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      Prednisolone has the same cardiovascular risk profile as hydrocortisone in glucocorticoid replacement

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          Abstract

          Introduction

          Patients who need glucocorticoid replacement in both primary and secondary adrenal insufficiency (AI) have the choice of either once-daily prednisolone or thrice-daily hydrocortisone. A recent European study found no difference between prednisolone and hydrocortisone users in several markers including glucose, weight, body mass index, systolic and diastolic blood pressure and waist circumference, although an increase in cholesterol and low-density lipoprotein (LDL) was suggested in a subgroup of these patients. The aim of this study was to expand the evidence base for the use of these agents as replacement therapy.

          Methods

          Data from 82 patients on hydrocortisone and 64 patients on prednisolone for AI at Imperial College Healthcare NHS Trust were analysed.

          Results

          There was no significant difference in total cholesterol, LDL levels or any other risk factors between hydrocortisone and prednisolone patients. Prednisolone was subjectively significantly more convenient than hydrocortisone ( P = 0.048).

          Conclusions

          Prednisolone once daily is more convenient than hydrocortisone thrice daily, and there is no difference in the markers of cardiovascular risk measured. Because prednisolone mimics the circadian rhythm better than other glucocorticoids, it should be considered as an alternative to hydrocortisone for AI.

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          Most cited references19

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          Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription.

          Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation.
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            Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.

            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. 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. We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers. The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM). The same daily dose of hydrocortisone was administered as OD dual-release or TID. We evaluated cortisol pharmacokinetics. 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). 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.
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              Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas.

              Incidental benign adrenocortical adenomas, adrenal incidentalomas are found in 4.5% of abdominal computed tomography scans, with the incidence increasing to 10% in patients older than 70 years of age. These incidentalomas frequently show evidence of excess cortisol secretion but without overt Cushing's syndrome. The mortality rate is increased in Cushing's syndrome.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                November 2017
                29 September 2017
                : 6
                : 8
                : 766-772
                Affiliations
                [1 ]Department of Endocrinology Imperial College Healthcare NHS Trust, London, UK
                [2 ]Department of Clinical Biochemistry Imperial College Healthcare NHS Trust, London, UK
                [3 ]Department of Investigative Medicine Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
                Author notes
                Correspondence should be addressed to K Meeran; Email: k.meeran@ 123456imperial.ac.uk
                Article
                EC170257
                10.1530/EC-17-0257
                5682416
                29018153
                67bcf828-ec34-46fb-a2d3-3155029346b1
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 27 September 2017
                : 29 September 2017
                Categories
                Research

                prednisolone,hydrocortisone,adrenal insufficiency,cardiovascular risk

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