Intended for healthcare professionals


Glucocorticoid replacement

BMJ 2014; 349 doi: (Published 30 July 2014) Cite this as: BMJ 2014;349:g4843

Glucocorticoid replacement: Insufficient evidence to favour prednisolone over hydrocortisone

Endocrine therapeutics is largely based on the principle that restoring the physiological pattern of hormonal secretion will lead to symptom control and optimal long-term health outcomes. Individuals with adrenal insufficiency have increased morbidity and mortality from vascular disease, and excess fracture risk (1,2). As such people will be treated lifelong with glucocorticoid replacement, even apparently minor degrees of overtreatment should be avoided (3). In addition to the total daily dose, glucocorticoid exposure at the wrong time of day is likely to contribute to adverse metabolic and cardiovascular outcomes (4).

With respect to hydrocortisone, plenadren and prednisolone, Amin and colleagues assert that ‘there is no evidence of any difference between the three replacement options’. However, this refers largely to an evidence vacuum, rather than to documented evidence of equivalence for the different treatments. Lack of a difference in subjective health is not sufficient reason to recommend prednisolone over hydrocortisone for adrenal insufficiency. If we prioritised symptom control over long-term health outcome, there would be virtually no market for drug treatments for type 2 diabetes. I fully support their call for carefully conducted trials of different glucocorticoid replacements with a focus on these long-term outcomes. However, our therapeutic choices shouldn’t be determined by distorted market forces while we wait for this important evidence of safety to emerge.

1. Bergthorsdottir R, Leonsson-Zachrisson M, Odén A, Johannsson G. Premature mortality in patients with Addison's disease: a population-based study. J Clin Endocrinol Metab 2006; 91:4849-4853.
2. Björnsdottir S, Sääf M, Bensing S, Kämpe O, Michaëlsson K, Ludvigsson JF. Risk of hip fracture in Addison's disease: a population-based cohort study. J Intern Med 2011; 270:187-95.
3. Husebye ES, Løvås K, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, Falorni A, Gan EH, Hulting A-L, Kasperlik-Zaluska A, Kämpe O, Mayer G, Pearce SH. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275:104-15
4. Plat L, Leproult R, L'Hermite-Baleriaux M, Fery F, Mockel J, Polonsky KS, Van Cauter E. Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning. Journal of Clinical Endocrinology and Metabolism 1999; 84: 3082–3092.

Competing interests: I have received speaker fees from Viropharma who manufacture plenadren.

10 August 2014
Simon HS Pearce
Professor of Endocrinology
Newcastle University
Newcastle upon Tyne, UK