REI/Office Flashcards
OCPs, STI, HRT, osteoporosis
ddx of vulvar ulcers in young woman
Genital herpes, Folliculitis, Hidradenitis suppurativa, Trauma, Syphilis, Chancroid, Lymphogranuloma venerum, Granuloma inguinale
what is lupron used to treat?
precocious puberty
fibroids
prostate cancer in men
PCOS
When do you evaluate primary amenorrhea and what is on your DDX?
no secondary sex characteristics by 13
secondary sex characteristics, but no menses by age 15
Hypo-/normogonadotropic hypogonadism
- constitutional delay
- Kallman’s Syndrome
- Prolactinoma
- PCOS
- CAH
- stress, weight loss, anorexia
- pituitary tumor
Hypergonadotropic hypogonadism
-ovarian failure
IF there is breast development,
- Mullerian agenesis
- AIS
- imperforate hymen
- vaginal septum
Primary amenorrhea. What is your evaluation?
hcg
TSH
prolactin
and check for breast develop.
Primary amenorrhea. hcg -negative TSH-normal prolactin-normal Normal breast development.
What is on your differential? What is your next step?
AIS
Mullerian Agenesis
imperforate hymen, vaginal septum
pelvic exam, if normal
karyotype
Primary amenorrhea. hcg -negative TSH-normal prolactin-normal NO breast development.
What is on your differential? What is your next step?
Constitutional delay
Kallman’s
stress, weight loss, anorexia
PCOS
ovarian failure
pituitary tumor
Order FSH
How do you counsel a patient with Mullerian agenisis?
- cause unknown
- 15-40% have renal anomalies (horseshoe kidney, renal agenesis)
- 10-15% have skeletal malformations
- IVF with gestational carrier as the ovaries are normal
- treatment goal is the creation of functional vagina to allow intercourse
- McIndoe vaginoplasty-skin graft to form vagina
- Vecchietti- abdominal or vaginal procedure where a spring loaded device is used to maintain tension on the vagina to stretch it and allow for intercourse.
How do you counsel a patient with AIS?
- high testosterone, but absent receptor
- 40% have no family history
- Fertility is not possible
- gonadectomy after puberty to decrease the risk of germ cell cancer
- treatment goal is the creation of functional vagina to allow intercourse
Primary amenorrhea. hcg -negative TSH-normal prolactin-normal NO breast development.
FSH-high
What is on your differential? What is your next step?
hypergonadotropic hypogonadism
Turners Swyer syndrome Fragile X premutation idiopathic premature ovarian failure chemo/rads ovarian surgery
Autoimmune disorders
Primary amenorrhea. hcg -negative TSH-normal prolactin-normal NO breast development.
FSH-low or normal
What is on your differential? What is your next step?
hypogonadotropic hypogonadism irreversible causes Hypothalamic tumor kallman's-GnRH deficiency idiopathic
reversible
anorexia, exercise, stress
secondary amenorrhea.
What is on your differential and how do you evaluate?
hypothyroidism hyperprolatinemia pregnancy ovarian failure PCOS anovulation Brain tumor functional hypothalamic amenorrhea
acquired end organ problem
- cervical stenosis
- ashermans
TSH, prolactin, estradiol, FSH, progestin challenge test
What is a progestin challenge test?
- Give oral medroxyprogesterone acetate (Provera) 10 mg daily for 5-10 days or one intramuscular injection of 100-200 mg of progesterone in oil.
- should see bleeding within 2 weeks after progestin is given
Withdrawal bleeding will usually be seen if the patient’s estradiol level has been over about 40 pg/ml.
Secondary amenorrhea.
TSH-normal
prolactin-normal
progestin challenge test- bleeding within 2 weeks.
DDX
This means that the patient is building a uterine lining and the problem is anovulation/PCOS.
Secondary amenorrhea.
TSH-normal
prolactin-normal
progestin challenge test- NO bleeding within 2 weeks.
