ORCID Profile
0000-0002-7450-5808
Current Organisations
Queen Elizabeth Hospital
,
Universidade de São Paulo Faculdade de medicina
,
University of Adelaide
,
Royal Adelaide Hospital
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Publisher: Elsevier BV
Date: 04-2023
Publisher: The Endocrine Society
Date: 22-06-2021
Abstract: Corticosteroid-binding globulin (CBG) is the main transport protein for cortisol, binding up to 90% in a 1:1 ratio. CBG provides transport of cortisol within the circulation and targeted cortisol tissue delivery. Here, we describe the clinically novel “CBG Montevideo” a SERPINA6 pathogenic variant that results in a 50% reduction in plasma CBG levels. This was associated with low serum total cortisol and clinical features of hypoglycemia, exercise intolerance, chronic fatigue, and hypotension in the proband, a 7-year-old boy, and his affected mother. Previous reports of 9 human CBG genetic variants affecting either CBG concentrations or reduced CBG-cortisol binding properties have outlined symptoms consistent with attenuated features of hypocortisolism, fatigue, and hypotension. Here, however, the presence of hypoglycemia, despite normal circulating free cortisol, suggests a specific role for CBG in effecting glucocorticoid function, perhaps involving cortisol-mediated hepatic glucose homeostasis and cortisol-brain communication.
Publisher: Wiley
Date: 04-11-2020
DOI: 10.1002/PRO.3982
Publisher: American Diabetes Association
Date: 13-02-2018
DOI: 10.2337/DC17-1721
Publisher: Wiley
Date: 27-03-2022
DOI: 10.1111/CEN.14707
Publisher: Wiley
Date: 26-09-2019
DOI: 10.1111/CEN.13844
Abstract: Corticosteroid-binding globulin (CBG) and albumin transport circulating cortisol. Cleavage of high-affinity CBG (haCBG) by neutrophil elastase at inflammatory sites causes cortisol release into tissues, facilitating immunomodulatory effects. To determine whether depletion of haCBG is related to mortality in septic shock. A single-center prospective observational cohort study of patients recruited with critical illness or septic shock, using serum s les collected at 0, 8, 24, 48 and 72 hours. Serum total and haCBG, and total and free cortisol were assayed directly. Glucocorticoid treatment was an exclusion criterion. Mortality was assessed at 28 days from Intensive Care Unit admission. Thirty septic shock (SS) and 42 nonseptic critical illness (CI) patients provided 195 serum s les. SS/CI patients had lower total CBG, haCBG and low-affinity CBG (laCBG) than controls. Total CBG and haCBG were significantly lower in septic shock patients who died than in those that survived (P < 0.009, P = 0.021, respectively). Total and free cortisol were higher in septic than nonseptic in iduals. Free/total cortisol fractions were higher in those with low haCBG as observed in septic shock. However, cortisol levels were not associated with mortality. Albumin levels fell in sepsis but were not related to mortality. Low circulating haCBG concentrations are associated with mortality in septic shock. These results are consistent with an important physiological role for haCBG in cortisol tissue delivery in septic shock.
Publisher: Wiley
Date: 29-09-2021
Abstract: The aim of this study is to compare metrics specific for stress‐induced hyperglycemia (SIH) with glucose for predicting ischemic stroke outcome. This observational retrospective study (n = 300) included patients acutely hospitalized for ischemic stroke over a 3.8‐year period. We assessed the association between acute ischemic stroke outcome with the stress hyperglycemia ratio (SHR, relative increase in glycemia) and glycemic gap (GG, absolute increase in glycemia) using admission values and 5‐day maximum values, along with incidence of poor outcome above recognized clinical thresholds of glucose 10 mmol/L, SHR 1.14, and GG 2.5 mmol/L. At admission, only SHR was associated with outcome after adjustment for clinical covariates (odds ratio [OR] = 2.88 95% CI: 1.05‐7.91 P = .041), while glucose or GG were not. Admission SHR ≥ 1.14 was also an indicator of poor outcome (39.1% vs 23.4%, P = .016), but not glucose ≥10 mmol/L or GG ≥ 2.5 mmol/L. All 5‐day maximum glucose metrics were associated with outcome, as was any SHR ≥ 1.14 (40.9% vs 20.1%, P .001) or GG ≥ 2.5 mmol/L (42.9% vs 23.4%, P = .011), but not glucose ≥10 mmol/L. Increased comorbidity was strongly associated with worse outcome ( P .001) in all models. SHR provided the best prognostic insight at admission to assess the relationship between SIH and ischemic stroke outcome. Absolute glucose levels failed to account for natural interpatient variation in background glycemia and provided little prognostic insight. To assess the impact of SIH, future interventional studies need to be designed using designated markers of SIH such as SHR in preference to absolute glucose.
Publisher: The Endocrine Society
Date: 13-02-2022
Abstract: Hydrocortisone administration in septic shock remains controversial. Corticosteroid-binding globulin (CBG) transports cortisol to inflammatory sites and is depleted in septic shock. To determine whether severely deficient serum CBG < 200 nmol/L (reference range 269-641 nmol/L) independently predicts septic shock mortality. A prospective observational study in patients with septic shock. Patients were categorized into 2 groups: mean plasma CBG concentrations <200 nmol/L and ≥200 nmol/L (day 1/2), with additional categorization by nadir CBG. Primary outcome was intensive care unit (ICU) mortality. Secondary outcomes were 28- and 90-day mortality, norepinephrine requirements, renal replacement therapy, and clinician-instituted hydrocortisone. 135 patients were included. Mortality rates in ICU were higher in the CBG < 200 nmol/L vs the CBG ≥ 200 nmol/L group: 32.4% vs 13.9% [odds ratio (OR) 2.97 (95% CI 1.19, 7.41) P = 0.02] with 28-day mortality OR 2.25 (95% CI 0.99, 5.11) and 90-day mortality OR 2.21 (95% CI 0.99, 4.91). Multivariate analysis revealed 4 factors independently associated with ICU mortality: CBG 25 (adjusted OR 3.58, 95% CI 1.20, 10.68), Sequential Organ Failure Assessment (SOFA) liver score (adjusted OR 1.98, 95% CI 1.04, 3.72), and renal replacement therapy (adjusted OR 6.59, 95% CI 2.17, 20.01). Nadir CBG levels were associated with higher SOFA cardiovascular scores and norepinephrine total dose (μg P < 0.01) and duration (days P < 0.01). Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality. Septic shock patients with CBG < 200 nmol/L had higher norepinephrine requirements and 3.2-fold higher ICU mortality. CBG concentration was the only directly reversible independent mortality risk factor.
Publisher: MDPI AG
Date: 08-06-2018
Publisher: American Diabetes Association
Date: 21-03-2022
DOI: 10.2337/DC21-1870
Publisher: The Endocrine Society
Date: 27-09-2023
No related grants have been discovered for Emily Meyer.