Impact of the COVID-19 pandemic on the incidence, seasonal distribution, and characteristics of subacute thyroiditis.

PURPOSE: An increasing number of cases of subacute thyroiditis (SAT) related to the coronavirus disease 2019 (COVID-19) and its vaccines continue to be published. The aim of this study was to investigate any change in the incidence and characteristics of SAT by comparing the pre-pandemic and pandemic periods. METHODS: This retrospective, single-center study included 432 newly-diagnosed SAT patients between January 2018 and December 2021. The annual frequency of SAT was calculated as the number of newly-diagnosed SAT cases divided by the total number of outpatients that year. RESULTS: The frequencies of newly-diagnosed SAT were 0.136% in 2018, 0.127% in 2019, 0.157% in 2020, and 0.114% in 2021 (p = 0.19). While SAT patients were clustered in the autumn (35.1%) in 2018 and 2019, it was found that this cluster shifted to the winter (33.0%) in 2020 and 2021, in parallel with COVID-19 case peaks (p = 0.017). The patients were separated into two groups as pre-COVID-19 pandemic SAT (n = 272) and COVID-19 pandemic SAT (n = 160). The mean ages of the groups were similar. There were more male patients in the COVID-19 pandemic SAT group than in the pre-pandemic group (30.6% vs. 18.7%, p = 0.005). Frequencies of overt hyperthyroidism and median free-thyroxine levels were significantly higher in the COVID-19 pandemic SAT group (p = 0.029, p = 0.001). Treatment modalities, recurrence rates, and permanent hypothyroidism were similar in both groups. CONCLUSION: With the COVID-19 pandemic, although there was a change in seasonal variation of SAT and an increase in the number of male patients, there was no change in the incidence and clinical course of SAT.

Effect of thyroid nodule size on cytology reliability and incidence of malignancy: A large cohort of 1205 patients from a single center.

OBJECTIVE: There is controversy about whether the rates of malignancy and of false-negative malignancy are greater in large nodules. The aim of this study was to determine the reliability of cytology in ≥4cm nodules and to compare malignancy rates between ≥4cm and<4cm nodules. METHODS: The study included 1205 patients who underwent biopsy and subsequent thyroidectomy with the diagnosis of nodular thyroid disease between 2014 and 2019. The patients were separated into two groups, ≥4cm and<4cm, according to the size of the index nodule on ultrasonography. RESULTS: Two hundred and eleven index nodules (17.5%) were ≥4cm. Malignancy rate on definitive pathology was 51% in<4cm nodules and 30% in ≥4cm nodules. Malignancy risk was significantly lower in ≥4cm nodules than <4cm nodules (P<0.001). When<1cm nodules were excluded and 1-4cm and ≥4cm nodules were compared, malignancy risk was also significantly lower in ≥4cm nodules (P=0.001). On definitive pathology, there were 45 false-negative results among cytologically benign nodules. There was no difference in false-negative cytology rate between<4cm and ≥4cm nodules (P=0.209). CONCLUSION: The present study found no decrease in the reliability of cytology in ≥4cm nodules, and there may not be a linear relationship between nodule size and malignancy risk. Therefore, in asymptomatic cytologically benign ≥4cm nodules, surgery may not be recommended based on nodule size alone.

Subacute thyroiditis paranchime heterogeneity may mask thyroid nodules and higher EU-TIRADS scores.

