Paola Palma Sisto, MD Pediatric Endocrinology

Slides:



Advertisements
Similar presentations
Different Faces of PCOS (Polycystic Ovarian Syndrome)
Advertisements

Polycystic Ovarian Syndrome
Polycystic Ovarian Syndrome (PCOS)
Management of the Commonest Endocrine disorder in females Miss Bini Ajay.
Polycystic Ovary Syndrome & Metformin November 19, 2008.
Infertility and PCOS Erinn Myers, M4 Department of Obstetrics and Gynecology University of Tennessee Health Science Center January 28, 2007.
Biomarkers of ovarian cancer and cysts Reproductive Block 1 Lecture By: Reem Sallam, MD, MSc, PhD.
IN THE NAME OF GOD Elham Faghihimani endocrinologist.
Valerie Robinson, DO. Polycystic Ovarian Syndrome (PCOS) is a disorder that causes menstrual and ovulation irregularities, androgen excess, and infertility.
© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (3): ITC2-1. Terms of Use  The In the Clinic ® slide sets are owned and copyrighted by.
Polycystic ovarian syndrome PCO
Polycystic ovarian syndrome
PCOS Polycystic Ovary Syndrome
Anti-Mullerian Hormone in the pathophysiology of PCOS Roy Homburg Homerton University Hospital, London & Barzilai Medical Centre, Ashkelon, Israel.
Biomarkers of ovarian cancer and cysts Reproductive Block 1 Lecture By: Reem Sallam, MD, MSc, PhD.
Ovaries and the Fertility Cycle
General Medicine Conference “Hirsutism” General Medicine Conference “Hirsutism” Selim Krim, MD Assistant professor Texas Tech University Health Sciences.
Current Concepts in Polycystic Ovarian Syndrome Mark N. Simon, MD Exempla Uptown Women’s Healthcare Specialists October 17, 2003.
Polycystic Ovary Syndrome Krishna B. Singh, MD Department of Obstetrics & Gynecology LSU Health Sciences Center Shreveport, LA.
Polycystic Ovarian Syndrome Omar Al Omari, MRCOG Obstetrician & Gynaecologist Jordan Hospital Medical Center FQN0009.
HDR Women’s Health 11 th April 2012 By Dr Mahya Mirfattahi GP ST3 POLYCYSTIC OVARY SYNDROME A SUMMARY OF RCOG GREEN-TOP GUIDELINE.
Hyperandrogenism Dr. Mona Shroff
HIRSUTISM. Definition  Hirsutism Excessive growth of hair in abnormal position on the body  Virilism Masculinization of female i.e. deepening of voice,
Polycystic Ovary Syndrome
Christopher R. Graber, MD Salina Women’s Clinic 10 Dec 2010.
Roy Homburg. 2 Polycystic ovary syndrome (PCOS) Criteria*: oligo- or anovulation clinical and/or biochemical signs of hyperandrogenism polycystic ovaries.
Polycystic ovarian syndrome (PCOS)
POLYCYSTIC OVARY SYNDROME A COMMON FEMALE ENDOCRINE DISEASE SBI4U-01 Mr. Gajewski Bashour Yazji Jason Antrobus Narayan Wagle.
DR.ABHISHEK SINGH PARIHAR M.S (Obs & Gyne) ; FELLOW REPRODUCTIVE MEDICINE CONSULTANT : LIFECARE IVF CENTRE, NEW DELHI ABALONE CLINIC, NOIDA ETERNA IVF.
Polycystic Ovarian Disorder Max Brinsmead MB BS PhD August 2014.
Investigation of Infertility
Amenorrhea Dr Jack Biko.
ANOVULATION CEM FICICIOGLU, M.D, Ph.D.,AA.,MBA.
Pathogenesis (etiology?) Hypersecretion of adrenal androgens? Hypersecretion of ovarian androgens? A genetic disorder with an autosomal dominant mode.
HyperandrogenismHyperandrogenism Dr. Mona Shroff SOGOG CME 2007.
Investigating infertile couple
Diagnosis of PCOS: 3998 Chinese cases NIH, Rotterdam criteria or AES ? NIH, Rotterdam criteria or AES ? Zi-Jiang Chen M.D., Ph.D Center for Reproductive.
Please Be Sure You Have An Audience-Response Device (Clicker)
Physiopathology and diagnosis of PCOS Ertan SARIDOĞAN Consultant in Reproductive Medicine and Minimal Access Surgery University College London Hospitals.
Investigations of infertility
Hirsutism Andrew Rodin 1st March 2016.
Biomarkers of ovarian cancer and cysts Reproductive Block 1 Lecture Dr. Usman Ghani.
Polycystic Ovarian Syndrome Lindsay White. Polycystic Ovarian Syndrome (PCOS) is the most common cause of female infertility.
Biomarkers of ovarian cancer and cysts Reproductive Block 1 Lecture Dr. Usman Ghani.
DR.GARIMA TYAGI Senior Consultant Obstetrician,Gynaecologist Infertility consultant & Laparoscopic Surgeon SHREE NARAYAN HOSPITAL, INDIRAPURAM,GHAZIABAD.
How Does Body Maintain Normal Blood Sugar? a Insulin Resistance and Its Consequences Sidika E. Karakas, M.D Professor and Chief Division of Endocrinology,
Hyperprolactinaemia. Introduction.  Prolactine (PRL) is secreted from the Anterior Hypophisis.  Normal blood level of PRL: IU/L or 12.5 – 25.
PCOS : Long Term Sequelae BY Mohammad Emam Prof. OB& GYN Mansoura Faculty of Medicine Mansoura Integrated Fertility Center EGYPT 2009.
PCOS: Polycystic Ovarian Syndrome
POLYCYSTIC OVARY SYNDROME
Is it PCOS… or are your Adrenal Glands Overreacting?
Polycystic Ovary Syndrome (PCOS)
Polycystic Ovary Disease
Polycystic Ovary Syndrome: An overview
PCOS Khalid Akkour, MD FRCSC.
Orquidia Torres, MD Division of Adolescent and Young Adult Medicine
Division of Endocrinology, Diabetes and Metabolism
Polycystic ovarian syndrome Obesity and Insulin resistance
Diagnosis and Treatment of PCOS
Biomarkers of ovarian cancer and cysts
Biomarkers of ovarian cancer and cysts
CEM FICICIOGLU, M.D, Ph.D.,AA.,MBA
Polycystic Ovary Syndrome (PCOS)
Assessment of oxytocin level, glucose metabolism components
Polycystic ovary syndrome (PCOS) is extremely prevalent and probably constitutes the most frequently encountered endocrine (hormone) disorder in women.
Mohammad A. Emam Phenotypes Of Polycystic Ovarian Syndrome BY
Presentation transcript:

