23: Hirsutism and virilism

Question 1

Virilism

Answer 1

constellation of symptoms including hirsutism, deepening of the voice, frontal balding, clitoromegaly, and increased musculature.

Question 2

primary causes of hirsutism and virilization include

Answer 2

PCOS, ovarian tumors, adrenal tumors, CAH, and Cushing syndrome

Question 3

Diagnosis is made by ?

Answer 3

history and physical, serum assays for testosterone, DHEAS, and 17-OHP, and imaging studies.

Question 4

Management involves primary treatment for the underlying cause; ?

Answer 4

hormonal therapy with OCPs, GnRH, or progestins; and cosmetic treatment of hirsutism.

Question 5

An abnormal increase in terminal hair is due to androgen excess or increased activity of what enzyme? which converts ? to the more potent ?

Answer 5

5α-reductase

testosterone to dihydrotestosterone, believed to be the main stimulant of terminal hair development.

Question 6

In the adrenal glands, androgens are synthesized from the precursor ?, which is converted to ?

Answer 6

17α-hydroxypregnenolone–>dehydroepiandrosterone (DHEA) and its sulfate (DHEAS)–>androstenedione–>testosterone

Question 7

elevated ? levels increase all the steroid hormones, including the androgens

Answer 7

ACTH

Question 8

? is derived almost entirely from the adrenal glands, so its elevation is used as a marker for adrenal androgen production.

Answer 8

DHEAS

Question 9

In the ovary, any increase in ? appears to lead to excess androgen production. Further, tumors of both the ? can lead to excess androgens.

Answer 9

LH or in the LH:FSH ratio

adrenal gland and the ovary

Question 10

Cushing syndrome may be caused by ?

do not have cushing syndrome if plasma cortisol after dexamethasone suppression tests is less than ?

Answer 10

pituitary adenoma, ectopic sources of ACTH, and tumors of the adrenal gland.

5ug/dL
greater than 10 is diagnostic

Question 11

Congenital adrenal hyperplasia (CAH)
most common deficiency?
check?

Answer 11

21α-hydroxylase deficiency

• check 17-OHP: will accumulate (greater than 200 ng/dL) and is then shunted to the androgen pathway, will have salt wasting and adrenal insufficiency and ambiguous genitalia due to androgen excess
• others: 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiencies

Question 12

confirmation test for CAH

Answer 12

ACTH stimulation test in which Cortrosyn (ACTH) is given IV and a 17-OHP level is checked after 1 hour. A marked increase in 17-OHP is consistent with CAH, with lower elevated values being seen in late-onset CAH and heterozygote carriers for the 21α-hydroxylase deficiency

Question 13

cause of androgen excess in PCOS appears to be related to ? which are thought to be caused by an increase in the ?

Answer 13

excess LH stimulation leading to cystic changes in the ovaries and increased ovarian androgen secretion.

pulsatile frequency of GnRH but what causes this increased frequency is unclear.

Question 14

Stromal hyperthecosis

Answer 14

• characterized by foci of utilization within the hyper plastic stroma
• more likely than simple hyperplasia to result in virilization as the utilized cells continue to produce ovarian androgens

Question 15

Functional ovarian tumors that can produce varying amounts of androgen

Answer 15

sex-cord mesenchymal tumors, Sertoli-Leydig cell tumors (arrhenoblastoma), granulosa-theca cell tumors, hilar (Leydig) cell tumors, and germ cell tumors (gonadoblastomas)

Question 16

luteoma

Answer 16

a benign tumor that grows in pregnant women in response to hCG

• can result in high levels of testosterone and androstenedione and virilization in 25% of patients
• virilization of 65% of female fetuses

Question 17

Androgens and corticosteroids decrease ?, leaving a greater percentage of free testosterone circulating

Answer 17

SHBG

Question 18

drugs such as ? will cause hirsutism without using androgenic pathways.

Answer 18

minoxidil, phenytoin, diazoxide, and cyclosporin

Question 19

hirsute woman with normal free testosterone, an assay for ? is performed to determine whether increased peripheral enzymatic activity is responsible for the development of hirsutism.

Answer 19

5α-reductase activity

Question 20

Rapid onset of virilization and testosterone levels >200 ng/dL may indicate an ?

Answer 20

ovarian neoplasm.

Question 21

Adrenal nonneoplastic androgen suppression can be achieved with ?

Answer 21

glucocorticoid administration, such as prednisone 5 mg qhs. Finasteride (5α-reductase inhibitor), thus diminishes peripheral conversion of testosterone to DHT. Antiandrogens such as spironolactone have been helpful as well, but are temporizing at best.

Question 22

ovarian nonneoplastic androgen production can be suppressed with ? that will suppress ? as well as increase ?

Answer 22

OCPs (Progesterone alone may help patients with CI to estrogen use) GnRH (requires estrogen replacement)
will suppress LH and FSH
increase SHBG

Question 23

PCOS is a diagnosis of exclusion- when 2/3 Rotterdam criteria are met:

Answer 23

secondary amenorrhea/oligomenorrhea
evidence of hyperandrogenism or
evidence of polycystic ovaries as assessed by ultrasound.