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.

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.

Evaluation of chronic pruritus and associated skin findings in patients with diabetes mellitus.

Background/aim: To explore the dermatological lesions associated with chronic pruritus in patients who were followed up at our clinic for type 1 and type 2 diabetes mellitus (DM). Materials and methods: The study population consisted of 249 patients with DM, who presented to the endocrinology clinic at Ankara University Faculty of Medicine between January 2022, and March 2022, regardless of whether they had reported experiencing pruritus symptoms. The visual analog scale and 5-D itch scale were used to determine the severity of itching in patients. Dermatological examination findings were also evaluated. Results: Of the 249 patients with DM, mean duration since diabetes was diagnosed was 12 ± 9.2 [median 10 (0.3-46)] years, and the mean HbA1c levels were 8.1% ± 2.1%. Pruritus was detected in 77 (30.9%) patients and the mean duration of diabetes diagnosis was 13.4 ± 9.7 years. Examination of the microvascular and macrovascular complications showed that the incidence of retinopathy, nephropathy, neuropathy and peripheral arterial disease was 31.2% (p = 0.003), 31.2% (p = 0.005), 66.2% (p < 0.001) and 10.4% (p = 0.038), respectively, in the group with pruritus. These incidences were significantly higher in the group with pruritus than in those without pruritus. Dermatological examination showed that the most common condition was xerosis (64%), followed by fungal skin infection (16%) and bullous pemphigoid (8%). No skin findings were noted in 7% of patients who complained of itching. Conclusion: Chronic pruritus may be associated with several factors such as poor glycemic control, high BMI and microvascular and macrovascular complications in patients with DM. Especially in patients with severe generalized pruritus who do not respond to standard antipruritic treatments, the use of DPP-4 inhibitors, a class of oral antidiabetic agents, should be questioned and all medications being used by the patient should be reviewed.

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.

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.

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.

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.

Are thyroid nodules with spongiform morphology always benign?

OBJECTIVE: Fine needle aspiration (FNA) biopsy for evaluation of spongiform nodules ≥20 mm or observation without FNA was recommended by American Thyroid Association. However, this was a weak recommendation supported by moderate quality evidence. We aimed to assess malignancy risk in spongiform nodules. METHODS: From January 2015 to June 2016, an experienced endocrinologist performed B-mode greyscale ultrasonography and observed 96 spongiform nodules among 3748 ultrasound procedures. Power Doppler ultrasonography and ultrasound-guided FNA were performed to 96 spongiform nodules. Both colour elastography and strain ratio measurements of dominantly solid areas were performed. RESULTS: All spongiform nodules had benign cytology. Fifty-two (54.2%) nodules were ≥20 mm and 44 (45.8%) were smaller than 20 mm in maximum diameter. Presence of ultrasonography features related to malignancy was rare; 2% (n = 2) microcalcification, 9.4% (n = 9) taller than wide shape and 2% (n = 2) marked central blood flow were noted. None of the nodules had two or more suspicious features. Ultrasound elastography findings revealed that dominantly solid components of nodules were usually soft as 66.7% had an elasticity score 1 according to colour scale and mean strain ratio was 1.39 ± 0.99. CONCLUSIONS: Follow-up with ultrasonography seems to be an efficacious method even for spongiform nodules larger than 2 cm. Determination of soft appearance according to colour map on ultrasound elastography and low strain ratio values of dominantly solid areas may be useful to avoid unnecessary biopsies.

Diagnostic accuracy of parathyroid hormone levels in washout samples of suspicious parathyroid adenomas: A single-centre retrospective cohort study.

