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J Clin Endocrinol Metab. 2012 Feb;97(2):473-81. doi: 10.1210/jc.2011-1926. Epub 2011 Nov 23.

Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.

Author information

1
Department of Endocrinology, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden. Gudmundur.Johannsson@gu.se

Abstract

CONTEXT:

Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.

OBJECTIVE:

The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.

DESIGN AND SETTING:

We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.

PATIENTS:

The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).

INTERVENTION:

The same daily dose of hydrocortisone was administered as OD dual-release or TID.

MAIN OUTCOME MEASURE:

We evaluated cortisol pharmacokinetics.

RESULTS:

Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).

CONCLUSION:

The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

PMID:
22112807
DOI:
10.1210/jc.2011-1926
[Indexed for MEDLINE]

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