Should there be a paradigm shift for the evaluation of isthmic thyroid nodules?

PURPOSE: Although the thyroid isthmus seems like a rudimentary structure that connects bilateral lobes, it is an undiscovered area that needs to be explored. Currently, the data is evolving that the increase in the risk of malignancy is higher in the isthmic nodules, and extrathyroidal extensions and lymph node metastases are more common in isthmic-derived malignant thyroid nodules. Therefore, we aimed to compare the malignancy rate of isthmic and lobar nodules, the ultrasonographic features of isthmic and lobar nodules, and presence of lymph node metastases, distant metastases, and extrathyroidal invasions in malignant isthmic nodules. METHODS: In this retrospective study, we enrolled patients between the ages of 18-80 years, who had thyroid nodule/nodules cytology and/or pathology results from January 2009 to November 2022. 9504 nodules were selected for the analysis of US findings, cytopathology results, and malignancy rates. RESULTS: A mean ± SD age of 55.3 ± 13.0 years with a female to male ratio of [7618 (80.2%)/1886(19.8%)] were included in the study. 962 of the nodules were at isthmic localization; whereas 8542 nodules were at lobar localization. 1188 nodules were resulted as malignant from histopathological evaluation. Of the 1188 malignant nodules, 986 nodules were (83.0%) PTC, 114 nodules (9.6%) were FTC, 55 nodules were (4.6%) MTC, 16 nodules 1.3% were Hurtle cell carcinoma, 8 nodules (0.7%) were anaplastic thyroid carcinoma, and 9 nodules (0.8%) were thyroid tumors of uncertain malignant potential (TT-UMP). 156 of the malignant nodules (13.1%) were located in the isthmus, whereas the majority of the malignant nodules (n = 1032, 86.9%) were located at the lobar parts (right or left) of the thyroid. When the metastasis patterns of isthmic and lobar thyroid cancers were examined, no significant relationship was found between isthmic and lobar cancers in terms of capsule invasion (p = 0.435), muscle invasion (p = 0.294), and lymph node metastasis (p = 0.633). A significant relation was found between nodule localization (isthmus-upper-middle and lower lobes) and malignancy (p < 0.001). In our logistic regression analysis, isthmic and upper pole nodule localizations, age and TI-RADS were evaluated as independent risk factors for malignancy (p < 0.001 for all factors). CONCLUSION: We recommend nodule localization has to be considered an additional risk factor when performing a Fine Needle Aspiration Biopsy for the increased malignancy risk in this localization.

Determination of the Relationship Between the Development and Recurrence of Subacute Thyroiditis and Human Leukocyte Antigen Subtypes.

Background: There are several studies investigating the role of human leukocyte antigens (HLA) in the development and recurrence of subacute thyroiditis (SAT). The HLA subtypes associated with SAT were usually determined in a population-based manner and HLA-B*35, HLA-B*18:01, HLA-C*04:01, and HLA-DRB1*01 were detected to play a role in the disease susceptibility and prognosis. The aim of this study was to determine HLA alleles associated with the tendency of recurrence and prevention of SAT within the Turkish population. Methods: This prospective study was conducted with 51 SAT patients and 720 healthy bone marrow donor volunteers. HLA-A, -B, -C, -DRB1, and -DQB1 were genotyped using next-generation sequencing. Results: The frequency of HLA-A*02:09, HLA-B*35:01/35:02/35:03, HLA-C*04:01, HLA-DRB1*12:01, and DRB1*13:03 were associated with an increased risk of SAT development (Odds Ratio: 22.4, 9.5, 10.3, 4.2, and 3.5, respectively). While HLA-A*02:09, HLA-B*35:01, HLA-B*44:02 HLA-C*07:18, and HLA-C*16:04 were associated with nonrelapsing SAT, HLA-DR*12:01was associated with relapsing SAT. HLA-B*35:02, HLA-B*35:03, and HLA-C*04:01 were more frequent both in relapsing and nonrelapsing groups according to control group. The frequency of HLA-B*18:01, reported as a risk factor previously, was similar in the SAT and control groups (p = 0.959). HLA-DRB1*11:01 was associated with a lower risk of SAT development. Conclusions: Along with -B*358 and -C*04, HLA-A*02:09 was detected as an important risk factor for SAT development in our population. HLA-DRB1*11:01 appears to be the protective HLA subtype against SAT. HLA-A*02:09, HLA-B*35:01, HLA-B*44:02, HLA-C*07:18, HLA-C*16:04, HLA-DQ*06:03, and HLA-DR*12:01 subtypes can establish a tendency to relapsing or nonrelapsing SAT.

