title: Bilateral Adrenal Hyperplasia as a Possible Mechanism for Hyperandrogenism in Women With Polycystic Ovary Syndrome.
abstract: Androgen excess may be adrenal and/or ovarian in origin; we hypothesized that a subgroup of patients with polycystic ovarian syndrome (PCOS) may have some degree of abnormal adrenocortical function.
  
  
  
  The objective of the study was to evaluate the pituitary adrenal axis with an oral low- and high-dose dexamethasone-suppression test (Liddle's test) in women with PCOS.
  
  
  
  This was a case-control study.
  
  
  
  The study was conducted at the National Institutes of Health Clinical Center.
  
  
  
  A total of 38 women with PCOS and 20 healthy volunteers (HV) aged 16-29 years participated in the study.
  
  
  
  Urinary free cortisol (UFC) and 17-hydroxysteroids (17OHS) before and after low- and high-dose dexamethasone and assessment of adrenal volume by computed tomography scan were measured.
  
  
  
  Twenty-four-hour urinary 17OHS and UFC were measured during day 1 to day 6 of the Liddle's test. Baseline UFC levels were not different between PCOS and HVs; on the day after the completion of high-dose dexamethasone administration (d 6), UFC was higher in the PCOS group (2.0 ± 0.7 μg/m(2)·d) than the HV group (1.5 ± 0.5) (P = .038). On day 5, 17OHS and UFC were negatively correlated with adrenal volumes (left side, rp = -0.47, P = .009, and rp = -0.61, P < .001, respectively). PCOS patients above the 75th percentile for UFC and/or 17OHS after high-dose dexamethasone (n = 15) had a significantly smaller total adrenal volume (6.9 ± 1.9 cm(3) vs 9.2 ± 1.8 cm(3), P = .003) when compared with the remaining PCOS patients (n = 22), but they did not have worse insulin resistance or hyperandrogenism.
  
  
  
  In a subset of young women with PCOS, we detected a pattern of glucocorticoid secretion that mimicked that of patients with micronodular adrenocortical hyperplasia: they had smaller adrenal volumes and higher steroid hormone secretion after dexamethasone compared with the group of PCOS with appropriate response to dexamethasone.
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Gourgari
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Maya
authors.initials: M
authors.lastname: Lodish
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Meg
authors.initials: M
authors.lastname: Keil
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Ninet
authors.initials: N
authors.lastname: Sinaii
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Evrim
authors.initials: E
authors.lastname: Turkbey
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Lyssikatos
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Maria
authors.initials: M
authors.lastname: Nesterova
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Maria
authors.initials: M
authors.lastname: de la Luz Sierra
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Xekouki
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Divya
authors.initials: D
authors.lastname: Khurana
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ten
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Adrian
authors.initials: A
authors.lastname: Dobs
authors.affiliation: Section on Endocrinology and Genetics (E.G., M.L., M.K., C.L., M.N., M.S., P.X., C.A.S.), and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Department of Radiology (E.T.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Division of Pediatric Endocrinology (E.G.), Georgetown University Medical Center, Washington, DC 20007; Biostatistics and Clinical Epidemiology Service (N.S.), National Institutes of Health Clinical Center, Bethesda, MD; Division of Pediatric Endocrinology (D.K., S.T.), Infants and Children's Hospital of Brooklyn at Maimonides and Children and Hospital at Downstate, State University of New York, Brooklyn, New York 11219. and Department of Endocrinology (A.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000728:Androgens / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017588:Hyperandrogenism / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology*; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D055815:Young Adult
chemical_list: D000728:Androgens; D015415:Biomarkers