Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia

Background: * Congenital adrenal hyperplasia (CAH) is a genetic disorder of the adrenal gland. The adrenal gland is located in the abdomen and produces small amounts of hormones such as cortisol, aldosterone, and androgen. These hormones help control blood pressure, protect the body, and maintain good health, especially during development. People with CAH do not make enough cortisol and aldosterone, and make too much androgen. This can lead to serious medical problems. The standard treatment is to take pills that mimic the effects of cortisol and aldosterone. However, treatment with pills can have long-term side effects because of the higher doses needed, and may not work well for some people. * A possible new treatment for CAH is to use a pump to deliver cortisol under the skin. Similar pumps are often used to give insulin to people with diabetes. Researchers think that a cortisol pump might be able to help the body use the cortisol more effectively than taking pills. They want to compare the results of a cortisol pump and standard pill treatments for CAH. Objectives: \- To compare the effectiveness of a cortisol pump with standard cortisol pill therapy for CAH. Eligibility: \- Men and women at least 18 years of age who have CAH (see more details in Eligibility section below). Design: * This study will involve four inpatient hospital stays at the National Institutes of Health in Bethesda, MD over 6 months (spaced 2 months apart). The first and last stays will last about 5 days. The second and third stays will last about 3 days. * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * At the first study visit, participants will provide regular blood and urine samples. They will also have imaging studies. These studies will look at the bones, fat, and muscles in the abdomen and pelvis. * Participants will receive a cortisol pump during the first visit. They will be shown how to use the pump. They will also learn what to do, if they need to take extra "stress dose" cortisol pills. * At the second and third visits, the cortisol dose given with the pump will be adjusted as needed. Blood and urine samples will also be collected. No imaging studies are scheduled for these visits. * The last study visit will have the same tests as the first visit. Participants will be offered the chance to continue with the pump treatment for 1 more year, or go back to their standard pill treatment. Study type: Interventional non-randomized trial Official title: A Pilot Study Assessing the use of Continuous Subcutaneous Hydrocortisone Infusion In the Treatment of Congenital Adrenal Hyperplasia Estimated enrollment: 8 Study Start Date: May 2013 Estimated Study Completion Date: December 2016 Sponsoring Institute: National Institute of Child Health and Human Development \<TAB\>ELIGIBILITY Inclusion criteria 1. Men and women 18 years of age or older with classic congenital adrenal hyperplasia (21-Hydroxylase deficiency) 2. High adrenal androgens in the blood, and 3. One or more of the following conditions: obesity, fatty liver, risk for diabetes, low bone mass, inability to tolerate cortisol pills Exclusion criteria 1. Pregnancy 2. Breast feeding 3. Use of inhaled or oral steroids for diseases other than CAH 4. Use of estrogen-containing birth control pills 5. Use of medicines that cross-react with hydrocortisone 6. Use of stress dose steroids for illness during the last 30 days prior to joining the study

Congenital adrenal hyperplasia (CAH) is a common genetic endocrine disorder, with 21-hydroxylase enzyme deficiency accounting for 95% of the cases. 21-hydroxylase deficiency presents with a spectrum of clinical manifestations ranging from salt-wasting and virilization of female neonates (classic CAH) to symptomatic (precocious puberty, short stature, acne) or asymptomatic hyperandrogenemia (non-classic CAH). Classic CAH is characterized by impaired cortisol and mineralocorticoid biosynthesis, which triggers adrenocorticotropic hormone (ACTH) hyper-secretion and accumulation of adrenal androgens. Glucocorticoid treatment of patients with classic CAH focuses on cortisol replacement and prevention of the ACTH-driven androgen excess. Current conventional glucocorticoid treatment regimens (short or long-acting agents dosed once, twice or thrice daily) have failed to simulate physiological cortisol secretion and suppress adrenal androgen overproduction, without supraphysiologic replacement. Short-term overtreatment with glucocorticoids can lead to iatrogenic Cushing syndrome and long-term use has been associated with the development of obesity, visceral adiposity, insulin resistance and osteoporosis. Isolated case reports have provided evidence that continuous subcutaneous hydrocortisone infusion (CSHI) can mimic physiologic cortisol release and lead to improved CAH control at doses similar to or lower than the traditional treatment. This pilot study aims to test the hypothesis that difficult-to-treat adult patients with classic CAH will have better adrenal androgen control and improved CAH and glucocorticoid-related comorbidities, when they receive near-physiologic cortisol replacement therapy via CSHI compared to conventional glucocorticoid treatment. In addition, this study will provide information on the safety and tolerability of CSHI, and will generate data that will be used in the design of future pediatric studies.