Asymptomatic pyuria and bacteriuria are not risk factors for urinary tract infection in women with type 2 diabetes mellitus initiated SGLT2 inhibitors.

PURPOSE: Asymptomatic pyuria and bacteriuria are more prevalent in diabetic patients and may be associated with urinary tract infection (UTI). The aim of this study is to investigate the association between asymptomatic pyuria/bacteriuria at the initiation of SGLT2 inhibitor and UTI risk in female patients with type 2 diabetes. METHODS: The study was designed as a practical, single-center, prospective, cohort study. The female outpatients with type 2 diabetes initiated SGLT2 inhibitor were included. Patients who were symptomatic or treated in the past 3 months for urinary or genital tract infection, had a high risk for UTI were excluded. Hospitalization/antibiotic use for indications other than UTI were exclusion criteria during follow-up. All patients were followed up for 3 months. Pyuria and bacteriuria were exposure and, UTI was the outcome. Cumulative incidence and relative risk of UTI were analyzed for pyuria and bacteriuria. RESULTS: 143 female patients were included among 1132 female type 2 diabetic patients. 13 patients were excluded during follow-up. 41.5% of the patients (n = 54) had pyuria and 28.5% (n = 37) had bacteriuria. The cumulative incidence of UTI was 20% in the whole cohort, 25,9% (n = 14/54) in the pyuria group and 18.9% (n = 7/37) in the bacteriuria group. The relative risk of UTI was 1.64 (95% CI: 0.82-3.26, p = 0.15) for pyuria, 0.92 (95% CI: 0.42-2.01, p = 0.84) for bacteriuria, and 1.2 (95% CI: 0.47-3.08, p = 0.69) for pyuria plus bacteriuria. Adjusted odd ratios revealed similar results. CONCLUSIONS: Asymptomatic pyuria/bacteriuria at the initiation of SGLT2 inhibitors are not risk factors for UTI in women with type 2 diabetes.

Cancer rates and characteristics of thyroid nodules with macrocalcification.

AIMS: The aim of this study was to determine the malignant potential of thyroid nodules with macrocalcifications and to evaluate the role of other sonographic findings in the diagnosis of malignancy in thyroid nodules besides macrocalcifications. METHODS: The findings of 8250 patients who applied to our outpatient clinic and underwent thyroid ultrasonography(US) between 2008 and 2021 were retrospectively reviewed. We included a total of 296 patients with 296 macrocalcified nodules (macrocalcification group) and an age- and sex matched group of 300 patients (control group) with the cytopathologic and/or histopathologic data of fine-needle aspiration biopsy (FNAB) of thyroid nodules without calcification. Demographic characteristics of these patients, US characteristics of the nodules, and thyroid function tests were recorded. Cytopathological data of FNAB were classified according to BETHESDA. RESULTS: The malignancy rate was 14.2% (42/296) in the macrocalcification group and 5.3% (16/300) in the control group (p < 0.001). There was no significant relationship between interrupted peripheral calcification and malignancy. Hypoechoic or markedly hypoechoic appearance, irregular border, solid structure, presence of accompanying pathological lymphadenopathy on sonographic examination and upper and middle zone localization were other sonographic features that increased the risk of malignancy of a nodule. The presence of autoimmunity was not found to be associated with the risk of malignancy. TSH and calcitonin levels of malignant nodules were higher than benign nodules. There was no significant difference between gender and malignancy. In the univariate analysis, it was found that the presence of macrocalcification increased the risk of malignancy 2.935 times. (OR:2.935, p < 0.001.95% CI for OR 1.611-5.349) In addition, being younger, being in the high TIRADS category, and being in the upper and middle zones were factors that increased the risk of malignancy. Gender, TSH level, nodule volume and structure were not associated with malignancy. However, after multivariate analysis, factors that significantly increased the risk of malignancy were younger age, higher TIRADS category, and nodule localization. CONCLUSION: In our study, the malignancy rate was higher in the macrocalcification group than in the control group. However, no correlation was found after multivariate analysis. In the multivariate analysis, younger age, higher TIRADS category, and nodules located in the upper and middle zone were other factors associated with malignancy. There was no association between peripheral interrupted calcification and malignancy risk.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

