Metabolic syndrome and Visceral Adiposity Index in non-functional adrenal adenomas

ABSTRACT Objective: We aimed to identify metabolic dysfunction in non-functioning adrenal adenomas (NFAAs) and Visceral Adiposity Index (VAI) predictability in the practical estimation of metabolic syndrome (MetS) in NFAAs. Subjects and methods: 134 NFAA patients and 68 control subjects matched for age, sex, and body mass index (BMI) were included in the study. After physical, biochemical, and endocrine evaluation, IDF and NCEP ATP III criteria were used to determine MetS. HOMA-IR and VAI were calculated for both study group subjects. Results: MetS was significantly higher in the NFAA patients. The incidence of MetS by IDF and NCEP criteria was 52.9%,48.5% in the NFAI and 32.3%,30.8% in the control group (p < 0.01, p = 0.02). The risk of MetS was increased in NFAA (75.6 vs. 24.4%, p = 0.017, OR = 1.34, 95% CI = 1.06-1.68). Glucose, HOMA IR, hypertension, and VAI were significantly increased in NFAA patients. The risk of MetS was independently associated with high VAI (79.2 vs. 20.8%, p = 0.001, OR = 2.22; 95% CI = 1.70-2.91). Conclusion: MetS, insulin resistance, and VAI are more prevalant in NFAA patients than in healthy individuals. VAI can be used with high specificity to estimate MetS in NFAA patients.

Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19.

OBJECTIVE: The present study aimed to investigate the in vivo activity of nasal irrigation (NI) with saline, NI with povidone-iodine (PVP-I) 1%, NI with a mix of hypertonic alkaline and PVP-I 1% against Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). DESIGN: This study was a prospective randomised clinical trial. SETTING: A multicenter study involving tertiary care centres. PARTICIPANTS: The study included adult outpatients whose qualitative SARS-CoV-2 RT-PCR tests in nasopharyngeal swabs were positive. One hundred twenty patients were divided into four equal groups. Standard COVID-19 treatment was given to Group 1, NI containing saline was added to patients' treatment in Group 2, NI containing 1% PVP-I solution was added to patients' treatment in Group 3, and NI containing 1% PVP-I solution and the hypertonic alkaline solution was added to patients' treatment in Group 4. MAIN OUTCOME MEASURES: On the first day of diagnosis (Day 0), nasopharyngeal swab samples were taken, on the third and fifth days the nasopharyngeal viral load (NVL) reduction in quantitative RT-PCR test was calculated. RESULTS: Between the zeroth to third days and zeroth to fifth days, the NVL reduction was significant in all groups (p < .05). In paired comparisons of groups, the NVL decrease in Group 4 in the first 3 days was significantly lower than all groups (p < .05). The NVL decrease in Groups 3 and 4 in the first 5 days were significantly lower than Group 1 (p < .05). CONCLUSION: This study revealed that the use of NI of 1% PVP-I and the hypertonic alkaline solution mixture was more effective in reducing NVL.

Metabolic syndrome and Visceral Adiposity Index in non-functional adrenal adenomas.

Objective: We aimed to identify metabolic dysfunction in non-functioning adrenal adenomas (NFAAs) and Visceral Adiposity Index (VAI) predictability in the practical estimation of metabolic syndrome (MetS) in NFAAs. Subjects and methods: 134 NFAA patients and 68 control subjects matched for age, sex, and body mass index (BMI) were included in the study. After physical, biochemical, and endocrine evaluation, IDF and NCEP ATP III criteria were used to determine MetS. HOMA-IR and VAI were calculated for both study group subjects. Results: MetS was significantly higher in the NFAA patients. The incidence of MetS by IDF and NCEP criteria was 52.9%,48.5% in the NFAI and 32.3%,30.8% in the control group (p < 0.01, p = 0.02). The risk of MetS was increased in NFAA (75.6 vs. 24.4%, p = 0.017, OR = 1.34, 95% CI = 1.06-1.68). Glucose, HOMA IR, hypertension, and VAI were significantly increased in NFAA patients. The risk of MetS was independently associated with high VAI (79.2 vs. 20.8%, p = 0.001, OR = 2.22; 95% CI = 1.70-2.91). Conclusion: MetS, insulin resistance, and VAI are more prevalant in NFAA patients than in healthy individuals. VAI can be used with high specificity to estimate MetS in NFAA patients.

