ovarian disorders Flashcards
PCOS is characterized by
chronic anovulation
polycystic ovaries
hyperandrogenism
PCOS is associated with these diseases
hirsutism obesity DM CBD metabolic syndrome dyslipidemia NAFLD OSA
What is the pathophysiology behind PCOS
Abnormal androgen and estrogen metabolism
Unregulated androgen control
Insulin resistance= hyperinsulinemia
Decreased adiponectin
What are the hormonal inhibitions in PCOS
Inhibin (released from granulosa cells) inhibits FSH
Estrone (released from adipocytes) inhibits FSH= less aromatase= androgens NOT converted to estrogen
How does high insulin affect PCOS
- Positive feedback on androstenedione, making more testosterone, and more estrone, therefor further inhibiting FSH
- Increased LH secretion
- Decreases SHBG and IGF= more free testosterone
How does decreased adiponectin affect PCOS
It is an insulin sensitizer, and regulates lipid metabolism and glucose levels
What does increased LH stimulate
Theca cells to produce androgens
What does adipose to to androgens
converts them to estrogen, which causes negative feedback to the anterior pituitary, decreasing FSH
How does PCOS present
Infertility (PCOS is MCC***) Oligomenorrhea, Amenorrhea (anovulation) Obesity acne hirsutism male pattern baldness acanthosis nigricans
NIH 1990 criteria for PCOS (disorder of ovarian androgen excess) Dx says
Must have: oligomenorrhea + hyperandrogenism
Must exclude: hyperprolactinemia, CAH, and Cushing’s
Rotterdam 2003 crteria for PCOS says
Need 2/3: Ovulatory dysfunction, hyperandrogenism, or polycystic ovaries (12+ follicles)
Must exclude related disorders
(this criteria expands on the NIH criteria, does not replace it)
To have PCOS you must exclude
premature ovarian failure physical stress obesity anovulation 2/2 d/c hormonal contraceptives pituitary adenoma/ hyperprolactinemia thyroid disorder
First line test if you suspect PCOS
Ultrasound! you may see: 12+ follicles, 2-9 mm in diameter "string of pearls" ovarian volume >10mL No evidence of dominant follicle or corpus luteum
To evaluate hyperandrogenism, start with
total testosterone. If normal (40-60), no further eval.
If >60, more testing
Further testing for hyperandrogenism (total testosterone >60) includes
17-OH progesterone (8AM): if >200, CAH
DHEA-S: >700, adrenal source of androgens
Cortisol: >10mcg, cushings
Prolactin: >25 is elevated. normal is PCOS (?)
TSH: Hyperthyroid causes oligo/amenorrhea
B-HCG: always order if amenorrhea!!
Other PCOS labs to get are
Fasting glucose
OGTT or HbA1c
Lipid profile
How do you treat PCOS
Weight loss (increase SHBG, decrease free T) Metformin IF hyperinsulinemic COC (w/ low androgen) Fertility consult Provera (endometrial protection) Life-long lifestyle modification
What can you add to metformin to help treat infertility
Clomid!
How do you treat hirsutism
COC!
+/- antiandrogen (spironalactone), Topical vaniqa (anti-protozoal), mechanical hair removal
COC effects include
Increase SHBG= less free T
Decrease LH= decrease T production
Risks for PCOS include
Endometrial hyperplasia T2DM HTN HLD CVD stroke infertility metabolic syndrome sleep apnea
What should the ovaries feel like by age
Pre-menarche: not palpable
Reproductive: palpable 50% of time
Peri-menopause: very likely to have functional cysts
Post-menopause: not palpable w/in 3 years
What are characteristics of benign adnexal masses (US)
thin walls <3cm pre-menopause, <1cm post (simple cyst) hyperechoic (teratoma) linear curved pattern (hemorrhagic) homogenous echoes (endometrioma)
What are characteristics of malignant adnexal masses on US
Thick separations >2mm
solid, nodular
increased blood flow to solid component
Functional ovarian cysts include
Follicular cysts (MC**)
Corpus luteum cysts
Theca Lutein cysts
Non-functional ovarian neoplasms include
Epithelial cell: serous, mucinous, endometrioid
Germ cell: benign cystic teratoma
Stromal cell: granulosa, sertoli-leydig, ovarian fibroma
What is the normal ovarian cycle
- At start of each cycle, many primordial follicles fill with follicular fluid.
- ONE follicle in ONE ovary matures into Graafian follicle, and has the ovum (other non-dom follicles regress)
- At ovulation, Graafian follicle ruptures and ovum is released, becoming corpus luteum
- No fertilization= corpud luteum degenerates into corpus albicans
- Fertilization= corpus luteum persists and secretes progesterone to support pregnancy
Describe Follicular cysts
2-8cm
non-malignant
regress after 1-2 cycles
occur 2/2 failure of mature follicle to rupture and release ovum, or, failure of non-dom follicles to regress
Describe a corpus luteum cyst
3-11 cm
Regress after 1-2 cycles
After ovulation, blood accumulates in cavity of corpus luteum stimulating resorption.
