Insulin Resistance, Metabolic Syndrome, Obesity, PCOS, Hirsutism PDF

Insulin Resistance, Metabolic Syndrome, Obesity, PCOS, Hirsutism PA 511 - Clinical Medicine I Misty T.Justus,DMSc, PA-C  Insulin Resistance Gestational Resistance Metabolic Syndrome Outline Obesity Hirsutism PCOS Insulin Resist...

Insulin Resistance, Metabolic Syndrome, Obesity, PCOS, Hirsutism PA 511 - Clinical Medicine I Misty T.Justus,DMSc, PA-C  Insulin Resistance Gestational Resistance Metabolic Syndrome Outline Obesity Hirsutism PCOS Insulin Resistance   Condition in which cells fail to respond normally to insulin  Feature of a number of clinical disorders, including type 2 diabetes, obesity, dyslipidemia & hypertension Insulin  Insulin resistance is a component of Resistance the metabolic syndrome  25% of the general nonobese, nondiabetic population has insulin resistance of a magnitude similar to that seen in type 2 diabetes  Much higher risk for developing type 2 diabetes   Insulin - hormone that allows glucose to enter cells which also reduces blood glucose (blood sugar) Insulin  Released by the pancreas in response to Resistance - carbohydrates consumed in the diet Pathophysiology  Insulin resistance = Normal insulin levels do not have the same effect in controlling blood glucose levels  Etiology poorly understood   Obesity  Sedentary lifestyle  Family history of diabetes  Genetic & environmental factors Insulin  Various health conditions – HTN, Hyperlipidemia, PCOS, Resistance – NAFLD, Hepatitis C, Hx of GDM, other disorders of acute or chronic inflammation Risk Factors  Age > 45  African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander American ethnicity  Certain medications – corticosteroids, protease inhibitors, atypical anti-psychotics   Initially asymptomatic  Signs & symptoms start to appear as blood glucose levels elevate & may include:  Fatigue/Malaise Insulin  Polyuria, Polydipsia, polyphagia Resistance-  Nausea Clinical  Difficulty concentrating  Dizziness Presentation  Vision problems  Slow healing  Skin lesions – Acanthosis Nigricans  Paresthesias Diagnosis of Insulin Resistance   Can be improved or reversed with lifestyle changes  Attain & maintain healthy body weight  Diet  Increase physical activity Insulin  The Diabetes Prevention Program (DPP) showed that Resistance – exercise & diet were nearly twice as effective as metformin at reducing the risk of progressing to Treatment type 2 diabetes  Pharmacologic Tx: Metformin  More frequent monitoring for dx of T2DM  Metabolic Syndrome - Definition Consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) & diabetes mellitus Central obesity Hypertriglyceridemia Low levels of high-density lipoprotein (HDL) cholesterol Hyperglycemia/Insulin Resistance/Impaired fasting glucose .Hypertension NCEP-ATP III Diagnostic Definition of Metabolic Syndrome  Central Obesity The most challenging feature of metabolic syndrome to define is waist circumference Intra-abdominal circumference (visceral adipose tissue) is the most strongly related to insulin resistance & risk of diabetes & CVD. For any given waist circumference, the distribution of adipose tissue between subcutaneous (SC) & visceral depots varies substantially Thus, within & between populations, there is a lesser vs greater risk at the same waist circumference Harmonizing Definition of Metabolic Syndrome Harmonizing Diagnostic Definition of Metabolic Syndrome  Metabolic Syndrome - Epidemiology Prevalence in US 34.7% Prevalence increases with age: 21.3% at 20-39 yrs. 48.6% at >60 yrs. Women: men - generally equal Varies with populations Metabolic Syndrome – Risk Factors/Epidemiology Metabolic Syndrome - Etiology Insulin Resistance- most accepted hypothesis to describe pathophysiology of metabolic syndrome Obesity epidemic: Over nutrition Atherogenic diet (↑ fats, sugars, salt) Sedentary lifestyles Genetic contributions Polycystic Ovarian Syndrome (PCOS): Many common characteristics  Metabolic Syndrome - Principles ↑ overweight/obese