21A2 mutated so often?

Answer 8

—most frequently mutated gene in human autosomal genome.

—homologous recombination w/ homologue CYP21A1 nearby

Question 9

Epidemiology of 21-hydroxylase deficiency

Answer 9

Classic form:
—1:14,500 live births
—1:61 are heterozygotes!
—1:27 Ashkenazi Jews
—1:5 Aleuts

Question 10

Provocation test

Answer 10

give ACTH and then measure 17-OH-Progesterone

Question 11

Goals of tx?

—Why?

Answer 11

Reverse adrenal insufficiency
—cortisol Rx
—fludrocortisone Rx
Suppress androgen excess
Female
—in utero: prevent genital ambiguity
—child: short stature, hirsutism, genital surgery
—adult: hirsutism, fertility, psychological
Male
—Child: behavior problems, short stature

Avoid adverse effects
—Short stature (too much androgen suppression)
—iatrogenic Cushing’s syndrome (if you overdo it w/ the cortisol Rx)