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Hirsutism and Virilization Pathophysiology

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About what percentage of hirsute women have cases due to hyperandrogenism?
50
Is the number of hairs per unit area on the body identical for men and women?
yes
What Ferriman-Gallwey score diagnoses hirsutism?
>8
Which type of hair growth is under androgen control?
terminal (other type is fine, unpigmented - vellus)
What is responsible for Tanner Stage 2 hair growth?
adrenal gland
What is responsible for Tanner stages 3-5 hair growth?
gonads (at puberty, normal pubic and axillary)
Does menses or breast development usually occur first?
breast development (2 yrs)
At what age should a caucasian girl with signs of puberty be evaluated for precocious puberty? African-American?
7, 6
What happens to terminal scalp hairs as a result of androgen stimulation?
recede, become vellus
What does 17-ketosteroid reductase do?
convert androstenedione to testost
What does 5alpha-reductase do?
convert testost to dihydrotest
What do testosterone and dihydrotestosterone do to hair? Are they necessary for hair growth?
stimulate growth, pigmentation, sebum production, yes
What controls adrenal androgen secretion? ovarian?
ACTH, LH
Where does androstenedione come from?
50% adrenal, 50% ovary
Where do dehyroepiandrosterone and DHEAS come from? What level indicates an androgenizing adrenal tumor?
adrenal, >18.5 (micromol/L)
Where does testosterone come from? What level indicates a virilizing tumor?
ovaries and extra-gland tissue, >12 (nmol/L)
What substances are precursors of testosterone?
androstenedione, DHEA
When does idiopathic hirsutism usually begin?
adolescence
Are menses, ovarian size, adrenal function and androgen concentrations normal in idiopathic hirsutism?
yes
What is most likely responsible for idiopathic hirsutism?
increased 5alpha reductase activity
What characterizes pathologic hirsutism?
increased androgens (usually w/ virilization/defeminization proportional to amount of androgen production)
When does pathologic hirsutism usually begin?
anytime (not coordinated with adolescence)
What is the most common cause of pathologic hirsutism?
PCOS
What is the classic triad of PCOS?
obesity, hirsutism, secondary amenorrhea
What causes the secondary amenorrhea of PCOS?
chronic anovulation
When does PCOS usually present?
teenage
Is insulin resistance a frequent finding in PCOS? What increases incidence?
yes, obesity
What is the most elevated steroid in PCOS?
androstenedione of ovarian origin
What is the result of increased GnRH and LH pulse frequencies in PCOS?
(1) increase androstenedione (via ovarian theca cells)
(2) androstenedione to testost (in theca via 17-ketosteroid reductase)
(3) aromatization to estrone (granulosa cells, hep, adipose)
(4) estrone to estradiol (17bOH dehydrog in skin, adipose, breast)
What does insulin do to ovarian theca cells?
increase testost (works w/ LH)
What does insulin do to the liver?
decrease SHBG, increasing free testost/estradiol
What result does elevated insulin and estrone have for LH and FSH?
increase LH (both), decrease FSH (estrone), increased ratio (often >2.5)
What are the cutaneous manifestations of androgen production?
hirsutism, acne, male-pattern hair loss
What causes the chronic anovulation of PCOS?
excess LH, def FSH
What cancer has increased risk with PCOS?
endometrial (also increases risk for Type 2 DM, high lipids, CAD, metabolic syndrome)
What is the most sensitive lab measure of androgen excess in PCOS?
free testost
How is the hirsutism of PCOS treated? Why?
combination OCP, decrease LH and ovarian androgens, lower risk of endometrial cancer
What 2 interventions will induce ovulation in the majority of PCOS patients?
weight loss, clomiphene (increases FSH and LH secretion, anti-estrogen)
What effect does metformin or tzds have on PCOS?
decrease insulin resistance, lower androgen levels, allow ovulation
Why shouldn't spironolactone be given for hirsutism? After all, it blocks the androgen receptor in the hair follicle.
teratogen
What diseases are characterized by rapid hirsutism development?
adrenal or ovarian tumors (pituitary adenoma/cushings?)
When in life does an androgen secreting tumor typically present?
3rd decade+
What abnormality causes a marked testosterone increase without much DHEA increase?
ovarian tumor
What abnormality causes a marked DHEA increase without much testosterone change?
adrenal tumor
What three enzyme deficiencies cause hirsutism, oligomenorrhea, and virilization?
21alpha, 11beta (hydroxylase), 3beta (hydroxysteroid dehydrog)
What is the most common adrenal gland enzyme defect causing hirsutism?
21alpha def
When does late-onset 21alpha hydrox def usually present?
puberty (clitoromeg, short height, acne, hirsutism)
Does 21alpha hydroxy def have a normal speculum exam?
yes
What disease elevates ACTH, DHEA and 17-OHP?
adrenal hyperplasia
What disease causes LH/FSH ratio of >2.5?
PCOS
What substance will be elevated diagnostically on ACTH administration in adrenal hyperplasia?
17alphahydroxyprogesterone
What is the treatment for adrenal hyperplasia?
glucocorticoids
What is the difference between the adrenal hyperplasia variants?
11 has HTN from deoxycorticosterone, 3 does not have 17OHP elevation on ACTH challenge
What will be increased if Cushing's is a cause for hirsutism?
cortisol, DHEA
What will be increases if a pituitary adenoma is the cause for hirsutism?
DHEA (also see gynecomastia etc.)
What meds cause hirsutism? Do they cause virilization?
mioxidil, phenothiazines, cyclosporine, phenytoin, no
What disease may have normal levels of DHEA, ACTH, 17-OHP and testost but still show hirsutism?
PCOS (LH/FSH will be elevated)
What will be particularly elevated in an androgen-secreting ovarian tumor?
testost
What will be particularly elevated in an androgen-secreting adrenal tumor?
DHEA
What can androstenedione be made into?
estrone (aromatase), testost (17ketoreduct)
What can testosterone be made into?
estradiol (aromatase)
What can estrone be made into?
estradiol (17ketoreduct)
What can DHEA be made into?
androstenedione (3beta)
What can 17-OH progesterone be made into?
androstenedione (17hydrox), cortisol (21, 11 via 11-deoxcortisol)
What can progesterone be made into?
17-OH progest (17 hydrox), corticosterone then aldo (21, 11 via deoxycort, aldo)
What is the initial precursor of adrenal hormones?
cholesterol to pregnenolone via desmolase