If resorption does NOT occur and CL is >3cm, it’s a cyst
If corpus does not rupture, you don’t get a drop in progesterone, and miss a period
Describe Theca lutein cysts
Seen with high HCG levela (abn pregnancy) 2/2 Hydatidiform moles, choriocarcinoma, clomid therapy
Bilateral
Clear, straw fluid
Regress spontaneously w/ underlying d/o Tx
more likely to have septations
Describe a Serous cystadenoma
MC epithelial cell neoplasm, MC in 30-50 y/o
70% benign, 20% malignant
Treat w/ surgery (cyctectomy or oopherectomy)
Describe a mucinous cystadenoma
15% malignancy rate
get very large
US shows multiocular septations
Treatment is surgical
Describe a benign cystic teratoma
MC in reproductive aged women (30)
Originate from primordial cells and found along the path of germ cells from yolk sac to gonads
Composed of well differentiated tissue from ectoderm, mesoderm, or endoderm (germ cell)
Benign cystic teratomas contain
keratinized squamous lining with abundant sebaceous and apocrine glands
Ectoderm is MC origin (hair, teeth, etc)
How do teratomas present
Asymptomatic! found via pelvic exam or incidentally on imaging
Pelvic pain (2/2 torsion or rupture)
Urinary frequency/urgency, back pain
*Pelvic mass on bimanual exam
Labs for a teratoma should include
Transvaginal US (unilateral, complex cyst) CEA, CA-125, AFP, bets HCG (should all be normal)
How do you treat a teratoma
Laparotomy vc Laparoscopy
Ovarian cystectomy vs Oopherectomy
10% recurrence
Describe Theca cell tumors
produce ESTROGEN!
develop along female cell types
can be malignant. develop across lifespan
Describe Sertoli-Leydig cell tumora
produce ANDROGENS!
develop along male gonadal tissue type
can be malignant. develop across lifespan
Describe how ovarian fibromas present
MC in middle age, NO hormone production
result from spindle cell collagen production
Small, solid tumors with smooth surface. Associated with ascites
Ovarian cancer has the highest incidence among
women >63
RF for ovarian cancer include
nulliparity early menarche, late menopause infertility endometriosis FHx ovarian, colorectal, or breast CA (BRCA 1/2, Lynch) High saturated animal fat diet obesity talcum powder Turner's syndrome ERT caucasian
How can you reduce the risk of ovarian cancer
multiparity breast feeding long term oral contraceptive use (5 years) B/l tubal ligation low fat diet *B/l salpingectomy
What are the 4 major histologic types of ovarian cancer
Epithelial
Germ cell
Sex cord and stromal
Neoplasm mets to ovary
Epithelial ovarian cancer subcategories are
- High grade serous carcinoma: MC, arise in fallopian tube
- Endometrioid: arise from ovary, but look like endometrium
- Clear cell carcinoma: arise from ovary, malignant transformation of endometriosis
- Mucinous carcinoma: arise from cervix, but look like cervical epithelium
What is the pathophys theory behind ovarian cancer (ovary theory)
Follicular rupture= ovarian epithelial trauma
Incessant ovulation and subsequent epithelial repair leads to malignant transformation
associated with endometrioid, clear cell, and mucinous ovarian cancer (not serous)
What is the fallopian tube theory behind ovarian cancer
-Mutant p53 (tumor suppressor) creates a signature on the distal fallopian tube
-Distal fallopian tube is where epithelial stem cells are susceptible to DNA damage and malignant change
-Serous tubal intraepithelial cancer results
STIC is a precursor to high grade serous papillary cancer
The fallopian tube theory confirms why
salpingectomy is considered a method to reduce risk of ovarian cancer
No fallopian tube= No signature= no STIC= no cancer
What are the types of germ cell ovarian cancers
Dysgerminoma Endodermal sinus tumor Immature teratoma Mixed Embryonal tumors
How do germ cell ovarian cancers usually grow
quickly, with lymph spread, MC unilaterally, containing a mix of tumor types
*They make markers that help with treatment response!
Describe a dysgerminoma
MC germ cell ovarian tumor
Unilateral
MC in women <30
Produce LDH, some produce hCG
Describe endodermal sinus tumors
Rare Bilateral Occur in childhood and teens Most rapid growing of germ cell neoplasm Produce AFP
Describe an immature teratoma
MC <20
Unilateral
Produce AFP
Describe Embryonal carcinomas
Rare
Occur in childhood and teens
Rapid growth, extensive spread
Produce AFP and HCG
What are the sex cord/stromal ovarian cancers
Granulosa cell, and Sertoli-Leydig
Describe a Granulosa cell ovarian cancer
MC
Causes hyperestrogenism= precocious puberty, post-menopausal bleeding
Seen in 50’s
Describe a Sertoli-Leydig stromal cell ovarian cancer
Rare
Causes hyperandrogenism
Seen in 30’s-40’s
MC ovarian cancer symptoms are
Abdominal bloating or distention Abd/pelvic pain Decreased energy (lethargy) Early satiety Urinary urgency
Other ovarian cancer Sx are
increased abd size indigestion constipation back pain unexplained weight loss abnormal vaginal bleeding
Acute symptoms associated with ovarian cancer are
Pleural effusion
Bowel obstruction
On an ovarian cancer physical exam you MC see
Ascites
inguinal LAD
pelvic mass
Ovarian cancer imaging should include
transabd/transvag US
mammogram/colonoscopy
CT
MRI
CXR
CA-125 (will be >65 is epithelial cancer)
hCG, AFP, LDH (will be high with germ cell tumors)
Why don’t we screen with CA-125
-Because it can be elevated with other conditions, like:
endometriosis, uterine leiomyomata
PID
pregnancy
menstruation
cirrhosis
-Also, it is only elevated 50% of the time in early stage ovarian cancer, and even less in late stage
How is ovarian cancer staged
FIGO!
Treatment for ovarian cancer includes
Surgery (remove tumor and mets, peritoneal washing, remove nodes, hysterectomy)
Chemo (Paclitaxel and Carboplatin 6 cycles at 3 wk intervals)
Why do we want to diagnose early (obvs, but like why)
you can preserve the contralateral adnexa and uterus
