1. Adolescent Case Presentation Kelli L. McDermott LT MC USNR

2. Case history 14 y/o female CC: 3-6 months of irregular periods and unexplained weight gain In USOH, has not been ill in last few months PMH- not significant

3. Case History HEADS interview negative Home: lives with parents, no sibs, gets along fine Education: 9 th grade, A-B student, has good group of friends Activities: rows for school crew team, movies & hanging out with friends

4. Case History Drugs: never smokes, drank, or tried any drugs, no friends hace either Diet: parents MD’s and help her eat a balanced diet, she reports no increased eating habits since weight gain Sex: never been active, never had a girl/boyfriend Suicide: no h/o depression

5. Case History Menstrual hx- menarche at age 12 Regular periods over past year and then irregular for about 6months; no periods for about 3 months now Never been sexually active

6. Case History FHx- NC, no female family member with abnormal periods, no problems with cycle, fertility. No cancers

7. Physical Exam VS: HR 65; RR18; BP112/80; wt 93.5kg (>99 th %); ht 160cm (50 th %); BMI= 36 HEENT: fat pad behind neck, thickening & slight hyperpigmentation of posterior neck skin, nl thyroid CV: S1+S2, no R/G/M, RR Lungs: CTA bilat Abd: obese, soft, +BS, striae across abdomen and lower hips

8. Physical Exam Ext: FROM, nl muscle tone, 2+ cap refill, pulses normal Skin- dry but no lesions, rashes, acne noted over face, chest, back, no excess hair. GU- no external abnormalities, Tanner 5, normal clitoris

9. QUESTIONS on H& P???

10. How about a differential for secondary amenorrhea?

11. Differential Diagnosis Pregnancy PCO Hypothyroidism Ovarian tumor Pituitary tumor

12. Less likely differential CAH Female Athlete Triad (hypothalamic amenorrhea) Turner’s syndrome Testicular Feminization

13. Which labs would you think about at this initial presentation?

14. Laboratory Tests B-HCG Thyroid LH/FSH Prolactin Free/total testosterone

15. Laboratory Tests Fasting glucose Fasting Insulin level Fasting Lipid profile Androstenedione Fasting 17-OPH and cortisol DHEAS Karyotype

16. Our patient Nl TFT’s Glucose 81 Lipid profile all WNL LH 4.17 FSH 6.8 PRL 5.75 Andro 181 17-OHPS 58 Insulin 5.1 Ttest 36 Free test 6.7 (only abn lab)

17. What is PCOS? Increased androgen production from ovaries and adrenal glands

18. What does it mean to have PCOS? Well, unfortunately, it means a lot of difficult things for many women. I started to have facial hair growth in early highschool -- this was pretty embarassing, especially when I realized that it wasn't "normal" compared to my other friends. Of course, I had lots of hair on my legs and arms too, at an even younger age -- growing up in Southern California meant that I was doing a lot of hair removal all the time so as to not look like a freak in shorts or a bathing suit. My skin just didn't ever seem to clear up -- I spent many hours at the dermatologist. I also "learned" early on that I couldn't eat very much at all -- if I did, I immediately gained a lot of weight and it didn't want to come off. My cycles were horrible, when I had them, I understood why some women called it "the curse".

19. I was diagnosed when I was 17 and immediately went on birth control pills to control my symptoms. This was the only practical "treatment" known at that time. Later on, PCOS was the reason I couldn't easily conceive and then miscarried the 2 times I did conceive naturally. I think this is the most acutely painful aspect of this syndrome, and it is certainly the focus of many women's pain. Wanting a child and being unable to have one was one of the most difficult times of my life. Needing to take in order to conceive and carry a pregnancy can have some very subtle effects on how a woman thinks about herself, and when she has a condition that already makes her feel less attractive, less desirable and less feminine (at least by our culture's standards), she can end up seeing herself as pretty defective. Later in life, PCOS presents some serious health problems. Women with PCOS are significantly more likely to have type II diabetes and heart disease and there appears to be a link to breast and colon cancer, so it isn't just a "cosmetic" or "infertility" condition -- it can be ugly.

20. PCOS Spectrum of clinical d/o’s not diagnosed by lab Clinical presentation includes: Hirsuitism & acne Obesity Oligomenorrhea Anovulation Infertility

22. PCOS Pituitary gland is heightened to GnRH  Exaggerated pulsatile LH release  LH/FSH ratio may be elevated   LH stimulate ovary to secrete  androgen 

23. Androgens are converted to estrone and estradiol  Estrogens secreted tonically  Augment pituitary sensitivity to GnRH  And vicious cycle continues to  LH  ovaries overproduce androstenedione and testosterone

24. Other interesting findings Androgens  SHBG;  free testosterone Anovulation and insulin resistance- exact pathogenesis unclear in basal insulin secretion in hepatic uptake B-cell dysfunction insulin has direct effect on pituitary in LH secretion and the ovary for androgen production

26. Problems associated with high levels of sex hormones: Anovulation results in amenorrhea & infertility Hirsuitism, acne Male pattern baldness/thinning Obesity- android-type with waist-hip ratios Cancer- endometrial

27. Problems associated with high levels of sex hormones: Insulin resistance Hyperinsulinemia Diabetes Cardiovascular disease

28. Theories to etiology of PCOS Genetic predisposition is most likely although no gene isolated; believe in 2-hit hypothesis Premature adrenarche (<8 y/o) Heterozygosity for CAH IUGR

29. Treatment Cosmetic interventions

30. OCP’s: suppress LH  androgens SHBG  free testosterone adrenal production of androgen  5alpha-reductase Spironolactone

31. Treatment Cyclic progestins GnRH agonists Weight control Low carb diets Exercise to reduce weight and CV risk factors

32. Treatment- controversial Insulin sensitizing drugs: biguanides & thiazolidinediones  insulin R  hirsuitism restore nl ovulatory patterns

33. Metformin Reduces hyperinsulinemia Decreases risk factors for CHD Improved weight-loss Normalization of circulating androgens Resumption of normal ovulatory menses and therefore reversal of infertility

34. Resources and Websites www.pcosupport.org www.pcosupport/pcoteen www.obgyn.net/pcos/pcos.asp