Examining Genetic Differences Among People With 21-Hydroxylase Deficiency
Condition: 21-hydroxylase Deficiency
MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome
Study type: Interventional

Summary: 
      Congenital adrenal hyperplasia (CAH) is a genetic disorder that affects the amount of
      steroids that the body forms. The most common form of CAH is 21-hydroxylase deficiency
      (21OHD), which leads to cortisol deficiency. This, in turn, causes the development of mature
      masculine characteristics in newborn, prepubescent, and grown females and in prepubescent
      males. 21OHD is known to be caused by the mutation of a specific gene. However, symptom
      severity among people with 21OHD varies, and adults seem to be less affected than children.
      This study will examine participants' DNA to determine what other genes may affect the
      severity of 21OHD and may make the disease milder in adults than in children.
    

Detailed description: 
      CAH is a genetic steroidogenesis disorder. The most common form, 21OHD, leads to cortisol
      deficiency and, in turn, an excess of androgen, a hormone that promotes the development and
      maintenance of male sex characteristics. As a result of this androgen excess, prepubescent
      males and newborn, prepubescent, and grown females exhibit mature masculine characteristics.
      The symptoms and severity of 21OHD vary among individuals with the disease and in adults
      versus children. The reasons for these differences are not yet known. Current therapy for
      21OHD consists of administration of glucocorticoids to replace cortisol and suppress
      excessive pituitary function. With more information about what genes or factors contribute to
      the severity of 21OHD, researchers may be able to better treat children and adults with the
      disease. This study will examine participants' DNA to determine what other genes may affect
      the severity of 21OHD and may make the disease milder in adults than in children.

      People interested in participating in this 3-day inpatient study will first undergo a
      physical exam and provide a blood sample to determine eligibility. Eligible participants will
      be admitted to the study site in the morning on the first study day. A blood sample will be
      taken and participants will receive one 10-mg pill of hydrocortisone. Heart rates and blood
      pressures will be taken every 4 hours throughout the day. In the morning of Day 2, a blood
      sample will be taken and participants will be asked to urinate in the toilet. After this
      point and until the end of the study, participants will collect all urine in a jug. On the
      morning of Day 3, participants will complete urine collection and a blood sample will be
      taken. Participants will then receive intravenously a medicine called cosyntropin, a
      synthetic form of a hormone that the body makes. About 1 hour after this, participants will
      provide a final blood sample. Participants will receive one last pill of hydrocortisone prior
      to the end of the study.
    

Intervention name(s): Hydrocortisone withdrawal
Intervention type(s): Procedure
Intervention description(s): This is considered a non-standard treatment. On Day 1, participants will receive one 10-mg pill of hydrocortisone. On Day 3, participants will receive intravenously a medicine called cosyntropin, a synthetic form of a hormone that the body makes. Participants will receive one last pill of hydrocortisone prior to the end of the study.
Intervention MeSH terms: Hydrocortisone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Adrenal Hyperplasia, Congenital; Steroid Biosynthesis Disorders