Prolactinoma - which patients react favorably to cabergoline medication?

Objective. Prolactinoma, as a common endocrine disorder and the most frequent type of pituitary tumor, acts primarily as a suppressor on the gonadal functions. It is generally successfully treated with dopamine agonists; however, treatment resistance still remains in an unneglectable ratio. In this study, we aimed to identify factors, which may play a role in the treatment response. Methods. Seventy-six patients with prolactinoma, who have been routinely followed between 2018 and 2022 in Istanbul Research and Educational Hospital Endocrinology Outpatient Clinic, were included into the study. Initial prolactin level, adenoma size, baseline weight, body mass index (BMI), glucose, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels were obtained from the patient's medical records. The patients were divided into two groups: treatment respondent and non-respondent (refractory) ones, according to treatment response in the duration as suggested by the guidelines. The treatment respondent and non-respondent groups were compared according to the initial and the 3rd month prolactin levels, adenoma size, weight, BMI, and metabolic values. Results. The initial tumor diameter was 15.27±10.62 mm in the refractory and 7.42±4.42 mm in the treatment respondent groups (p=0.01). The refractory group had higher prolactin baseline level 269.96±275.78 µg/l vs. 124.55±67.35 µg/l of the respondent group (p=0.01). The refractory group had higher the 3rd month prolactin level 50.97±52.55 µg/l vs. 29.70±27.31 µg/l of the respondent group (p=0.04). The refractory group had higher frequency of cystic/hemorrhagic adenoma (47.6%, n=11/21) (p=0.01), baseline pituitary failure (33.3%, n=7/21) (p=0.01), and baseline cavernous sinus invasion (25.8, n=5/21) (p=0.01). The treatment respondent group had lower initial body weight (69.54±17.51 kg vs. 83.29±16.21 kg) (p<0.01), and lower BMI (25.98±5.47 kg/m2 vs. 27.69±6.42 kg/m2) (p=0.02). Conclusions. In this study, initial tumor size, male gender, weight, BMI, the 3rd month prolactin level, initial pituitary deficiency, and cystic/hemorrhagic component in pituitary imaging in patients with prolactinoma were associated with a lower treatment response.

Increased mitochondrial common deletion in platelets from patients with type 2 diabetes is not associated with abnormal platelet activity or mitochondrial function.

The present study examined the presence and frequency of the 4,977­base pair mitochondrial (mt)DNA (mtDNA4977) deletion in blood platelets, and whether increased mtDNA4977 deletion was associated with abnormal mitochondrial and platelet function in type 2 diabetes mellitus. A total of 66 patients with type 2 diabetes mellitus and 23 healthy subjects were included in the present study. Patients were divided into three subgroups according to glycemic control, and the presence or absence of chronic diabetic complications: i) Good glycemic control [glycated hemoglobin (HbA1c) <7] without complications; ii) poor glycemic control (HbA1c ≥7) without complications; and iii) poor glycemic control (HbA1c ≥7) with complications. mtDNA4977 deletion, mtDNA copy number, adenine nucleotides, mitochondrial membrane potential and P­selectin expression levels were analyzed in platelets. Although the frequency of mtDNA4977 deletion in platelets of the patient (96.9%) and control groups (95.6%) was extremely similar, the deletion level significantly increased in all the diabetic groups, compared with the healthy control group. However, the data from the present study revealed that an increased deletion frequency in platelets was not associated with disease severity, although there was clear interindividual variability. Furthermore, all other parameters were not significantly different among the groups, and there were no correlations between mtDNA4977 deletion frequency and all other studied parameters for any of the case groups. The results indicated that the mtDNA4977 deletion occurred in platelets, and increased deletion in patients with type 2 diabetes did not have a marked influence on mitochondrial and/or platelet dysfunction, when compared with the non­diabetic subjects. Further research is required to elucidate the sources of inter­individual variability observed in certain parameters.

