Hydrocortisone Versus Prednisolone for Treatment of Adrenal Insufficiency Disease (HYPER-AID Study)

In the UK, oral immediate release hydrocortisone divided in three doses daily has been the traditional treatment. The most common regimen in clinical practice uses doses of 10 mg on waking, 5 mg at lunch time and 5 mg in the afternoon. Once daily prednisolone is another regimen in clinical use and now prescribed at less than 5mg daily. It has a longer duration of action and a smoother pharmacokinetic profile compared to hydrocortisone. Moreover, prednisolone is much more cost-effective than hydrocortisone with 5mg tablets. Prednisolone is less commonly used due to perceived concerns regarding loss of bone mineral density leading to osteoporosis, increased insulin resistance leading to steroid induced diabetes, and rises in blood pressure and weight leading to increased cardiovascular risk. This belief is perhaps driven by the fact that most clinicians encounter prednisolone in the context of the treatment of asthma, rheumatoid arthritis etc. where far higher doses are employed. Where effects on bone health have been noted, they have been in association with higher doses of prednisolone (7.5mg) than those employed today (2-5mg).

Although conventionally prednisolone 5 mg is assumed to be bioequivalent to HC 20 mg (ratio 1:4), newer studies suggest that the ratio may be nearer 1:6-8 i.e. lower doses can be used.