Bone safety of dual-release hydrocortisone in patients with hypopituitarism

Frara, Stefano; Chiloiro, Sabrina; Porcelli, Teresa; Giampietro, Antonella; Mazziotti, Gherardo; Marinis, Laura De; Giustina, Andrea

doi:10.1007/s12020-017-1512-1

Cited by 37 publications

(61 citation statements)

References 22 publications

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“…In the group of patients with modified-release HC no spontaneous fractures appeared during the study period. In a recent, longitudinal study, 14 patients with secondary AI (ten females: median age 55 years, range 31–77 years) who had used conventional GC regimens for at least 12 months were changed to modified-release HC ( 41 ). After 24 months of treatment with modified-release HC, a significant increase in BMD values at lumbar spine and femoral neck was observed, without statistically significant change in total hip BMD.…”

Section: Discussionmentioning

confidence: 99%

Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency

Frey

Kienitz

Schulz

et al. 2018

Endocrine Connections

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ContextPatients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) therapy. Daily GC doses are often above the physiological cortisol production rate and can cause long-term morbidities such as osteoporosis. No prospective trial has investigated the long-term effect of different GC therapies on bone mineral density (BMD) in those patients.ObjectivesTo determine if patients on hydrocortisone (HC) or prednisolone show changes in BMD after follow-up of 5.5 years. To investigate if BMD is altered after switching from immediate- to modified-release HC.Design and patientsProspective, observational, longitudinal study with evaluation of BMD by DXA at visit1, after 2.2 ± 0.4 (visit2) and after 5.5 ± 0.8 years (visit3) included 36 PAI and 8 CAH patients. Thirteen patients received prednisolone (age 52.5 ± 14.8 years; 8 women) and 31 patients received immediate-release HC (age 48.9 ± 15.8 years; 22 women). Twelve patients on immediate-release switched to modified-release HC at visit2.ResultsPrednisolone showed significantly lower Z-scores compared to HC at femoral neck (−0.85 ± 0.80 vs −0.25 ± 1.16, P < 0.05), trochanter (−0.96 ± 0.62 vs 0.51 ± 1.07, P < 0.05) and total hip (−0.78 ± 0.55 vs 0.36 ± 1.04, P < 0.05), but not at lumbar spine, throughout the study. Prednisolone dose decreased by 8% over study time, but no significant effect was seen on BMD. BMD did not change significantly after switching from immediate- to modified-release HC.ConclusionsThe use of prednisolone as hormone replacement therapy results in significantly lower BMD compared to HC. Patients on low-dose HC replacement therapy showed unchanged Z-scores within the normal reference range during the study period.

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Section: Discussionmentioning

confidence: 99%

Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency

Frey

Kienitz

Schulz

et al. 2018

Endocrine Connections

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“…There has been variation in bone composition among the patients with adrenal insufficiency treated with various glucocorticoid replacement options with lower scores noted in patients treated with prednisolone [17,18]. On the other hand, the use of modified release hydrocortisone has been shown to result in improved BMD values [19] although the overall evidence remains conflicting and contentious. A recent study following up patients with primary adrenal insufficiency over 5.5 years showed lower BMD values with prednisolone than hydrocortisone, and no improvement in the values was seen after a change to modified release hydrocortisone [20].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Various Glucocorticoid Replacement Regimens Used in Chronic Adrenal Insufficiency: A Systematic Review

Kiko¹,

Kalhan²

2020

Dubai Diabetes Endocrinol J

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Objective: Patients with adrenal insufficiency require life-long glucocorticoid replacement therapy. Hydrocortisone (15–30 mg/day) and prednisolone (3–7.5 mg/day) are the preferred agents used although there is a lack of consensus among endocrinologists regarding the impact of different steroid regimens on quality of life, bone metabolism, cardiometabolic outcomes, adrenal crisis and infections. We carried out a retrospective systematic review of the literature to compare the efficacy and side effects of various glucocorticoid replacement regimens in patients with chronic adrenal insufficiency. Methods: We searched PubMed, Cochrane Reviews and Google Scholar databases up to March 14, 2019, for studies evaluating various clinical outcomes with glucocorticoid replacement therapy. The abstracts and full studies were appraised and data extracted from the eligible studies. The quality of evidence was evaluated and risk of bias carried out. Results: A total of 47 studies including 9 randomised controlled trials (RCTs) and 38 observational studies were evaluated in this systematic review. Prednisolone therapy was observed to be safe as well as efficacious as hydrocortisone although a higher dose was associated with an increased risk of cardiovascular (CV) disease. A lower hydrocortisone dose (15–20 mg/day) was associated with a reduction of blood pressure and improved clinical outcomes although this observation was based on a solitary RCT. Modified release hydrocortisone was observed to reduce the risk of CV disease based upon results from 2 of the RCTs. However, there was no conclusive evidence of benefit of modified release hydrocortisone and continuous subcutaneous hydrocortisone infusion in improving subjective health status. Conclusion: Prednisolone therapy remains a safe and efficacious alternative to hydrocortisone although there are concerns of dyslipidaemia and CV disease with higher doses. There is limited level I evidence suggestive of a positive effect of modified release hydrocortisone on CV and metabolic outcomes, particularly weight reduction.