PURPOSE: Nonhomogenous and ill-defined hypoechoic areas are typical ultrasonographic features of subacute thyroiditis (SAT). Evaluating a thyroid nodule accurately in this heterogeneous paranchime may be troublesome. This study aims to compare thyroid nodules, their characteristics, and European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories at the time of the diagnosis and in the remission of SAT. METHODS: Ultrasonographic features of SAT and characteristics and EU-TIRADS categories of thyroid nodules in the initial and control ultrasonography (US) of 350 patients with SAT have been evaluated in this retrospective observational study. Fine needle aspiration biopsy (FNAB) results and postsurgical data, if performed, have been estimated. RESULTS: A hundred patients (28.6%) with SAT had thyroid nodules at the time of the diagnosis, while 152 (43.4%) patients had a nodule in remission US (p < 0.001). The number of thyroid nodules was found to be higher in the control US as against the initial US (p = 0.001). EU-TIRADS scores of the nodules in the remission US were significantly higher than the scores at the time of the diagnosis (p < 0.001). FNAB was performed in 23% of nodules observed in the remission US, and the rate of thyroid carcinoma within them was 3.3%. CONCLUSION: Thyroid nodules, malignancy suspected features, and EU-TIRADS categories of them may not be appropriately evaluated due to heterogenous paranchime of SAT. Performing a control US examination after resolution of hypoechoic areas may be beneficial to avoid missing clinically significant nodules with high EU-TIRADS scores.

HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey.

BACKGROUND: The molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population. METHODS: All diabetic patients (N = 565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n = 46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n = 30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n = 486) and non-diabetic controls (n = 263) were included. Genetic analyses for the HNF1A gene p.S487 N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group. RESULTS: p.S487 N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p > 0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR = 1.68, 95% CI: [1. 21-2.13]; p = 0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR = 1.56, 95% CI: [1. 14-2.57]; p = 0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (ß = 1.45, 95% CI: [1. 2-4.2]; p = 0.036). CONCLUSIONS: The HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.

VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer.

This is the first study to investigate the effect of vitamin D receptor ( VDR) gene single-nucleotide polymorphisms on the clinicopathologic features of papillary thyroid cancer in Turkey. A total of 165 patients with papillary thyroid cancer and 172 controls were included in this case-control study. VDR gene single-nucleotide polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were evaluated using reverse-transcription polymerase chain reaction. VDR gene polymorphisms BsmI, ApaI, and TaqI did not differ between the papillary thyroid cancer group and control group (p > 0.05, each). BsmI, ApaI, and TaqI were not associated with papillary thyroid cancer risk. The VDR gene FokI CT/TT genotype was associated with an increased papillary thyroid cancer risk (CT vs CC: odds ratio = 1.71, 95% confidence interval = 1.15-2.76, p = 0.028; TT vs CC: odds ratio = 2.44, 95% confidence interval = 1.29-4.62, p = 0.005; CT/TT vs CC: odds ratio = 1.88, 95% confidence interval = 1.20-2.96, p = 0.006; CT/CC vs TT: odds ratio = 1.80, 95% confidence interval = 1.05-3.20, p = 0.041). VDR gene polymorphisms were not in linkage disequilibrium. The FokI TT genotype was associated with having T3 and T4, stage III/IV, extra-thyroidal invasion. The FokI CT/TT or TT genotype was associated with developing N1 status, multifocality, tumor size ≥10 mm, and treatment with radioiodine therapy. Persistence/recurrence did not differ between the FokI genotypes. Carriers of the FokI T allele were at an increased risk of more advanced tumor-node-metastasis stage, greater tumor size, multifocality, and extra-thyroidal invasion of papillary thyroid cancer compared with the CC genotype. VDR gene FokI T allele and TT genotype correlated with aggressiveness of papillary thyroid cancer; thus, FokI could be useful as a poor prognostic factor to assess the high risk of papillary thyroid cancer.

The effects of single high-dose or daily low-dosage oral colecalciferol treatment on vitamin D levels and muscle strength in postmenopausal women.

