REI CASE(S) Laura L. Tatpati, MD Division of REI, Dept of OB/GYN KUSM - W
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.
WHAT S THE DIFFERE NTIAL DIAGNO SIS?
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
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
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
HISTOR Y SHOUL D YOU OBTAIN?
FURTHER HISTORY Other symptoms: Hair loss Voice deepening Endocrine ROS Family history menstrual, reproductive, endocrine, cancers Medications: Danazol, valproate, antipsychotics, androgens
IMPORTANT HISTORICAL Timing of onset of symptoms CONTEXT Menstrual history Tempo of progression of symptoms Severity of symptoms
L FINDING S WOULD YOU BE LOOKING FOR?
PHYSICAL EXAMINATION Hair Pattern/Distribution Ferriman-Gallwey Acne Mediterranean, hispanic, middle eastern > 9-10 AA/C - >8 Asian > 2 Male pattern hair loss Virilization Clitoromegaly (L > 10mm, LxW > 35mm2) Voice deepening Increased muscle mass Temporal / Crown balding
SPECIAL CONSIDERATION Acanthosis nigricans S Striae Easy bruising
TEST WOULD YOU LIKE TO ORDER?
YOUR INITIAL TEST RESULT WAS: TESTOSTERONE - 150 NG/DL YOU ALSO ORDERED A: DHEAS - 720 MCG/DL Further evaluation at this point?
TRANSVAGINAL ULTRASOUND Result : Normal
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
CT - ADRENAL GLANDS Results: left adrenal mass - 6 cm
HOW DO YOU TREAT HER HIRSUTI SM?
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) - $$$
CASE #2
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?
WHAT TESTIN G WOULD YOU DO?
IRREGULAR MENSES, hcg HIRSUTISM Testosterone Prolactin TSH 17OHP FSH/E2
CONFIRMED PCOS OR OTHER RISK FACTORS A1c or 2h GTT Fasting lipid profile Screen for cardiometabolic risk factors
HOW DO YOU DIAGNOS E PCOS?
ROTTERDAM CRITERIA Need 2 of 3 Hyperandrogenism or hyperandrogenemia Oligo or amenorrhea Polycystic appearance on US FNPO > 12, volume > 10cm 3
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.
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 overexpression 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
LONG-TERM HEALTH CONSIDERA TIONS SHOULD YOU ADVISE HER ABOUT?
4 AREAS OF CONCERN Infertility Diabetes/Gestational DM/Insulin resistance Dyslipidemia Uterine hyperplasia/endometrial cancer
IN PREMENOPAUSAL WOMEN, THE MENSTRUAL CYCLE IS A VITAL SIGN!