DDX and next step
Order FSH
High FSH
Ovarian failure
Low or normal FSH
- tumor
- functional hypothalamic amenorrhea
Hypergonadotropic hypogonadism
Turner Syndrome
-work up
-cardiac echo-bicuspid aortic valve, coarctation of aorta renal sonogram-renal anomalies TFT-hypothyroidism CBC- Glucose screening-prone to diabetes Lipid profile celiac screen hearing test
hypergonadotropic hypogonadism
Turner syndrome treatment
goal is to use exogenous hormones to mimic puberty.
Growth hormone when height is <5th%, usually age 2-5
Estrogen starting at age 13-14.
0.25-0.5mg daily, increase q 3-6 monhts until 2mg daily.
ADD progestin monthly after first bleed or after 12-24 months of estrogen
can turner’s patients get pregnant with their own eggs?
no, donor egg, with a gestational carrier (ideally)
relative contraindication to pregnancy
hypergonadotropic hypogonadism
What is swyer syndrome?
46 XY karyotype
Genetic condition where testes fail to differentiate, thus no testosterone or AMH production, thus no DHT production and thus no male external genitalia
10-15% have SRY gene mutations
hypergonadotropic hypogonadism
Swyer Syndrome counseling
gonadectomy at time of dx to avoid 20-30% risk of gonadoblastoma
- mullerian structure present
- no other medical problems
hypergonadotropic hypogonadism
Can patients w/Swyer Syndrome get pregnant?
yes, but need donor egg.
What kind of autoimmune disorders would cause hypergonadotropic hypogonadism?
How to dx?
autoimmune polyglandular syndrome type 1 and type 2
type 1-childhood onset caused by a mutation in regulator gene on chromosome 21
- hypoparathy in 89%
- adrenal insufficiency (60-80%)
type II is adult onset
- adrenal insufficiency (100%)
- thyroid (70%)
Dx: look for auto-antibiodies to 21 hydroxylase antibodies, anti-thyroid peroxidase and anti-thyroglobulin.
hypo/hypo
define anorexia
define bulimia
A-refusal to maintain normal body weight either through restricting or binging/purging
B-binging with a lack of self control with compensatory purging via vomiting, laxatives, fasting or exercise.
-2x weekly for 3 months
what is the female athlete triad?
disordered eating
amenorrhea
osteoporosis
If your patient is both hypothroid and hyperprolactemic, which do you treat first? why?
thyroid because low t3 and t4 will cause high TRH which will also cause high prolactinemia.
What is kallman syndrome?
hypogonadotropic hypogonadism
congenital GnRH deficiency caused by mutation in KAL gene
-X-linked
-anosmia because the KAL gene encodes the anosmia-1 neural adhesion molecule that promotes GnRH neuron migration
DDX for hyperprolactinemia
Physiologic increases in prolactin Pregnancy breastfeeding stress sexual intercourse eating exercise REM sleep menses
Pathologic causes
- anything that decreases dopamine such as adenoma, hypothalamic stalk interruption bc that is where dopamine is transported, empty sella syndrome
- hypothyroidism
- reduced elimination of prolactin-renal failure, hepatic insufficiency, macroprolactinemia
Decreased excretion
-renal or hepatic dysfunction
neuro-chest wall injury
What medications cause hyperprolactinemia?
antipsychotics-haldol, risperidone, tricyclics, SSRI, chlorpromazine, thioridizine
prokinetics-metoclopromide
anti-HTN-alpha methyldopa, verapamil
morphine, ramitidine
buspirine
How does prolactin cause irregular menses and infertility?
- increased prolactin causes a decrease GnRH which causes a decrease in FSH/LH which causes a decrease in Estaradiol
- prolactin decrease androgen synthesis
- prolactin decreases aromatase activity
- prolactin causes early luteolysis
How high of a prolactin suggests adenoma?