INTRODUCTION: Vitamin D deficiency is a common health problem. Vitamin D supplements are used to improve vitamin D status; however, there are contradictory data related to what doses to give and how often they should be given. Many studies have investigated the effects of vitamin D supplementation on muscle strength, but the results remain controversial. We aimed to compare the effects and safety of single high-dose with daily low-dose oral colecalciferol on 25(OH)D levels and muscle strength in postmenopausal women with vitamin D deficiency or insufficiency. METHODS AND DESIGN: Sixty healthy postmenopausal women who had serum vitamin D levels < 20 ng/mL (50 nmol/L) were enrolled in the study. Group 1 (n = 32) was given daily oral dosages of 800 IU vitamin D3, and group 2 (n = 28) was given a single oral dose of 300,000 IU vitamin D3. Serum vitamin D levels and muscle strengths were measured at the beginning, 4th, and 12th week. Muscle strength tests were performed at 60° using a Biodex system 3 isokinetic dynamometer. RESULTS: Pretreatment vitamin D levels did not differ between the two groups (10.2 ± 4.4 ng/mL (25,4 ± 10,9 nmol/L); 9.7 ± 4.4 ng/mL (24,2 ± 10,9 nmol/L), p > 0.05). A significant increase in vitamin D levels was observed in both groups at 4 and 12 weeks after vitamin D3 treatment. The increase in the single-dose group was significantly higher than the daily low-dosage group at the 4th week (35.9 ± 9.6 ng/mL (89,6 ± 23,9 nmol/L), 16.9 ± 5.8 ng/mL (42,1 ± 14,4 nmol/L), p = 0.01). The increase in the single-dose group was significantly higher than in the daily low dosage group at the 12th week (23.4 ± 4.7 ng/mL (58,4 ± 11,7 nmol/L), 19.8 ± 7.2 ng/mL (49,4 ± 17,9 nmol/L), p = 0.049). The quadriceps muscle strength score increased significantly in the daily group at the 4th week (p = 0.038). The hamstring muscle strength score increased significantly in the daily group at the 12th week (p = 0.037). CONCLUSION: Although daily administration routes are more effective in improving muscle strength, a single administration is more effective in increasing vitamin D levels. TRIAL REGISTRATION NUMBER: ISRCTN14226530 (04.07.2018), Name of the registry: ISRCTN registry, The study was retrospectively registered.

Vitamin D Replacement Improves Tear Osmolarity in Patients with Vitamin D Deficiency.

BACKGROUND: Vitamin D deficiency is a common health problem worldwide. Many parts of the human eye, including the epithelium of the cornea, lens, ciliary body, and retinal pigment epithelium, as well as the corneal endothelium, ganglion cell layer, and retinal photoreceptors, contain vitamin D receptor (VDR). Dry eye is also a common health problem. An adequate tear film is required for maintaining health and function of the eye. Tear hyperosmolarity is considered to be the cause of ocular surface inflammation, symptoms, and tissue damage. It is well-documented that vitamin D has an anti-inflammatory action. We aimed to investigate the effect of vitamin D replacement on tear osmolarity in patients with vitamin D deficiency. METHODS: A total of 44 patients (38 females, six males, mean age:43.5 ± 12.8 years) with vitamin D deficiency currently managed by the Endocrinology and Metabolism Department of Diskapi Training and Research Hospital in Turkey were enrolled in the study. Patients were given 50,000 units of 25(OH)D3 intramuscularly, once weekly, over a period of eight weeks. All of the patients underwent tear function osmolarity (TFO) measurement initially and eight weeks after vitamin D replacement. Demographic, anthropometric, and biochemistry data of patients were recorded. RESULTS: The mean TFO was significantly decreased (313.7 ± 17.3 mOsm/L; 302.7 ± 14.2 mOsm/L, p<0.001) at the end of the second month; 25(OH)D3 concentrations increased from 8.3 ± 3.5 ng/mL to 68.8 ± 22.3 ng/mL (p<0.001). The mean levels of hsCRP, FPG, P were 2.5 ± 2.5 mg/L, 5.09 ± 0.48 mmol/L, 1.06 ± 0.16 mmol/L initially, and 3.8 ± 5.9 mg/L, 5.11 ± 0.68 mg/dL, 1.09 ± 0.16 mmol/L after vitamin D replacement, respectively (p>0.05). The mean Ca level was 2.37 ± 0.07 mmol/L initially and 2.35 ± 0.07 mmol/L after vitamin D replacement (p<0.05). The change of TFO was negatively correlated with the variation of 25(OH)D3 before and after replacement in patients with dry eye disease (r=-0.390, p=0.049). CONCLUSIONS: As a consequence of the presence of VDR and 1α-hydroxylase in different parts of the eye, vitamin D replacement improves tear hyperosmolarity that is considered to be induced by ocular surface inflammation.

