Summer 2007 Newsletter
CARES Foundation, Inc.
NIH Update: Natural History Study of CAH
Since July 2005, CARES has generously provided an annual gift to the NIH Clinical Center in support of clinical research in congenital adrenal hyperplasia. This annual gift was used to hire a Nurse Practitioner, Ms. Carol VanRyzin, for 32 hours per week and allowed Dr. Deborah Merke to start a new clinical research protocol to study the natural history of CAH. Prior to July 2005, 20 percent of one pediatric nurse practitioner’s time was dedicated to supporting one CAH clinical research study at the NIH Clinical Center. New clinical research protocols were not in the realm of possibility because of the lack of clinical personnel and budget cuts. In October 2005, Dr. Merke received final approval of this Natural History Study. In October 2006, Dr. Merke reported that 148 patients had been enrolled in this new protocol (140 with CAH and 8 misdiagnoses; 95 children and 45 adults; 130 classic CAH and 18 nonclassic CAH). As of March 2007, Dr. Merke and Carol have seen 153 patients with CAH (104 children and 49 adults; 131 classic CAH and 22 nonclassic CAH) on the Natural History Protocol! Many patients have also returned for follow-up visits.
Although Dr. Merke has only accepted patients with an established diagnosis of CAH, 8 patients have been seen who were misdiagnosed (about 5 percent of patients evaluated to date). These patients include: an 8 year old male with a testicular tumor, a 10 year old female with precocious puberty, 3 young adult females with polycystic ovary syndrome, 2 unaffected carriers (1 year old male and 7 year old female) and a 27 year old female with 21-hydroxylase deficiency who was misdiagnosed with 11-hydroxylase deficiency. Seven of these 8 patients were receiving glucocorticoid medication unnecessarily. These patients represent the need for a greater understanding of CAH in our medical community. The Natural History Study is helping to educate physicians in numerous ways including: physicians-in-training in endocrinology (fellows) are seeing the patients with CAH who come to the NIH; letters are being sent to all patients’ local physicians; and findings will lead to publications and expand our general knowledge of CAH.
All patients enrolled in the Natural History Study have a comprehensive medical evaluation including physical examination, a review of prior medical records, confirmation of the diagnosis, genotyping (21-hydroxylase deficiency only), endocrine evaluation including adrenal hormones and an evaluation for insulin resistance, bone age for children, ultrasound of the ovaries and uterus in females and testes in males, neurocognitive testing and extensive one-on-one teaching regarding sick day rules and management of illnesses. Full reports are provided to the patients and their local physicians.
NIH Accomplishments to Date as a Result of the CARES donation
Because of the large number of CAH patients being seen and also because of the contributions of Carol VanRyzin and the gift by the CARES Foundation, 2 studies were completed this year that further evaluate the adrenal medulla in patients with CAH. One manuscript, Patients with Classic Congenital Adrenal Hyperplasia Have Decreased Epinephrine Reserve and Defective Glycemic Control During 90-Minute Moderate-Intensity Exercise, was recently accepted by the Journal of Clinical Endocrinology and Metabolism. This manuscript describes abnormal glucose regulation in patients with classic CAH during 90-minutes of exercise equivalent to brisk walking. This study shows that epinephrine (adrenaline) secretion is impaired with mild to moderate stressors, or in situations other than high-intensity physical stress. This study also reports further evidence of insulin resistance in patients with classic CAH. A second manuscript, The Degree of Epinephrine Deficiency Observed in Patients with Classic and Nonclassic CAH in Response to High-Intensity Exercise is Associated with the Severity of Disease, is in preparation. The results of the latter study will be presented at the Endocrine Society’s 89th Annual Meeting in June 2007. It is the first study ever evaluating the function of the adrenal medulla in patients with nonclassic CAH and is the first description of abnormal epinephrine (adrenaline) secretion in patients with nonclassic CAH.
Another accomplishment is the development of an extensive database for the Natural History Study.
One advantage of having a center of excellence for a rare disease is that clinical observations across a large number of patients can lead to the discovery of new aspects of the disease expression. In the Natural History Study, Dr. Merke and her colleagues at the NIH are exploring new clinical aspects of CAH in relation to specific genetic mutations and possible risk for cardiovascular disease. Preliminary results are promising and they hope to be able to report new findings in the coming year.
Goals of the NIH Natural History Study
The ultimate goal of the NIH Natural History Study is to achieve a comprehensive description of CAH in the largest ever group of patients leading to novel findings and a greater understanding of CAH, and to the development of new treatment approaches.
In the next year, Dr. Merke will be continuing to recruit patients for the Natural History Study and will also be seeing those enrolled for follow-up visits; her group will be analyzing data and writing a manuscript to report the Natural History Study experience to date; and they will be completing a novel phenotype/genotype study.
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Disclaimer: Any communication from CARES Foundation, Inc. is intended for informational and educational purposes only and in no way should be taken to be the provision or practice of medical, nursing or professional healthcare advice or services. The information should not be considered complete or exhaustive and should not be used in place of the visit, call, consultation or advice of your physician or other healthcare provider. You should not us the information in this or any CARES Foundation, Inc. communication to diagnose or treat CAH or any other disorder without first consulting with your physician or healthcare provider. The articles presented in this newsletter are for informational purposes only and do not necessarily reflect the views of CARES Foundation, Inc.