200 ng/mL
Hyperprolactinemia workup
- repeat the level while fasting because a high-protein meal can elevate prolactin.
- check TSH, medications
- CMP to rule out real/hepatic dysfunction
- bHCG
- IGF-1 if concerned fro growth hormine excess
- brain MRI
macroadenoma workup
The question is which hormone is in overproduction?
- TSH for thyrotrophic adenoma
- FSH/LH for gonadotroph
- IGF-1 for somatotropin-secreting hormone
- 24hr urine free cortisol for corticotropin-secreting lesion
visual field testing
dopamine agonist
-q6months MRI
What are the treatment options for hyper PRL
- do nothing
- dopamine agonists
- surgery
- radiation
Name 2 dopamine agonists?
side effects?
bromocriptine 1.25mg PO at dinner or bedtime or give as vaginal suppository
-n/v, orthostatic hypotension, depression, nasal congestion
Cabergoline
- 25mg twice weekly or 0.5 weekly
- rare n/v
- well tolerated
When to operate on prolactinoma?
recurrence rate?
complications?
failed meds, has biparietal visual field defects, ademona size is unchanged despite normal prolactin level
microadenomas- <10%
macro->80%
complications-pit insufficiency, diabetes, CSF leak, meningitis, loss of vision, mortality
treatment for microprolactinoma
asymptomatic? rpt q 6-12 months
symptomatic-dopamine agonist, check PRL 1 months after starting, then 4-6 months, then yearly once stable.
follow with q2yr MRI
When to stop dopamine agonist?
2 years, asymptomatic, normal prolactin level, no tumor on MRI
Pregnancy, can they continue cabergoline or bromocriptine?
no, stop in 1st trimester
Only give meds for visual impairment
What is empty sella syndrome?
the subarachnoid space herniates down into the pituitary fossa which compresses the gland against the sella floor
80% occur in women
75% obese
40-50 yrs old
<1/3 are symptomatic
New patient infertility ddx
Ovarian
- low egg count and/or quality
- PCOS
- endometriosis
- primary ovarian insufficiency-turners, swyers, chemo/rad, ovarian surgery
- hypogonadotropic hypogonadism-anorexia, stress, exercise, Kallman
- hyper-PRL
Uterine/Cervical
- polyp
- fibroid
- endometrial scarring
Fallopian tube
-PID
Male factor
define fertility, fecundibility, fecundity
fertility- abilty to achieve a clinicaly recognized pregnancy
fecundibility- ability to get pregnant in a single cycle
fecundity-ability to achieve a life birth
When to refer to REI for infertility?
- oligomenorrhea
- uterine, tubal disease, or peritoneal disease
- stage III or IV endo
- male factor
infertility work up
Women
- prenatal labs-CBC, Hep C, HIV, Type and screen
- Ovarian reserve testing
- TSH/Vit D
- prolactin ONLY IF menstrual abnormality
- US/Hysterosalpingogram
- screen for CF, SMA, hemoglobinopathies
Men
- Hep C, HIV, Type and screen
- Semen analysis
How to perform a clomiphene citrate challenge test?
Check FSH on cycle day 3, then give clomiphene 100mg PO on CD 5-9.
FSH should stay under 10, if it rises then E2 is not suppressing FSH and the pt may have diminished ovarian reserve
Check FSH/estradiol cycle day 2-4
- Normal FSH <10 mIU/mL, High is >15
- normal estradiol is 60-80pg/mL
YOU NEED BOTH FSH & E2, bc E2 suppresses FSH.
How to diagnose diminished ovarian reserve?
what is it predictive of?
Next step if diagnoses?
- AMH <1 on any cycle day
- elevated FSH on clomiphene citrate challenge test
- FSH >10 with normal estradiol on CD 2-3
- antral follicle count <5-7 by sono
- <4 ooctyes retrieved during IVF
predicts response to stimulation NOT ability to get pregnant
Consider testing for fragile X if unexplained diminished ovarian reserve.