The role of TMPRSS6 gene variants in iron-related hematological parameters in Turkish patients with iron deficiency anemia.

TMPRSS6 gene mutations can result in iron deficiency anemia (IDA) and cause an increased iron-regulatory hormone, hepcidin, levels. TMPRSS6 encodes a serine protease, matriptase-2, which functions as negative regulatory protein of hepcidin transcription. Thus, TMPRSS6 variations might be risk factors for IDA. The aim of the study was to investigate the association of rs855791, rs4820268, rs5756506, rs2235324, rs2413450, rs2111833, rs228919, and rs733655 SNPs in TMPRSS6 gene with IDA susceptibility and iron-related clinical parameters. The study consisted of 150 IDA patients and 100 healthy controls. We analyzed the genotype distributions by using Real-Time polymerase chain reaction (Real-Time PCR) technique. We did not find any statistically differences for all SNPs between patients and controls (P > 0.05). In IDA patients, variations rs855791 and rs2413450 were associated with increased RBC (P = 0.03) and TIBC (P = 0.04), respectively. Also, increased of TIBC for rs4820268 (P < 0.05). On the other hand, in control group, rs5756506 was associated with two parameters, Hb (P = 0.02) and Hct (P = 0.03). We did not find markedly hepcidin levels in IDA patients compared to controls (P = 0.32). Our findings suggest that TMPRSS6 variations may not be risk factors for IDA. However, TMPRSS6 polymorphisms are associated with increased many iron-related hematological parameters.

Clinical and angiographic predictors of persistently ischemic fractional flow reserve after percutaneous revascularization.

AIMS: Despite optimal angiographic results after percutaneous coronary intervention (PCI), some lesions may continue to produce ischemia under maximal hyperemia. We evaluated the factors associated with persistently ischemic fractional flow reserve (FFR) after angiographically successful PCI. METHODS AND RESULTS: A total of 574 consecutive patients with 664 lesions undergoing PCI who had FFR pre- and post-PCI were analyzed. Percutaneous coronary intervention led to effective ischemia reduction from pre-FFR (0.65±0.14) to post-FFR (0.87±0.08; ∆FFR 0.22±0.16, P<.001). There were 63 (9.5%) lesions with a persistently ischemic FFR of ≤0.80 despite optimal angiographic PCI results. Multivariate analysis revealed the presence of diffuse disease (odds ratio [OR] 3.54, 95% CI 1.80-6.94, P<.01), left anterior descending artery PCI (OR 8.35, 95% CI 3.82-18.27, P<.01), use of intravenous adenosine for inducing hyperemia (OR 3.95, 95% CI 2.0-7.84, P<.01), and pre-PCI FFR (OR 0.03, 95% CI 0.004-0.23, P<.01) as independent predictors of persistently ischemic FFR (≤0.80) after PCI. The predictive accuracy of this model was robust, with an area under the curve of 0.85 (95% CI 0.82-0.88). CONCLUSION: Multiple factors are associated with persistently ischemic FFR after angiographically optimal PCI. It is recommended that in lesions with the above-identified factors, FFR should be remeasured after PCI, and if abnormal, further measures should be undertaken for functional optimization.