INTRODUCTION: Minimally invasive surgery is an alternative surgical approach for primary hyperparathyroidism with less surgical trauma and anaesthesia complications. When combined with intraoperative measurement of parathyroid hormone (PTH), cure rates are exceeding 97%. Preoperative intact PTH determination in washout samples is really very useful when parathyroid lesions cannot be easily distinguished from thyroid lesions or sometimes lymph nodes. Herein, we aimed to report our institutional experience about parathyroid fine-needle aspiration (FNA) method and suggest a cut-off ratio for this purpose. METHODS: In our clinic, we performed ultrasonography (USG)-guided parathyroid FNA procedure for 131 patients diagnosed with primary hyperparathyroidism between January 2005 and January 2016. Both cytologic evaluation and intact PTH determination were performed in washout samples. Eighty-seven of the study group also had a parathyroid scintigraphy. Both demographic features and laboratory results were all recorded. RESULTS: Median serum PTH level was 142 (113-197), while mean PTH washout level was 1824 (0-3953). When three of the localization techniques are compared with each other, FNA-PTH washout group had a better diagnostic accuracy (90.8%) when compared to cytology (7.92%) and MIBI (67.8%) groups. Both MIBI and FNA-PTH washout group had 100% positive predictive value (PPV) and 100% specificity. We found values greater than 436.5 pg/mL for FNA-PTH washout with a sensitivity of 90.3% and specificity of 88.9% (P < 0.01 and AUC 94.3 (87.8-100)) and a cut-off for FNA/serum PTH greater than 3.05 with a sensitivity of 91.2% and specificity of 89% (P = 0.02 and AUC 94.5 (88.8-100)) which implicate parathyroid lesions. CONCLUSION: According to the literature, PTH determination in washout samples has a specificity of 75%-100% and sensitivity of 70%-100%. This approach has better results than both cytology and scintigraphy in case of concomitant multinodular thyroid disease in experienced hands. Although there is not a definite cut-off for PTH levels in washout samples, we agree with the need of ratios rather than cut-offs in this issue.

Association between circulating irisin levels and epicardial fat in patients with treatment-naïve overt hyperthyroidism.

BACKGROUND: Hyperthyroidism is associated with increased metabolic activity and thermogenesis. Irisin is a key molecule in thermogenesis and energy expenditure via adipose tissue browning. Epicardial fat was previously defined as brown-like fat. Thus, here we aimed to evaluate the association between serum irisin level and epicardial fat thickness (EFT) in patients with hyperthyroidism. METHODS: A total of 25 hyperthyroid patients and 24 age-, sex- and BMI-matched healthy controls were enrolled. Serum irisin levels, thyroid hormone levels, and body compositions were compared. EFT was measured via transthoracic echocardiography. RESULTS: Serum irisin level and EFT were significantly higher in the hyperthyroid group (p < 0.001 and p = 0.001, respectively). The distributions of fat-free mass, muscle mass and fat mass were similar between the study groups. Serum irisin level was negatively correlated with TSH (p < 0.001) and positively correlated with fT3 (p < 0.001), fT4 (p < 0.001) and TSH receptor antibody (p = 0.002) levels and EFT (p = 0.001). In multivariate linear regression analysis, TSH (ß = -0.475, p < 0.001) and EFT (ß = 0.290, p = 0.023) levels were significantly associated with serum irisin levels. CONCLUSIONS: An increased serum irisin level associated with EFT might contribute to metabolic derangement in hyperthyroidism. Further studies are needed to elucidate whether irisin levels and EFT are affected by hyperthyroidism or vice versa.

Is primary hyperparathyroidism a cause of endothelial dysfunction?

OBJECTIVE: Symptomatic primary hyperparathyroidism (PHPT) is thought to be related to increased cardiovascular morbidity and mortality. In our study, we aimed to investigate endothelial dysfunction and markers of subclinical atherosclerosis in patients with PHPT. Also we aimed to demonstrate the effect of vitamin D supplementation on these parameters. MATERIALS AND METHODS: Twenty-nine patients followed by medical treatment (A), 25 preoperative (B) and 23 postoperative patients with PHPT (C), and 26 normocalcaemic subjects (D) were included. Groups were assessed by measurements of flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), serum levels of sCD40L, high-sensitivity CRP (hs-CRP) and interleukin-8 (IL-8). Thirteen patients with low levels of 25-hydroxy-vitamin D (25OHD) in the medical treatment group were assessed before and 3 months after vitamin D replacement. RESULTS: The median FMD was 5% in group A, 5.1% in group B, 7.6% in group C and 7.7% in group D. The FMD measurement in group A was significantly lower than groups C and D (P=.02) and was similar to the FMD measurement in group B. FMD measurements of group B were not significantly lower than groups C and D. In 13 patients with low 25OHD in group A, the median FMD increased to 7.07% from 4.71% after vitamin D replacement (P=.02). CONCLUSION: Flow-mediated dilation was impaired in patients with PHPT, particularly in the medically observed group. Vitamin D supplementation seems to provide improvements in FMD in medically observed PHPT patients with low 25OHD levels, and this was the novel observation of our study.

DISCORDANCE BETWEEN GH AND IGF-1 LEVELS IN TURKISH ACROMEGALIC PATIENTS.

