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J R Soc Med. 1988 September; 81(9): 514–516.
PMCID: PMC1291759

Corticosteroid replacement therapy: twice or thrice daily?


Although glucocorticoid replacement is conventionally administered twice daily, the pharmacokinetics of hydrocortisone would predict very low levels of plasma cortisol by mid-afternoon. This study compared plasma cortisol day profiles in 7 hypoadrenal patients while on twice daily and thrice daily hydrocortisone replacement. The twice daily regimen was associated with very low levels of cortisol at 16.00 and 18.00 h. This was eliminated by administering the same total dose in a thrice daily regimen. Furthermore, estimates of 'well-being' by visual analogue scale correlated significantly with simultaneous plasma cortisol levels and 5 of the patients expressed a preference for the thrice daily regimen. The findings suggest that thrice daily glucocorticoid replacement therapy should be adopted routinely.

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Selected References

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  • Feek CM, Ratcliffe JG, Seth J, Gray CE, Toft AD, Irvine WJ. Patterns of plasma cortisol and ACTH concentrations in patients with Addison's disease treated with conventional corticosteroid replacement. Clin Endocrinol (Oxf) 1981 May;14(5):451–458. [PubMed]
  • Kehlet H, Binder C, Blichert-Toft M. Glucocorticoid maintenance therapy following adrenalectomy: assessment of dosage and preparation. Clin Endocrinol (Oxf) 1976 Jan;5(1):37–41. [PubMed]
  • Scott RS, Donald RA, Espiner EA. Plasma ACTH and cortisol profiles in Addisonian patients receiving conventional substitution therapy. Clin Endocrinol (Oxf) 1978 Dec;9(6):571–576. [PubMed]
  • Nickelsen T, Schulz F, Demisch K. Studies on cortisol substitution therapy in patients with adrenal insufficiency. Exp Clin Endocrinol. 1983 Jul;82(1):35–41. [PubMed]
  • Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Hellman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971 Jul;33(1):14–22. [PubMed]
  • Levin J, Zumoff B, Kream J, Fukushima DK. Cortisol measurements in patients receiving oral corticosteroid replacement treatment. J Clin Pharmacol. 1981 Jan;21(1):52–56. [PubMed]

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