Determination and distribution of left ventricular size as measured by noncontrast CT in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Left ventricular (LV) volume and mass have prognostic relevance. Overall size of the left ventricle as it appears in noncontrast CT is a composite of the ventricular volume and myocardial mass. We describe a method to estimate the LV size using a single cross-section in noncontrast CT and determined normal ranges on the basis of a large population cohort. METHODS: The Multi-Ethnic Study of Atherosclerosis with 6814 participants from 4 ethnicities who were free of known cardiovascular disease and enrolled between 2000 and 2002 form the basis of our analysis. LV size was calculated from a single cross-sectional slice obtained by either nonenhanced electron beam or multidetector CT. LV size was adjusted to body surface area to obtain the LV size index, which was adjusted for age, sex, race or ethnicity, hypertension, hyperlipidemia, and diabetes. RESULTS: There were significant differences in LV size index by race which were further influenced by age and sex. Higher values were noted in men in all ethnic groups across all age groups. Similarly, LV size index uniformly decreased with age across all ethnic and sex categories. Caucasians had the lowest and African Americans had the highest LV size index across all age and sex categories. In multivariate regression analyses adjusted for age, sex, race or ethnicity, hypertension, hyperlipidemia, smoking, and diabetes mellitus, the significant differences were noted between male vs female (median difference, 17.5 cc/m(2); P < .001), ethnic groups (Caucasian, reference group; Asian, 3.7 cc/m(2); African American, 8.3 cc/m(2); and Hispanic, 5.6 cc/m(2); P < .001), and age groups (45-54 years, reference group; 55-64 years, -5.2 cc/m(2); 65-74 years, -11.4 cc/m(2); and 74-84 years, -12.5 cc/m(2)). CONCLUSIONS: This study provides normative values for LV size as determined from a single, nonenhanced CT cross-section and indexed to body surface area, and it demonstrates that the LV size index varies by age, sex, and ethnic background.

Serum survivin increases in prolactinoma.

BACKGROUND: Prolactinoma is the most common adult pituitary adenoma. Survivin is a member of the family of inhibitors of apoptosis proteins. Its expression is observed in many tumors. Survivin expression has shown in prolactinoma tissue before but no study exists showing serum survivin level. The aim of the present study was to investigate serum survivin levels in patients with prolactinoma and demonstrate its value in diagnosis of the disease. METHODS: The group of patients consisted of 25 women, aged from 17 to 51 years. As a control group, 21 healthy women, aged from 22 to 45 years were included. Twenty patients had microprolactinoma, while five patients had macroprolactinoma. All patients had received dopamine agonist treatment. Serum survivin levels were measured in all of the groups. RESULTS: Survivin levels were significantly higher in prolactinoma patients compared to controls (19.04 (10 - 38) pg/mL; 15.05 (8 - 22) pg/mL; P = 0.042). There was no difference between microadenoma and macroadenoma patients in survivin levels (19.22 (10 - 38) pg/mL; 18.40 (16 - 22) pg/mL; P = 0.914). In correlation analysis, survivin was not correlated with other parameters. CONCLUSIONS: We consider that higher survivin levels might be a molecular marker predicting the presence of prolactinoma and may be useful for the diagnosis. But large-scale research is needed to clarify its role in diagnosis of prolactinoma patients.

Differences in coronary atherosclerotic plaque burden and composition according to increasing age on computed tomography angiography.