Heart-type fatty acid binding protein levels in elderly diabetics without known cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is reported to be higher in elderly diabetics. Serum heart-type fatty acid binding protein (H-FABP) is a serum marker of myocardial ischemia. We aimed to investigate the association between serum H-FABP level and conventional cardiovascular risk factors, inflammatory markers and subclinical atherosclerosis in elderly diabetics without overt CVD. PATIENTS AND METHODS: A total of 50 elderly diabetic patients without overt CVD and 30 age-, sex- and body mass index (BMI)-matched healthy controls were enrolled. Anthropometric and biochemical parameters, serum H-FABP, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and carotid intima-media thickness (CIMT) were measured. Logistic regression analyses (adjustments for age, sex, hypertension, smoking, diabetes, BMI, blood pressure, lipid, blood glucose, hemoglobin A1c, hs-CRP and fibrinogen) were performed to evaluate the association between H-FABP and cardiovascular risk factors and atherosclerosis indices. RESULTS: Serum fibrinogen (421.50±85.52 mg/dL vs 319.17±30.77 mg/dL, p=0.023), CIMT (0.70±0.12 mm vs 0.59±0.06 mm, p<0.001) and hs-CRP (5.72±4.50 mg/dL vs 1.60±0.72 mg/dL, p<0.001) were significantly higher in diabetic patients than controls. The mean serum H-FABP level did not differ between groups (1571.79±604.60 ng/mL vs 1500.25±463.35 ng/mL, p=0.905). H-FABP was positively correlated with fibrinogen (r2=0.473, p<0.001), hs-CRP (r2=0.323, p=0.003) and CIMT (r2=0.467, p<0.001). After full adjustments, the serum H-FABP level was independently associated with an increase in the fibrinogen level (odds ratio [OR] =4.21, 95% confidence level [CI] =1.49-11.90). CONCLUSION: Serum H-FABP was similar in the elderly diabetic patients without known CVD when compared with the nondiabetic control group. H-FABP does not possess a high diagnostic value as a cardiovascular marker when used alone; however, it may add supplementary information in patients with a high fibrinogen level.

Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes?

ABSTRACT Objective This study was designed to compare the serum levels of fibroblast growth factor 23 (FGF23) among patients with gestational diabetes mellitus (GDM) and healthy pregnant women, and to evaluate the association between hormonal and metabolic parameters. Subjects and methods A total of 82 pregnant women were consecutively enrolled in the study. Of these, 46 were diagnosed as having GDM; the remaining 36 healthy pregnant women served as controls in a cross-sectional study design. The womens' ages ranged from 22 to 38 years and gestational ages, from 24 to 28 weeks. Serum samples were analyzed for FGF23 levels using an enzyme-linked immunosorbent assay. Results Serum FGF23 levels were increased in patients with GDM compared with controls (median, 65.3 for patients with GDM vs. 36.6 ng/mL for healthy controls; p = 0.019). Mean fasting glucose (105.6 ± 7.4 vs. 70.2 ± 7.2 mg/dL, p < 0.001), HbA1c (5.6 ± 0.5 vs. 4.9 ± 0.5%, p < 0.001), insulin (median, 11.1 vs. 8.7 µIU/mL, p = 0.006) and HOMA-IR (3.0 (1.8) vs 1.4 (0.6), p < 0.001) levels were significantly higher in patients with GDM than in controls. Serum FGF23 level was positively correlated with body mass index (r2 = 0.346, p < 0.05), FPG (r2 = 0.264, p < 0.05), insulin (r2 = 0.388, p < 0.05), HOMA-IR (r2 = 0.384, p < 0.05). Conclusion Serum FGF23 levels were higher in women with GDM compared with controls. The present findings suggest that FGF23 could be a useful marker of cardiovascular disease in GDM.

Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes?