Polycystic Ovarian Syndrome (PCOS) in the Adolescent: Where we've been and where are we going Paola Palma Sisto, MD Pediatric Endocrinology Children’s Hospital of Wisconsin Department of Pediatrics Medical College of Wisconsin September 26, 2017

Disclosure Nothing to disclose

Agenda History Diagnosis (2017) Case Assessment Management Future of PCOS

History Vallisneri (1721) Chereau and Rokitansky (1844) Tait (1879) First to describe infertile woman with “shiny large ovaries” Chereau and Rokitansky (1844) Tait (1879) Bulius and Kretschmar (1897) Von Kahlden (1902) McGlinn (1915) Stein and Leventhal (1935) Szydlarska et al. Adv Clin Exp Med (2017)

History Stein and Leventhal 7 women with menstrual irregularities, hirsutism, enlarged ovaries with many small follicles Ovarian wedge resection – resumed menses and allowed for pregnancy >65% Szydlarska et al. Adv Clin Exp Med (2017)

Names Polcystic ovaries disorder A syndrome of polycystic ovaries Functional ovary androgenism Hyperandrogenic chronic anovulation Polycystic ovarian syndrome Ovarian dysmetabolic syndrome Sclerotic polycystic ovary syndrome Polycystic ovary syndrome Szydlarska et al. Adv Clin Exp Med (2017)

Pathophysiology

Infants and childhood: Anti-Muellerian hormone (AMH) Hyperresponsive glucose release Insulin excess Increases steroidogenesis in ovary Reduced liver production of SHBG increased free testosterone

Genetics Of PCOS

Diagnosis 1960’s Elevated LH, testosterone, and urinary 17-ketosteroids Elevated LH/FSH ratio Bilateral cystic ovaries Szydlarska et al. Adv Clin Exp Med (2017)

Diagnosis NIH (1991) Unexplained hyperandrogenic anovulation Criteria Clinical or biochemical excess androgens Rare ovulations Exclusion of other disorders Franks et al. J Clin Endocrinol Metab (1991)

Diagnosis Rotterdam Criteria (2004) 2 out of 3 necessary Anovulation or rare ovulation Clinical and/or biochemical hyperandrogenism Polycystic ovaries on US (after exclusion of other causes) Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Hum Reprod.(2004)

Diagnosis Androgen Excess-PCOS Society consensus criteria (2006) Clinical and/or biochemical hyperandrogenism Ovarian dysfunction and/or polycystic ovaries on US (after exclusion of other causes) Azziz et al. J Clin Endocrinol Metab (2006)

Diagnosis Obesity and insulin resistance Intrinsic to condition Exacerbate PCOS symptoms Not included in diagnostic criteria

Diagnosis in Adolescence Controversial Diagnostic criteria (acne, irregular menses, PCO) normal pubertal events Hyperandrogenemia Disease VS lack of regulated hypothalamic-pituitary-ovarian axis during typical peripubertal anovulatory cycles Witchel et al. Horm Res Paediatr (2015)

