Catecholamine Reserve and Exercise Tolerance in Healthy Volunteers and Patients With Congenital Adrenal Hyperplasia
Condition: Congenital Adrenal Hyperplasia; Healthy
MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Hyperplasia
Study type: Observational

Summary: 
      This study will examine and compare the effects of intense exercise on the release of
      catecholamines in patients with congenital adrenal hyperplasia (CAH) and in healthy persons.
      Catecholamines are hormones (adrenaline and noradrenaline) that are produced by the adrenal
      glands and released into the blood stream during stress, such as trauma, illness, intense
      exercise, or low blood sugar. The study will also assess exercise tolerance in patients with
      CAH, compared with healthy persons.

      Patients with CAH between the ages of 10 and 40 years who are managing well on standard
      treatment (glucocorticoids, mineralocorticoids) may be eligible for this study. Healthy
      volunteers that match the enrolled patients in age, sex, race and body fat will be recruited
      as control subjects. All candidates will be screened with a medical history, physical
      examination and electrocardiogram (EKG). Body fat will be measured using an instrument called
      a Bod Pod. The body fat measurement has two parts: first, the subject sits quietly in a large
      egg-shaped capsule for about 2 to 3 minutes; then the subject breathes into a plastic tube
      for one minute, followed by three quick panting breaths. Women will have a urine pregnancy
      test; pregnant women cannot participate in the study.

      Participants will undergo three exercise sessions on separate consecutive mornings after
      fasting overnight. Before each test, patients (not healthy volunteers) will take either an
      additional morning dose of hydrocortisone or a placebo (a lookalike pill with no active
      ingredient). Before each test a thin catheter (plastic tube) will be placed into an arm vein
      through a needle. A numbing cream can be applied to make the needle stick hurt less. Blood
      will be drawn through this intravenous (IV) line before, during and after the exercise tests.
      The first test is a maximal exercise test to determine the individual's maximum exercise
      fitness capacity. The second two and third tests are a standardized exercise tests. Before
      the two standardized tests, patients (not healthy volunteers) will take either an additional
      morning dose of hydrocortisone or a placebo (a lookalike pill with no active ingredient). All
      tests are done on a stationary bicycle.

      Maximal Exercise Test - The subject pedals on a stationary bicycle for about 10 minutes.
      After a 3-minute warm-up, the workload is increased continuously until either the subject can
      no longer continue or the physician stops the test for medical reasons. During the exercise,
      heart rate and heart activity are monitored with an EKG, and the subject wears a nose clip
      and mouthpiece connected to a breathing tube to measure oxygen use. Blood is drawn before and
      during the test, totaling no more than 2 tablespoons.

      Standardized Exercise Test - The subject pedals on a stationary bicycle for 20 minutes, while
      wearing the nose clip and mouthpiece to measure oxygen use. For the first 5 minutes, the
      subject pedals at a speed that elicits 50 percent of maximal effort (determined by the
      maximal exercise test); the next 10 minutes are at 70 percent of maximal effort; and the last
      5 minutes are at 90 percent. Blood samples drawn before, during (at 15 and 20 minutes) and
      after exercise (at 30, 40 and 60 minutes) total less than 1/2 cup. Heart rate and heart
      activity are monitored during the test with an EKG, and temperature is measured before and at
      the end of the test.
    

Detailed description: 
      Congenital adrenal hyperplasia (CAH) denotes a family of inherited disorders with defects in
      the cortisol biosynthesis. CAH has been traditionally considered a disease restricted to the
      adrenal cortex. However, recently observed abnormal adrenomedullary structures in three
      adrenalectomized patients with classic CAH, as well as low baseline urinary and plasma
      epinephrine levels in children with CAH suggest that this condition is associated with marked
      morphological and functional abnormalities of the adrenal medulla.

      The adrenal medulla synthesizes and secretes catecholamines, mainly epinephrine.
      Catecholamines influence virtually all tissues. Yet, the clinical implications of epinephrine
      deficiency in humans are not clear.

      Short-term intense exercise is a natural, quantifiable stimulus of the adrenal cortex and
      medulla as well as of the sympathetic nervous system. We would like to employ a standard
      cycle ergometer exercise protocol to study the adrenomedullary and systemic sympathetic
      function of patients with CAH. This protocol has been run by the Clinical Center
      Rehabilitation Medicine Department (RMD) for 10 years. No serious adverse effects have been
      observed or reported in adults and children with a healthy cardiovascular system.

      The goal of this protocol is to evaluate adrenomedullary and systemic sympathetic function
      and exercise tolerance in patients with CAH and in appropriately matched healthy controls
      using the above standardized cycle ergometer test. Subjects with CAH will exercise with and
      without doubling their morning dose of hydrocortisone to evaluate whether impairments - if
      present - can be corrected by a "stress dose" of hydrocortisone. We hypothesize that subjects
      with CAH have a reduced epinephrine reserve and impaired exercise tolerance, which can at
      least partially, be corrected by an increase in exogenous hydrocortisone. We will also
      determine whether the systemic sympathetic nervous system compensates for the adrenomedullary
      deficiency as observed in states of acquired adrenal insufficiency. The results of this study
      will increase the understanding of the physiologic interactions between adrenal cortex and
      adrenal medulla.
    

Keywords: CAH; Catecholamines; Adrenal Medulla; Endocrine; Congenital Adrenal Hyperplasia; Exercise; Healthy Volunteer