OBJECTIVE: This study was designed to compare the serum levels of fibroblast growth factor 23 (FGF23) among patients with gestational diabetes mellitus (GDM) and healthy pregnant women, and to evaluate the association between hormonal and metabolic parameters. SUBJECTS AND METHODS: A total of 82 pregnant women were consecutively enrolled in the study. Of these, 46 were diagnosed as having GDM; the remaining 36 healthy pregnant women served as controls in a cross-sectional study design. The womens' ages ranged from 22 to 38 years and gestational ages, from 24 to 28 weeks. Serum samples were analyzed for FGF23 levels using an enzyme-linked immunosorbent assay. RESULTS: Serum FGF23 levels were increased in patients with GDM compared with controls (median, 65.3 for patients with GDM vs. 36.6 ng/mL for healthy controls; p = 0.019). Mean fasting glucose (105.6 ± 7.4 vs. 70.2 ± 7.2 mg/dL, p < 0.001), HbA1c (5.6 ± 0.5 vs. 4.9 ± 0.5%, p < 0.001), insulin (median, 11.1 vs. 8.7 µIU/mL, p = 0.006) and HOMA-IR (3.0 (1.8) vs 1.4 (0.6), p < 0.001) levels were significantly higher in patients with GDM than in controls. Serum FGF23 level was positively correlated with body mass index (r2 = 0.346, p < 0.05), FPG (r2 = 0.264, p < 0.05), insulin (r2 = 0.388, p < 0.05), HOMA-IR (r2 = 0.384, p < 0.05). CONCLUSION: Serum FGF23 levels were higher in women with GDM compared with controls. The present findings suggest that FGF23 could be a useful marker of cardiovascular disease in GDM.

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

BACKGROUND: Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control. METHODS: IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency. RESULTS: Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%). CONCLUSIONS: The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.

PENTRAXIN 3 AS A NEW CARDIOVASCULAR MARKER IN ADRENAL ADENOMAS.

OBJECTIVE: Pentraxin 3 (PTX3) is an acute-phase glycoprotein, which is increased in patients with cardiovascular disease (CVD) and considered as a predictor of CVD in the general population. Both functional and nonfunctional adrenal tumors are associated with a higher risk of cardiovascular events and mortality. We aimed to investigate plasma PTX3 levels in patients with functioning and nonfunctioning adrenal tumors and determine its relationship with cardiovascular risk factors. METHODS: Twenty-one patients with functional adrenal tumors (11 pheochromocytomas, 9 Cushing syndrome, and 1 primary hyperaldosteronism), 28 patients with nonfunctional adrenal incidentalomas, and 40 healthy controls were enrolled in the study. Serum PTX3 levels were measured using a human PTX3 enzyme-linked immunosorbent assay. RESULTS: PTX3 concentrations were significantly higher in the adrenal tumor group compared with the control group (3,001.64 ± 374.64 pg/mL vs. 1,173.59 ± 168.89 pg/mL; P<.001). PTX3 concentrations were positively correlated with carotid intima media thickness (CIMT) (r2, 0.464; P<.001), high-sensitivity C-reactive protein (hsCRP) (r2, 0.551; P<.001), diastolic blood pressure (r2, 0.334; P = .003), systolic blood pressure (r2, 0.312; P = .006), and urinary metanephrine concentrations (r2, 0.320; P = .041). Serum PTX3 concentrations in patients with functional adrenal tumors and comorbidities including hypertension, diabetes mellitus, or CVD were higher than in those without comorbidities (3,654.54 ± 447 pg/mL vs. 1,026.96 ± 447.97 pg/mL; P = .008). CONCLUSION: We found that serum PTX3 concentrations increased in both functional and nonfunctional adrenal tumors. PTX3 levels were correlated with cardiovascular risk factors such as CIMT, hsCRP, and blood pressure. ABBREVIATIONS: BMI = body mass index; CIMT = carotid intima-media thickness; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; FGF2 = fibroblast growth factor 2; hsCRP = high-sensitivity C-reactive protein; PA = primary hyperaldosteronism; PTX3 = pentraxin 3.