scholarly journals SUN-614 Prediction of Hypertension, Diabetes and Fractures in Eucortisolemic Women by Measuring Parameters of Cortisol Milieu

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Iacopo Chiodini ◽  
Valentina Morelli ◽  
Carmen Aresta ◽  
Agostino Gaudio ◽  
Cristina Eller-Vainicher ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Fragility Fractures ◽  
Urinary Free Cortisol ◽  
Sensitivity Index ◽  
Cortisol Secretion ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Free Cortisol ◽  
Peripheral Activation

Abstract Purpose. Cortisol secretion, peripheral activation and sensitivity seem to be associated with hypertension (HY), type-2 diabetes (T2D) and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cut-off(s) of the parameters of cortisol secretion and peripheral activation for predicting the presence of HY, T2D and FX (comorbidities). Methods. In 206 postmenopausal females (157 with ≥1 comorbidities and 49 without any), we assessed the ratio between 24-hour urinary free cortisol and cortisone (R-UFF/UFE, cortisol activation index), cortisol after 1mg-overnight-dexamethasone (F-1mgDST, cortisol secretion index), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP, cortisol sensitivity index). Results. The cut-offs for F-1mgDST and R-UFF/UFE set at 0.9 μg/dL (Area Under the Curve, AUC 0.634±0.43, p=0.005) and 0.17 (AUC 0.624±0.5, p=0.017) respectively, predicted the presence of ≥1 comorbidities. The presence of F-1mgDST >0.9 μg/dL plus R-UFF/UFE >0.17 showed 82.1% specificity for predicting the presence of ≥1 comorbidities, while the simultaneous presence of F-1mgDST ≤0.9 μg/dL and R-UFF/UFE ≤0.17 showed 88% sensitivity for predicting the absence of comorbidities. The F-1mgDST >0.9 μg/dL or R-UFF/UFE >0.17 was associated with 2.8 and 2.1 fold increased risk of having ≥1 comorbidities, respectively. The F-1mgDST ≤0.9 μg/dL plus R-UFF/UFE ≤0.17 or F-1mgDST >0.9 μg/dL plus R-UFF/UFE >0.17 was associated with 2.8 fold reduced or 4.9 fold increased risk of having ≥1 comorbidities regardless of age, BMI and N363S-SNP. Conclusions. F-1mgDST >0.9 μg/dL and R-UFF/UFE >0.17 may be used for predicting the presence of ≥1 among HY, T2D and fragility FX.

scholarly journals Cortisol Secretion, Sensitivity, and Activity Are Associated With Hypertension in Postmenopausal Eucortisolemic Women

2019 ◽  
Vol 104 (10) ◽  
pp. 4441-4448 ◽  
Author(s):  
Iacopo Chiodini ◽  
Agostino Gaudio ◽  
Cristina Eller-Vainicher ◽  
Valentina Morelli ◽  
Carmen Aresta ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Postmenopausal Women ◽  
Fragility Fractures ◽  
Urinary Free Cortisol ◽  
Progressive Increase ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Heterozygous Variant ◽  
Free Cortisol ◽  
Peripheral Activation

Abstract Context Previous data suggest a possible association between type 2 diabetes (T2D) and fragility fractures (FX) with the degree of glucocorticoid suppressibility (GCS) and peripheral activation or sensitivity even in persons without hypercortisolemia. Objective To investigate whether the degree of GCS, GC sensitivity, and peripheral activation in persons without overt or mild hypercortisolism are associated with hypertension and with the number of the possible consequences of cortisol excess among patients with T2D, fragility FX, and hypertension. Design Case-control study. Setting Outpatient clinic. Patients A total of 216 postmenopausal women without hypercortisolemia (age, 50 to 80 years; 108 with hypertension); 68 and 99 patients had fragility FX and T2D, respectively Main outcome measures We assessed 24-hour urinary free cortisol (UFF), cortisone (UFE), their ratio (R-UFF/UFE), (F-1mgDST), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP). Results Hypertension was associated with F-1 mgDST [odds ratio (OR), 3.3; 95% CI, 1.5 to 7.5; P = 0.004) and R-UFF/UFE (OR, 101.7; 95% CI, 2.6 to 4004.1; P = 0.014), regardless of age, body mass index, and presence of the N363S single nucleotide polymorphism and of T2D. The progressive increase in the number of possible consequences of cortisol excess was significantly associated with F-1mgDST levels (R2 = 0.125; P = 0.04), R-UFF/UFE (R2 = 0.46; P = 0.02), and the prevalence of N363S heterozygous variant (T = 0.46; P = 0.015), after adjustment for age. Conclusions In postmenopausal women without hypercortisolemia, hypertension is associated with GCS and GC peripheral activation. The number of possible consequences of cortisol excess (among patients with hypertension, T2D, and fragility FX) is associated with GCS, GC peripheral activation, and the prevalence of the N363S heterozygous variant.

