Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study.

OBJECTIVE: Although the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up. METHODS: In this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons. RESULTS: This study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease. CONCLUSION: Applying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

Risk of hypercalcemia in patients with very high serum 25-OH vitamin D levels.

OBJECTIVE: We aimed to evaluate the risk of hypercalcemia in patients with very high levels of 25-hydroxy vitamin D (25(OH)D). METHODS: The distribution of patients who were screened for 25(OH)D in our hospital between January 2014 and December 2018 was evaluated and patients with serum concentrations of 25(OH)D >88 ng/mL were selected. Then, biochemical parameters of the cases with 25(OH)D >88 ng/mL were compared according to calcium status, vitamin D level (group 1, 88-100 ng/mL; group 2, 100-150 ng/mL, and group 3, >150 ng/mL), and gender. RESULTS: A total of 282 932 patients who underwent 25(OH)D tests in our hospital were evaluated. A total of 1311 (0.5%) patients had very high 25(OH)D levels (>88 ng/mL). Four hundred and ninety-five patients who met our inclusion criteria and had complete data participated in the study. The median age was 58 years (interquartile range [IQR] = 41-71 years) and the median level of 25(OH)D was 104.6 mg/mL (IQR = 94.9-124.9 ng/mL). Most of the subjects (83.7%) with very high 25(OH)D levels were normocalcemic. A weak inverse correlation was observed between 25(OH)D level and intact parathyroid hormone (iPTH) level (r = -0.118, P = .01), but no correlation between 25(OH)D and calcium levels was observed. Alkaline phosphatase (ALP) levels were significantly higher in males (P = .032), and age and iPTH levels were higher in females (P < .001 and P = .004). ALP, phosphorus levels, and iPTH suppression rates were higher in hypercalcemic patients (P < .001, P < .001, and P < .001, respectively), while the iPTH level was significantly lower in hypercalcemic patients (P < .001) than in normocalcemic patients. Amongst the three groups with different 25(OH)D levels, no difference was found in levels of iPTH, calcium, phosphorus, ALP, or age. CONCLUSION: Most patients with very high vitamin D levels were normocalcemic, but severe hypercalcemia was also observed. Vitamin D replacement therapy and follow-up should be performed according to clinical guideline recommendations.

External Validation of the GREAT Score in Turkish Patients with Graves' Hyperthyroidism Treated with the Titration Regimen Method of Antithyroid Drugs: A Multicenter Study.

Recently, the Graves' Recurrent Events After Therapy score (GREAT) was proposed as a useful tool to predict relapse before starting antithyroid drugs (ATD) in patients with Graves' disease (GD). Therefore, we intended to assess the validity of the GREAT score in Turkish patients with GD, including patients who experienced a poorly controlled disease (multiple episodes of hyperthyroidism followed by euthyroidism or rarely hypothyroidism) during ATD dose titration. This is a retrospective multicenter study including 517 patients with the first episode of GD who were treated for at least 12 months. The patients were classified as relapse+poorly controlled disease (non-remission) and remission groups. During a median follow-up time of 35 months (12-144 months), 191 (37%) patients experienced a relapse, 136 (26.3%) a poorly controlled disease, and 190 (36.7%) remained in remission. Patients with non-remission disease tended to have significantly higher serum levels of TRAb, fT4, and fT3, and have larger goiter sizes on palpation at baseline, as compared with the remission group. Non-remission disease occurred in 12, 35, and, 53% of the patients falling into GREAT class I, II, and III, respectively (hazard ratio 2.56, 95% CI 2.02-3.51, p=0.012, and hazard ratio 3.54, 95% CI 2.12-5.91, p<0.001, for GREAT class II and III against class I, respectively). According to our study, the GREAT score is a useful tool to predict the risk of relapse as well as the occurrence of poorly controlled disease before starting treatment with ATDs.

Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study.

BACKGROUND: The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia. METHODS: We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality. FINDINGS: Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality. INTERPRETATION: Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day). FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

High circulating levels of sICAM-1 and sVCAM-1 in the patients with Hashimoto's thyroiditis.

