Autoimmune Addison’s disease (AAD) is a chronic condition where affected patients require steroid replacement for life. They are also faced with the ever-present risks of adrenal crisis and complications associated with over-replacement with corticosteroids. In the UK, the common glucocorticoid replacement regimen for AAD is hydrocortisone (15-20mg) taken in divided doses and the synthetic mineralocorticoid, 9a-fludrocortisone, taken once daily at a dose of 50-200mcg, as guided by blood pressure, electrolytes and plasma renin level. For most patients, daily steroid replacement is adequate to control symptoms but does not restore them to full health.
Our group has previously established that AAD is a heterogeneous condition where some patients demonstrated various degrees of residual adrenal function. This suggests that an individualised steroid replacement regimen may be more appropriate for some AAD patients. However, an accurate objective outcome measure of clinical benefits to assess the adequacy and efficacy of steroid replacement is still lacking. Current practice relies on subjective clinical judgement to assess the adequacy of glucocorticoid replacement. A 24-hour serum cortisol profile could be performed on some patients but serial measurement of cortisol level lacks practicality for frequent monitoring purposes. Hence, robust biomarkers that could inform clinical outcome from fast and accurate read-outs will be highly desirable.
In light of this, we aims to carry out a pilot study to uncover the glucocorticoid-responsive biomarkers that could be retrieved from a one-off blood sample. Advances in proteomic technology have allowed broad-based assessment of protein concentrations using only small amounts of blood. Steroid deficiency is highly likely to be reflected in the proteomic pattern in the blood. We hope to identify protein patterns that would distinguish patients who are adequately replaced with steroids from those who are not. We hope to achieve this by collaborating with the Newcastle University Protein and Proteome Analysis Unit, using advanced proteomic techniques (mass spectrometry). In the longer term, we would like to develop a simple, fast and accurate read-out to allow rapid and objective assessments of the efficacy and safety of steroid therapy, on an individual basis. This will prevent the side effects associated with over-replacement with steroids, such as osteoporosis and diabetes; as well as reducing the health burden from under-replacement with steroids. I am grateful to the ADSHG for supporting my research and I look forward to letting you know my findings in the future.
Dr Earn Gan
Dr Earn Gan is a NIHR academic clinical lecturer from Newcastle University who completed a PhD in 2015 under the supervision of Professor Simon Pearce. She investigated the novel therapeutic approaches and pathophysiology in autoimmune Addison’s disease (AAD). She continues to develop her research experience in the field of AAD and has had 8 publications related to AAD in various peer-reviewed journals.
This article was first published in the September 2017 edition of the ADSHG newsletter.