scholarly journals Plasma Free Cortisol in States of Normal and Altered Binding Globulins: Implications for Adrenal Insufficiency Diagnosis

2019 ◽  
Vol 104 (10) ◽  
pp. 4827-4836 ◽  
Author(s):  
Laura E Dichtel ◽  
Melanie Schorr ◽  
Claudia Loures de Assis ◽  
Elizabeth M Rao ◽  
Jessica K Sims ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Outcome Measure ◽  
Cross Sectional ◽  
Free Cortisol ◽  
Receiver Operator Curve Analysis ◽  
Liquid Chromatography Tandem Mass ◽  
Healthy Control ◽  
Low Cortisol ◽  
The Relationship ◽  
Operator Curve

Abstract Context Accurate diagnosis of adrenal insufficiency is critical because there are risks associated with overdiagnosis and underdiagnosis. Data using liquid chromatography tandem mass spectrometry (LC/MS/MS) free cortisol (FC) assays in states of high or low cortisol-binding globulin (CBG) levels, including cirrhosis, critical illness, and oral estrogen use, are needed. Design Cross-sectional. Objective Determine the relationship between CBG and albumin as well as total cortisol (TC) and FC in states of normal and abnormal CBG. Establish the FC level by LC/MS/MS that best predicts TC of <18 μg/dL (497 nmol/L) (standard adrenal insufficiency diagnostic cutoff) in healthy individuals. Subjects This study included a total of 338 subjects in four groups: healthy control (HC) subjects (n = 243), patients with cirrhosis (n = 38), intensive care unit patients (ICU) (n = 26), and oral contraceptive (OCP) users (n = 31). Main Outcome Measure(s) FC and TC by LC/MS/MS, albumin by spectrophotometry, and CBG by ELISA. Results TC correlated with FC in the ICU (R = 0.91), HC (R = 0.90), cirrhosis (R = 0.86), and OCP (R = 0.70) groups (all P < 0.0001). In receiver operator curve analysis in the HC group, FC of 0.9 μg/dL (24.8 nmol/L) predicted TC of <18 μg/dL (497 nmol/L; 98% sensitivity, 91% specificity; AUC, 0.98; P < 0.0001). Decreasing the cutoff to 0.7 μg/dL led to a small decrease in sensitivity (92%) with similar specificity (91%). Conclusions A cutoff FC of <0.9 μg/dL (25 nmol/L) in this LC/MS/MS assay predicts TC of <18 μg/dL (497 nmol/L) with excellent sensitivity and specificity. This FC cutoff may be helpful in ruling out adrenal insufficiency in patients with binding globulin derangements.

scholarly journals Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort

2021 ◽  
Author(s):  
Elena Gonzalez Rodriguez ◽  
Pedro Marques-Vidal ◽  
Bérengère Aubry-Rozier ◽  
Georgios Papadakis ◽  
Martin Preisig ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Salivary Cortisol ◽  
Population Based ◽  
Cross Sectional Study ◽  
Body Composition Assessment ◽  
Cross Sectional ◽  
X Ray ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
The Relationship

AbstractSarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = − 0.153, p < 0.001) and sc-8PM (r = − 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

scholarly journals Differentiating combined pulmonary fibrosis and emphysema from pure emphysema: utility of late gadolinium-enhanced MRI

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Hannah Fleming ◽  
Simon M. Clifford ◽  
Aoife Haughey ◽  
Roisin MacDermott ◽  
Niall McVeigh ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Area Under The Curve ◽  
Resonance Imaging ◽  
High Resolution Computed Tomography ◽  
Antifibrotic Therapy ◽  
Control Subjects ◽  
Receiver Operator Curve Analysis ◽  
Healthy Control ◽  
Traction Bronchiectasis ◽  
Operator Curve

Abstract Background Differentiating combined pulmonary fibrosis with emphysema (CPFE) from pure emphysema can be challenging on high-resolution computed tomography (HRCT). This has antifibrotic therapy implications. Methods Twenty patients with suspected CPFE underwent late gadolinium-enhanced (LGE) thoracic magnetic resonance imaging (LGE-MRI) and HRCT. Data from twelve healthy control subjects from a previous study who underwent thoracic LGE-MRI were included for comparison. Quantitative LGE signal intensity (SI) was retrospectively compared in regions of fibrosis and emphysema in CPFE patients to similar lung regions in controls. Qualitative comparisons for the presence/extent of reticulation, honeycombing, and traction bronchiectasis between LGE-MRI and HRCT were assessed by two readers in consensus. Results There were significant quantitative differences in fibrosis SI compared to emphysema SI in CPFE patients (25.8, IQR 18.4–31.0 versus 5.3, IQR 5.0–8.1, p < 0.001). Significant differences were found between LGE-MRI and HRCT in the extent of reticulation (12.5, IQR 5.0–20.0 versus 25.0, IQR 15.0–26.3, p = 0.038) and honeycombing (5.0, IQR 0.0–10.0 versus 20.0, IQR 10.6–20.0, p = 0.001) but not traction bronchiectasis (10.0, IQR 5–15 versus 15.0, IQR 5–15, p = 0.878). Receiver operator curve analysis of fibrosis SI compared to similarly located regions in control subjects showed an area under the curve of 0.82 (p = 0.002). A SI cutoff of 19 yielded a sensitivity of 75% and specificity of 86% in differentiating fibrosis from similarly located regions in control subjects. Conclusion LGE-MRI can differentiate CPFE from pure emphysema and may be a useful adjunct test to HRCT in patients with suspected CPFE.