Serotoninergic findings in habitual violence and impulsivity. A review

1990 ◽  
Vol 2 (3) ◽  
pp. 66-71 ◽  
Author(s):  
M.D. Virkkunen
Keyword(s):  
Blood Platelet ◽  
Urinary Free Cortisol ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Central Feature ◽  
Cortisol Secretion ◽  
Platelet Mao ◽  
Free Cortisol ◽  
Familial Alcoholism

SummarySeveral lines of evidence suggest that there may be abnormal brain serotonin metabolism in habitually biolent and impulsive offenders. These personality disorders are usually connected with early onset, male limited type 2 alcoholism in which one central feature is the abnormal tendency to behave aggressively and impulsively under the influence of alcohol repeatedly. Low CSF 5-HIAA has been found to correlate with familial alcoholism tendencies; paternal alcoholism. Both this and with it the tendency to abnormal oral glucose tolerance test (tendency to low blood glucose nadir) predict the new violent and impulsive crimes under the influence of alcohol. Also peripheral measures such as platelet MAO, abnormal tryptophan/LNAA ratio in plasma, whole blood serotonin, blood platelet uptake of serotonin, platelet 3H-IMI dinging (Bmax), abnormal prolactin and Cortisol secretion in fenfluramine challenge, and possibly daily urinary free Cortisol secretion correlate with impulsive aggressive behavior.

scholarly journals Patients With Apparently Nonfunctioning Adrenal Incidentalomas May Be at Increased Cardiovascular Risk Due to Excessive Cortisol Secretion

2014 ◽  
Vol 99 (8) ◽  
pp. 2754-2762 ◽  
Author(s):  
Ioannis I. Androulakis ◽  
Gregory A. Kaltsas ◽  
Georgios E. Kollias ◽  
Athina C. Markou ◽  
Aggeliki K. Gouli ◽  
...  
Keyword(s):  
Low Dose ◽  
Area Under The Curve ◽  
Urinary Free Cortisol ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Acth Stimulation ◽  
Adrenal Imaging ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

Context: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. Objective: Our objective was to investigate CVR in patients with NFAI. Design and Setting: This case-control study was performed in a tertiary general hospital. Subjects: Subjects included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. Main Outcome Measures: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. Results: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. Conclusions: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.

scholarly journals Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

2015 ◽  
Vol 22 (4) ◽  
pp. 545-559 ◽  
Author(s):  
Rafael Ríos ◽  
Carmen Belén Lupiañez ◽  
Daniele Campa ◽  
Alessandro Martino ◽  
Joaquin Martínez-López ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Multiple Myeloma ◽  
Prediction Models ◽  
Disease Risk ◽  
Association Studies ◽  
Area Under The Curve ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Stratified Analysis

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10−06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

Values for Urinary Free Cortisol during Treatment with Amino-Glutethimide for Cushing’s Syndrome

1973 ◽  
Vol 19 (9) ◽  
pp. 1067-1068 ◽  
Author(s):  
Karl W Schmitt ◽  
Roger Juselius ◽  
James Hanlon ◽  
David Steed
Keyword(s):  
Cushing’S Syndrome ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Sensitive Indicator ◽  
Cortisol Secretion ◽  
Clinical Correlation ◽  
Free Cortisol ◽  
Amino Glutethimide

Abstract Of the chemical tests used, we found that values for urinary free cortisol had the best clinical correlation and were the most sensitive indicator of cortisol secretion in a patient with Cushing’s syndrome who was treated with amino-glutethimide.

Cortisol secretion pattern in overweight/obese and normal-weight infants: a cross-sectional study

2020 ◽  
Vol 33 (2) ◽  
pp. 241-246
Author(s):  
Ana Cristina Resende Camargos ◽  
Pedro Henrique Scheidt Figueiredo ◽  
Sueli Ferreira da Fonseca ◽  
Mariana Aguiar de Matos ◽  
Katherine Simone Caires Oliveira ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Area Under The Curve ◽  
Cross Sectional Study ◽  
Normal Weight ◽  
Control Group ◽  
Cortisol Secretion ◽  
Cross Sectional ◽  
Increased Risk ◽  
Highly Sensitive ◽  
Cortisol Levels

AbstractBackgroundThe salivary circadian diurnal cortisol plays an important role in growth and development. Inappropriate levels may induce changes associated with an increased risk of obesity later in life. It is unknown if there are differences in cortisol secretion pattern between overweight/obese infants when compared with theirs peers in infancy. Thus, this study aimed to compare the salivary cortisol secretion pattern in overweight/obese and normal-weight infants.MethodsThirty-three (overweight/obese = 17 and normal weight = 16) infants between 6 and 24 months of age had saliva samples collected upon awakening (T1), 30 min after waking (T2), at 12:00 am or before the baby’s meal (T3), and prior to bedtime (T4). Highly sensitive enzyme immunoassays were used for cortisol analyses.ResultsSalivary cortisol levels were similar between the groups: T1 (p = 0.22; 95% confidence interval [CI]: −5.65, 1.37), T2 (p = 0.24; 95% CI: −8.23, 2.17), T3 (p = 0.95; 95% CI: −3.16, 2.96), and T4 (p = 0.81; 95% CI: −1.39, 1.08); and no differences were observed between area under the curve (AUC) (p = 0.80; 95% CI: −4.58–13.66). The cortisol level reduced in T4 (95% CI: 1.35–2.96) compared to T1 (95% CI: 5.15–8.49) and T2 in the overweight/obese group (p < 0.001; 95% CI: 6.02–11.04). In the normal-weight group, the cortisol reduced in T3 (95% CI: 2.86–8.18) compared to T1 (95% CI: 5.64–12.28) and decreased until T4 (p = 0.001; 95% CI: 1.25–3.37).ConclusionsThe overweight/obese infant group presented a different pattern of cortisol secretion, although cortisol levels did not differ between the control group.

