ESPE Abstracts (2016) 86 S9.2

Recent Advances in CAH: New Approaches to Glucocorticoid Replacement

Richard Ross

Sheffield, UK

Adult CAH patients have poor health outcomes and these in part relate to the method of glucocorticoid replacement in children and adults. Life-saving glucocorticoid replacement was introduced in the 1950s and the majority of children are treated with immediate release hydrocortisone whereas adults are treated with a mixture of hydrocortisone, prednisolone, prednisone and dexamethasone from one to four times daily and in circadian and reverse circadian regimens. Despite these personalised glucocorticoid treatments adult patients remain shorter than the normal population, have an increase in obesity and osteoporosis and impaired fertility and QoL. There are two major challenges in glucocorticoid replacement for CAH patients; prescribing the correct dose and replicating the cortisol circadian rhythm. At the present time there are no paediatric dose specific formulations of glucocorticoids making it challenging to titrate therapy in neonates and infants. Cortisol has a distinct circadian rhythm with low levels at night, rising in the early hours of the morning, peaking on waking, and declining over the day to low levels in the evening. Loss of this diurnal rhythm in CAH results in an early morning rise in androgen levels which is not controlled with current therapy. New technologies are being developed that deliver more physiological glucocorticoid replacement including a paediatric dose specific formulation, Infacort, hydrocortisone by subcutaneous pump, and Chronocort a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. Infacort is a multi-particulate hydrocortisone formulation with taste masking provided in doses of 0.5, 1, 2 and 5 mg that is bioequivalent to currently available immediate release hydrocortisone. Subcutaneous hydrocortisone infusions using insulin technology have been demonstrated to improve control of CAH in small case series. Chronocort has been shown to improve androgen control of adult patients with CAH in a phase 2 clinical trial. Future work will focus on optimising glucocorticoid replacement in CAH patients from birth to old age and demonstrating these treatments improve health outcomes.

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