scholarly journals Plasma Aβ ratios in autosomal dominant Alzheimer’s disease: the influence of genotype

2021 ◽  
Author(s):  
Antoinette O’Connor ◽  
Josef Pannee ◽  
Teresa Poole ◽  
Charles Arber ◽  
Erik Portelius ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Cross Sectional ◽  
Autosomal Dominant Alzheimer’S Disease ◽  
Liquid Chromatography Tandem Mass ◽  
The Relationship

AbstractIn-vitro studies of autosomal dominant Alzheimer’s disease (ADAD) implicate longer Aβ peptides in pathogenesis, however less is known about the behaviour of ADAD mutations in-vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from ADAD family members who were at-risk of inheriting a mutation or were already symptomatic. We tested for differences in plasma Aβ42:38, 38:40 and 42:40 ratios between Presenilin1 (PSEN1) and Amyloid Precursor Protein (APP) carriers. We examined the relationship between plasma and in-vitro models of Aβ processing and, among PSEN1 carriers, tested for associations with parental age at onset (AAO). 39 participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma Aβ between APP and PSEN1: higher Aβ42:38 in PSEN1 versus APP (p<0.001) and non-carriers (p<0.001); higher Aβ38:40 in APP versus PSEN1 (p<0.001) and non-carriers (p<0.001), while Aβ42:40 was higher in APP and PSEN1 compared to non-carriers (both p<0.001). Aβ profiles were reasonably consistent in plasma and cell lines. Within PSEN1, sex-adjusted models demonstrated negative associations between (i)Aβ42:40 (ii)Aβ42:38 and parental AAO. In-vivo differences in Aβ processing between APP and PSEN1 provide insights into ADAD pathophysiology which can inform therapy development.

scholarly journals Apolipoprotein D Concentration in Human Plasma during Aging and in Parkinson’s Disease: A Cross-Sectional Study

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Andreas Waldner ◽  
Sarah Dassati ◽  
Bernhard Redl ◽  
Nicola Smania ◽  
Marialuisa Gandolfi
Keyword(s):  
Healthy Subjects ◽  
Neurological Impairment ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Age Related ◽  
Healthy Control ◽  
Apolipoprotein D ◽  
The Relationship ◽  
Small Hydrophobic

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an important role in several neurodegenerative diseases. ApoD is expressed in and secreted from a variety of peripheral and brain tissues. Increments of ApoD have been reported in relation with oxidative stress conditions, aging, and degeneration in the nervous system. Preliminary findings support the role of ApoD in neuroprotection. However, its role in PD remains unclear. To date, no studies have been performed on the relationship between ApoD in the blood and PD, as neurodegenerative pathology related to oxidative damage. We investigated the concentration of ApoD in the blood of healthy control subjects and PD patients with mild-to-moderate neurological impairment. ApoD plasma levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA) in 90 healthy subjects (aging-analysis cohort) and in 66 PD patients at different stages compared with 19 age-matched healthy subjects. Significant age-related increase of ApoD was detected in subjects older than 65 years of age (p<0.002). In PD patients, a significant increase in ApoD plasma concentration was found compared with healthy subjects of the same age (p<0.05). ApoD and PD stage are significantly correlated (p<0.05). ApoD might be a valid marker for the progression of PD.