population = ↑ Metabolic Syndrome incidence No known common single cause Reflects sedentary lifestyle & over nutrition = excess adiposity of modern world Endothelial dysfunction & atherosclerosis = ↑ CVD & Type II DM Dx Met. Syndrome = identifies people at high-risk CVD & Diabetes  Metabolic Syndrome - H&P PMHx: Type II DM, HTN, hyperlipidemia, insulin resistance, HIV infection Meds: glucocorticoids, antipsychotics, anti-viral drugs (HIV) Family Hx CVD, type II DM, hyperlipidemia, obesity, PCOS Social Hx: ↓ exercise, ↑↑caloric consumption, alcohol intake, smoking H&P: Sx: polyuria, polydipsia, weight loss, angina, PCOS, obstructive sleep apnea BP, BMI, waist & hip circumference, waist to hip ratio CV system, respiratory system, abdomen exams Corneal arcus & xanthelasma, hepatomegaly, hirsutism, acne, acanthosis nigricans Corneal Arcus caused by lipid deposit Xanthelasma: Multiple creamy-orange, slightly elevated dermal papules on the eyelids of a normolipemic individual  Acanthosis nigricans & multiple small pedunculated acrochordons (skin tags) in the neck crease. Both are dermatologic signs of insulin resistance Hirsutism: face & chest (A) Increased hair growth in androgen-dependent hair follicles of the sideburn area, associated with androgen excess. (B) Increased hair growth in androgen-dependent hair follicles of the presternal & periareolar regions. Metabolic Syndrome - Labs Fasting glucose: Normal: 125 (on 2 occasions) 101-125: proceed with 2 hr OGTT (75g glucose load) Glucose < 140: normal Glucose ≥ 200: Type II DM Glucose 141-199: impaired glucose tolerance  Metabolic Syndrome - Labs Obtain these (in addition to fasting glucose): Lipid panel (fasting) CMP - evaluate renal & liver functions UA - proteinuria assess for renal damage (HTN & DM) _TSH & free T4_ - possible cause of obesity Uric acid - ↑risk of metabolic syndrome with hyperuricemia Consider these in appropriate patients: Sleep study - Symptoms of obstructive sleep apnea PCOS - suspected based on clinical features & anovulation - testosterone, luteinizing hormone, & follicle-stimulating hormone. Metabolic Syndrome - Diagnosis 7 different sets of criteria for diagnosis from various organizations Suggested approach: Treat all CVD risk factors individually & aggressively achieving this goal removes the need for a Dx of metabolic syndrome NCEP-ATP III Diagnostic Definition of Metabolic Syndrome 102cm = ~ 40 inches 88cm = ~35 inches Know these criteria for exam  Metabolic Syndrome - Treatment Treat specific conditions separately (HTN, glucose etc.) Goal = reduce CVD & type II DM risk ↓ excess adiposity & resultant insulin resistance Lifestyle modification: Diet & exercise Diet: Low saturated fat, high complex carbohydrates & fiber, no added sugar, low sodium Mediterranean Diet recommended Eliminate sugar sweetened beverages Team-based, interactive approach with frequent contact & motivated patients contributes to weight management  Metabolic Syndrome - Treatment Exercise: Regular moderate-intense physical activity = preventive Aerobic exercise = removal of abdominal fat Minimum 30 minutes moderate exercise daily (~150min/week) Significant impact in pediatric population Caloric value of 1 hour of various exercise based on body weight Smoking cessation – Discuss & offer support/treatment options Pharmaceuticals: Orlistat (Xenical, Alli) - 120 mg PO Tid Sibutramine (Meridia) – removed from market (↑MI, CVA) Phentermine – exact MOA unknown, schedule IV drug Bariatric surgery  Metabolic Syndrome - Treatment Bariatric Surgery Patients with the metabolic syndrome who have a body mass index >40 kg/m2 Patients with metabolic syndrome & BMI of >35 kg/m2 with comorbidities Evolving application - patients with a body mass index as low as 30 kg/m2 & type 2 diabetes Surgical options include: Information about procedures in next section Gastric bypass Vertical sleeve gastrectomy  Metabolic Syndrome - Treatment Insulin resistance & hyperglycemia: Metformin Pioglitazone