OBJECTIVE: To investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels are increased in euthyroid patients with Hashimoto's thyroiditis (HT) and whether they are associated with thyroid autoimmunity and metabolic parameters. DESIGN: Cross-sectional. SUBJECTS AND METHODS: In total, 80 euthyroid patients with HT and 80 age- and body mass index (BMI)-matched control participants were included. Serum sICAM-1, sVCAM-1, free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), fasting blood glucose (FBG), insulin, and lipid levels and homeostasis model assessment for insulin resistance (HOMA-IR) were assessed in all participants. RESULTS: The patients with HT had significantly higher levels of sICAM-1 and sVCAM-1 than controls (both p < 0.001). The difference was sustained after adjustment for TSH and levothyroxine use. Regression analysis demonstrated that sICAM-1 was related to anti-TPO (p < 0.001), and sVCAM-1 was related to both anti-TPO and-TG (p < 0.001 and p = 0.03, respectively); this relationship was sustained after adjustment for age and BMI. Although FBG and HOMA-IR were higher in the HT group, logistic regression analysis revealed that there was no effect of anti-TPO, anti-TG, sICAM-1, sVCAM-1, and C-reactive protein (CRP) on the occurrence of high FBG and high HOMA-IR. CONCLUSION: sICAM-1 and sVCAM-1 levels were significantly elevated in the patients with euthyroid HT and correlated closely with thyroid autoimmunity. However, soluble adhesion molecules had no relation with glucose metabolism parameters in the HT patients.

IS BIOCHEMICAL ASSESSMENT OF PHEOCHROMOCYTOMA NECESSARY IN ADRENAL INCIDENTALOMAS WITH MAGNETIC RESONANCE IMAGING FEATURES NOT SUGGESTIVE OF PHEOCHROMOCYTOMA?

OBJECTIVE: Currently, it is unclear whether pheochromocytomas can be ruled out based on low intensity on T2-weighted sequences and signal loss on out-of-phase magnetic resonance imaging (MRI) sequences. Hence, in this study, we investigated whether biochemical screening for pheochromocytoma in patients with adrenal incidentalomas (AIs) showing MRI features not suggesting pheochromocytoma would prove beneficial. METHODS: We performed MRI for 300 AIs in 278 consecutive patients. All patients were screened for pheochromocytoma with plasma metanephrine and normetanephrine. Patients with high plasma levels of metanephrine and/or normetanephrine were also assessed for pheochromocytoma by urinary metanephrines. RESULTS: Hyperintensity was detected on T2-weighted MRI sequences in 28 (9.3%) of the 300 AIs. Among these 28 incidentalomas, pheochromocytoma was diagnosed in 13 (46.4%) of the cases by histopathologic analysis. Hyperintensity on T2-weighted MRI was significantly higher in pheochromocytomas compared to the remaining AIs (P<.001). All 13 pheochromocytomas were characterized by hyperintensity on T2-weighted sequences and the absence of signal loss on out-of-phase MRI sequences. Pheochromocytoma was not detected in any of the 272 AIs that appeared hypointense or isointense on T2-weighted MRI sequences or in the 250 cases with signal loss on out-of-phase sequences. CONCLUSION: The results of this study suggest that AIs that appear hypointense or isointense on T2-weighted MRI sequences and those with signal loss on out-of-phase sequences may not require routine biochemical screening for pheochromocytoma. Further studies including a higher number of pheochromocytomas are required to confirm our results.

Patients with normocalcemic primary hyperparathyroidism may have similar metabolic profile as hypercalcemic patients.

Primary hyperparathyroidism is well known to be associated with cardiovascular morbidity and mortality. However, it is unclear whether normocalcemic primary hyperparathyroidism (NC-PHPT) and hypercalcemic primary hyperparathyroidism (HC-PHPT) share the same risk factors. We aimed to determine prevalence of metabolic syndrome in NC-PHPT and compare metabolic syndrome parameters and insulin resistance in NC-PHPT subjects with those in HC-PHPT and control subjects. After excluding patients with secondary hyperparathyroidism, the study enrolled 25 patients with NC-PHPT, 24 patients with HC-PHPT and 30 age-gender matched controls. All participants were evaluated using the International Diabetes Federation (IDF)-2006 metabolic syndrome criteria. Compared with HC-PHPT patients, NC-PHPT patients had similar prevalence of metabolic syndrome, glucose intolerance, and previous history of hypertension/anti-hypertensive medications, but compared with controls, NC-PHPT patients had significantly higher prevalence of glucose intolerance and previous history of hypertension/anti-hypertensive medications. Not serum calcium but PTH concentration was found to be significantly higher in those with glucose intolerance. Serum fasting triglyceride concentration and waist circumference were found to be positively correlated only with serum PTH concentration. In conclusion, patients with NC-PHPT may be prone to similar metabolic disturbances linked to higher cardiovascular risk like patients with HC-PHPT. Although NC-PHPT is thought to occur early in the development of the classical disease, it should be monitored regularly because of its metabolic consequences.

