BMJ 2014;349:g5518 doi: 10.1136/bmj.g5518 (Published 9 September 2014)
Page 1 of 1
Letters
LETTERS GLUCOCORTICOID REPLACEMENT
Mimicking the circadian rhythm in glucocorticoid replacement Peter C Hindmarsh professor of paediatric endocrinology Institute of Child Health, University College London, London WC1N 1EH, UK
To reduce mortality and morbidity in patients with adrenal disorders, it is essential to understand glucocorticoid replacement. I agree with Amin and colleagues that we should mimic the circadian rhythm, but once daily treatment with any of the drugs suggested would not do this.1
Studies on cortisol in people with normal production show that cortisol is always present in the blood.2 Concentrations do drop in the late evening for several hours, but not to zero. Prednisolone cannot mimic this situation because it stays in the circulation for no more than eight hours.3 Even if given at 2 am, all of the drug would be out of the circulation by 10 am and drug concentrations would have peaked at about 4-5 am, leaving the individual deficient in glucocorticoid for the whole of the day and evening, at a crucial point when cortisol should be around. The side effects of prednisolone can be dramatic, particularly in children.4 We know from a few young patients who have
taken prednisolone they have become suicidal and once back on hydrocortisone those tendencies and thoughts disappear.
The only way to minimise side effects is for treatment to mimic the circadian rhythm as closely as possible. This can be achieved with hydrocortisone three or four times daily or pump therapy.5 Competing interests: None declared. 1 2 3 4 5
Amin A, Sam AH, Meeran K. Glucocorticoid replacement. BMJ 2014;349:g4843. (30 July.) Krieger DT, Allen W, Rizzo F, Krieger HP. Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab 1971;32:266-84. Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 2005;44:61-98. Allen DB. Growth suppression by glucocorticoid therapy. Endocrinol Metab Clin North Am 1996;25:699-717. Hindmarsh PC. Management of the child with congenital adrenal hyperplasia. Best Prac Res Clin Endocrinol Metab 2009;23:193-208.
Cite this as: BMJ 2014;349:g5518 © BMJ Publishing Group Ltd 2014
[email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
Page 1 of 1
Letters
LETTERS GLUCOCORTICOID REPLACEMENT
Mimicking the circadian rhythm in glucocorticoid replacement Peter C Hindmarsh professor of paediatric endocrinology Institute of Child Health, University College London, London WC1N 1EH, UK
To reduce mortality and morbidity in patients with adrenal disorders, it is essential to understand glucocorticoid replacement. I agree with Amin and colleagues that we should mimic the circadian rhythm, but once daily treatment with any of the drugs suggested would not do this.1
Studies on cortisol in people with normal production show that cortisol is always present in the blood.2 Concentrations do drop in the late evening for several hours, but not to zero. Prednisolone cannot mimic this situation because it stays in the circulation for no more than eight hours.3 Even if given at 2 am, all of the drug would be out of the circulation by 10 am and drug concentrations would have peaked at about 4-5 am, leaving the individual deficient in glucocorticoid for the whole of the day and evening, at a crucial point when cortisol should be around. The side effects of prednisolone can be dramatic, particularly in children.4 We know from a few young patients who have
taken prednisolone they have become suicidal and once back on hydrocortisone those tendencies and thoughts disappear.
The only way to minimise side effects is for treatment to mimic the circadian rhythm as closely as possible. This can be achieved with hydrocortisone three or four times daily or pump therapy.5 Competing interests: None declared. 1 2 3 4 5
Amin A, Sam AH, Meeran K. Glucocorticoid replacement. BMJ 2014;349:g4843. (30 July.) Krieger DT, Allen W, Rizzo F, Krieger HP. Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab 1971;32:266-84. Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 2005;44:61-98. Allen DB. Growth suppression by glucocorticoid therapy. Endocrinol Metab Clin North Am 1996;25:699-717. Hindmarsh PC. Management of the child with congenital adrenal hyperplasia. Best Prac Res Clin Endocrinol Metab 2009;23:193-208.
Cite this as: BMJ 2014;349:g5518 © BMJ Publishing Group Ltd 2014
[email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