Rosiglitazone Dyslipidemia: Statins Other lipid-lowering drugs (many choices) HTN: Lifestyle modification Antihypertensive Meds (many choices) +/-Low-dose aspirin (81 mg PO daily) – Risk of bleeding vs benefit Metabolic syndrome = pro-thrombotic & pro-inflammatory state Metabolic Syndrome - Treatment Summary   Fatty liver disease with steatosis, leading to fibrosis, & cirrhosis Metabolic  Hepatocellular carcinoma & intrahepatic cholangiocarcinoma Syndrome  Chronic kidney disease (CKD; defined as a glomerular filtration rate less than 60 mL/min per 1.73 m2) Clinical  Polycystic ovary syndrome Implications  Male Hypogonadism  Sleep-disordered breathing, including obstructive sleep apnea  Hyperuricemia & gout  metabolic syndrome has been associated with an increased risk of cognitive decline & dementia Obesity  Obesity - Diagnosis Body Mass Index: Measure of excess adipose tissue BMI = weight (kg)/height (m)2 BMI > 30 = Obese BMI classifications: 18.5-24.9 = Normal 25-29.9 = Overweight 30-34.9 = Class I obesity 35-39.9 = Class II obesity >40 = Extreme obesity  BMI Discussion BMI used > 100 yrs. to calculate whether people are over or under weight BMI does not distinguish between muscle & fat BMI 18.5 – 24.99 = considered to be healthy: Some people are healthy with other BMIs Some people are unhealthy in this BMI range Examples: BMI 27 (overweight) = Person with no exercise, 6 ft. 203 lbs BMI 28 (overweight) = Olympic athlete, 6 ft. 211 lbs Obesity - Risks Increased risk of multiple health problems: Hypertension Diabetes Dyslipidemia Obstructive sleep apnea Nonalcoholic fatty liver disease Some malignancies Obesity - Risks Upper body obesity (abd & flank) = greater health risk vs. lower body (buttocks & thighs) obesity Centripetal Obesity (>40 inches in men, >35 inches in women) leads to: ↑ DM ↑ CVA ↑ CAD ↑ Early death Obesity – Demographics (Americans) ADULTS 30.7% = overweight 42.4% = obese 9.2% = Severe obesity 60% with obesity have metabolic syndrome 40-70% of obesity = genetic influences < 1% = secondary obesity (hypothyroid, Cushing syn.) Prevalence of obesity among children & adolescents ages 2 to 19 years: United States, 2017–2018 NHANES data3 Projected U.S. State- Level Prevalence of Adult Obesity & Severe Obesity Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity & Severe Obesity. N Engl J Med. 2019;381(25):2440-2450. doi:10.1056/NEJMsa1909301 Obesity Prevalence Increasing over last 3 decades Steadily Increasing with ages 20-60 yrs. Peaks at 60 yrs. then slightly declines Obesity – Approach to the Patient Five main steps in the evaluation of obesity 1. A focused History 2. Physical examination to determine the degree & type of obesity 3. Assessment of comorbid conditions 4. Determination of fitness level 5. Assessment of the patient’s readiness to adopt lifestyle changes Obesity – History considerations What factors contribute to the patient’s obesity? How is the obesity affecting the patient’s health? What is the patient’s level of risk from obesity? What does the patient find difficult about managing weight? What are the patient’s goals & expectations? Is the patient motivated to begin a weight management program? What kind of help does the patient need?  Obesity – H&P Fam Hx obesity: If negative search for extraneous causes Weight gain Hx (over time): Recent vs. chronic Diet & exercise routine: Sedentary vs. active vs. athletic Degree & distribution of body fat: ↑health risks with centripetal obesity Signs of secondary obesity: Cushing syndrome – round face, buffalo hump, striae Hypothyroidism – depression, fatigue, constipation, cold intolerance, etc. Obesity – Evaluation Initial Workup: Measurements: BP Weight & height → Calculate BMI Waist circumference Labs: TSH & Free T4 Fasting lipid panel Fasting Glucose  Obesity – Differential Dx ↑ caloric intake (life changes) Fluid retention (heart failure, cirrhosis, renal failure) Hypothyroidism DM (type 2) Drugs (antipsychotics, antidepressants, corticosteroids) Insulinoma