Expression of voltage gated potassium channel ether à go-go in pituitary adenomas of patients with acromegaly: A preliminary study.

OBJECTIVE: To determine immunohistochemical expression of Eag1 in pituitary adenomas of patients with acromegaly and to assess the correlation between Eag1 expression with cavernous sinus invasion, tumoral Ki-67 labeling index (LI), age and gender of the patients. METHODS: The paraffin embedded pituitary adenoma tissue sections of 28 patients with acromegaly who were diagnosed as monohormonal growth hormone (GH) secreting adenomas were immunostained for Eag1 using the avidin-biotin-peroxidase complex method. Eag1 immunoreactivity was scored according to the extensity of the cytoplasm and cell membrane immunoreactivity for Eag1 (score 1 = <10%, score 2 = 10-25%, score 3 = 25-50% and score 4 = >50% of the adenoma cells showed immunoreactivity for Eag1, respectively). RESULTS: Overall, GH secreting pituitary adenomas displayed diverse levels of Eag1 immunoreactivity, however, 64% of the adenomas displayed a strong Eag1 immunoreactivity (score 3 and 4). Five of the tumors displayed Eag1 immunoreactivity score 1, 5 displayed score 2, 10 displayed score 3 and 8 displayed score 4, respectively. No correlation was found between Eag1 immunoreactivity with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. CONCLUSIONS: Our results suggest Eag1 is strongly expressed in the majority of GH secreting pituitary adenomas. However, we could not find any correlation between immunoreactivity of Eag1 with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. Further studies with larger sample sizes are required to demonstrate the role of Eag1 on tumorigenesis, angiogenesis, invasion and response to the treatment in GH secreting pituitary adenomas.

Interleukin-10-1082 gene polymorphism is associated with papillary thyroid cancer.

The etiopathogenesis of thyroid cancer has not been clearly elucidated although the role of chronical inflammation and the imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with papillary thyroid cancer (PTC), and to evaluate the relationship between genotypes and clinical/laboratory manifestation of PTC. Tumor necrosis factorα (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 A-1082G (rs 1800896) single nucleotide polymorphisms in DNA from peripheral blood leukocytes of 190 patients with thyroid cancer and 216 healthy controls were investigated by real-time PCR combined with melting curve analysis. There was no notable risk for PTC afflicted by TNFα-308 and IL-6-174 alone. However, IL-10-1082 G allele frequency were higher among PTC patients than healthy controls (p=0.009). The patients with IL-10-1082 GG geotype have twofold increased risk of developing thyroid cancer according to AA genotype (OR 2.07, 95% CI 1.21-3.55). In addition, the concomitant presence of IL-10-1082 G allele (GG+AG genotypes) together with IL-6 -174 GG genotype has a nearly twofold increased risk for thyroid cancer (OR 1.75 with 95% CI 1.00-3.05, p=0.049). We suggest that IL-10-1082 G allele is associated with an increased risk of PTC. The polymorphism of IL-10 gene can improve our knowledge about the pathogenesis of PTC, and could provide to estimate people at the increased risk for PTC.

The Diagnostic Utility of Color Doppler Ultrasonography, Tc-99m Pertechnetate Uptake, and TSH-Receptor Antibody for Differential Diagnosis of Graves' Disease and Silent Thyroiditis: A Comparative Study.

OBJECTIVE: The differential diagnosis of Graves disease (GD) and silent thyroiditis (ST) is important for the selection of appropriate treatment. To date, no study has compared the diagnostic utility of color Doppler ultrasonography (CDUSG), Tc-99m (technetium-99m) pertechnetate uptake, and thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) for the differential diagnosis of these two conditions. In the present study, we compared the diagnostic utility of inferior thyroid artery (ITA) peak systolic and end diastolic velocities (PSV and EDV) measured by CDUSG, Tc-99m pertechnetate uptake, and TRAb for differential diagnosis of GD and ST. METHODS: A total of 150 subjects with GD, 79 with ST, and 71 healthy euthyroid controls were included in the study. Diagnoses of GD and ST were made according to patient signs and symptoms, physical examination findings, the results of TRAb and Tc-99m pertechnetate uptake, and follow-up findings. All subjects underwent CDUSG for the quantitative measurement of ITA blood-flow velocities. RESULTS: The mean ITA-PSV and EDV in patients with GD were significantly higher than in ST patients. In receiver operating characteristic analysis, the sensitivity/specificity of the 30 and 13.2 cm/s cutoff values of the mean ITA-PSV and EDV for discrimination of GD from ST were 95.3/94.9% and 89.3/88.6%, respectively. The sensitivity/specificity of the 1.0 international unit (IU)/L and 3% cutoff values of the TRAb and Tc-99m pertechnetate uptake analyses were 93.0/91.0% and 90.7/89.9%, respectively. CONCLUSION: The measurement of ITA-PSV by CDUSG is a useful diagnostic tool and is a complementary method to the TRAb and Tc-99m pertechnetate uptake methods for differential diagnosis of GD and ST.

