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Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1–FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1–FGF1 fusion gene was identified in two cases without FN1–FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1–FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1–FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1–FGFR1 and FN1–FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary fibrous tumors (positive in 40%), chondroblastomas (40%), and giant cell tumors of bone (38%), suggesting a possible role for FGFR1 immunohistochemistry in the diagnosis of phosphaturic mesenchymal tumor. With the exception of one case reported in our prior study, none of the remaining tumors resembling phosphaturic mesenchymal tumor had either fusion type or expressed significant FGFR1. Our findings provide insight into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway. The novel FN1–FGF1 protein is expected to be secreted and serves as a ligand that binds and activates FGFR1 to achieve an autocrine loop. Further study is required to determine the functions of these fusion proteins.

Prior cross-sectional analyses have demonstrated an association between subclinical hypothyroidism and metabolic syndrome and selected components. However, the temporal relation between metabolic syndrome and declining thyroid function remains unclear. In a prospective study, an unselected cohort of 66,822 participants with and without metabolic syndrome were followed. A proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs for hypothyroidism. Exploratory analyses for the relation between components of metabolic syndrome and declining thyroid function were also undertaken. During an average follow-up of 4.2 years, the incident rates for subclinical hypothyroidism were substantially higher in participants who began the study with metabolic syndrome compared with metabolically normal controls. After controlling for risk factors, patients with metabolic syndrome were at a 21% excess risk of developing subclinical hypothyroidism (adjusted HR 1.21; 95% CI 1.03–1.42). When individual components were analyzed, an increased risk of subclinical hypothyroidism was associated with high blood pressure (1.24; 1.04–1.48) and high serum triglycerides (1.18; 1.00–1.39), with a trend of increasing risk as participants had additional more components. Individuals with metabolic syndrome are at a greater risk for developing subclinical hypothyroidism, while its mechanisms and temporal consequences of this observation remain to be determined.

The current method of diagnosing diabetes mellitus (DM) using fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) without oral glucose tolerance tests (OGTT) results in inaccuracy and underdiagnosis of diabetes. This study aimed to investigate the mortality of individuals with improperly classified glycemic status and suggest new screening methods for diabetes. A total of 1935 subjects were prospectively followed for 10 years, with vital status obtained through linkage to the National Health Insurance Research Database (NHIRD). Hazard ratios (HR) of all-cause mortality were analyzed. The percentage of all-cause mortality was significantly higher in subjects with improperly classified glycemic status than those correctly classified (8.3% vs. 3.6%, p  = 0.004; unadjusted HR 2.537, p  = 0.002). The risk of mortality associated with underdiagnosis was highest in those over the age of 60 (adjusted HR 2.043, p  = 0.036). Using components of metabolic syndrome, three screening strategies were developed to determine the need for OGTT in elderly subjects with improved sensitivity in diagnosing DM. Diagnosis of diabetes based solely on FPG and HbA1c leads to underdiagnosis of glycemic status and higher all-cause mortality in older adults. Age and the presence of components of metabolic syndrome-based screening strategies can improve diagnostic accuracy and reduce the need for OGTT.

The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. ClinicalTrials.gov: NCT03488134.

Aims/Introduction We sought to determine if postmenopausal women who develop breast cancer are at increased risk of developing diabetes mellitus. Materials and Methods The Taiwan National Health Insurance Research Database was searched from 2001 to 2015 for women aged ≥55 years (postmenopausal) with a diagnosis of primary breast cancer. Participants were age‐matched with women without breast cancer in a 1:5 ratio. Cox proportional hazards analyses were used to examine associations between breast cancer, risk factors and the development of diabetes mellitus. Results A total of 4,607 women with primary breast cancer and 23,035 age‐matched controls without breast cancer were included (mean age 58.6 ± 9.1 years). Adjusting for age, income, urbanization, Charlson Comorbidity Index and medical conditions, the risk of diabetes mellitus for participants with breast cancer at 1, 5, 10 and 15 years was 1.70‐, 1.34‐, 1.27‐ and 1.24‐fold higher, respectively, than for participants without breast cancer (adjusted hazard ratio [aHR] 1.70, 95% confidence interval [CI] 1.40–2.05; aHR 1.34, 95% CI 1.17–1.54; aHR 1.27, 95% CI 1.13–1.44; aHR 1.24, 95% CI 1.11–1.40). The risk of diabetes mellitus at 1 year for breast cancer patients receiving hormone therapy was 1.22‐fold higher than in those not receiving hormone therapy (aHR 1.22, 95% CI 0.86–1.74), but without statistical significance. Conclusions Postmenopausal women with breast cancer are at increased risk of developing diabetes mellitus, independent of receiving hormone therapy, and should be closely monitored to establish an early diagnosis and therapeutic intervention for improving related outcomes. Postmenopausal women who develop breast cancer are at higher risk of developing diabetes mellitus than women in the same age group who do not have breast cancer. Women who have received hormonal therapy for breast cancer show no significantly increased risk for developing diabetes mellitus than those who have not received hormonal therapy. These results suggest that postmenopausal women with breast cancer should be closely monitored for the development of diabetes mellitus to establish an early diagnosis and therapeutic intervention for improving related outcomes.