Binge eating disorder  Obesity Treatment – Primary Approach If no underlying condition: 1. Diet & Exercise 2. Diet & Exercise 3. Diet & Exercise Goal: Decrease in 10% body weight over 6 months or 1-2lbs per week Ex: 15 lbs. off 150 lbs, 20 lbs. off 200 lbs, 30 lbs. off 300 lbs Reassess Tx plan after 6 mos. For weight loss one must achieve: Caloric expenditure > caloric intake Obesity Treatment – Caloric Intake recs. Guidelines from the American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) Produce 500-750 kcal/day deficit from habitual diet or Consume 1200-1700 kcal/day – women Consume 1500-1800 kcal/day – men Consumption adjusted for the individual’s body weight Fast food nutrition facts: 1320 Cal = McDonalds Big Mac meal 1430 Cal = Burger King Whopper meal 1690 Cal = KFC 4 piece Chicken meal Weight Loss Diets No single diet superior to others for weight loss in F/U > 1 year (Mediterranean Diet shown to reduce ASCVD) Low-carbohydrate/high-protein diet > wt. loss at 6 mos. Adherence to diet & accurate caloric intake reporting by pts. = problems for studies in dietary intervention for obesity (inconsistency & inaccuracy)  Obesity Treatment - Exercise Combination of dietary modification & exercise is the most effective behavioral approach for the treatment of obesity Exercise-only usually not effective for maintained wt. loss (> 1 yr.) The 2008 Physical Activity Guidelines for Americans) recommend that adults should engage in: 150 min of moderate-intensity or 75 min a week of vigorous-intensity aerobic physical activity per week performed in episodes of at least 10 min preferably spread throughout the week. Focus on simple ways to add physical activity into the normal daily routine: brisk walking, using the stairs, doing housework & yard work, & engaging in sports Wear pedometer or accelerometer to monitor total accumulation of steps or kcal expended as part of the activities of daily living Step counts are highly correlated with activity level  Obesity Treatment – Adjunctive Behavioral Therapy Cognitive behavioral therapy strategies to help change & reinforce new dietary & physical activity behaviors self-monitoring techniques (e.g., journaling, weighing, & measuring food & activity) stress management stimulus control (e.g., using smaller plates, not eating in front of the television or in the car) social support problem solving cognitive restructuring to help patients develop more positive & realistic thoughts about themselves When recommending any behavioral lifestyle change, the patient should be asked to identify what, when, where, & how the behavioral change will be performed  Obesity Treatment – Adjunctive Pharmacological Tx Should be considered for patients with: A BMI ≥30 kg/m2 A BMI ≥27 kg/m2 who have concomitant obesity-related diseases & for whom dietary & physical activity therapy has not been successful Pharmacologic options include: Gastrointestinal fat blockers - Orlistat (xenical, Alli) Appetite suppressants (anorexiants) - Lorcaserin (Belviq), Phentermine + topiramate, Naltrexone + bupropion, Liraglutide (Saxenda, Victoza)  Obesity Treatment – Adjunctive Pharmacological Tx Orlistat (xenical, Alli), 120 mg PO Tid with meals 5% body wt. loss MOA: reduces fat absorption in GI tract SE: may cause GI distress = diarrhea, cramping, flatulence Low fat diet reduces Sx = pt. motivator to stay on diet Lorcaserin (Belviq) 10 mg PO Bid 5% body wt. loss MOA: may promote satiety through serotonin agonist activity SE: possible breast tumors, valvular heart disease, psychiatric problems Obesity Treatment – Adjunctive Pharmacological Tx Phentermine + topiramate 5-10% wt. loss MOA: An amphetamine + anticonvulsant SE: Addictive potential, HTN, tachycardia Distribution in US restricted (class IV drug) Naltrexone + bupropion 2-4% wt. loss MOA: An opioid antagonist + NE-dopamine reuptake inhibitor SE: Possible suicide, seizures, HTN, tachycardia Current CV outcomes trial to assess safety Obesity Treatment – Adjunctive