Consensus meeting (2015) Pediatrics specialists and Androgen Excess-PCOS Society Criteria for defining PCOS in adolescence Witchel et al. Horm Res Paediatr (2015)

Consensus meeting (2015) Hyperandrogenism (clinical) Excess coarse sexual hair presenting in male-like pattern Moderate-severe inflammatory acne And/or menstrual irregularities Rare-alopecia Witchel et al. Horm Res Paediatr (2015)

Consensus meeting (2015) Hyperandrogenism (biochemical) Assay determines normal range Persistent elevation of serum total and/or free testosterone levels Elevated testosterone in presence of asymptomatic patient NOT considered evidence for hyperandrogenism Witchel et al. Horm Res Paediatr (2015)

Consensus meeting (2015) Oligo-anovulation Menstrual intervals <20 days or >45 days for 2 or more years after menarche Menstrual interval >90 days Lack of onset of menses by 15 years or by >2 years after thelarche Witchel et al. Horm Res Paediatr (2015)

Consensus meeting (2015) Polycystic ovaries by US Limited data Ovarian volume > 12 cubic cm Mulifollicular NORMAL in adolescence NOT a criteria DEFER imaging to make diagnosis Witchel et al. Horm Res Paediatr (2015)

Cases 15 year old Caucasian female 12 year old African American female Breast bud age 9, pubic hair age 10, menarche age 12 Increasing acne, excess facial hair, weight gain (BMI increased from 60th percentile to 85th), menses every 3-4 months Mother with irregular menses, acne, and overweight Breast bud age 9, pubic hair age 8, menarche age 10 Facial acne, sideburns, lower back hair, elevated BMI (consistently >90th percentile since age 8), menses <6 in 1 year Mother with regular menses and obese, facial hair

15 yr old… Questions Thoughts

12 yr old… Questions Thoughts

Physical Findings 15 yr old… 12 yr old… Hirsutism: chin, moustache, sideburns, lower back, linea alba (FG 22) Acne: forehead and upper back No clitoromegaly No acanthosis nigricans Normal thyroid, no galactorrhea Hirsutism: chin, sideburns, lower back (FG 10) Acne: forehead No clitoromegaly Acanthosis nigricans cervical neck Normal thyroid, no galactorrhea

Differential Diagnosis (Hyperandrogenism/Irregular menses) Congenital Adrenal Hyperplasia 21 hydroxylase deficiency (nonclassic) Cushing’s Syndrome McCune Albright Syndrome Glucocorticoid resistance Ovarian androgen secreting tumors Thyroid dysfunction Hyperprolactinemia Adrenal tumors

Assessment: History will direct testing 17-OH progesterone Morning levels >200 ng/dl-- consider CAH Total testosterone Free testosterone SHBG Androstenedione DHEAS Consider.. TSH LH,FSH Prolactin ACTH stimulation testing for CAH Bone age (younger age)

Assessment: Obesity Metabolic workup directed by history (patient and family) and physical exam Fasting: Glucose BUN/creatinine LFTs Lipids ?insulin/c-peptide ?HbA1c

PCOS and mental health Study in adult women from multiple countries including US 2.8 times more likely to report anxiety symptoms vs control 3.5 times more likely to report depressive symptoms vs control Blay et al. Neuropsychiatric Disease and Treatment(2016)

Management Lifestyle Metformin OCP Anti-androgen (spironolactone) Co-morbidities

Management Lifestyle – weight loss reduces insulin resistance reduced androgens Metformin OCP Anti-androgen (spironolactone) Co-morbidities

Management Lifestyle Metformin – improves insulin resistance/reduces androgen production/free testosterone OCP Anti-androgen (spironolactone) Co-morbidities

Management Lifestyle Metformin OCP – puts the ovary “to rest” preventing chronic androgen exposure; protective to reproductive organs Anti-androgen (spironolactone) Co-morbidities

Management Lifestyle Metformin OCP Anti-androgen (spironolactone) – reduces the sensitivity of the hair follicle to testosterone Co-morbidities

Management Lifestyle Metformin OCP Anti-androgen (spironolactone) Co-morbidities – hypertension, hyperlipidemia, acne/hair management

Future Prediction and prevention Epigenetics

EPIGENETICS MODEL PCOS Heritability is high 50% risk of PCOS if mother has it 75% identical twin 35% sister Epigenetic factors Post conception exposure Androgens Endocrine disruptors If in germ cells can be transferred transgenerationally Obesity and PCOS Link to SGA and future insulin resistance

Support for Patients Androgen Excess and PCOS Society (ae-society.org) PCOS Awareness Association (pcosaa.org)

RESOURCES Pedsendo.org

Summary 6-15% women diagnosed with PCOS Complex condition arising from genetic and epigenetic influences, intra and extrauterine environmental factors, exacerbated by insulin resistance Diagnosis in the adolescent needs to take into account the associated risk factors Lifestyle is the mainstay of therapy, support with metformin and OCP, +/- anti androgen to improve symptoms and quality of life

Questions?? Thank you…