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

Guarnotta, Valentina; Ciresi, Alessandro; Pillitteri, Giuseppe

doi:10.1111/cen.13554

Cited by 28 publications

(42 citation statements)

References 34 publications

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“…Several studies have shown that DR-HC treatment is associated with a reduction in weight, WC, systolic and diastolic blood pressure, HbA1c and lipids and an improvement of quality of life (6, 7, 9, 15). Furthermore, a recent study by our group documented a decrease in BMI, WC, HbA1c and an increase in HDL-C in patients treated with DR-HC for 36 months, showing a significant improvement in insulin secretion and sensitivity, even in patients with pre-diabetes (8).…”

Section: Discussionmentioning

confidence: 77%

“…It is characterized by an immediate-release fraction of HC in the outer layer of the tablet and an extended-release fraction in the core, able to provide an adequate concentration of cortisol within 50 min of administration, half-cortisol plasma concentration for 6 h thereafter and a minimal cortisol level 18–24 hours after intake (4). This characteristic formulation has been shown to improve anthropometric and metabolic parameters and quality of life, appearing to be safe in the long term (5, 6, 7, 8, 9, 10).…”

Section: Introductionmentioning

confidence: 99%

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Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency

Guarnotta

Stefano

Santoro

et al. 2019

Endocrine Connections

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Background Dual-release hydrocortisone (DR-HC) improves metabolism in patients with adrenal insufficiency. The aims of this study were to compare the cardiovascular and metabolic effects of conventional glucocorticoids (GCs) vs. DR-HC and of high vs. low doses of GCs, after 48 months of observation. Methods We selected 27 patients on hydrocortisone (mean dose 17.5 ± 4.2 mg/day) and 20 patients on cortisone acetate (mean dose 37.5 ± 12.1 mg/day) who maintained this treatment (group A) and 53 patients switched to DR-HC (mean dose 22 ± 4.8 mg/day) (group B). At baseline and after 48 months, clinical and metabolic parameters and Framingham Risk Score (FRS) were obtained. Results After 48 months, patients in group A had a significant increase from baseline in BMI (P < 0.001), waist circumference (P = 0.001), systolic blood pressure (P = 0.001), LDL cholesterol (P = 0.018), HbA1c (P = 0.020) and FRS (P = 0.002). By contrast, patients in group B had a significant decrease in BMI (P = 0.002), waist circumference (P = 0.015), diastolic blood pressure (P = 0.031), total (P = 0.006) and LDL cholesterol (P = 0.005), HbA1c (P < 0.001) and FRS (P = 0.015) compared to baseline. No significant differences between high and low doses of both conventional GCs and DR-HC were observed. Conclusions DR-HC is associated with an improvement of metabolic parameters and cardiovascular risk compared to conventional GCs, which are associated with a worsening of these parameters, regardless of the dose used.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency

Guarnotta

Stefano

Santoro

et al. 2019

Endocrine Connections

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“…13 DR-HC has been reported to improve anthropometric and metabolic parameters, appearing to be safe even in the long term. 14–19…”

Section: Introductionmentioning

confidence: 99%

Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: a real-life study

Guarnotta¹,

Mineo²,

Radellini³

et al. 2019

Therapeutic Advances in Endocrinology

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Background: Conventional glucocorticoid treatment has a significant impact on liver in patients with adrenal insufficiency. Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement in anthropometric and metabolic parameters. We aimed to evaluate the effects of 12-month DR-HC treatment on the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, in patients with secondary adrenal insufficiency (SAI). Methods: A total of 45 patients with hypopituitarism, 22 with hypogonadism, hypothyroidism, ACTH, and GH deficiencies, and 23 with hypogonadism, hypothyroidism, and ACTH deficiency, on replacement therapy for all the pituitary deficiencies, were switched from conventional hydrocortisone to DR-HC. At baseline and after 12 months, glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis were evaluated through ultrasonography and HSI. Results: At diagnosis, ultrasonography documented steatosis in 31 patients (68.8%) while 33 (73.3%) showed high HSI. Hydrocortisone (HC) dose (β = 1.231, p = 0.010), insulin resistance index (HOMA-IR) (β = 1.431, p = 0.002), and insulin sensitivity index (ISI)-Matsuda (β = −1.389, p = 0.034) were predictors of HSI at baseline. After 12 months of DR-HC, a significant decrease in body mass index (BMI) ( p = 0.008), waist circumference (WC) ( p = 0.010), fasting insulin ( p = 0.041), HOMA-IR ( p = 0.047), HSI ( p < 0.001) and number of patients with HSI ⩾36 ( p = 0.003), and a significant increase in sodium ( p < 0.001) and ISI-Matsuda ( p = 0.031) were observed. HOMA-IR (β = 1.431, p = 0.002) and ISI-Matsuda (β = −9.489, p < 0.001) were identified as independent predictors of HSI at 12 months. Conclusions: In adults with SAI, DR-HC is associated with an improvement in HSI, regardless of the dose used, mainly related to an improvement in insulin sensitivity.

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“…In addition, in pre-diabetic patients only a significant decrease in insulinemia ( p = 0.014), AUC 2hinsulinemia ( p = 0.038) and VAI ( p = 0.001), in concomitance with a significant increase in the oral disposition index (DIo; p = 0.041) and Matsuda index of insulin sensitivity (ISI-Matsuda; p = 0.038) were observed. No differences in metabolic parameters, insulin secretion and sensitivity index were found comparing PAI and SAI patients ( 56 ).…”

Section: Glycometabolic Effects Of Gc Replacement Therapymentioning

confidence: 88%

Glycometabolic Alterations in Secondary Adrenal Insufficiency: Does Replacement Therapy Play a Role?

et al. 2018

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Secondary adrenal insufficiency (SAI) is a potentially life-threatening endocrine disorder due to an impairment of corticotropin (ACTH) secretion from any process affecting the hypothalamus or pituitary gland. ACTH deficit can be isolated or associated with other pituitary failures (hypopituitarism). An increased mortality due to cardiovascular, metabolic, and infectious diseases has been described in both primary and secondary adrenal insufficiency. However, few studies have provided compelling evidences on the underlying mechanism in SAI, because of the heterogeneity of the condition. Recently, some studies suggested that inappropriate glucocorticoid (GCs) replacement therapy, as for dose and/or timing of administration, may play a role. Hypertension, insulin resistance, weight gain, visceral obesity, increased body mass index, metabolic syndrome, impaired glucose tolerance, diabetes mellitus, dyslipidemia have all been associated with GC excess. These conditions are particularly significant when SAI coexists with other pituitary alterations, such as growth hormone deficiency, hypogonadism, and residual tumor. Novel regimen schemes and GC preparations have been introduced to improve compliance and better mimick endogenous cortisol rhythm. The controlled trials on the improved replacement therapies, albeit in the short-term, show some beneficial effects on cardiovascular risk, glucose metabolism, and quality of life. This review examines the current evidence from the available clinical trials investigating the association between different glucocorticoid replacement therapies (type, dose, frequency, and timing of treatment) and glycometabolic alterations in SAI.

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

Cited by 28 publications

References 34 publications

Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency

Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency

Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: a real-life study

Glycometabolic Alterations in Secondary Adrenal Insufficiency: Does Replacement Therapy Play a Role?

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