Pharmacological Tx  Liraglutide (Saxenda, Victoza) 3-4% wt. loss MOA: Injectable glucagon-like peptide-1 receptor agonist which regulates appetite & caloric intake Concerns = thyroid tumors, pancreatitis, gallbladder disease, renal impairment, tachycardia, suicidal thoughts SE = N&V, diarrhea & constipation, hypoglycemia Cardiovascular outcomes trial in progress  Obesity Treatment – Bariatric Surgery Bariatric surgery can be considered for patients with: Severe obesity (BMI, ≥40 kg/m2) Those with moderate obesity (BMI, ≥35 kg/m2) associated with a serious medical conditions/co-morbidities Obesity co-morbidities: joint disease, OSA, DM, HTN, GERD Surgical Procedures Include: Roux-en-Y gastric bypass Gastric banding Sleeve gastrectomy Complications: Infection, hernia, nutritional def., neuropathy, blood clots Mortality – Post-op 1%, 1 year higher Multidisciplinary approach: Diet, exercise, behavior modification, social support, pre-meal planning Obesity Treatment – Additional procedures Intraluminal Gastric Balloon - Recently FDA approved Gastric balloon devices placed in the stomach endoscopically. Two devices approved RESHAPE device consists of two silicone balloons attached to a central silicone shaft ORBERA is a single-balloon device Mean weight loss of 7.2 kg & 8.8 kg, respectively, was seen for these devices in short-term pivotal trials Both systems are approved only for up to 6 months of use in adults with a BMI of 30–40 kg/m2 Adverse effects: nausea, vomiting, & abdominal pain Obesity - Outcomes HTN & Hyperlipidemia CAD Type 2 DM Degenerative joint disease (DJD) Psychosocial disability ↑ Cancers (colon, rectum, prostate, uterus, biliary tract, breast, ovary) Thromboembolic disorders (MI, CVA, PE) Digestive tract diseases (gallstones, reflux esophagitis) Skin disorders (Hidradenitis suppurativa, striae, acanthosis nigricans, delayed wound healing, infections) Obesity – Prognosis & Outcomes 20% lose 20 lbs. & maintain loss > 2 yrs 5% lose 40 lbs. & maintain > 2 yrs Very low-calorie diets: 2 lbs/wk wt. loss (length of time varies) Stop daily 16 0z. Soda: 20 lbs. wt. loss/yr Diet soda = weight gain or loss Orlistat (Xenical, Alli) = 4-8 lbs. wt. loss over 2 years Roux-en-Y gastric bypass = 50% initial body wt. loss 50% wt. regain by 5 yrs. Obesity - Summary To achieve weight loss: caloric expenditure > caloric intake Maintaining weight loss is very difficult, requires: Permanent Behavior Modification (diet & exercise)  Polycystic Hirsutism Ovarian Syndrome (PCOS)  Definition: ▪ Excessive male-pattern hair growth in women of reproductive age ▪ Affects 5-10% of females of reproductive age Hirsutism - ▪ Most common cause: PCOS Definition Clinical Presentation: Course, pigmented, hair on the face, chest, abdomen, back in a female  Hirsutism - Epidemiology 20% American women have hirsutism 80% of women with androgen excess have hirsutism (not all) Extent of terminal hair varies by ethnic background: East Asian & Native American women < body hair Southern European women (Mediterranean) > body hair Hirsutism may occur with virilization: Male pattern alopecia, voice deepening, ↑muscle bulk, clitoromegaly Virilization = moderate/severe androgen excess Hirsutism Etiology Idiopathic Hirsutism: Females with hirsutism Normal androgen concentrations No menstrual irregularities No identifiable cause of the hirsutism. Androgens & Androgen Action Hirsutism results from the interaction of circulating serum androgens & the sensitivity of the hair follicle to those androgens, as well as local growth factors Androgens Testosterone: usually ovarian origin Dehydroepiandrosterone sulfate (DHEAS): Adrenal origin Androstenedione: adrenal or ovarian origin  Hair on the scalp, eyebrows, & eyelashes grow in the absence of androgens At other body sites (face, axilla, pubis, arms, legs, trunk, & ears) androgens increase hair growth Androgens & This is manifested by increased follicle size, hair fiber diameter, & proportion of time terminal hairs spend in Hair