The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency

2018 ◽  
Vol 31 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Kate C. Verbeeten ◽  
Alexandra H. Ahmet
Keyword(s):  
Adrenal Insufficiency ◽  
Serum Cortisol ◽  
Serum Cortisol Level ◽  
Total Serum ◽  
Oral Contraceptive Pills ◽  
Total Cortisol ◽  
Contraceptive Pills ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Liquid Chromatography Tandem Mass

AbstractCortisol is a hydrophobic molecule that is largely bound to corticosteroid-binding globulin (CBG) in the circulation. In the assessment of adrenal insufficiency, many clinicians measure a total serum cortisol level, which assumes that CBG is present in normal concentrations and with a normal binding affinity for cortisol. CBG concentration and affinity are affected by a number of common factors including oral contraceptive pills (OCPs), fever and infection, as well as rare mutations in the serine protease inhibitor A6 (SERPINA6) gene, and as such, total cortisol levels might not be the ideal way to assess adrenal function in all clinical circumstances. This paper reviews the limitations of immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the measurement of total cortisol, the challenges of measuring free serum cortisol directly as well as the difficulties in calculating an estimated free cortisol from total cortisol, CBG and albumin concentrations. Newer approaches to the evaluation of adrenal insufficiency, including the measurement of cortisol and cortisone in the saliva, are discussed and a possible future role for these tests is proposed.

Impact of Preterm Birth on Glucocorticoid Variability in Human Milk

2017 ◽  
Vol 34 (1) ◽  
pp. 130-136 ◽  
Author(s):  
Shikha Pundir ◽  
Cameron J. Mitchell ◽  
Eric B. Thorstensen ◽  
Clare R. Wall ◽  
Sharon L. Perrella ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Human Milk ◽  
Preterm Infant ◽  
Infant Health ◽  
Stressful Event ◽  
Free Cortisol ◽  
Liquid Chromatography Tandem Mass ◽  
Mothers Of Preterm Infants ◽  
The Relationship ◽  
Initiation Of Breastfeeding

Background: Preterm birth is a stressful event for both the mother and infant. Whereas the initiation of breastfeeding is important for preterm infant health, little is known of the glucocorticoid hormones (cortisol and cortisone) in human milk following preterm birth. Research aim: The aim of this study was to investigate the relationship between human milk glucocorticoid concentrations and preterm birth. Methods: Human milk was sampled weekly for up to 6 weeks from 22 women who delivered a preterm infant at 28 to 32 weeks’ gestation. Human milk was analyzed for total and free cortisol and cortisone concentrations using liquid chromatography-tandem mass spectrometry. Results: Milk sampled from mothers of preterm infants had more cortisone than cortisol ( p < .001), with a strong correlation between both hormones ( p = .001, r = .85). The cortisone was significantly higher in the milk of mothers who delivered infants after 30 weeks compared with those who delivered before 30 weeks of gestation ( p = .02). Glucocorticoid concentrations did not change over the sampling time (weeks 1 to 6 postpartum) and did not differ by infant gender. Conclusion: Glucocorticoids were present in all milk samples following preterm birth. Cortisone concentration tended to be higher in those who delivered after 30 weeks’ gestation but did not increase further over the weeks following birth.

scholarly journals Occult Adrenal Insufficiency in Renal Amyloidosis Patients

2021 ◽  
Author(s):  
Didem Turgut ◽  
Serhan Vahit Pişkinpaşa ◽  
Havva Keskin ◽  
Kemal Agbaht ◽  
Ezgi Coşkun Yenigün
Keyword(s):  
Adrenal Insufficiency ◽  
Renal Involvement ◽  
Stimulation Test ◽  
Renal Amyloidosis ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Cross Sectional ◽  
Control Subjects ◽  
Free Cortisol ◽  
Cortisol Levels

Objective: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. Methods: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 μg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. Results: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients’ stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). Conclusion: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.

scholarly journals Perceived stress, life events, fatigue and temperament in patients with psoriasis

2019 ◽  
Vol 47 (9) ◽  
pp. 4284-4291 ◽  
Author(s):  
Esra Pancar Yuksel ◽  
Dilek Durmus ◽  
Gokhan Sarisoy
Keyword(s):  
Life Events ◽  
Perceived Stress ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
Stress Scale ◽  
Significant Difference ◽  
Healthy Control ◽  
The Relationship

Objective To evaluate the perceived stress, life events, fatigue and temperament profile in patients with psoriasis and to investigate the relationship between these factors. Methods This cross-sectional study included patients with psoriasis and healthy control subjects. The two groups were compared regarding the number of life events, Perceived Stress Scale (PSS) and Multidimensional Assessment of Fatigue scores. The Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire was used to evaluate the personality traits among the two groups. Results A total of 75 patients with psoriasis (mean ± SD age, 44.94 ± 13.62 years) and 75 healthy controls (mean ± SD age, 41.10 ± 8.89 years) were included in the study. A statistically significant difference was found between the two groups in terms of the presence of life events, PSS score, fatigue and temperament profiles. Patients with psoriasis with depressive, cyclothymic and anxious temperament profiles were found to have higher PSS scores. In the psoriasis group, the PSS scores were positively correlated with the number of life events. Conclusions Stress and life events were found to be correlated with psoriasis. In the patients with psoriasis, depressive, cyclothymic and anxious temperament profiles seemed to be associated with higher perceived stress.

