Inadvertent treatment of hypoadrenalism with prednisolone in pemphigus: A case report

Choudhury, Sirazum; Machenahalli, Pratibha; Tan, Tricia; Meeran, Karim

doi:10.1002/ccr3.2132

Cited by 5 publications

(6 citation statements)

References 5 publications

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“…Arriving at the minimum required dose to maintain a patient with hypoadrenalism is difficult in the absence of established biomarkers. Slowly reducing the steroid dose can be dangerous but was inadvertently undertaken in a patient with secondary hypoadrenalism, where a replacement dose of 3 mg was found to be optimal ( 62 ). There has been progress in managing hypoadrenal patients with prednisolone following the development of mass spectrometry methods to quantify prednisolone levels ( 37 ).…”

Section: Prednisolonementioning

confidence: 99%

The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism

Choudhury

Tan

Lazarus

et al. 2021

Endocrine Connections

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The introduction of adrenocortical extract in 1930, improved life expectancy to between two and five years with further increases seen with the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multi-dose regimens. Today there remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with detrimental risk of excess glucocorticoid at later times in the day. The way forwards involves replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2-4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.

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Section: Prednisolonementioning

confidence: 99%

The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism

Choudhury

Tan

Lazarus

et al. 2021

Endocrine Connections

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“…25 It is however clear that previously used doses have been excessive and 3-4 mg once daily is sufficient replacement in most patients. 26,27 Currently, there are two NIHR adopted studies actively recruiting, comparing lowdose prednisolone with standard regimens of hydrocortisone. 28,29 Low-dose prednisolone has been shown to be superior in reducing androgens, 17-hydroxy progesterone and improving growth velocity in patients with congenital adrenal hyperplasia compared to thricedaily hydrocortisone.…”

Section: Oral Preparations Of Glucocorticoidsmentioning

confidence: 99%

“…Further data from a prospective observational study in Germany recorded the frequency of crises experienced by patients on different treatment regimens, and showed that the proportion of patients on prednisolone experiencing a crisis was not greater than expected . It is however clear that previously used doses have been excessive and 3‐4 mg once daily is sufficient replacement in most patients . Currently, there are two NIHR adopted studies actively recruiting, comparing low‐dose prednisolone with standard regimens of hydrocortisone .…”

Section: Introductionmentioning

confidence: 99%

Improving glucocorticoid replacement profiles in adrenal insufficiency

Choudhury

Lightman

Meeran

2019

Clinical Endocrinology

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There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long‐term benefits is not yet clear. There is a dearth of evidence and high‐quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.

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“…At Imperial College Healthcare NHS Trust (ICHNT), an 8-h prednisolone level between 15 and 25 μg/L indicates adequate replacement ( 13 , 15 ). However, the 8-h time point may be inconvenient for patients attending outpatient clinics, and therapeutic levels at other time points are important.…”

Section: Introductionmentioning

confidence: 99%

Optimising prednisolone or prednisone replacement in adrenal insufficiency

Sharma

Lazarus

Papadopoulou

et al. 2023

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Context: Patients with adrenal insufficiency (AI) have higher mortality than the general population, possibly because of excess glucocorticoid exposure at inappropriate times. The cortisol circadian rhythm is difficult to mimic with twice or thrice-daily hydrocortisone. Prednisolone is a once-daily alternative which may improve patient compliance and convenience. Objectives: Prednisolone day curves can be used to accurately down-titrate patients to the minimum effective dose. We aimed to review prednisolone day curves and determine therapeutic ranges at different timepoints after administration. Methods: Between August 2013 and May 2021, 108 prednisolone day curves from 76 individuals receiving prednisolone replacement were analysed. Prednisolone concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Spearman’s correlation coefficient was used to determine the relationship between 2-, 4- and 6-hour prednisolone levels compared to the validated standard 8-hour prednisolone level (15-25 μg/L). Results: The median dose was 4mg prednisolone once daily. There was strong correlation between the 4-hour and 8-hour (R=0.8829, p ≤0.0001), and 6-hour and 8-hour prednisolone levels (R=0.9530, p ≤ 0.0001). Target ranges for prednisolone were 37-62 μg/L at 4-hours, 24-39 μg/L at 6-hours and 15-25 μg/L at 8-hours. Prednisolone doses were successfully reduced in 21 individuals and of these, three were reduced to 2mg once daily. All patients were well upon follow-up. Conclusion: This is the largest evaluation of oral prednisolone pharmacokinetics in humans. Low dose prednisolone of 2-4mg is safe and effective in most patients with AI. Doses can be titrated with either 4-hour, 6-hour, or 8-hour single timepoint drug levels.

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Inadvertent treatment of hypoadrenalism with prednisolone in pemphigus: A case report

Abstract: Key Clinical Message Pituitary and adrenal insufficiency must not be overlooked when weaning patients down from high‐dose steroids. Prednisolone can be used as glucocorticoid replacement therapy, with most patients needing 3‐4 mg once daily.

Cited by 5 publications

References 5 publications

The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism

The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism

Improving glucocorticoid replacement profiles in adrenal insufficiency

Optimising prednisolone or prednisone replacement in adrenal insufficiency

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