RATIONALE AND OBJECTIVES: Few data were available regarding the underlying burden of specific plaque types with increasing ages. The aim of this study was to assess the relationship of coronary artery calcium (CAC) score with total coronary plaque burden and the difference of underlying coronary plaque composition across differing aging groups using 64-slice multidetector computed tomography. MATERIALS AND METHODS: Multidetector computed tomographic images of 781 consecutive patients were evaluated using a 15-coronary segment model. Segment involvement score (the total number of segments with any plaque), segment stenosis score (the sum of maximal stenosis score per segment), total plaque score (the sum of the plaque amount per segment), and plaque composition were measured to compare with total CAC scores stratified by age tertile (lowest [n = 274], <55 years; middle [n = 242], 55-65 years; highest [n = 265], >65 years). RESULTS: The mean age of the study population was 59 ± 13 years (481 men [62%]). With increasing age, higher segment involvement scores, segment stenosis scores, and total plaque scores were noted. Plaque burden was correlated significantly with total CAC scores in all tertiles. The percentage of partially calcified (P < .001) and calcified (P < .001) plaque increased with age, and in the highest age tertile, 87% of plaque contained calcium (calcified or mixed), compared to only 63% in the younger patients (P < .001). Those aged >65 years were highly unlikely to have isolated noncalcified plaque (in the setting of a calcium score of 0). Younger patients were 10 times more likely to have isolated noncalcified plaque (P < .001). CONCLUSIONS: The absence of CAC strongly excludes obstructive disease, and CAC predicts the presence of coronary atherosclerotic plaque. However, the absence of any CAC does not exclude the presence of coronary atherosclerotic plaque, especially in patients aged <55 years. Plaque composition shifted from noncalcified to calcified plaque with increasing age, which may affect the vulnerability of these lesions over time.

Relation of subclinical left and right ventricular dysfunctions measured by computed tomography angiography with the severity of coronary artery disease.

OBJECTIVE: Ventricular dysfunction in asymptomatic patients is directly linked to the eventual development of symptomatic congestive heart failure. This study investigates whether subclinical left ventricular (LV) and right ventricular (RV) dysfunctions measured by computed tomography angiography is associated with the severity of coronary artery disease (CAD). METHODS AND RESULTS: We studied 1608 consecutive patients with suspected CAD (age 62 ± 10 years, 64% male), who underwent coronary artery calcium (CAC) scanning and computed tomography angiography. RV and LV volumes at end systole and end diastole were measured, and stroke volume and ejection fraction were calculated using the Simpson method and piecewise smooth subdivision surface (PSSS) method. Analysis by Simpson was performed on short axis and apical four-chamber views. Axial images were used to measure RV and LV volumes by the PSSS method. CAD was defined as normal, nonobstructive, and obstructive (0% stenosis, luminal stenosis 1-49 and 50%+, respectively). There was a strong agreement between PSSS and Simpson method RV ejection fraction (RVEF) and LV ejection fraction (LVEF) measurement. RVEF and LVEF decreased proportionally from CAC 0 to CAC 100+, also from normal-to-diseased coronaries (P=0.001). After adjustment for cardiovascular risk factors, the mean LVEF and RVEF decreased 2.8 and 2.4%, respectively in CAC 100+ compared with CAC 0. Similarly, LVEF and RVEF decreased significantly in nonobstructive CAD (-3.5 and -3.1%, respectively) and obstructive CAD (-5.9 and -4.5%, respectively) compared with normal coronaries, respectively (P<0.05). The relative risk of each 5% decrease in LVEF and RVEF was 1.33 and 1.29 for nonobstructive CAD and 1.54 and 1.33 for obstructive CAD, respectively. CONCLUSION: The presence and severity of coronary atherosclerosis is significantly associated with subclinical RV and LV dysfunctions.

Left ventricular volume: an optimal parameter to detect systolic dysfunction on prospectively triggered 64-multidetector row computed tomography: another step towards reducing radiation exposure.