How to rule out anovulation?
- monthly menses
- LH surge on ovulation kit
- day 21 progesterone >3 ng/mL
DDX of male factor infertility
Pre-testicular
- kallmann syndrome
- idiopathic low GnRH–> low LH–>low T–> low sperm
- steroids
- pituitary mass
- Hyper-PRL
Testicular
- klinefelters, Y microdeletion
- chemo/rads
- trauma
- varicocele
Post-testicular
-absent vas deferens, retrograde ejaculation, ED, ejaculatory duct or epididymal obstruction
How to perform semen analysis?
What is a normal result?
Next step if abnormal
2-4 days abstinence
Volume-1.5ml Concentration-15 mil/mL Motility-40% Morphology - AT LEAST 4%, 14% is excellent -absent agglutination
-repeat semen analysis then refer to REI or urologist
Minimal sperm counts for:
- intercourse
- IUI
- IVF
- ICSI
-Intercourse: >20mil
-IUI: >5 million total motile count
-IVF: 30k-100k per oocyte
-ICSI: 1 viable sperm per oocyte
intracytoplasmic sperm injection
What factors make tubal reversal more successful?
- Otherwise good fertility workup-must do semen analysis
- method of tubal ligation-clips
- isthmic is better than ampullary ligation (Isthmus, ampulla, infundibulum, fimbria)
- tubal length greater than 4cm
- 50-75% success
When should you remove fibroids for fertility purposes?
ONLY if recurrent miscarriages, highly symptomatic or impinging on uterine cavity
Ovulation induction w/clomiphene citrate
MOA
estrogen agonist/antagonist (SERM), binds to estrogen receptor on hypothalamus, which blocks estrogen’s negative feedback on hypothalamus. This creates a pseudo-hypoestrogenic state. Hypothalamus increases GnRH, which increases FSH, and thus follicle development.
Ovulation induction w/clomid
administration and side effects
50mg daily on days 5-9 max 150-200mg for 3 months if regular cycles 6 months if abnormal cycles then refer to REI for IUI
hot flashes, headaches, visual changes
visual changes associated with increased risk of stroke.
Ovulation induction w/letrozole
MOA
aromatase inhibitor leading to true hypoestrogenic state which increases GnRH, which increases FSH, stimulates follicle development.
Ovulation induction w/letrozole
administration and side effects
2.5mg - 5mg PO x 5 days CD 3-7
hot flashes, headache, decreased bone mineral density, nausea, constipation
PCOS which is better clomid vs letrozole
Letrozole is first line for induction
When to do intracytoplasmic sperm injection?
- male factor infertility
- genetic conditions
- few oocytes (cant take chances)
- -frozen eggs
When to do intracytoplasmic sperm injection?
- male factor infertility
- genetic conditions
- few oocytes (cant take chances)
- frozen eggs
- failed traditional IVF
recurrent pregnancy loss definition
2+ losses at <20wks
excluding molar, ectopic, biochemical pregnancies
recurrent pregnancy loss ddx
Anatomic-fibroids, polyps, septumm adhesions
Genetics-autosomal trisomies due to aneuploid gametes, balanced translocations
Endocrine-hypothyroid, diabetes, PCOS,
Immunologic-lupus
Smoking, EtOH >2/day, caffeine (>300 mg/day)
Infectious-no strong evidence, perhaps BV and chlamydia
Thrombotic-only test if personal DVT hx of familial thrombophilia risk
recurrent pregnancy loss workup
- TVUS
- saline sono
- parental karyotypes
- AMH, day 3 FSH/E2
- prolactin
- TSH (goal <2.5)
- A1C <7%
- anti-phospholipid work up ONLY if 3+ losses <10 wks
Treatment for antiphospholipid syndrome
heparin 5k BID with ASA 81mg or lovenox 40mg daily with ASA 81mg
When to test for antiphospholipic syndrome?