OBJECTIVE: Discordance between insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels is an important problem in the follow-up of patients diagnosed with acromegaly. Our aims were to evaluate the discordance between IGF-1 and GH levels and compare the performance of different cut-off levels for the nadir in GH (GHn) in acromegalic patients. METHODS: The study included 63 acromegalic patients in a follow-up at a tertiary care university hospital facility. Levels of IGF-1, IGF binding protein-3 (IGFBP-3), and GH were investigated. The baseline GH and GHn levels were evaluated after an oral glucose tolerance test (cut-offs of 0.4 and 1 ng/mL, respectively). The discordance rates between GHn and IGF-1 levels, and IGF-1/IGFBP-3 ratios were determined. RESULTS: We first adopted a GHn cut-off value of 1 ng/mL and found that 27 patients (42.9%) exhibited biochemical remission (BR) (IGF-1 <95th percentile, GH <1), and 25 patients (39.7%) had no BR (NBR) (IGF-1 ≥95th percentile, GH >1). Discordance in the presence of normal IGF-1 and nonsuppressed GH (DC1) occurred in 2 of 63 (3.2%) patients; discordance in the presence of high IGF-1 and suppressed GH (DC2) occurred in 9 of 63 (14.3%) patients. If the GHn cut-off value adopted was 0.4 ng/mL, the distributions were 17 of 63 (27.0%) patients in BR, 29 of 63 (46.0%) patients in NBR, 12 of 63 (19.0%) in DC1, and 5 of 63 (7.9%) patients in DC2. If only the baseline GH values were considered, the distributions were very similar to those with a GHn cut-off value of 0.4 ng/mL. The IGF-1/IGFBP-3 ratio was lowest in the BR group. CONCLUSION: Adopting a GHn cut-off value of 0.4 ng/mL did not increase the test performance compared with baseline GH only. In contrast, in the follow-up of acromegalic patients, the IGF-1/IGFBP-3 ratio might be a useful measurement when discordance between IGF-1 and GH levels occurs. We propose that these values be considered in clinical practice. ABBREVIATIONS: BR = biochemical remission DC1 = discordance group 1 DC2 = discordance group 2 DM = diabetes mellitus GH = growth hormone GHn = nadir in GH IGF-1 = insulin-like growth factor-1 IGFBP-3 = IGF binding protein-3 LAR = long-acting release NBR = not in biochemical remission OGTT = oral glucose tolerance test.

Acute suppurative thyroiditis following fine-needle aspiration biopsy in an immunocompetent patient.

The thyroid gland is remarkably resistant to infectious agents owing to several protective mechanisms. Acute suppurative thyroiditis after fine-needle aspiration (FNA) in an immunocompetent patient is very rare. We report the case of a 50-year-old immunocompetent male patient who presented with painful cervical swelling, fever, and chills after an FNA of the thyroid. His physical and laboratory examination suggested an acute suppurative thyroiditis. Repeat FNA results were consistent with thyroid abscess. Physicians should be aware of the probability of acute bacterial thyroiditis after FNA.

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.

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.

Common human leucocyte antigensassociated with the development of subacute thyroiditis and COVID-19.

PURPOSE: Case reports of subacute thyroiditis (SAT) following coronavirus disease-19 (COVID-19) have been reported. Because the relationship between SAT and human leucocyte antigen (HLA) alleles is known, we aimed to determine HLA alleles that may predispose a patient to coronavirus infection and/or post-COVID-19 SAT. METHOD: This retrospective study was conducted in 51 patients with SAT and 190 healthy bone marrow donor volunteers. HLA-A, -B, -C, -DRB1, and -DQB1 were genotyped using next-generation sequencing. The study population was grouped into four groups according to SAT and COVID-19 history. RESULTS: The frequency of HLA-DQB1*04:02 was higher in the COVID-19(-) participants than in the COVID-19(+) participants (=0.045). The presence of HLA-DQB1*04:02 was associated with a lower risk of developing COVID-19 in all groups. The frequencies of HLA-B*35:01, HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were different in the SAT(+) group than in the SAT(-) group in COVID-19(-) group. The frequencies of HLA-C*12:03, HLA-DQB1*06:04, HLA-DRB1*13:02, and HLA-DRB1*13:03 were different in the SAT(+) group than in the SAT(-) group in the COVID-19 (+) group. The difference in the frequency of these HLA types remains significant when the four groups are included together as follows: In the COVID-19(+) group, the frequencies of HLA-DRB1*13:02, and HLA-DRB1*13:03 were higher in the SAT(+) group than in the SAT(-) group. In the COVID-19(-) group, the frequencies of HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were higher in the SAT (+) group than in the SAT(-) group. CONCLUSION: HLA alleles associated with SAT susceptibility may vary with COVID-19 history.

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.

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.