In this study, we define the correlation between LV volumes (both LV end-diastolic volume [LVEDV] and LV end-systolic volume [LVESV]) and ejection fraction (EF) on 64 slice multi-detector computed tomography (MDCT). We also determine the accuracy of all the LV volume (LVV) parameters to detect LV systolic dysfunction (LVSD) and investigate the feasibility of using LVV as a surrogate of LVSD on prospectively gated imaging to prevent the radiation exposure of retrospective imaging. 568 patients undergoing 64-detector MDCT were divided into 2 groups: Group 1-subjects without any heart disease and LVEF ≥ 50%; and Group 2-patients with coronary artery disease and LVEF < 50% (defined as LVSD). The LVV (LV cavity only) and Total LV volume (cavity + LV mass) at end-systole and end-diastole (LVESV, Total LVESV, LVEDV and Total LVEDV) were measured. The upper limit values (mean + 2 SD) of all LVV parameters in Group 1 were used as the reference criterion to diagnose LVSD in Group 2. An exponential correlation was found between LVEF and all the LVV parameters. The specificity to detect LVSD in Group 2 was >90% and the sensitivity was 88.9, 83.3, 61.3 and 74.9% by using LVESV, Total LVESV, LVEDV and Total LVEDV, respectively. Systolic and diastolic LV volumes had a high correlation with LVEF and a high accuracy to detect LVSD. Thus, on prospectively triggered imaging, ventricular volumes can predict patients with reduced LVEF, and appropriate referrals can be made.

Noninvasive anatomical coronary artery imaging versus myocardial perfusion imaging: which confers superior diagnostic and prognostic information?

Myocardial perfusion imaging (MPI) has been a valuable diagnostic and prognosticating tool for decades, but recently it has been challenged by the growing evidence about either comparable or superior diagnostic and prognostic value of computed tomography (CT)-based anatomical imaging modalities. Although there are some studies suggesting synergy and potential for combined use of these modalities to better diagnose coronary artery disease (CAD), it is important to evaluate these approaches separately, given cost and other restraints. This review compares the noninvasive anatomical imaging modalities of coronary artery calcium scoring and coronary CT angiography to the functional assessment modality of MPI in the diagnosis and prognostication of significant CAD in symptomatic patients. A large number of studies investigating this subject are analyzed with a critical look on the evidence, underlying the strengths and limitations. Although the overall findings of the presented studies are favoring the use of CT-based anatomical imaging modalities over MPI in the diagnosis and prognosticating of CAD, the lack of a high number of large- scale, multicenter randomized controlled studies limits the generalizability of this early evidence. Further studies comparing the short- and long-term clinical outcomes and cost-effectiveness of these tests are required to determine their optimal role in the management of symptomatic patients with suspected CAD.

Relationship between two estrogen receptor-alpha gene polymorphisms and angiographic coronary artery disease.

OBJECTIVE: To investigate the association of estrogen receptor-alpha PvuII and BtgI polymorphisms with angiographic presence and severity of coronary artery disease (CAD). METHODS: Our cross-sectional study included 140 patients with >or=50% coronary stenoses (CAD group) and 47 patients with normal angiograms (CAD-free group) (total n=187, age 59.6+/- 13.2 years; 66 women). PvuII and BtgI genotype and allele distributions were determined by standard method of polymerase chain reaction and restriction fragment length polymorphism. The CAD subgroups by the number of diseased vessels were also defined. Variable associations and group differences were analyzed by independent t test, one-way ANOVA, Pearson's Chi-square, Spearman's correlation tests and logistic regression analyses. RESULTS: While there was no association between PvuII polymorphism and angiographic CAD (p=0.384), BtgI polymorphism was more prevalent in CAD-free group (23.4% vs. 10% (CAD group), OR=2.75, 95% CI=1.150 to 6.579, p=0.019). This difference was more pronounced in women (28.6% vs. 4.4%; OR=8.6; 95% CI=1.564 to 47.303; p=0.005) compared to men (p=0.391). Logistic regression analysis confirmed BtgI polymorphism as the most important predictor for a normal coronary angiogram among parameters such as body mass index, diabetes and age (OR 8.13, 95% CI 1.257 to 52.627, p=0.028). However, no significant association between BtgI polymorphism and the number of stenotic arteries was detected. CONCLUSION: ESR1 PvuII polymorphism is not associated with angiographically significant CAD. ESR1 BtgI polymorphism is strongly associated with the presence of normal coronary angiograms in women, which suggests protective effect. Further confirmation of these findings is required.