Comparison of Two Estimated Glucose Disposal Rate Methods for Detecting Insulin Resistance in Adults with Type 1 Diabetes Mellitus.

Background: The presence of insulin resistance (IR) in patients with type 1 diabetes mellitus (T1DM) is a significant indicator of all chronic diabetic complications, independent of other risk factors. The estimated glucose disposal rate (eGDR) is a practical method that can be easily used in daily practice to determine IR. This study aimed to determine the cutoff values for two eGDR methods and compare their diagnostic value for determining IR in adult T1DM patients with metabolic syndrome (MetS). Methods: This cross-sectional study was performed on 184 adults admitted to the endocrinology outpatient clinic diagnosed with T1DM. Demographic characteristics, anthropometric measurements, and the presence of hypertension (HT) were recorded. The eGDR of all patients was calculated using two formulas based on HbA1c level, presence of HT, waist-to-hip ratio (WHR), or waist circumference (WC). Diagnostic cutoff values for both eGDRs were defined using receiver operating characteristic (ROC) analysis. Patients were divided into two groups according to the cutoff values. The accuracy of the diagnostic cutoffs for eGDRwhr and eGDRwc was compared using a Bland-Altman plot. Results: The cutoff value for eGDRwhr was 7.37 mg/(kg·min) with 83.3% specificity and 86.7% sensitivity [area under the curve (AUC) = 0.901; P < 0.001; 95% confidence interval (CI), 0.824-0.977] and for eGDRwc 7.50 mg/(kg·min) with 79.8% specificity and 83.3% sensitivity (AUC = 0.895; P < 0.001; 95% CI, 0.817-0.972) for the presence of MetS. Further ROC analysis showed that the difference between the two AUCs (0.901 and 0.895) was not significant (P = 0.923). Conclusion: Assessment of eGDR would lead to early prevention of diabetic complications. eGDR is measured using either WHR or WC. This study is the first to compare WHR and WC in calculating eGDR in adults. WHR and WC are not superior to each other for calculating eGDR in determining IR in T1DM.

Comparative Analysis of FSE T2 Weighted, Chemical Shift and Dynamic Contrast-Enhanced MR Imaging in the Characterization of Adrenal Masses Based on Qualitative and Quantitative Parameters.

Objectives: The purpose of our study was to investigate the role of different magnetic resonance imaging (MRI) parameters in the characterization of adrenal masses. Methods: A total of 150 patients who presented with 186 adrenal tumors were retrospectively evaluated in this study. Final patient cohort consisted of 17 pheochromocytomas, 3 adrenocortical carcinomas, 24 metastases, 31 lipid-poor adenomas and 111 lipid-rich adenomas. We carried out a visual assessment on FSE (Fast spin echo)T2 weighted images and also calculated T2 signal intensity ratio of all adrenal masses and also performed a qualitative assessment on chemical shift imaging (CSI) together with quantitative calculation using Adrenal to spleen signal intensity (si) ratio and Adrenal si index formulas. On dynamic contrast-enhanced sequences, visual assessment based on enhancement patterns on late-arterial phase images was performed and also mean signal intensity measurements were carried out. All examinations were interpreted by two abdominal radiologists in consensus who were blinded to the clinical and pathological findings. Statistical analysis was performed. Results: On FSE T2 weighted imaging, isointense to liver and slightly hyperintense than liver was found higher in benign cases, however, in malignant cases moderately and strikingly hyperintense than liver was higher than in benign cases (p=0.001, p<0.01). There was a statistically significant difference between the T2 signal intensity ratio values of adrenal tumor groups (p=0.001, p<0.01). In lipid-rich and lipid-poor adenoma groups, T2 signal intensity ratio values was significantly lower than in pheochromocytoma and metastasis cases. In malignant group, T2 signal intensity ratio values were found statistically significantly higher than in the benign group (p=0.001, p<0.01). There was a statistically significant difference between CSI visual assessment of adrenal tumor groups (p=0.001, p<0.01). Although moderate and significant signal intensity loss was usually detected in lipid-rich adenoma group, never detected in other tumor groups. There was also a statistically significant difference between benign and malignant adrenal tumor groups (p=0.001, p<0.01). In the malignant group, Adrenal to spleen si ratio values were found significantly higher whereas, Adrenal si index values were significantly lower compared to benign tumors (p=0.001, p<0.01). Based on malignancy, there was a statistically significant difference between adrenal tumor groups (p=0.001, p<0.01). Although capillary blush and homogenous type enhancement were more common in benign cases than in malignant ones, peripheral-patchy and strikingly capillary blush type enhancement was more frequent in malignant tumors. Based on malignancy, mean arterial signal intensity values of malignant tumors were statistically higher than benign tumors (p=0.001; p<0.01). Conclusion: Dynamic contrast-enhanced MRI protocol including CSI aids in the characterization of indeterminate adrenal masses. Herein, the combined use of qualitative and quantitative parameters enables more tumors to be recognized that otherwise would be indeterminate.

