Lecture 9 - PCOS & Adrenal Disorders Flashcards
PCOS
Polycystic Ovary Syndrome
diagnosed by presence of 2 of 3 following criteria…
Hyperandrogenism
ovulatory dysfunction
polycystic ovaries
PCOS Pathophysiology
Never get to Corpus Luteum stage and make the primary follicle
Abnormal LH/FSH production in anterior pituitary. Pts with PCOS have 2-3 times normal ratio LH/FSH (Making more LH)
LH prevents primary follicle
Can have infertility
LH causes a lot of excess androgen production
convert cholesterol to testosterone more efficiently = more test
have some insulin resistance, and hyperinsulinemia = more test
Menstral irregularities
Oligomenorrhea = < 8 periods per year or menstruation cycle with duration > 35 days
Amenorrhea = no menstration for > 3 months w/o pregnancy
PCOS Clinical presentation, any of the 2 to be diagnosed
Central irregularities
Hyperandrogenism
Polycystic ovaries
Insulin resistance
Obesity
Polycystic ovaries defintion
> 20 follicles measuring 2-9mm or an inc in ovarian volume of 10ml in either ovary with no evidence of dominant folicclesa or corpora lutea
PCOS complications
Reproductive consequences
Endometrial cancer
Metabolic consequences
CVD risk
Obstructive sleep apnea
Depression
PCOS Risk factors
Menarche at early age
Weight
Family history of PCOS
Clomiphene MOA:
Selective estrogen receptor modulator
Clomiphene Clinical benefit
Management of infertility
higher risk of multiple births compared to letrozole
rec adding metformin in pts > 28yrs old who have clomiphene resistance and visceral obesity
Clomiphene Dosing
50mg PO 5 days, start 5th day of cycle
can titrate up to 100-150mg in subsequent cycles
dont do more than 6 cycles
Clomiphene CI
Preg or breastfeeding
preg test before each cycle
Clomiphene ADE
Vasomotor symptoms
Flushing
headache
vision changes
Letrozole MOA
Aromatase inhibitor, reduces estrogen production
Letrozole Clinical Benefit
Management of infertility
1st line option
Alternative for clomiphene failures
Letrozole dosing
2.5-7.5mg PO QD on cycle days 3-7
can take up to 5 cycles
Letrozole ADE
Edema
hot flashes
Headache
Fatigue
nausea
dizziness
bone pain
Letrozole CI
Preg
Letrozole DI
CYP3A4 and CYP2A6 substrate
Gonadotropins info
second line therapy for those who failed other treatments
MOA: ovulation induction
Metformin for infertility
2nd line
can add to clomiphene for resistance
can be used as adjunctive therapy during IVF
Dosing: 500mg TID
helps with weight loss, improvement in menstrual cycle, hyperandrogegism symptoms, and insulin resistance
PCOS treatment Algorithm
Obese = start Lifestyle mod 3-6 months then meds
Non obese = meds
if still no preg add metformin
if ovulation returns, try for 6 months
if ovulation not return, see expert
Contraception info PCOS
use very low doses of estrogen (NMT 35mcg ethinyl estradiol)
preference for middle to low androgen or anti androgen progestin
can do intermittent or continuous progestin only
PCOS Oligomenorrhea Treatment Algo
Obese = lifestyle mod for 3-6 months, then continue previous pathway if they want baby
Non obese = if want baby then do previous pathway, if no baby then contraception
Preferred Hyperandrogenism treatment
Spironolactone
Dose: 50-100mg BID
ADE: Hyperkalemia, HA, fatigue
Pt ed : use contraception to prevent feminization of male fetuses; months to see benefit maybe
DI: ACE/ARBs
Finasteride for Hyperandrogenism
Dosing: 5-7.5mg QD
ADE: Hypersensitivity, dec libido
DI: St. Johns Wart
CI: dont use pregnancy
Pt ed: use contraception, can take months
Used for management of hirsutism/alopecia
Eflornithine info
used for Hyperandrogenism
Applied to face BID
ADE: stinging, burning, rash
Pt ed: stop if preg, effects not permanent, weeks to see benefit, apply 5min after hair removal & dont wash for 4hrs after, can apply lotion/sunscreen once dry
PCOS Hirsutism Algo
Obese = lifestyle changes = Contraception for 6 months then can add on meds