scholarly journals 2396

2017 ◽  
Vol 1 (S1) ◽  
pp. 37-37
Author(s):  
Sarah Youssof ◽  
Carol Romero-Clark
Keyword(s):  
Muscular Dystrophy ◽  
Disease Duration ◽  
Outcome Measure ◽  
Late Onset ◽  
Objective Measure ◽  
Cross Sectional Study ◽  
Barium Swallow ◽  
Cross Sectional ◽  
Study Population ◽  
The Relationship

OBJECTIVES/SPECIFIC AIMS: Oculopharyngeal muscular dystrophy (OPMD) is a rare, late-onset muscular dystrophy that causes severe swallowing impairment (dysphagia). Although promising therapies are in the pipeline, validated dysphagia outcome measures for use in OPMD trials have not been established. Videofluoroscopic swallow studies (VFSS) are considered the clinical gold standard for dysphagia assessment, yet the optimal objective measure of VFSS in OPMD is not known. Our aim was to investigate the utility of the Modified Barium Swallow Impairment Profile (MBSImP) as an objective measure of VFSS in OPMD patients. METHODS/STUDY POPULATION: This was a single-center, prospective, cross-sectional study. In total, 26 individuals with OPMD underwent VFSS and other measures of dysphagia including 50-mL water swallow time (ST). Validity was assessed by examining correlations with an OPMD Global Severity Score (GSS) and with dysphagia duration. RESULTS/ANTICIPATED RESULTS: The MBSImP demonstrated moderate correlations with GSS (Pearson r=0.52, p=0.006) and ST (r=0.39, p=0.049). The relationship between MBSImP and dysphagia duration appeared nonlinear, and levelled off with long dysphagia duration. In contrast, ST did not correlate significantly with GSS (r=0.27, p=0.18), nor with disease duration (r=0.05, p=0.83). DISCUSSION/SIGNIFICANCE OF IMPACT: Objective measurement of VFSS is a promising outcome measure in OPMD. With long disease duration, the MBSImP may not be sufficiently sensitive to detect disease progression. More sensitive measures for scoring dysphagia severity on VFSS should be explored for application to future s of OPMD.

scholarly journals PCSK9 in African Americans and Caucasians in Relation to Lp(a) Level, Apo(a) Size and Heritability

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Byambaa Enkhmaa ◽  
Kyoungmi Kim ◽  
Wei Zhang ◽  
Nishant Prakash ◽  
Kevin Truax ◽  
...  
Keyword(s):  
African Americans ◽  
Outcome Measure ◽  
Total Plasma ◽  
Cross Sectional ◽  
Main Outcome Measure ◽  
Apolipoprotein A ◽  
Significant Heritability ◽  
Age Range ◽  
Relationship Of ◽  
The Relationship

Abstract Context Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces lipoprotein(a) [Lp(a)] levels, but the association of PCSK9 with Lp(a) level and its major determinant, apolipoprotein(a) [apo(a)] size, is not fully understood. Objective To assess the relationship between PCSK9, Lp(a) level, apo(a) size, age, and ethnicity/race. Design Cross-sectional Setting General population Participants Healthy African Americans and Caucasians (n = 267); age range: 6 to 74 years. Interventions None. Main outcome measure(s) PCSK9 levels, apo(a) isoform and LPA allele sizes, and isoform-specific Lp(a) levels. Results Plasma PCSK9 levels were significantly higher in African Americans vs Caucasians, in females vs males, and in adults vs children. PCSK9 levels were not associated with total plasma Lp(a) levels either in all participants or in ethnicity-specific analyses. However, PCSK9 levels were significantly positively associated with isoform-specific Lp(a) levels carried by the larger apo(a) size in all participants (r = 0.139, P = 0.0361). In ethnicity/race analyses, a significant association was seen for African Americans (r = 0.268, P = 0.0199), but not for Caucasians. In contrast, there were no significant associations of PCSK9 with isoform-specific Lp(a) levels for the smaller apo(a) sizes in all participants nor in ethnic-specific analyses. Furthermore, heritability (h2) analyses revealed a significant heritability for PCSK9 level in both ethnic groups, with a higher estimate in Caucasians than in African Americans (47% vs 22%, respectively). Conclusions Among African Americans, but not Caucasians, PCSK9 levels were associated with isoform-specific Lp(a) levels carried on larger, but not smaller, apo(a) sizes. The findings illustrate a diverging relationship of PCSK9 with isoform-specific Lp(a) levels across ethnicity.

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