Hirsutism & Virilism

Question 1

Hirsutism

Answer 1

Caused by inc androgens.

Male hair growth pattern (diamond shaped, not triangle shaped)

Question 2

Virilization

Answer 2

Development of male features: deepening of voice, frontal balding, inc muscle mass, clitoromegaly, breast atrophy, male body habitus

Question 3

In the adrenal glands, what is the precursor to androgen synth? What are the most common adrenal androgens?

Answer 3

17-a-hydroxypregnenolone–> DHEA, DHEAS, androstenedione–> Testosterone.

DHEA and DHEAS.

Question 4

Cushing’s syndrome? Possible causes?

Answer 4

Excess cortisol. The intermediate is androgens, so there’s also a hyperandrogenic state.

Pituitary adenoma, ectopic ACTH, tumor of adrenal gland

Question 5

MCC of Cushing’s syndrome?

Answer 5

Cushing’s DISEASE- pituitary adenoma that hypersecretes ACTH

Question 6

Clinical sx of Cushing’s

Answer 6

Hirsutism, acne, menstrual irregularities

Question 7

Cushing’s diagnosis

Answer 7

Overnight dexamethasone suppression test.

If normal, negative feedback from dexamethasone will suppress the ACTH and decrease the adrenal’s production of cortisol.

Morning cortisol > 10ug/dL is diagnostic.
Confirmation by collecting 24 hr urine specimen to check for free cortisol levels.

Question 8

CAH

Answer 8

MC is 21-a-hydroxylase deficiency w/ inc 17-a-hydroxyprogesterone.
Female infant with ambiguous genitalia due to androgen excess.

THIS IS CLASSIC “SALT WASTING” CAH

Question 9

Diagnosis/confirmation of CAH?

Answer 9

Inc 17-OHP level, then confirm with ACTH stimulation test.

If the ACTH results in a marked inc in 17-OHP it is CAH.
Lower levels are later onset CAH or hets

Question 10

Functional ovarian tumors that cause virilization?

Answer 10

PCOS
Theca lutein cysts
Stromal hyperplasia & hyperthecosis

Question 11

Theca lutein cyst diagnosis? Pathophys? Predisposing factors?

Answer 11

Ovarian biopsy

LH stims the theca cells to produce androstenedione and testosterone.

Molar pregnancy, multiple pregnancies, gonadotropin stim during infertility treatment.

Question 12

Stromal hyperplasia age? Ovary appearance?

Answer 12

50-70 yo. Uniformly enlarged.

Question 13

Stromal hyperthecosis?

Answer 13

More likely than hyperplasia is to cause virilization. Ovaries enlarged and fleshy. Younger patients they appear more florid.

Question 14

Drugs that can cause decreases in SHBG?

Answer 14

Androgens and corticosteroids

Question 15

Drugs that cause H&V?

Answer 15

Minoxidil, phenytoin, diazoxide, cyclosporin.

THEY DON’T USE THE ANDROGENIC PATHWAY.

Question 16

Rx for idiopathic hirsutism?

Answer 16

• Glucocorticoid eg. prednisone
• Finasteride
• OCPs

Question 17

How does clomiphene citrate work?

Answer 17

It’s an anti-estrogen that removes the negative feedback of hyperestrogenism so a woman w/ PCOS can ovulate and get pregnant. Ovary then “sees” more FSH.

Question 18

Why is OCP such a great treatment for hyperandrogenism of various causes?

Next step if this fails?

Refractory rx?

Answer 18

It stims the production of SHBG thus binding up some of that circulating androgen!

Try for at least 6 months before you move to something else.

It DOES NOT reduce the hirsutism that is already present.

Next, add spironolactone

GnRH agonists (eg. leuprolide). Good at treating hirsutism but bad side effects. Cause a state of menopause by dec androgens AND estrogens in the serum.