Adrenal Hyperplasia Among Young People With PCOS
Condition: Adrenal Hyperplasia; Polycystic Ovarian Syndrome; Oligomenorrhea; Obesity; Hyperandrogenism
MeSH terms: Polycystic Ovary Syndrome; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Hyperandrogenism; Adrenocortical Hyperfunction; Syndrome; Hyperplasia; Oligomenorrhea
Study type: Observational

Summary: 
      Background:

      - Polycystic ovarian syndrome (PCOS) is a group of disorders related to problems with the
      secretion of certain hormones, which can lead to reproductive and other issues in women.
      Frequent complications of PCOS include irregular menstruation, development of ovarian cysts,
      and insulin resistance. The adrenal glands, which sit on top of the kidney, are involved in
      the production of certain hormones and the regulation of steroid levels in the blood, and may
      be affected in women with PCOS. Researchers are interested in studying possible connections
      between the adrenal glands and PCOS in young women who have been diagnosed with PCOS and
      healthy volunteers with normal menstrual function.

      Objectives:

      - To investigate possible connections between adrenal gland steroid hormone secretion and
      polycystic ovarian syndrome.

      Eligibility:

        -  Women between 16 and 29 years of age who have been diagnosed with PCOS, or who are
           healthy volunteers with normal menstrual function.

        -  Participants must be willing to discontinue the use of oral contraceptives or any other
           medications that alter steroid hormone production for at least 1 month before the start
           of the study.

      Design:

        -  Participants will be screened with a physical examination, medical history, and blood
           and urine tests. All participants will also have a pelvic (ovarian) ultrasound.

        -  All participants will be admitted to the hospital for a 1-week testing period, which
           will involve the following tests:

        -  Regular blood draws for two 2-hour periods (late evening and early morning) to measure
           hormone levels

        -  Fasting blood draws with a dose of corticotropin to test the body's adrenal function

        -  Hormone level measurement following regular doses of dexamethasone (a drug that controls
           the function of the adrenal gland)

        -  Daily urine collection for 6 days.

        -  Other studies, such as imaging studies of the adrenal glands, may be conducted as
           required by the study researchers.
    

Detailed description: 
      Polycystic ovarian syndrome (PCOS) is a heterogeneous group of disorders presenting with
      hyperandrogenism in adolescents and young women. The etiology of this condition remains
      unknown, despite its many identified links to insulin resistance, hypertension and metabolic
      syndrome, as well as its potential connection to the various forms of congenital adrenal
      hyperplasia (CAH).

      The adrenal glands are the only source in the body of adrenocortical steroids. In normal
      physiology, the pituitary hormone ACTH regulates the secretion of glucocorticoids, while the
      secretion of mineralocorticoids is controlled by the renin-angiotensin system. In addition to
      these two steroids, the adrenal gland secretes lesser amounts of intermediate metabolites of
      these steroids, as well as the sex-steroids DHEA, DHEAS, androstenedione, testosterone,
      estrogen, and estrone. Dysregulated secretion of any of these hormones can be caused by the
      development of hyperplasia of the adrenocortical tissue, which may be mild and lead to
      specific clinical syndromes depending on the identity of the secreted hormones. Bilateral
      adrenocortical hyperplasia (BAH) is now an increasingly diagnosed cause of adrenal
      dysfunction.

      We propose that there is a subgroup of patients with PCOS who actually have non-CAH primary
      forms of BAH. To investigate this possibility, we propose to study the
      hypothalamic-pituitary-adrenal axis (HPAA) over the next 2 years in 120 young girls and women
      (ages 16 to 25 years) that we will compare to 30 age- and race-matched normal females.
      Patients will be recruited primarily (although not exclusively) from a busy New York City
      clinic run by the Pediatric Endocrine Division at the Infants and Children's Hospital of
      Brooklyn at Maimonides and SUNY Downstate. All patients will undergo standard testing of the
      HPAA including oral low- and high-dose dexamethasone (DEX)-suppression testing (Liddle s
      test). Paradoxical rise of cortisol and/or other steroid metabolites in response to DEX is
      considered a sensitive test for the diagnosis of BAH. Patients with such responses will be
      molecularly investigated for the known causes of BAH (GNAS, PRKAR1A, PDE11A, PDE8B and other
      mutations).

      The first goal of this study is to identify any possible contributions of the BAH phenotypes
      and genotypes to the pathophysiology of PCOS, a yet unknown factor in the etiology of this
      multifaceted disorder. The second goal is to perform a comparative analysis of the expression
      of large sets of genes in cells of these patients using gene arrays and other genetic
      analyses. This study will generate important information about the molecular pathways that
      are affected in this subgroup of patients with PCOS. Thirdly, this study will also allow for
      the collection of DNA from affected and non-affected relatives of the patients to perform
      genetic studies and identify causative genetic defects. Finally, the study is expected to
      lead to new diagnostic and therapeutic methods for at least certain forms of PCOS.
    

Time perspective: Prospective
Keywords: Oligomenorrhea; Adrenal Hyperplasia; Obesity; Hyperandrogenism; Polycystic Ovarian Syndrome; PCOS; Polycystic Ovary; Healthy Volunteer; HV