rei case(s) - wesley ob/gyn · gene alterations genes regulating gonadotropin secretion/action,...
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REI CASE(S)Laura L. Tatpati, MD
Division of REI, Dept of OB/GYNKUSM - W
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CASE #1
➤ 46 year old female presents
with complaint of increased
facial and abdominal hair
growth for 6-8 months.
➤ She has had increased acne.
Her hair stylist noted to her
that she is having hair thinning
at the crown.
➤ She has history of slightly
irregular menstrual cycles but
only 2 in the last 8 months.
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WHAT’S THE
DIFFERENTIAL
DIAGNOSIS?
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DIFF DX: HIRSUTISM
➤ PCOS (75-80%)
➤ Ovarian tumors (SertoliLeydig, stromal cell) - (0.2%)
➤ Adrenal tumors
➤ Stromal hyperthecosis (severe insulin resistance & mostly
post-menopausal)
➤ Late-onset 21-hydroxylase deficiency
➤ Drugs (androgens, androgenic progestins)
➤ Idiopathic
➤ Luteoma of pregnancy/ hyperreactio luteinalis
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PRINCIPAL CAUSES OF HIRSUTISM
➤ Increase in circulating androgens
➤ Ovarian, adrenal, or exogenous
➤ Increase in target hair follicle sensitivity
➤ Due to excess 5α- reductase activity
➤ Normal androgen levels
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MAIN CONDITIONS OF EXCESS HAIR
GROWTH➤ Hirsutism: male pattern, affects 5-10%
➤ Virilization: androgenic state
➤ hirsutism, deepening of the voice, breast atrophy, increased muscle bulk, clitoromegaly, increased libido, acne, and male-pattern balding (androgenic alopecia)
➤ Hypertrichosis: diffusely increased total body hair
➤ drugs such as phenytoic, minoxidil, cyclosporine
➤ hypothyroidism, anorexia, malnutrition
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HISTORY
SHOULD YOU
OBTAIN?
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FURTHER
HISTORY➤ Other symptoms:
➤ Hair loss
➤ Voice deepening
➤ Endocrine ROS
➤ Family history
➤ menstrual, reproductive,
endocrine, cancers
➤ Medications:
➤ Danazol, valproate,
antipsychotics, androgens
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IMPORTANT
HISTORICAL
CONTEXT➤ Timing of onset of symptoms
➤ Menstrual history
➤ Tempo of progression of
symptoms
➤ Severity of symptoms
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PHYSICAL
FINDINGS WOULD
YOU BE LOOKING
FOR?
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PHYSICAL
EXAMINATION➤ Hair Pattern/Distribution
➤ Ferriman-Gallwey
➤ Mediterranean, hispanic, middle eastern
> 9-10
➤ AA/C - >8
➤ Asian > 2
➤ Acne
➤ Male pattern hair loss
➤ Virilization
➤ Clitoromegaly
➤ (L > 10mm, LxW > 35mm2)
➤ Voice deepening
➤ Increased muscle mass
➤ Temporal / Crown balding
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SPECIAL
CONSIDERATION
S➤ Acanthosis nigricans
➤ Striae
➤ Easy bruising
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TEST WOULD
YOU LIKE TO ORDER
?
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YOUR INITIAL TEST RESULT WAS:
TESTOSTERONE - 150 NG/DL
YOU ALSO ORDERED A:DHEAS - 720 MCG/DL
Further evaluation at this point?
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TRANSVAGINAL ULTRASOUND
Result : Normal
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SUSPICIOUS
FINDINGS➤ large cysts (> 8 cm)
➤ solid masses
➤ complex cysts which do not
resolve in 2-4 wks
➤ **hilus cell / sex cord stream
tumors may not be visible on US
or even at surgery
➤ Sertoli-Leydig
➤ ave. 16cm at dx
➤ 2nd/3rd decade
➤ nearly completely solid without
polycystic appearance and
increased storm - hyperthecosis
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CT - ADRENAL GLANDS
Results: left adrenal mass - 6 cm
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HOW DO YOU
TREAT HER
HIRSUTISM?
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COMMON METHODS FOR HAIR
REMOVAL➤ Permanent:
➤ Electrolysis
➤ Laser
➤ Eflornithine hydrochloride (Vaniqua) improves outcomes
➤ Temporary:
➤ Depilatory
➤ Shaving
➤ Waxing/Bleaching
➤ Prevention for those w/ chronic hyperandrogenism
➤ OCPs
➤ Spironolactone (antiandrogens)
➤ Finasteride (limited data) - $$$
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CASE #2
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CASE #2
➤ 18 year old female with menses q 1-2 months for 3 years and
none x 4 months
➤ + hirsutism
➤ + acne - utilizes topical antibiotics with some benefit
➤ BMI = 46
➤ Reports fatigue is affecting her grades in college
➤ What is the most likely diagnosis?
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WHAT TESTIN
G WOULD
YOU DO?
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IRREGULAR
MENSES,
HIRSUTISM➤ hCG
➤ Testosterone
➤ Prolactin
➤ TSH
➤ 17OHP
➤ FSH/E2
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CONFIRMED PCOS OR
OTHER RISK FACTORS
➤ A1c or 2h GTT
➤ Fasting lipid profile
➤ Screen for cardiometabolic
risk factors
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HOW DO YOU
DIAGNOSE PCOS?
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ROTTERDAM CRITERIA
➤ Need 2 of 3
➤ Hyperandrogenism or hyperandrogenemia
➤ Oligo or amenorrhea
➤ Polycystic appearance on US
➤ FNPO > 12, volume > 10cm3
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PATHOGENESIS: FUNCTIONAL
OVARIAN HYPERANDROGENISM➤ Complex genetic trait
➤ multiple genetic variants and environmental factors interact
➤ twin studies: monozygotic correlation 71%, dizygotic 38%
➤ 20-40% prevalence in mothers/sisters
➤ Ovarian hyperinsulinemia: upregulate androgen production in
response to LH and stimulates adipogenesis.
➤ Incr androgens causes secondary LH elevation and interferes
w/ negative feedback.
➤ LH aggravates ovarian dysfunction.
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GENE ALTERATIONS
➤ Genes regulating gonadotropin secretion/action, insulin
secretion/action, weight/energy regulation; androgen
biosynthesis/action
➤ Altered LH action (incr pulse frequency/amplitude); LH receptor over-
expression in granulosa cells
➤ Granulosa cells prematurely luteinize: overexposed LH receptor,
secrete E2 due to LH inappropriately early; hyper-responsive to FSH
and overproduce E2
➤ Androgen excess from theca cells (enhanced by granulosa
dysfunction) promotes small follicles (increased responsiveness)
➤ Oocyte gene expression dysregulated.
➤ Reduced developmental capacity of oocytes : excessive
androgens and epigenetic metabolic signals
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WHAT LONG-TERM
HEALTH CONSIDERA
TIONS SHOULD
YOU ADVISE HER
ABOUT?
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4 AREAS OF
CONCERN➤ Infertility
➤ Diabetes/Gestational
DM/Insulin resistance
➤ Dyslipidemia
➤ Uterine
hyperplasia/endometrial
cancer
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IN PREMENOPAUSAL WOMEN,
THE MENSTRUAL CYCLE IS A VITAL SIGN!