| 1. |
- Espiard, Stéphanie, et al.
(författare)
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Improved Urinary Cortisol Metabolome in Addison's disease: a Prospective Trial of Dual-Release Hydrocortisone.
- 2021
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:3, s. 814-825
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Tidskriftsartikel (refereegranskat)abstract
- Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.To study cortisol metabolism during DR-HC and TID-HC.Randomized, 12-week, crossover study.DC-HC and same daily dose of TID-HC in patients with primary adrenal insufficiency (n=50) versus healthy subjects (n=124) as control.Urinary corticosteroid metabolites measured by gas chromatography/mass spectrometry on 24-hour urinary collections.Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < 0.001) and reached control values (P = 0.089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol+5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < 0.05), but remained increased versus controls (P < 0.001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC versus controls (P < 0.01) but normalized with DR-HC (P = 0.358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change towards normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.
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| 2. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy.
- 2015
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 82:1
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoid replacement therapy in patients with adrenal insufficiency (AI), whether primary (Addison's disease) or secondary (due to hypopituitarism), has been established for some 50 years. The current standard treatment regimen involves twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone. Based on previous small-scale studies and clinical perception, life expectancy with conventional glucocorticoid replacement therapy has been considered normal, with a low incidence of adverse events. Data from the past 10-15 years, however, have shown that morbidity remains high and life expectancy is reduced. The increased morbidity and decreased life expectancy appear to be due to both increased exposure to cortisol and insufficient cortisol coverage during infections and other stress-related events. This is thought to reflect a failure of treatment to replicate the natural circadian rhythm of cortisol release, together with a failure to identify and deliver individualized cortisol exposure and to manage patients adequately when increased doses are required. The resulting over- or under-treatment may result in Cushing-like symptoms or adrenal crisis, respectively. This review summarizes the morbidity and mortality seen in patients receiving the current standard of care for AI and suggests areas for improvement in glucocorticoid replacement therapy.
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| 4. |
- Stewart, Paul M, et al.
(författare)
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Exploring Inpatient Hospitalizations and Morbidity in Patients With Adrenal Insufficiency.
- 2016
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 101:12, s. 4843-4850
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Tidskriftsartikel (refereegranskat)abstract
- Patients with adrenal insufficiency (AI) (primary AI [PAI], secondary AI due to a pituitary disorder [PIT] and congenital adrenal hyperplasia [CAH]) have reduced life expectancy; however, the underlying explanation remains unknown.To evaluate characteristics, comorbidities, and hospitalizations in AI patients.Retrospective observational.Using a United States-based national payer database comprising of more than 108 million members, strict inclusion criteria including diagnostic codes and steroid prescription records were used to identify 10 383 adults with AI; 1014 with PAI, 8818 with PIT, and 551 with CAH. Patients were matched 1:1 to controls, based on age (±5 y), gender, insurance, and region and followed for more than 12 months.None.Demographic variables, comorbidities (diabetes mellitus [DM] types 1 and 2, depression, anxiety, hyperlipidemia, hypertension) and hospitalization incidence.Compared with controls, patients with AI had higher odds of DM, hypertension, hyperlipidaemia, depression, and anxiety, ranging from an odds ratio (OR) of 1.51 for hyperlipidaemia in PAI to 3.85 for DM in CAH. Odds of having DM (OR, 3.85; 95% confidence interval, 2.52-5.90) or anxiety (OR, 2.99; 95% confidence interval, 2.02-4.42) compared with controls were highest in CAH, whereas depression was highest in PAI and PIT (OR, 2.40 and 2.55). ORs of hyperlipidaemia and hypertension (OR, 1.98 and 2.24) were highest in the PIT cohort. Inpatient admissions were more frequent in PAI (4.64:1; P < .0001) and PIT (4.00:1; P < .0001) than controls; infection was the most common cause for admission.Patients with AI carry a significant metabolic and psychiatric burden, with higher risk of comorbidities and hospital admissions than matched controls.
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