Combined levothyroxine and testosterone treatment for restoring erectile dysfunction in propylthiouracil-induced hypothyroid rats.

BACKGROUND: Sexual dysfunction may indicate severe endocrine diseases. Recent research has suggested a link between hypothyroidism, low testosterone (T) levels, and erectile dysfunction (ED); however, the exact cause is unknown. AIM: We sought to investigate possible beneficial effects of levothyroxine and T alone or in combination on ED in propylthiouracil (PTU)-induced hypothyroid rats. METHODS: Adult Wistar rats (n = 35) were divided into 5 groups: control, PTU-induced hypothyroidism, PTU + levothyroxine, PTU + Sustanon (a mixture of 4 types of T: propionate, phenylpropionate, isocaproate, and decanoate) and PTU + levothyroxine + Sustanon. PTU was given in drinking water for 6 weeks. Four weeks after PTU administration, levothyroxine (20 µg microgram kg/day, oral) and Sustanon (10 mg/kg/week, intramuscular) were given for 2 weeks. Serum levels of total T, triiodothyronine (T3), and thyroxine (T4) were determined. In vivo erectile response and in vitro relaxant responses were measured. Localization of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and phosphodiesterase type 5 (PDE5) were determined using immunohistochemical analysis. The relative area of smooth muscle to collagen was measured using Masson trichrome staining. OUTCOMES: Outcome variables included in vivo erectile function, in vitro relaxant and contractile responses of corpus cavernosum (CC) strips; protein localization of eNOS, nNOS, and PDE5; and smooth muscle content in penile tissue. RESULTS: The rat model of hypothyroidism showed a significant decline in serum levels of total T, T3, and T4. Levothyroxine increased T3 and T4 levels, whereas Sustanon normalized only total T levels. Combined treatment enhanced all hormone levels. Rats with hypothyroidism displayed the lowest erectile response (P < 0.001 vs controls). Combined treatment returned reduced responses, while partial amelioration was observed after levothyroxine and Sustanon treatment alone. Acetylcholine (P < 0.01 vs controls), electrical field stimulation (P < 0.001 vs controls), and sildenafil-induced relaxant responses (P < 0.05 vs controls) were decreased in the CC strips from hypothyroid rats. The combined treatment increased the reduction in relaxation responses. Levothyroxine and Sustanon restored decreases in eNOS and nNOS expression in the hypothyroid group. There was no significant difference in PDE5 expression among groups. Monotreatment partially enhanced reduced smooth muscle mass, while combined therapy completely recovered. CLINICAL IMPLICATIONS: The combination of thyroid hormones and T is likely to be a therapeutic approach for treatment of hypothyroidism-induced ED in men. STRENGTHS AND LIMITATIONS: Beneficial effects of levothyroxine and Sustanon treatment were shown in vitro and in vivo in PTU-induced hypothyroid rats. The main limitation of the study was the lack of measurement of androgen-sensitive organ weights and luteinizing hormone, follicle-stimulating hormone, and prolactin levels. CONCLUSION: These findings demonstrate that neurogenic and endothelium-dependent relaxation responses are reduced by hypothyroidism, which is detrimental to T levels and erectile responses. Levothyroxine and Sustanon combination medication was able to counteract this effect.

The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism.

BACKGROUND: It has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. METHODS: A total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. RESULTS: In the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. CONCLUSIONS: Vitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Relationship Between Vitamin D Levels and ß Cell Function and Insulin Resistance.