scholarly journals Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Filip Ottosson ◽  
Ulrika Ericson ◽  
Peter Almgren ◽  
Jeanette Nilsson ◽  
Martin Magnusson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Aromatic Amino Acids ◽  
Fish Meat ◽  
Increased Risk ◽  
Fasting Glycaemia ◽  
Dairy Protein ◽  
Amino Acid Concentrations

High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia.

scholarly journals In vivo reporter assays uncover changes in enhancer activity caused by type 2 diabetes associated SNPs

2020 ◽  
Author(s):  
Ada Admin ◽  
Ana Eufrásio ◽  
Chiara Perrod ◽  
Marta Duque ◽  
Fábio J.Ferreira ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nucleotide Polymorphisms ◽  
Enhancer Activity ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Nucleotide Mutation ◽  
Reporter Assays ◽  
Coding Snp

Many single nucleotide polymorphisms (SNPs) associated to type 2 diabetes overlap with putative endocrine pancreatic enhancers, suggesting that these SNPs modulate enhancer activity and consequently, gene expression. We performed <i>in vivo</i> mosaic transgenesis assays in zebrafish to quantitatively test the enhancer activity of type 2 diabetes-associated <i>loci</i>. Six out of ten tested sequences are endocrine pancreatic enhancers. The risk variant of two sequences decreased enhancer activity, while in another two incremented it. One of the latter (rs13266634) locates in a <i>SLC30A8 </i>exon, encoding a tryptophan-to-arginine substitution that decreases <i>SLC30A8 </i>function, being the canonical explanation for type 2 diabetes risk association. However, other type 2 diabetes associated SNPs that truncate SLC30A8, confer protection to this disease, contradicting this explanation. Here, we clarify this incongruence showing that rs13266634 boosts the activity of an overlapping enhancer, suggesting a SLC30A8 gain-of-function as the cause for the increased risk for the disease. We further dissected the functionality of this enhancer finding a single nucleotide mutation sufficient to impair its activity. Overall, this work assesses <i>in vivo</i> the importance of disease-associated SNPs in the activity of endocrine pancreatic enhancers, including a poorly explored case where a coding SNP modulates the activity of an enhancer.

scholarly journals Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yijun Wang ◽  
Gang Chen ◽  
Qingyun Tu ◽  
Junxia Wu ◽  
Yu Qin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Diseases ◽  
Proteinase K ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Polymerase Chain ◽  
And Gender

Objectives. AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population. Methods. Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol–chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results. The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk. Conclusions. AQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.

scholarly journals Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

2013 ◽  
Vol 168 (2) ◽  
pp. 235-241 ◽  
Author(s):  
V Morelli ◽  
S Palmieri ◽  
A S Salcuni ◽  
C Eller-Vainicher ◽  
E Cairoli ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Adrenal Incidentalomas ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

ObjectiveThe possible different prevalence of arterial hypertension (AH), type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and vertebral fractures (FX) between patients with bilateral and unilateral adrenal incidentalomas (BAI and UAI, respectively) with and without subclinical hypercortisolism (SH) is unknown. In this study we compared the prevalence of AH, T2DM, DL and FX in BAI and UAI patients in relation to SH.DesignProspective study.MethodsIn 175 UAI and 38 BAI patients, we evaluated BMI, spinal and femoral bone mineral density (LS and FN BMD, respectively) and the presence of AH, T2DM, DL and FX. SH was diagnosed in the presence of ≥2 of the following: urinary free cortisol levels >193 nmol/24 h, serum cortisol levels after 1 mg dexamethasone suppression test >83 nmol/l or ACTH levels <2.2 pmol/l.ResultsAge, BMI and cortisol secretion were comparable, while FN BMD was lower in BAI than in UAI patients (−0.45±0.86 vs 0.09±1.07, P=0.004). The prevalence of SH, AH, T2DM, and DL was comparable, while the prevalence of FX was higher in BAI than in UAI (52.6 vs 28%, P=0.007). The presence of FX was associated with BAI (odds ratio (OR) 2.6, 95% confidence interval (95% CI) 1.2–5.6, P=0.016), after adjusting for SH (OR 1.77, 95% CI 0.85–3.7, P=0.12), BMI (OR 1.06, 95% CI 0.98–1.13, P=0.1), age (OR 1.07, 95% CI 1.04–1.11, P=0.0001) and LS BMD (OR 1.31, 95% CI 1.03–1.67, P=0.03).ConclusionBAI patients have an increased FX risk than UAI ones. Further studies should investigate the causes of bone involvement in BAI patients.

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