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study.

OBJECTIVES: Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC. METHODS: The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox's proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02-5.81, p = 0.043; HR: 4.38, 95% CI: 1.7-11.2, p = 0.002, respectively). CONCLUSIONS: In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.

Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

The Role of Serum Inflammation-Based Scores in Diagnosis and Assessing Remission in Cushing's Disease.

Objectives: Chronic hypercortisolism causes diverse alterations in the immune system and inflammatory disruptions. Serum inflammation-based scores (SIBS) are indicators of systemic inflammatory status. This study aims to determine the role of SIBS in the diagnosis and evaluation of remission in patients with Cushing's disease (CD). Methods: This retrospective cross-sectional study was conducted on 195 participants; 52 patients diagnosed and followed up after treatment with CD, 65 patients with subclinical Cushing's syndrome (SCS), and 78 healthy individuals whose complete blood counts (CBC) were obtained for analysis. Participants with additional diseases or drug use that could affect CBC were excluded from the study. SIBS of the three groups were compared. Scores considered were neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). The correlations between SIBS and initial diagnostic tests for hypercortisolism were analyzed. The SIBS of patients with CD at the diagnosis were compared with those after remission. In addition, receiver operator characteristic curve analyses were used to determine the diagnostic accuracy, specificity, and sensitivity of the scores significantly high in the CD group. Results: MLR and SII values were significantly higher in CD patients than in the healthy group (p<0.01). NLR and SII were significantly higher in patients with CD than those with SCS (p<0.05). There were no significant differences between the SCS and the control groups in all SIBS. We determine significant, positive, and moderately correlated findings between SIBS and initial diagnostic tests for hypercortisolism in the CD group (0.30

Assessment of Health-Related Quality of Life in Patients with Idiopathic Hirsutism Compared to Patients with Polycystic Ovary Syndrome.

Objective: Hirsutism affects 5-15% of women of reproductive age. Health-related quality of life (HQOL) is a multidimensional assessment of well-being that considers the physical, social, and emotional aspects associated with a specific disease. The aim of this study is to evaluate HQOL in patients diagnosed with idiopathic hirsutism (IH) and compare it with patients diagnosed with polycystic ovary syndrome (PCOS). Methods: This cross-sectional observational study was performed on 183 female individuals, consisting of 51 patients diagnosed with idiopathic hirsutism, 76 patients diagnosed with PCOS, and 56 healthy volunteers. Participants with a history of neuropsychiatric disorders, under 18 and over 45 years of age, during pregnancy and lactation, with any chronic disease that could interfere with diagnostic laboratory tests, and who had previously been treated for IH or PCOS were excluded from the study. Demographic, anthropometric, laboratory, and clinical data on the cases were recorded. The Short Form-36 (SF-36) questionnaire, the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI) were administered in a face-to-face interview by related authors involved in the study. Results: The mean age, level of education, lifestyle, and marital status of all three groups were similar. There were no significant differences in body mass index (BMI) or waist circumference between the groups. Mean modified Ferriman-Gallwey (mFG) scores were similar in the IH and PCOS groups. In the IH patients, the general health and mental health domains of the SF-36 questionnaire scores were significantly lower than in the control group (p<0.001 and p=0.026, respectively). When the SF-36 questionnaire scores were compared between the IH and PCOS groups, the general health and role emotional domains were significantly lower in the PCOS group (p=0.013 and p<0.001, respectively), and the other domains were similar. All SF-36 questionnaire domains were significantly and negatively correlated with BMI and waist circumference measurements in IH patients. Both BDI and BAI scores were significantly and positively correlated with BMI (r=0.348, p<0.001, and r=0.162, p=0.012, respectively) and waist circumference (r=0.326, p<0.001, and r=0.344, p<0.001, respectively). Six out of eight domains of the SF-36 QOL scores were significantly and negatively correlated with the mFG scores. Conclusion: Patients diagnosed with IH have impaired HQOL, similar to patients diagnosed with PCOS. Improving HQOL should be a goal when deciding on a management approach for hirsutism, which is one of the most common reasons for referral to endocrinology and dermatology outpatient clinics.