Non obese = contraception for 6 months, then add on meds
nonpharm: shaving, waxing, etc
PCOS monitoring
Height, weight, BMI
ADE of pharm therapy
BP
Lipids
Depression/Anxiety
Quality of life
Clinical signs/symptoms of PCOS
Which zone releases mineralcorticoids
Zona glomerulosa, adrenal cortex
Which zone releases glucocorticoids
Zona fasciculata, adrenal cortex
Which zone releases androgens
Zona reticularis, adrenal cortex
Which zone releases stress hormones
Epi & Norepi
Adrenal medulla
Adrenal Gland Excess is called…
Cushing syndrome
hyeraldosteronism
Adrenal Gland excess is called…
Cushing syndrome
Hyperaldosteronism
Adrenal Glass insufficiency is called…
Addison disease
Addison Disease info
also known as primary adrenal insufficiency
severe and life threatening
cortex doesnt produce enough glucocorticoids, mineralocorticoids, dehydroepiandrosterone
Primary vs secondary Adrenal insufficiency
Primary #1 cause = autoimmune, happens at adrenal gland
Secondary #1 cause = long-term glucocorticoid therapy, happens outside adrenal gland
PAI clinical presentation
Hyperkalemia
Hyperpigmentation
Vitiligo
SAI clinical presentation
Pale Skin
Small balls
secondary hypothyroidism
Headache, Visual symptoms
Amenorrhea, dec libido
PAI and SAI clinical presentations that overlap
Tiredness, weakness
Dizziness, orthostatic hypotension
Hyponatremia, hypolycemia
Pharm therapy PAI
Corticosteroids
Mineralocorticoids
potentially DHEA
Pharm therapy SAI
Corticosteroids
preferred therapy for adrenal deficiency
Hydrocortisone
Glucocorticoid dosing
Hydrocortisone = 15-25mg/day
Cortisone acetate 20-35mg/day in 2-3 divided doses preferred
avoid late due to insomnia, give majority in morning and rest later
Glucocorticoid pt education
Take w/ food minimize GI discomfort
dont self D/c, have to be tapered slowly over time
wear med ID indicating on long term steroids
Fludrocortisone (Mineralocorticoids)
ADE: Edema, hypokalemia, HA, muscle weakness, inc BP, hypernatremia
DI: diuretics and AA
used adjunctive therapy PAI
DHEA info
used women on appropriate therapy with low libido
ADE: acne, hirsutism
DI: SSRI, lithium, triazolmam, carbamazepine, estrogen, testosterone
Monitor: morning serum DHEA lvls before taking dose
DHEA implement and monitoring
Pt ed is key
consequences of missed dose
Signs/symptoms of adrenal insufficiency and crisis
stress management
wearing medical alert bracelet
Signs and symptoms of adrenal insufficiency or adrenal excess
Body weight
postural BP
energy lvls
Signs of frank glucocorticoid excess (edema, weight gain)
ACTH Dependent (80%)
known as Cushing Disease (Pituitary Adenoma)
produce too much cortisol
ACTH Dependent (20%)
at level of cortex
General diagnosis of Cushing syndrome
too much cortisol
non-pharm Cushing Syndrome therapy
Surgical intervention (1st line)
radiation therapy
Pharm Cushing Syndrome therapy
Adjunctive to surgery or potential use in pts unable to get surgery
Etomidate info
AE: sedation, nausea, vomiting, hypotension
IV, rarely used
Ketoconazole info
v high dose
ADE: GI, elevated LFTs, gynecomastia
CI: Pts w/ hepatic disease, strong CY3A4 substrate and inhib
not preferred in men
Metyrapone
ADE: Androgenic effect
CYP3A4 inducer
Not preferred In women
need special permission to use in USA
Cabergoline
ADE: Nausea, Dizziness, psychiatric syndromes
not best option if already psychiatric
Pasireotide
$$$$
Hepatic dose adjustment
potential DDI w/ Ketoconazole
Monitoring: Serum glucose, potassium, A1C, LFTs, UFC, thyroid function, HR, ECG
Mifepristone
Abortifacient, cant use in preg women
ADE: Hypokalemia
Req renal and hepatic dosing
preg testing before take
Mitotane
ADE: GI upset, nausea, vomiting, diarrhea, lethargy, somnolence, CNS
Take w/ food for GI, CYP3A4 inducer
Avoid women designing pregnancy, stay in fat for years
monitor: UFC and Urinary steroid production
Cushing Monitoring
Sodium conc
Free T4 conc
Prolactin conc
Cortisol conc
improvement in signs/symptoms
SE of meds