Growth the anagen phase (growth phase) Androgen excess in females leads to increased hair growth in the most androgen –sensitive sites (upper lip, chin, midsternal, upper abdomen, back, & buttocks However, this leads to scalp hair loss due the time hairs spend in the anagen phase A. Facial hirsutism. (Used with permission from Dr. Tamara Chao.) B. Male pattern escutcheon. Source: Polycystic Ovarian Syndrome & Hyperandrogenism, Williams Gynecology, 3e Citation: Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. Williams Gynecology, 3e; 2016 Available at: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=118170069 Accessed: January 28, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved Hirsutism: face & chest (A) Increased hair growth in androgen-dependent hair follicles of the sideburn area, associated with androgen excess. (B) Increased hair growth in androgen-dependent hair follicles of the presternal & periareolar regions. Source: DISORDERS OF HAIR FOLLICLES & RELATED DISORDERS, Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology, 8e Citation: Wolff K, Johnson R, Saavedra AP, Roh EK. Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology, 8e; 2017 Available at: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=154896456 Accessed: January 28, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved Nonclassical Adrenal Hyperplasia Excess androgens is a key feature of most forms of congenital adrenal hyperplasia Usually recognized at birth or early infancy Nonclassical forms ( primary 21-hydroxylase deficiency) Affected females present with hirsutism around the time of puberty , sometimes have menstrual irregularities, or primary amenorrhea No manifestations of cortisol deficiency Females with Virilization or Severe Hyperandrogenemia Rapid Virilization refers to acute onset of exaggerated masculine characteristics usually in a female, often because of the adrenal glands overproducing androgens Usually due to an androgen secreting tumor Ovarian Adrenal Ovarian hyperthecosis Ovarian hyperthecosis refers hyperplasia of the theca interna of the ovary with clusters of thecal cells in the ovarian stroma producing excessive amounts of testosterone leading to hirsutism & virilization  Usually occurs later in life & progresses rapidly when compared to PCOS Androgen Androgen secreting ovarian tumors are about 5% of ovarian tumors Secreting May be identified by pathology Tumors (biopsy/surgery) or transvaginal ultrasound Most females have testosterone levels > 150- 200 ng/dl & they present with virilization Ovarian Hyperthecosis Nonmalignant ovarian disorder Increased production of testosterone by the luteinized thecal cells in the stroma Markedly increased testosterone concentrations >700ng/dl Unclear if this disorder is distinct or part of PCOS spectrum Primarily in postmenopausal females but can be premenopausal Androgen Secreting Tumors Adrenal Tumors rare causes of androgen excess Some are adrenal adenomas & secrete testosterone Most are adrenal carcinoma & secrete DHEA, DHEAS, & cortisol Women may have clinical manifestations of androgen excess & Cushing Syndrome Elevated DHEAS Suggest adrenal carcinoma Differential Dx -Other Cushing Disease-adrenal overactivity due to a corticotroph adenoma secreting ACTH Results in excess cortisol & excess androgens Uncommon causes of hirsutism: Hyperprolactinemia (pituitary adenoma) Acromegaly (pituitary adenoma) Hypothyroidism Severe Insulin resistance Drugs: androgen therapy (testosterone, DHEA), Danazol (used to treat endometriosis)  Hirsutism – Clinical Presentation Mild to moderate hirsutism: Regular menses, no identifiable cause of hirsutism Think - Idiopathic hirsutism Hirsutism with any of the following: Think - Polycystic ovarian syndrome (PCOS) acne male pattern alopecia acanthosis nigricans obesity oligomenorrhea ( 150 ng/dl require Evaluation evaluation for Ovarian or adrenal androgen secreting tumor or ovarian hyperthecosis PCOS Diagnostic Evaluation DHEAS-not