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“…Mongioi et al reported that a cohort of 9 patients with secondary hypoadrenalism showed no significant change in fasting glucose, serum insulin levels, serum glycated haemoglobin and HOMA index after 12 months of DR hydrocortisone treatment. Frara et al reported no significant change in serum glycated haemoglobin and lipid parameters in a cohort of 14 patients with secondary hypoadrenalism after 24 months of DR hydrocortisone therapy.…”

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confidence: 95%

Should all patients with adrenal insufficiency or a subgroup of patients with prediabetes be treated with dual‐release hydrocortisone?

Giordano

2018

Clinical Endocrinology

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Guarnotta et al 1 compare the effects of dual-release (DR) hydrocortisone 36 months' treatment in 13 patients with primary adrenal insufficiency and 36 with secondary adrenal insufficiency, compared to conventional glucocorticoid treatment. A retrospective evaluation was conducted on the effects of 36 months of DR hydrocortisone therapy on visceral adiposity, insulin secretion and insulin sensitivity.Forty-nine patients with adrenal insufficiency were recruited. They had been on stable conventional glucocorticoid treatment before entering the study and underwent clinical and metabolic evaluation at baseline (during conventional glucocorticoid treatment) and at 12, 24 and 36 months after switching to DR hydrocortisone. DR hydrocortisone is a formulation that consists of an extendedrelease core surrounded by an immediate release coating. DR hydrocortisone absorption is rapid (17-20 minutes for the 20 mg tablet in the fasting state) and can induce an adequate increase in morning cortisol levels with a peak concentration time similar to the one observed with conventional hydrocortisone. However, it produces a more gradual decline in cortisol concentrations than conventional hydrocortisone. DR hydrocortisone was developed to obtain a more physiological circadian cortisol exposure time after a once-daily administration. 2 Although a lot of work has been done to optimise glucocorticoid treatment with more physiological formulations of hydrocortisone in the last two decades, there has been no consistent evidence that more physiological replacement of corticosteroid therapy is superior to the conventional once, twice or thrice daily dosages of shortacting corticosteroids. However, previous studies did not carefully measure insulin sensitivity and secretion during DR hydrocortisone.Guarnotta et al report that long-term DR hydrocortisone is associated with an improvement in insulin secretion and sensitivity in patients with impaired fasting glucose and/or impaired glucose tolerance. The investigators also report an improvement of other parameters (body mass index, waist circumference, glycated haemoglobin and high-density-lipoprotein-cholesterol) in the entire cohort (including those patients without prediabetes).As reported by the Authors, the retrospective design is the main limitation to the study as a cross-over study design would have been preferable for the assessment and verification of the effects of DR hydrocortisone. The small sample size is another principal limitation.The cohort of patients studied by Guarnotta et al is too heterogeneous to draw a definitive conclusion on the role of DR hydrocortisone therapy on glucose homeostasis and insulin sensitivity, but these findings justify for future study on the topic. Future studies should contain adequate numbers of patients with primary and secondary hypoadrenalism.It is well known that exogenous glucocorticoids affect glucose metabolism, and induce peripheral insulin resistance by impairing insulin signalling. This will lead to decreased glucose disposal and incre...

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Bone safety of dual-release hydrocortisone in patients with hypopituitarism

Cited by 37 publications

References 22 publications

Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency

Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency

Comparison of Various Glucocorticoid Replacement Regimens Used in Chronic Adrenal Insufficiency: A Systematic Review

Should all patients with adrenal insufficiency or a subgroup of patients with prediabetes be treated with dual‐release hydrocortisone?

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