Background This study aimed to determine the relationship between vitamin D levels and ß cell function and insulin resistance in patients with diabetes, glucose tolerance disorder, or impaired fasting glucose. Methodology A total of 75 outpatients (55 females and 20 males) between the ages of 30 and 65 years were included in the study. There were 25 healthy individuals, 25 individuals with prediabetes, and 25 individuals with diabetes. The Homeostasis Model Assessment (HOMA) score was used to evaluate insulin resistance. Results The mean levels of vitamin 25(OH)D among the groups included in the study were 35 ± 16.9 nmol/L in the control group, 44.5 ± 34.5 nmol/L in the prediabetes group, and 35.7 ± 13.1 nmol/L in the diabetes group. There were no significant differences. The mean level of vitamin 1.25(OH)2D3 was 15.95 ± 8 pg/mL in the control group, 18.4 ± 7.5 pg/mL in the prediabetes group, and 21.5 ± 7.9 pg/mL in the diabetes group. While the levels of vitamin 25(OH)D were similar between the groups, the levels of vitamin 1,25(OH)2D3  were significantly higher in the diabetes group. Considering all individuals, no significant difference was found between the vitamin 25(OH)D and glucose levels at minutes 0, 30, 60, 90, and 120. While there was a significant positive relationship between the 1,25(OH)2D3 vitamin and glucose levels at minutes 0, 30, 60, and 90, there was no significant relationship between the levels at minute 120. When the 1,25(OH)2D3 vitamin and HOMA insulin resistance and HOMA ß scores were compared, a significant positive relationship was found between the 1,25(OH)2D3 vitamin and HOMA ß levels. Conclusions In our study, there was no significant difference between the groups (control, prediabetes, and diabetes) in 25(OH)D levels. Similarly, there was no significant relationship between the 25(OH)D levels and insulin sensitivity and resistance between the groups. The positive relationship identified between the 1,25(OH)2D3 vitamin levels and the glucose concentration at minutes 0, 30, 60, and 90 and the higher 1,25(OH)2D3 vitamin levels in the diabetes group compared to the control group in our study can be interpreted as the effort of the organism to prevent glucose-induced ß-cell apoptosis.

Glucagon-like peptide-1 receptor agonist treatment of high carbohydrate intake-induced metabolic syndrome provides pleiotropic effects on cardiac dysfunction through alleviations in electrical and intracellular Ca2+ abnormalities and mitochondrial dysfunction.

The pleiotropic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists on the heart have been recognised in obese or diabetic patients. However, little is known regarding the molecular mechanisms of these agonists in cardioprotective actions under metabolic disturbances. We evaluated the effects of GLP-1R agonist liraglutide treatment on left ventricular cardiomyocytes from high-carbohydrate induced metabolic syndrome rats (MetS rats), characterised with insulin resistance and cardiac dysfunction with a long-QT. Liraglutide (0.3 mg/kg for 4 weeks) treatment of MetS rats significantly reversed long-QT, through a shortening the prolonged action potential duration and recovering inhibited K+ -currents. We also determined a significant recovery in the leaky sarcoplasmic reticulum (SR) and high cytosolic Ca2+ -level, which are confirmed with a full recovery in activated Na+ /Ca2+ -exchanger currents (INCX ). Moreover, the liraglutide treatment significantly reversed the depolarised mitochondrial membrane potential (MMP), increased production of oxidant markers, and cellular acidification together with the depressed ATP production. Our light microscopy analysis of isolated cardiomyocytes showed marked recoveries in the liraglutide-treated MetS group such as marked reverses in highly dilated T-tubules and SR-mitochondria junctions. Moreover, we determined a significant increase in depressed GLUT4 protein level in liraglutide-treated MetS group, possibly associated with recovery in casein kinase 2α. Overall, the study demonstrated a molecular mechanism of liraglutide-induced cardioprotection in MetS rats, at most, via its pleiotropic effects, such as alleviation in the electrical abnormalities, Ca2+ -homeostasis, and mitochondrial dysfunction in ventricular cardiomyocytes.