suggested for everyone Measure for symptoms of severe hyperandrogenism Can be extremely elevated in patients with adrenal carcinoma Androstenedione: role unclear in evaluation of PCOS (mixed results) Serum 17-hydroyprogersone Measure morning level in early follicular phase to rule out congenital adrenal hyperplasia due to 21-hydroxylase deficiency >800 ng/dl =adrenal hyperplasia PCOS Diagnostic Evaluation FSH & estradiol - High in premature ovarian insufficiency (also have low estradiol) Check TSH Thyroid abnormalities causes irregular ovulation & menses) ↑ Prolactin (Pituitary adenoma: causes irreg. ovulation & menses, galactorrhea may or may not be present) If symptoms of Cushing Syndrome (24-hour urine free cortisol or low dose dexamethasone suppression test) (sx common to both oligomenorrhea, hirsutism, & obesity) Cushing: hypertension, striae, proximal muscle weakness, etc) PCOS Diagnostic Evaluation - Transvaginal US Transvaginal ultrasound (TVUS) is performed in some women to determine if they have polycystic ovarian morphology. Not all women with possible PCOS undergo ultrasound If the patient has both oligomenorrhea & evidence of hyperandrogenism & causes other than PCOS have been ruled out, she meets criteria for the diagnosis of PCOS & an ultrasound is not necessary. In women with hyperandrogenic symptoms & normal menstrual cycles, TVUS is often done to look for PCOM Biphasic pattern seen on this basal body temperature chart suggests ovulation. (Reproduced with permission from Chang WY, Agarwal SK, Azziz R: Essential Reproductive Medicine. New York: McGraw-Hill; 2005.) Source: Evaluation of the Infertile Couple, Williams Gynecology, 3e Citation: Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. Williams Gynecology, 3e; 2016 Available at: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=118170463 Accessed: January 27, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved  PCOS – Diagnostic Evaluation Pelvic ultrasound: ≥ 12 follicles in either ovary measuring 2-9 mm diameter or Ovarian volume > 10ml Basal body temperature chart: absence of biphasic pattern = anovulation Rarely used now  BP/BMI/Waist circumference - CVD risk Fasting lipid profile Other 2-hour OGTT or fasting glucose & hgbA1C Considerations Screen for OSA Liver enzymes (not recommended to use US to screen for fatty liver) Screen for depression & anxiety disorders  PCOS Treatment Obese patients: weight reduction & exercise often effective in reversing metabolic defects & inducing ovulation Patients who do not desire pregnancy combined hormonal OCP as first line for hyperandrogenism & menstrual irregularities Intermittent or continuous progestin therapy or hormonal IUD may be used for endometrial protection in women who choose not to use OCP Metformin therapy second line to improve menstrual function but has no benefit on hirsutism, acene, or infertility. Used for glucose abnormalities PCOS Treatment Patients who do not desire pregnancy: medroxyprogesterone (Provera) 10 mg q.d. PO for the first 10 days of each month Only initiates & regulates menses but does not inhibit androgen excess low-dose combination OCPs use low androgenic activity progestins Regulates menses & may decrease androgens while preventing pregnancy  PCOS - Treatment Patients who Desire pregnancy: Ovary stimulation Letrozole (first line) Clomiphene - Increased risk of twins with ovarian stimulation PCOS Treatment Hirsutism: Six months of combined OCP If not improved add spironolactone Topical eflornithine (Vaniqa) cream twice daily for six months Electrolysis, laser therapy  PCOS - Treatment Hirsutism: Low-dose combination OCPs 6 -12 mos. Spironolactone 25 mg PO tid (only use with contraception) Eflornithine cream (Vaniqa) applied to facial areas BID for six mos. Electrolysis / laser therapy PRN  Insulin resistance & hyperinsulinemia = ↑Type II DM PCOS - Anovulation causes unopposed Prognosis estrogen = ↑endometrial CA Pregnancy desired: 20-40 % live birth with Clomiphene Tx