How to test for APS?
You need one clinical and one lab criteria:
- hx of clots
- 3+ losses <10 wks
- PTD <34 wks due to PEC or placental insufficiency (IUGR).
- test two 12 weeks apart
- anti-cardiolipin
- lupus anticoagulant
- beta2 glycoprotein
When to evaluate for precocious puberty?
<6 w/breast or pubic hair development
<8 w/both breast AND pubic hair development
Precocious puberty
DDX
GnRH dependent- early activation of HPO axis
- constitutional/idiopathic
- CNS pathology
GnRH independent
- Ovarian tumors
- McCune allbright
- adrenal tumor/ CAH
- exogenous estrogen exposure
- hypothyroidism
Precocious puberty workup
bone age via left wrist x-ray
GnRH stim test to differentiate between GnRH dependent vs independent causes
Give leuprolide 20 microgram subQ, check LH 30-40 minutes later, if >6 then HPO axis is activated and the cause is GnRH dependent
Precocious puberty
workup
GnRH stim test with LH >6
next step?
MRI for CNS pathology looking for hamartoma
indications for treatment of precious puberty
- sexual maturity progresses to next stage in 3-6
- growth velocity is >6cm/yr
- bone age advanced more than 1 year
- predicted adult height is less than target range or is gradually decreasing
Treatment for GnRH dependent precocious puberty
what lab do you follow and how often?
GnRH agonist
check estradiol q3-6 months, goal <10 pg/mL
- psychological counseling
- treat the child like chronologic age.
What is McCune Allbright Syndrome? and how is it diagnosed?
-continuous estrogen production because the G protein cannot turn off adenlyate cyclase
-clinically, but can test for GNAS mutation Café-au-lait spots Polyostotic fibrous dysplasia (PFD) Precocious puberty Hyperthyroidism Growth hormone excess Cushing syndrome
Work up for premature adrenarche
treatment for isolated premature adrenarche
- x-ray for bone to differentiate precious puberty from isolated adrenarche.
- Exclude CAH by checking 17 OHP
- if isolated, serial exams/heigh checks
- consider imaging for adrenal mass
work up for premature thelarche
none usually self-limited, but check for precious puberty
work up premature menarche
consider McCune Allbright
check for other causes of vaginal bleeding in child-trauma, foreign body like tissue paper, infection, neoplasm
How to diagnose PCOS
2 out of 3
- anovulation
- signs of hyperandrogenism (hair, acne, elevated testosterone, DHEAS)
- polycystic ovaries (12+ antral follicle or total volume >10cc
PCOS workup
Are they ovulating?
-Check day 21 progestrone level to check for ovulation, >3 means ovulation
If anovulatory, rule out other causes of anovulation.
- bhcg
- TSH/PRL to rule out other causes of anovulation
- CD 3 FSH/estradiol to get for hypo/hypo as the cause of anovulation
Rule out other causes of hyperandrogenism
- testosterone
- DHEAS if concerned for tumor
- 17 OHP to rule of CAH
Check for metabolic syndrome 3/5 -fasting glucose >110 -waist >35in -triglycerides >150 HDL <40 -BP >130/85
Check for endometrial hyperplasia-EMB
Patient presents with excessive hair growth, acne, deepening of the voice
DDx
Elevated Androgens PCOS Exogenous androgens Non-classical CAH HAIR-AN syndrome Androgen secreting ovarian and adrenal tumors Cushing Syndrome idiopathic
Menstrual irregularities Thyroid dysfunction hyperPRL hypothalamic amenorrhea primary ovarian insufficiency obesity
Hyperandrogenism work up
testosterone DHEAS SHBG 17 OHP to rule out CAH TVS for ovarian tumor ONLY get CT if concerned if concerned for adrenal malignancy
What testosterone and DHEAS levels make you want to rule out tumors?