Determination of the frequency of hyperprolactinemia-related etiologies and the etiology-specific mean prolactin levels.

BACKGROUND: Prolactin (PRL) is a peptide hormone secreted by the anterior pituitary that provides lactation during the postpartum period. The causes of hyperprolactinemia are pituitary tumors, medications, primary hypothyroidism, polycystic ovary syndrome (PCOS), renal failure, idiopathic, and other physiological causes such as pregnancy and lactation. In this study, we aimed to investigate the prevalence of hyperprolactinemia etiologies and the mean/median prolactin levels in different etiologies. METHODS: The patients admitted to our outpatient clinic between January 2009-December 2019 were retrospectively screened from our hospital database with ICD-10 codes. RESULTS: Four hundred patients were included in the study. 69.5% of the patients were women. Their mean age was 43.67±13.42 years, the duration of illness was 7.8±5.6 years. The most frequent causes of hyperprolactinemia were found as follows: 52.5% (n:210) prolactinoma, 7%(n:28) gonadotropinoma, 6.5%(n:26) drug-related, 6.5%(n:25) PCOS, 5.8%(n:23) idiopathic, 5%(n:20) acromegaly, 4.8%(n:19) nonfunctioning adenoma 2.3%(n:9) craniopharyngioma. Patients with gonodotropinoma were significantly older, and the patients with PCOS were significantly younger than the patients with hyperprolactinemia due to the other etiologies. Patients with prolactinoma had significantly higher prolactin levels and longer duration of the illness when compared to other etiologies of hyperprolactinemia (168.00* ng/mL (14-23500 ) [168]; 8* years (0-39 ) [5.00] years respectively, *median values, (min- max levels) and [interquartile range], respectively. There was no significant difference between prolactin levels of other etiologic groups except prolactinoma. Surprisingly, we found PCOS patients with prolactin levels greater than 100 ng/ml and acromegaly or drug-induced hyperprolactinemia with prolactin levels greater than 200 ng/ml. DISCUSSION: In our study, unlike the literature, macroprolactinemia can be seen alone or together with other pathologies. Except for macroprolactinoma, it is not possible to diagnose according to prolactin level. Similar to the literature, prolactinoma was the most common cause of hyperprolactinemia. The causes of hyperprolactinemia, in order of decreasing frequency, were determined to be gonodotropinoma, drug-related, PCOS, idiopathic, and acromegaly. The range of prolactin detected in PCOS is given as new information. It was found that the pediatric group and the adult group had a similar etiology and PRL level. CONCLUSIONS: A large spectrum of physiologic/ pathologic conditions increases the prolactin levels, and prolactin levels may vary from person to person. So, the serum prolactin level alone does not guide a clinical diagnosis or make a differential diagnosis.

Calcitonin levels in washout samples vs. cytology in the detection of malignant lymph node metastasis in recurrent medullary thyroid cancer

Background/aim: Calcitonin level in fine-needle aspirate washout fluid (Ct-FNA) was extensively studied for thyroid nodules and lymph nodes (LN). However, the data was scarce for neck recurrences/metastases of medullary thyroid cancer (MTC). Thus, the diagnostic accuracy of Ct-FNA and cytology in the detection of neck LN metastases of recurrent MTC cases were assessed. Materials and methods: The database of MTC patients between 2010 and 2021 was retrospectively reviewed. A total of 32 patients with recurrent MTC and suspicious LN who underwent FNA and Ct measurement from washout samples were included in this study. Preoperative serum Ct (sCt), Ct-FNA, Ct-FNA/sCt ratio, cytology data were recorded for all participants. Results: Median sCt of 32 patients and Ct-FNA washout fluid levels of operated suspicious 44 LNs were 723 (54­9000) pg/mL and 1800 (151­9500) pg/mL, respectively. The diagnostic accuracy of Ct-FNA washout fluid was greater than cytology (95.4% vs. 86%, respectively). Using a cut-off level of >638.5 pg/mL, the Ct-FNA predicted the diagnosis of LN metastasis of recurrent MTC with a sensitivity of 80% and specificity of 94.9%. Furthermore, using a cut-off level of >1.16, the Ct-FNA/sCt ratio well predicted the diagnosis of LN metastasis of recurrent MTC with a sensitivity of 92.3% and specificity of 100%. Conclusion: As Ct-FNA has greater diagnostic accuracy in our study, it would be complementary to cytology results to localize metastatic LNs in recurrent MTC. Furthermore, for the first time, we demonstrated that the Ct-FNA/sCt ratio was a better predictor of metastatic LNs in recurrent MTC than a particular cut-off for Ct-FNA alone.

