Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a Randomized Controlled Trial

Buning, Jorien Werumeus; Faassen, Martijn van; Brummelman, Pauline; Dullaart, Robin P. F.; Berg, Gerrit van den; Klauw, Melanie M. van der; Kerstens, Michiel N.; Stegeman, Coen A.; Kobold, Anneke C. Muller; Kema, Ido P.; Wolffenbuttel, Bruce H. R.; Beek, André P van

doi:10.1210/jc.2016-2216

Cited by 35 publications

(24 citation statements)

References 45 publications

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“…Nevertheless, our findings are in line with findings in one experimental study in rats showing increased urinary (THF‐alloTHF)/THE ratio after syngeneic kidney transplantation, and with one case report, showing that urinary (THF‐alloTHF)/THE ratio, but not cortisol/cortisone ratio, remained high after kidney transplantation in a patient with the syndrome of apparent mineralocorticoid excess (AME), who was chronically treated with methylprednisolone after transplantation . In addition, our results of a dose‐dependent effect of prednisolone on urinary (THF‐alloTHF)/THE ratio are in line with two studies in patients with adrenal insufficiency treated with exogenous hydrocortisone, which showed increased urinary (THF + alloTHF)/THE ratio in patients treated with higher hydrocortisone doses …”

Section: Discussionsupporting

confidence: 91%

“…Its counterpart, 11beta‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2), converts active cortisol to inactive cortisone and is highly expressed in mineralocorticoid target tissues such as the kidney . Recent studies suggest that exogenous corticosteroids, in addition to their direct effect of suppression on the HPA axis, may stimulate cortisol regeneration from cortisone by induction of 11β‐HSD1 …”

Section: Introductionmentioning

confidence: 99%

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Endogenous urinary glucocorticoid metabolites and mortality in prednisolone‐treated renal transplant recipients

Vulto

Minovíc

Vries

et al. 2020

Clinical Transplantation

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Background: Chronic corticosteroid treatment suppresses HPA-axis activity and might alter activity of 11β hydroxysteroid dehydrogenases (11β-HSD). We aimed to investigate whether the endogenous glucocorticoid production and 11β-HSD activities are altered in prednisolone-treated renal transplant recipients (RTR) compared with healthy controls and whether this has implications for long-term survival in RTR. Methods: In a longitudinal cohort of 693 stable RTR and 275 healthy controls, 24-hour urinary cortisol, cortisone, tetrahydrocorisol (THF), allotetrahydrocortisol (alloTHF), and tetrahydrocortisone (THE) were measured using liquid chromatography tandemmass spectrometry. Twenty-four-hour urinary excretion of cortisol and metabolites were used as measures of endogenous glucocorticoid production; (THF + alloTHF)/ THE and cortisol/cortisone ratios were used as measures of 11β-HSD activity.Results: Urinary cortisol and metabolite excretion were significantly lower in RTR compared with healthy controls (P < .001), whereas (THF + alloTHF)/THE and cortisol/cortisone ratios were significantly higher (P < .001 and P = .002). Lower total urinary metabolite excretion and higher urinary (THF + alloTHF)/THE ratios were associated with increased risk of mortality, independent of age, sex, estimated glomerular filtration rate, C-reactive protein, body surface area, and daily prednisolone dose, respectively. Conclusions: Endogenous glucocorticoid production and 11β-HSD activities are altered in prednisolone-treated RTR. Decreased total urinary endogenous glucocorticoid metabolite excretion and increased urinary (THF + alloTHF)/THE ratios are associated with increased risk of mortality. K E Y W O R D S 11βHSD, cortisol, mortality, prednisolone, renal transplant recipients S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Vulto A, Minović I, de Vries LV, et al. Endogenous urinary glucocorticoid metabolites and mortality in prednisolone-treated renal transplant recipients. Clin

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Endogenous urinary glucocorticoid metabolites and mortality in prednisolone‐treated renal transplant recipients

Vulto

Minovíc

Vries

et al. 2020

Clinical Transplantation

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“…During the last decades, the average daily GC dose has gradually been reduced from approximately 30 to 20 mg HC/d. This was supported by studies showing a reduction in GC side effects such as osteoporosis, hypertension and metabolic effects due to daily dose reduction . However, critics stated that lower doses of short‐acting GC replacement therapy might actually predispose patients to ACs during illness by exposing them to periods of relatively profound hypocortisolaemia .…”

Section: Discussionmentioning

confidence: 99%

Daily adjustment of glucocorticoids by patients with adrenal insufficiency

Schöfl

Mayr

Maison³

et al. 2019

Clinical Endocrinology

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Background Patients with adrenal insufficiency (AI) require lifelong glucocorticoid (GC) replacement. AI patients need to adjust GC dosage in response to stressful events and illness in order to prevent life‐threatening adrenal crisis (AC). Aim To evaluate self‐management of patients with AI. Methods Four German centres, which are using patient's diary as part of their routine clinical practice, instructed AI patients to prospectively document any discomfort, intercurrent illness or stressful events as well as changes in GC therapy on a daily basis. Diaries of 80 patients (44 females, 52.9 ± 15.9 years, 34 primary AI) were collected and analysed. A symptom score sheet was used to evaluate severity of discomfort. Results In total, 34 074 patient days (93.4 years) were recorded. 4622 days with discomfort were documented. On 35% of those days (n = 1621), patients increased their GC dose (4.8% of all days). Patients who recorded discomfort had a median of four episodes of discomfort, which lasted a median of 2 days. Women documented significantly more episodes of discomfort than men (P = 0.014). Low‐to‐median symptom scores resulted in GC increase by 50%‐60%, whereas high symptom scores and/or fever resulted in doubling GC daily dose. However, dose increase was only 55% in situations indicating gastrointestinal (GI) infection. Conclusion Severe discomfort did not always result in dose increase, especially in GI infection. However, low symptom scores resulted in an inappropriate GC increase in some patients. This underscores an urgent need for improved training methods. Keeping daily records might be a useful tool for continued and individualized patient education.

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“…However, this conventional dosage scheme has been demonstrated to expose patients to supraphysiological levels of cortisol . Overexposure to GCs has been demonstrated to increase metabolic dysfunction, hypertension, sleep pattern disturbance and cardiometabolic risk, resulting in impaired quality of life and enhancing mortality and morbidity …”

Section: Introductionmentioning

confidence: 99%

Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual‐release hydrocortisone treatment: a 36‐month retrospective analysis

Guarnotta

Ciresi

Pillitteri

2018

Clinical Endocrinology

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Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a Randomized Controlled Trial

Cited by 35 publications

References 45 publications

Endogenous urinary glucocorticoid metabolites and mortality in prednisolone‐treated renal transplant recipients

Endogenous urinary glucocorticoid metabolites and mortality in prednisolone‐treated renal transplant recipients

Daily adjustment of glucocorticoids by patients with adrenal insufficiency

Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual‐release hydrocortisone treatment: a 36‐month retrospective analysis

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