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = -0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide ( o -BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o -BMVC test of FNA smears is the measurement of the digital number of o -BMVC foci in the nucleus. Thus, there are three categories classified in the o -BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o -BMVC foci, and malignant for more numbers of o -BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o -BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o -BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.

Graves’ disease is the leading cause of hyperthyroidism affecting 1.0–1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves’ disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend P combined =6.75 × 10 −32 ) and HLA-DRB1*08:03 ( P combined =1.83 × 10 −9 ) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13–41.48) and 6.13 (95% confidence interval=3.28–11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 ( P combined =3.32 × 10 −21 , 95% confidence interval=21.66–108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals. Graves’ disease is the leading cause of hyperthyroidism but treatment options can cause life-threatening complications. Chen et al . conduct two-stage direct HLA genotyping and genome-wide association studies to identify HLA-B *38:02 and HLA-DRB1 *08:03 as major pharmacogenetic determinants.

This study examined associations of thyroid hormone levels and insulin resistance (IR) in non-diabetic individuals. Using a cross-sectional design, 2007–2008 data from the National Health and Nutrition Examination Survey (NHANES) were analyzed. NHANES participants ≥20 years of age with complete data of interest were included. The homeostatic model assessment (HOMA) was used to quantify IR, and treated as a continuous variable. Self-reported diabetes or a fasting glucose ≥7 mmol/L were used as criteria to exclude diabetic subjects. Race, liver function, obesity, hypertension, dyslipidemia, smoking, physical activity, vigorous recreational activity, 2-hour glucose, hemoglobin A1C (HbA1C), high-density lipoprotein, triglyceride, vitamin D and C-reactive protein were covariates significantly associated with HOMA-IR. A total of 1,560 non-diabetic subjects were included in the analysis. When adjusted for all factors significant in the univariate analysis (race, liver function, obesity, hypertension, dyslipidemia, smoking, physical activity, vigorous recreational activity, 2-hour glucose, HbA1C, high-density lipoprotein, triglyceride, vitamin D, and CRP) low total triiodothyronine (TT3) and low free T3 (FT3) were significantly associated with decreased HOMA-IR (adjusted coefficient = −0.486, 95% confidence interval [CI]: −0.936, −0.036; adjusted coefficient = −1.151, 95% CI: −1.952, −0.350, respectively). Insulin resistance is associated with low thyroid hormone levels in non-diabetic individuals.

This pilot, randomized, open-label controlled study compared the basal–bolus regimens of insulin glargine (IG) and neutral protamine Hagedorn (NPH) insulin in stroke patients with hyperglycemia receiving intensive care. The study recruited acute stroke patients requiring intensive care within 72 h (h) of onset and had blood glucose > 200 mg/dL. 50 patients received IG (n = 26) or NPH (n = 24) with added short-acting prandial regular insulin over a 72-h period. The primary end point was the percentage of glucose within 80–180 mg/dL assessed through continuous glucose monitoring. The baseline characteristics were comparable, except the IG had higher glucose pre-randomization than the NPH (290.69 ± 82.31 vs. 246.04 ± 41.76 mg/dL, P  = 0.021). The percentage of time with glucose between 80 and 180 mg/dL was 45.88 ± 27.04% in the IG and 53.56 ± 22.89% in the NPH ( P  = 0.341) and the percentage of glucose reduction was 31.47 ± 17.52% in the IG and 27.28 ± 14.56% in the NPH ( P  = 0.374). The percentage of time with glucose < 60 mg/dL was 0.14 ± 0.49% in the IG and 0.47 ± 1.74% in the NPH. Poststroke outcomes were not significantly different. In conclusion, IG is safe and equally effective as an NPH-based basal-bolus regimen for acute stroke patients with hyperglycemia receiving intensive care. Trial registration ClinicalTrials.gov, NCT02607943. Registered 18/11/2015, https://clinicaltrials.gov/ct2/show/NCT02607943 .