The missing link between inflammation and arterial stiffness among different metabolic phenotypes.

OBJECTIVES: Although metabolically healthy obesity (MHO) has begun to be seen as a being benign phenomenon, this conclusion is still not completely certain. Obesity is also associated with low-grade systemic inflammation and endothelial dysfunction. Thus, we aimed to assess Pulse Wave Velocity (PWV) as a marker of arterial stiffness and CV risk among individuals with MHO, metabolically unhealthy obesity (MUO), and metabolically healthy normal-weight (MHN). METHODS: 150 participants (n = 50 MHO, n = 50 MUO, n = 50 MHN) who had been admitted to our outpatient clinics were enrolled in this cross-sectional study. Demographic, anthropometric, clinical, and laboratory data, including hs-CRP and PWV, were recorded for all subjects. RESULTS: hs-CRP and PWV were higher in MUO and MHO than MHN individuals (P < .05). hs-CRP showed a strong positive correlation with PWV (r = 0.85, P < .001). After adjusting for other risk factors, multivariate linear regression analysis showed that the PWV was independently associated with BMI (ß = 0.08, P = .03), WC (ß = 0.04, P = .04) and hs-CRP (ß = 6.08, P < .001). CONCLUSIONS: PWV, which is an important non-invasive marker of cardiovascular risk, is higher in MHO than in MHN as in MUO individuals. Moreover, PWV was positively correlated with the serum hs-CRP level as a conventional marker for systemic inflammation. Thus, MHO can be seen as a cardiometabolic risk marker.

Rates and associates of influenza and pneumococcus vaccination in diabetes mellitus: A nationwide cross-sectional study (TEMD vaccination study).

BACKGROUND: Vaccination against influenza and pneumococcus is effective in reducing morbidity and mortality in patients with diabetes. AIM: To investigate the prevalence of influenza and pneumococcal vaccinations and to search for the independent associates of vaccination in Turkish patients with diabetes. METHODS: In this cross-sectional, nationwide, multicenter study, adult patients with type 1 diabetes (T1DM) (n = 454) and type 2 diabetes (T2DM) (n = 4721), who were under follow-up for at least a year in the outpatient clinics, were consecutively enrolled. Sociodemographic, clinical, and laboratory parameters of patients were recorded. Vaccination histories were documented according to the self-statements of the patients. RESULTS: Patients with T1DM and T2DM had similar vaccination rates for influenza (23.6% vs 21.2%; P = 0.240) and pneumococcus (8% vs 7%; P = 0.451) vaccinations. Longer diabetes duration and older age were the common independent associates of having vaccination for both types of diabetes patients. Higher education level, using statin treatment, and having optimal hemoglobin A1c levels were the common independent associates of influenza and pneumococcal vaccination in patients with T2DM. CONCLUSION: TEMD Vaccination Study shows that patients with T1DM and T2DM had very low influenza and pneumococcal vaccination rates in Turkey. The lower rates of vaccination in certain populations urges the necessity of nationwide vaccination strategies targeting these populations.

The Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer.

