CaHASE: a Specialist Society Led Academic Collaboration to improve the management of CAH
Authors: R. Ross
Year: 2014

Clinical research is generally led by either academic institutions or industry and funded through competitive grants or R&D contracts. The CaH Adult Study Executive (CaHASE) is an example of a different model for managing and funding research where the research questions were raised by a specialist society and then answered through a collaboration managed and funded by the society. The model has a number of advantages including motivated collaborators, a strong project management infrastructure, access to funding, low cost and the ability to jointly own, store and manage data. Here, we describe the history behind CaHASE and its key outcomes with the view to sharing experience and promoting the value of specialist societies supporting the research. In 2000, the newly formed clinical committee of the Society for Endocrinology was considering areas of clinical management that could and should be audited. The suggestion was made to audit the management of adults with congenital adrenal hyperplasia (CAH); however, it was immediately apparent that there were no standards of care and research was required. CaHASE was therefore established to undertake research investigating current clinical care and health outcomes in adult CAH patients. CaHASE received a grant from the Clinical Endocrinology Trust and supported by a project manager from the Society for Endocrinology invited interested centres to join the project. Representatives joined from seventeen UK centres (Fig. 1) and working together established a protocol for a prospective cohort study of health outcomes in adult patients with CAH. The study was supported by a further grant from the Clinical Endocrinology Trust that underpinned project management. The CaHASE study was the first large cohort of CAH adults to be reported and found that: a minority of patients were under specialist care; glucocorticoid replacement was generally nonphysiological; androgen levels were poorly controlled; and this was associated with an adverse metabolic profile and impaired fertility and quality of life. CaHASE then investigated the basis for these poor health outcomes. Importantly, poor health outcomes were not associated with genotype, suggesting that they were more likely a result of treatment. Adult CAH patients are treated with a wide variety of glucocorticoid treatment regimens that include hydrocortisone, prednisolone and dexamethasone given alone, in combination, and in circadian and reverse circadian regimens. Looking at associations between the type of glucocorticoid, the prednisolone dose equivalent and health outcome, it was observed that dexamethasone use was associated with greater insulin resistance and increasing glucocorticoid dose with increased blood pressure and poor disease control. The impaired QoL was associated with increased adiposity, insulin resistance and use of prednisolone or dexamethasone. To investigate the impact of childhood treatment on adult health outcomes, CaHASE examined final height as a marker of successful childhood treatments. In the CaHASE cohort, final height was below that of the UK population, although height prognosis has improved over time. The shortest adults were those diagnosed late with moderate severity CAH, and being short was a risk factor for adult hypertension. The results suggest that the short patients are exposed in childhood to high androgens and/or excessive glucocorticoid with potential for programming hypertension. The results of the CaHASE analyses have recently been summarized in Nature Review Endocrinology, and a multidisciplinary consensus for guidelines is shortly to be published. The majority of poor health outcomes seem to relate to inadequate treatment rather than the genotype of the patient, and patients receiving high doses of glucocorticoids and the more potent synthetic long-acting glucocorticoids are at an increased risk of obesity, insulin resistance and a reduced quality of life. The overall CaHASE conclusion being that further research is required to optimize the treatment of adult patients with CAH. To undertake further research CaHASE has joined a recently established registry, I-CAH (https://www.i-cah.org/), created in part to disseminate the activities of the EC FP7 Grant (No 281654) ‘Treatment of Adrenal Insufficiency in Neonates and Infants (TAIN)’. The I-CAH registry has an executive committee with clinician and patient representatives from across Europe. Already, over 150 patients are registered, and the plan is to develop protocols for both observational and interventional studies to improve the care of patients with CAH. CaHASE provides a good example of a successful collaboration between endocrinologists from a significant number of clinical centres, representative of a geographic area, and promoted, supported and funded by the Society for Endocrinology and the Clinical Endocrinology Trust. Correspondence: Richard J. M. Ross, Department of Endocrinology, Medical School, University of Sheffield, Sheffield S10 2JF, UK. Tel.: 0114 2711634; E-mail: r.j.ross@sheffield.ac.uk