Clinical Trial: Catecholamine Reserve and Exercise Tolerance in Healthy Volunteers and Patients With Congenital Adrenal Hyperplasia

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Catecholamine Reserve and Exercise Tolerance in Subjects With Congenital Adrenal Hyperplasia and Healthy Controls

Brief 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 te

Detailed Summary:

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, whic
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: February 28, 2001
Date Started: February 22, 2001
Date Completion: May 10, 2011
Last Updated: January 24, 2017
Last Verified: May 10, 2011