The influence of chronic lymphocytic thyroiditis (CLT) on clinicopathological features and behavior of differentiated thyroid carcinoma (DTC) is still debated. In the present study, we aimed to evaluate the prognosis of DTC on the presence of CLT. A total of 649 total thyroidectomized patients (379 female, 270 male) with DTC, who had follow-up data for at least 36 months were included. Clinical, histopathological data, preoperative thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (Tg-ab), thyroid-stimulating hormone (TSH) levels, and presence of recurrent/persistent disease (R/PD) were evaluated retrospectively. Presence of CLT was defined by histopathology. Frequency of CLT was 32% (n = 208) among DTC patients. Mean tumor size (maximal diameter) was smaller in CLT group when compared to non-CLTs (p = 0.006). Capsular invasion, vascular invasion, tumor stage, risk groups, and R/PD were negatively associated with CLT (p < 0.01, p = 0.04, p = 0.03, p = 0.02, p < 0.01, respectively). Extrathyroidal extension was more frequent in non-CLT group when compared CLT (p = 0.052). Preoperative TSH level was positively associated with lymph node metastasis (LNM) and higher in patients with lateral LNM when compared to central LNM (p < 0.01). Central LNM, lateral LNM, stage 4 tumor, and intermediate- and high-risk tumor groups increased the risk of R/PH, 2.5-, 2.9-, 12.7-, 2.3-, and 4.2-fold, respectively. Presence of CLT was independently related with favorable outcomes, as the risk of R/PD was decreased by 0.49-fold. In conclusion, coexistence of CLT was negatively associated with tumor size, capsular invasion, vascular invasion, and tumor stage in DTC. Risk of R/PD was decreased by approximately half in patients with CLT.

Characteristics of patients with hypertension in a population with type 2 diabetes mellitus. Results from the Turkish Nationwide SurvEy of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Hypertension Study).

BACKGROUND: The present survey aimed to find out the demographical and clinical characteristics of patients with hypertension in a population with type 2 diabetes mellitus (T2DM) in Turkey. METHODS: Patients with T2DM who were followed-up in tertiary endocrine units for at least last one year were recruited. Demographic, clinical and biochemical data of the patients were collected. Hypertension was defined as taking anti-hypertensive medications or having office arterial blood pressure (ABP) ≥140/90 mmHg or home ABP ≥ 130/80 mmHg. RESULTS: A total of 4756 (58.9% women) diabetic patients were evaluated. The percentage of patients with hypertension was 67.5% (n = 3212). Although 87.4% (n = 2808) of hypertensive patients were under treatment, blood pressure was on target in 52.7% (n = 1479) of patients. Hypertension proportions were higher in woman (p = 0.001), older, more obese, and those who had longer diabetes duration, lower education levels, higher frequency of hypoglycemic events (all p < 0.001) and higher triglyceride levels (p = 0.003). LDL cholesterol level and the percentage of smokers were lower in hypertensive group than in non-hypertensive group (both p < 0.001). The percentage of macro and microvascular complications was higher in the hypertensive group than in the normotensive one (both p < 0.001). In multivariate logistic regression analysis, being a woman (OR: 1.26, 95% CI: 1.04-1.51, p = 0.016), smoking (OR: 1.38, 95% CI: 1.05-1.80, p = 0.020), regular physical activity (OR: 1.24, 95% CI: 1.01-1.53, p = 0.039) and the presence of macrovascular complications (OR: 1.38 95% CI: 1.15-1.65, p = 0.001) were the significant predictors of good ABP regulation. The ratios of masked and white coat hypertension were 41.2% and 5.7%, respectively. CONCLUSION: Our findings indicate that two-thirds (67.5%) of adult patients with T2DM have hypertension. Co-existence of hypertension increases the frequency of macro and microvascular diabetic complications in these patients. Despite the critical role of hypertension in morbidity and mortality, only half of the patients have favorable ABP levels. Masked hypertension seems to be another important issue in this population.