The effects of adequate dietary calcium intake in patients with hypoparathyroidism non-adherent to treatment: a prospective randomized controlled trial.

OBJECTIVE: A significant problem that compels clinicians in the conventional treatment of hypoparathyroidism is patients' non-adherence to treatment. This study aimed to evaluate the effects of adequate Ca intake with dietary recommendations among hypoparathyroidism patients who persistently use Ca supplementation irregularly on plasma Ca and phosphate levels. METHODS: This prospective, randomized, controlled study was conducted on patients diagnosed with chronic hypoparathyroidism who persistently interrupt Ca supplementation therapy and therefore have a hypocalcemic course. Patients with a total daily Ca intake below 800 mg were randomized. All patients were advised to keep the doses of active vitamin D and Ca supplements they were currently using. The patients in the study group (n=32) were advised to consume 1,000-1,200 mg of Ca daily, and the patients in the control group (n=35) were advised to continue their diet according to their daily habits. After 12 weeks of follow-up, the patients' laboratory values were compared between groups to assess treatment goals. RESULTS: The mean of the total Ca level was 8.56±0.36 mg/dL in the study group and was found to be significantly higher than that in the control group, which was 7.67±0.48 mg/dL (p<0.001). The mean serum phosphate and serum Ca-P product levels were significantly higher in the study group (p<0.001) but did not exceed the safe upper limits in any patient. CONCLUSION: A suitable increase in dietary Ca intake could effectively control hypocalcemia in patients with hypoparathyroidism who persistently interrupt the recommended calcium supplementation.

Risk Factors, Use of Preventive Drugs, and Cardiovascular Events in Diabetes Mellitus: The PURE Türkiye Cohort.

BACKGROUND: The risk of cardiovascular disease is correlated with the frequency and control of associated risk factors in diabetes mellitus and may vary according to country. We evaluated risk factors for cardiovascular disease, cardiovascular events, and the use of preventive medications in patients with diabetes mellitus using the Prospective Urban and Rural Epidemiological Türkiye cohort. METHODS: Patients with diabetes mellitus versus without diabetes mellitus were compared for risk factors, cardioprotective drugs (angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists, statins, and antiplatelets), and cardiovascular events. The primary outcome was major cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, or heart failure). RESULTS: Among 4041 participants, 549 (13.6%) had diabetes mellitus. The mean age (54.8 ± 8.4 vs. 49.3 ± 9.0 years, P <.001) and proportion of women (65.4% vs. 59.9%, P =.014) were higher in diabetics compared with non-diabetics. Hypertension, history of coronary heart disease, and use of statin, antiplatelets, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists were more common in diabetics; however, the use of these medications at baseline was lower than optimal even in patients with diabetes mellitus and concomitant coronary heart disease (statin 31.2%, antiplatelets 46.9%, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists 54.7%). During 11.5 years of follow-up, major cardiovascular events occurred in 288 (7.1%) patients, and the risk was higher in diabetics [hazard ratio (95% confidence interval) 1.71 (1.30-2.24); P <.001]. The increase in the risk of future events was comparable for those with diabetes mellitus alone without cardiovascular disease [hazard ratio 1.62 (1.20-2.20)] versus those with cardiovascular disease alone without diabetes mellitus [hazard ratio 1.31 (0.83-2.07)] and was additive in those with both conditions [hazard ratio 2.79 (1.65-4.69)]. The risk of major coronary events (myocardial infarction, angina, percutaneous, or surgical coronary intervention) was also higher in diabetes mellitus [hazard ratio 1.64 (1.26-2.15); P <.001]. CONCLUSION: Patients with diabetes mellitus have a higher risk of major cardiovascular events, and the risk is comparable to that observed in those with cardiovascular disease but no diabetes mellitus. The use of preventive medicines for cardiovascular diseases is disturbingly low in diabetics.