T> 200
DHEAS >700
What organ does DHEAS come from?
adrenal gland
Dehydroepiandrosterone sulfate
What organ does androstenedione come from?
50/50 ovary and adrenal cortex
What is HAIR-AN syndrome?
Hyperandrogenism, insulin resistance, and acanthosis nigricans.
Ovarian Theca cell hyperplasia causing excess androgens
You are testing for non-classical CAH. What lab do you order and how do you interpret the results?
17-OHP in the follicular phase early AM
<200 rules out non-CAH
>800 rules in non-CAH
in between 200 and 800–> repeat it, then perform ACTH stim test
What is an ACTH stim test?
adrenocorticotropic hormone
give ACTH, if 17 OHP is greater than 1500, non-classical CAH is diagnosed
Hyperandrogenism
elevated T and elevated DHEAS
CT showed adrenal mass,
Next Step?
rule of pheochromocytoma then perform FNA because most adrenal adenomas are malignant.
Clinical features seen in cushing syndrome but not PCOS?
proximal muscle weakness, moon facies, easy bruising, buffalo hump, moon facies,
both can have hirsutism, HTN, central obesity
If Hirsuitism patient has normal androgen levels and normal menstrual functions, which enzyme is likely the cause?
5-alpha reductase
Treatment for hirsuitism
hair removal-plucking, wax, cream, electrolysis, laser
Medical OCPs, spirnolactone, eflornithine, finasteride, flutamide
How do OCPs treat hirsuitism?
decrease LH and increase SHBG, decrease adrenal DHEAS, inhibits 5alpha reductase in the skin
60-80% of patients show improvement.
Can take 6 months.
What is in sprintec?
Norgestimate 250mcg, ethinyl estradiol 35mcg
spironolactone MOA, SE,
aldosterone antagonist
SE: dyspepsia, nausea, urinary frequency, fatigue, decreased libido, headache, sun sensitivity
USE WITH OCP-can cause feminization of male fetus
eflornithine MOA, SE
inhibits ornithine decarboxylase which inhibits cell division and synthesis functions, which decreases hair growth
SE: skin sensitivity
apply cream BID and use with hair removal technique
finasteride MOA, SE
5 alpha reductase inhibitor
least effective, few side effects
flutamide MOA, SE
androgen receptor blocker used in prostate cancer
SE: dry skin, green urine with liver function abnormalities.
last line option
What is the physiology of PCOS?
cycle of increased LH and insulin leading to high ovarian testosterone production. High T results in inhibition of follicular maturation resulting in many small follicles and anovulation.
PCOS management if pregnancy is desired
vs pregnancy not desired
diet and exercise for everyone
-letrozole with or w/o metformin for ovulation induction
OCPs is first line
Which type of male gonadal cells produce AMH?
serotli cells
Which type of male gonadal cells produce testosterone?
leydig cells
Describe the development of external male genitalia.
Leydig cells produce testosterone.
5a reductase converts T to DHT which leads to external genitalia and prostate.
SRY determine if gonads become ovaries or testes
Which structures come from the wolffian ducts?
epididymus, vas deferens, seminal vesicle, ejaculatory duct
mesonephric
Which structures come from the mullerian ducts?
fallopian tubes, uterus, cervix, and upper third of vagina
NOT Ovaries
paramesonephric duct
What is the recommended daily allowance of calcium?
Vitamin D?
The RDA for calcium is 1,000 mg per day from ages 19 to 50 years and 1,200 mg per day in older women.
For vitamin D, the RDA is 600 international units per day to age 70 years and 800 international units thereafter.
You get called for Ambiguous genitalia.
How do you evaluate this patient?
First get a hx and exam (drugs, maternal virilization, anybody in the family)
hyperpigmentation is suggestive of ACTH/adrenal origin.
17 OHP, karyotype, maternal u/s looking for luteoma
DDX
CAH- 17 OHP
aromatase deficiency
maternal tumor, drugs, luteoma