Progressive Muscle Relaxation and Mindfulness Meditation on Neuropathic Pain, Fatigue, and Quality of Life in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

PURPOSE: To examine the effects of progressive muscle relaxation and mindfulness meditation on the severity of diabetic peripheral neuropathic pain (DPNP), fatigue, and quality of life in patients with type 2 diabetes. DESIGN: An assessor-blinded prospective randomized controlled trial. METHODS: Participants were randomly assigned to the relaxation group (RG; n = 28), meditation group (MG; n = 25), or control group (CG; n = 24). The mean age of participants was 64.2 ± 8.1 years in the RG, 61.6 ± 8.0 years in the MG, and 64.1± 6.6 years in the CG. Patients in the intervention groups performed progressive muscle relaxation or mindfulness meditation at their home for 12 weeks, 20 min daily. The CG received only an attention-matched controlled education on pancreas anatomy and diabetes. Data collection was performed at baseline and at weeks 12 and 14 using the VAS, FACIT Fatigue Scale (FACIT-F), and Neuropathic Pain Impact on Quality of Life Questionnaire (NePIQoL). FINDINGS: VAS scores were significantly lower in the RG and MG at week 12 (p < .05) and were statistically significant in the RG at week 14. Additionally, fatigue severity decreased significantly in the RG at weeks 12 and 14, compared to that in the CG (p < .05). While no significant difference was found in the quality of life scores between the study groups at weeks 12 and 14 (p > .05), a significant improvement in quality of life scores in the RG were provided at week 12 compared to those at baseline and week 14 (p < .05). CONCLUSIONS: Both progressive muscle relaxation and mindfulness meditation had a positive impact on providing pain relief in patients with DPNP. Moreover, progressive muscle relaxation also appeared to have a beneficial effect on fatigue. CLINICAL RELEVANCE: Based on the results, progressive muscle relaxation and mindfulness meditation can be recommended as supportive therapies for the management of DPNP.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Frequency of thyroid nodules and thyroid cancer in thyroidectomized patients with Graves' disease.

INTRODUCTION: Incidental thyroid cancers are frequently detected in patients operated on for Graves' disease (GD). There are no clear data about the incidence and risk factors of incidental thyroid cancer in operated GD patients. The aim of this study is to evaluate the risk of thyroid carcinoma in surgically treated GD patients. MATERIAL AND METHODS: The data of 121 GD patients who underwent total thyroidectomy in a single center between 2005 and 2015 were retrospectively evaluated. The diagnosis of thyroid cancer was based on pathological examination. RESULTS: Thyroid cancer was demonstrated in postoperative pathology specimens of 34 patients who were surgically treated for GD (28.1%). Preoperative thyroid ultrasonography (USG) revealed a nodular goiter in 62 (51.2%) patients. Nodules were not detected in the other 59 (48.8%) patients with GD. The frequency of thyroid cancer was significantly higher in patients with nodules (38% vs. 16%; p = 0.009). Thirty-two of the 34 cancer cases had papillary thyroid cancer (PTC), and the remaining 2 had follicular thyroid cancer (FTC). Of the 32 PTC patients, 28 were classical type, 2 patients had the follicular variant, 1 was the oncocytic variant, and 1 was a tall cell variant. CONCLUSIONS: The incidence of thyroid cancer was higher in patients who underwent surgery for GD. In addition to a careful physical examination in the follow-up of the patients with GD, ultrasonographic evaluation should be performed. Surgical treatment should not be delayed in patients with GD when indicated.

Association of monocyte-to-high density lipoprotein-cholesterol ratio with peripheral neuropathy in patients with Type II diabetes mellitus.

Aim: We assessed the association of monocyte count to high-density lipoprotein cholesterol ratio (MHR) with diabetic peripheral neuropathy (DPN) and its role as a marker for identification of high-risk patients for DPN. Methods: A total of 180 patients with Type II diabetes mellitus (T2DM) were enrolled in the study. MHR, erythrocyte sedimentation rate and serum CRP along with other tests for T2DM and DPN were measured. Results: Duration of T2DM (p = 0.013), insulin use (p = 0.006) and serum CRP levels (p = 0.008) were significantly higher in patients with DPN. MHR was similar between groups (p = 0.447). Duration of diabetes (OR: 1.048; p = 0.038) and the serum CRP levels (OR: 1.073; p = 0.026) were found as independent predictors for the presence of DPN, however, MHR was not. Conclusion: Higher MHR indicates an enhanced inflammation and oxidative stress which was not found to be associated with the presence of DPN.