Diagnosis and treatment of thyroid nodules in Spain. Results of a national survey. / Diagnóstico y tratamiento del nódulo tiroideo en España. Resultados de una encuesta nacional.

INTRODUCTION: Thyroid nodule (TN) is a common reason for consultation in daily practice. The purpose of this study was to evaluate the diagnosis and treatment of TNs in our environment and to assess the current status regarding the existence and structure of high-resolution TN clinics. MATERIAL AND METHODS: Members of the Spanish Society of Endocrinology and Nutrition were invited in 2018 to participate in an online survey on the diagnostic and therapeutic processes of TN. RESULTS: A total of 211 valid surveys were received. Of all respondents, 30.8% stated that there were high-resolution TN clinics in their environment, with the endocrinologist being the main person responsible for performing ultrasonography (87.7%) and fine needle aspiration (FNA) (69.2%). For ultrasound classification of TNs, 32.7% used the ATA criteria, 32.2% the TI-RADS criteria, and 22.7% no classification. In situ verification of sample suitability was performed in 35.5% of the cases, and molecular analysis in 8.1%. With regard to clinical discharge, 65.4% would consider it after 5 years of follow-up and with a benign FNA. In the event of a Bethesda III result, 50.2% of respondents would repeat FNA and 35.5% would opt for surgery; if a Bethesda IV result was found, 95.8% would opt for surgery. CONCLUSIONS: High-resolution TN clinics are structures increasingly implemented in our environment where the endocrinologist is the main person responsible for performing ultrasonography and FNA. The standard clinical practice in our specialty is consistent with most recommendations concerning clinical practice guidelines for TNs.

Breaking Therapeutic Inertia in Type 2 Diabetes: Active Detection of In-Patient Cases Allows Improvement of Metabolic Control at Midterm.

Type 2 diabetes (T2D) exists in 25-40% of hospitalized patients. Therapeutic inertia is the delay in the intensification of a treatment and it is frequent in T2D. The objectives of this study were to detect patients admitted to surgical wards with hyperglycaemia (HH; fasting glycaemia > 140 mg/dL) as well as those with T2D and suboptimal chronic glycaemic control (SCGC) and to assess the midterm impact of treatment modifications indicated at discharge. A total of 412 HH patients were detected in a period of 18 months; 86.6% (357) had a diagnosed T2D. Their preadmittance HbA1c was 7.7 ± 1.5%; 47% (189) had HbA1c ≥ 7.4% (SCGC) and were moved to the upper step in the therapeutic algorithm at discharge. Another 15 subjects (3.6% of the cohort) had T2D according to their current HbA1c. Ninety-four of the 189 SCGC patients were evaluated 3-6 months later. Their HbA1c before in-hospital-intervention was 8.6 ± 1.2% and 7.5 ± 1.2% at follow-up (P < 0.004). Active detection of hyperglycaemia in patients admitted in conventional surgical beds permits the identification of T2D patients with SCGC as well as previously unknown cases. A shift to the upper step in the therapeutic algorithm at discharge improves this control. Hospitalization is an opportunity to break therapeutic inertia.

Regenerating gene Iα is a biomarker for diagnosis and monitoring of celiac disease: a preliminary study.

The regenerating gene (REG) is a multigene family in humans that plays a role in tissue regeneration. The REG Iα protein is expressed in the pancreas and the gastrointestinal tract and is involved in the pathophysiology of gastritis, pancreatitis, cancer, inflammatory bowel disease, and type 1 diabetes (T1D). Celiac disease (CD) is an autoimmune disease caused by the ingestion of gluten in genetically susceptible individuals. Our aim was to determine whether the serum REG Iα concentration reflects the destructive/regenerative process in the small bowel in CD. REG Iα was determined by enzyme-linked immunosorbent assay (ELISA) in 40 patients with active CD, and in 19 of them, REG Iα was assessed after following a gluten free diet. As controls, 35 healthy subjects were included in the study. Autoantibodies to transglutaminase, gliadin, and endomisium were measured also. We found a significant increase in REG Iα in the sera of CD patients when compared with controls. REG Iα levels decreased after a gluten-free diet together with a significant reduction in antitransglutaminase antibodies. T1D and pernicious anemia patients displayed normal serum REG Iα concentrations. This preliminary study suggests that REG Iα protein levels can be used as a biomarker for the diagnosis and monitoring of CD.

Analysis of the cumulative changes in Graves' disease thyroid glands points to IFN signature, plasmacytoid DCs and alternatively activated macrophages as chronicity determining factors.

Graves' disease (GD) is a chronic autoimmune process in the thyroid gland and involves IFN and IFN driven immune activation. Assuming the thyroid gland is the main site stimulating the autoimmune response, we investigated the role of IFNs and other factors in the chronic evolution of GD by comparing the transcriptomic profiles of thyroid glands from short clinical course (SC), long clinical course (LC) cases, and control glands (C). Over 200 differentially expressed genes of the immune system were identified. Results were extensively analyzed bioinformatically and validated by qPCR in 31 glands. The analysis indicated that GD involved a progressive accumulation of changes with clearly distinct profiles in the SC and LC glands. Humoral response, antigen presentation and chemokines & cytokines were overall the most represented gene ontology categories in LC cases. Ingenuity Pathway Analysis pointed to a few inflammatory pathways in SC cases whereas LC cases involved numerous complex pathways, such us "communication between innate and adaptive immune cells" and "autoimmune thyroid signaling". A broad IFN signature consisted of the over-expression of 74 and 84 type I and type II IFN responsive genes respectively (overall 96 out of 211, 45%), but many of these genes can also be directly activated through cytoplasmic viral receptors. For the first time, plasmocytoid dendritic cells were identified in GD thyroid, but surprisingly, the main producers of IFN-alpha were cells with a myeloid cell phenotype. In addition, cells with the phenotype of alternatively activated macrophages were detected in abundance in GD thyroids, confirming data from the transcriptomic analysis. Collectively, these results confirmed the role of IFNs, suggested other natural immunity triggers, identified new cell types in the local disease process, and expanded our knowledge of the processes that may determine the chronicity of GD.

A prospective study of cardiovascular disease in patients with Type 2 diabetes. 6.3 years of follow-up.

OBJECTIVE: Type 2 diabetes mellitus (DM-2) is an important cardiovascular risk factor, although hardly any data are available in our country. Therefore, we decided to study the incidence of cardiovascular disease (CVD) and the related variables with its appearance in a group of patients with DM-2. RESEARCH DESIGN AND METHODS: 176 DM-2 patients without CVD at baseline (63.6% women, mean age 54+/-8.9), mean follow-up 6.3 years. We collected data at 6-month intervals concerning new micro- and macrovascular complications, glucose, HbA(1C), lipid profile, and renal function. We analyzed values at baseline and at the end of follow-up. For numeric variables, the mean value during follow-up was calculated. In renal function variables, we also worked out the difference between baseline and final values, considering the time until the first episode of CVD as the independent variable. Kaplan-Meier analysis was used in categorical variables and Cox regression tests for numeric data and also for multivariate analysis. In multivariate analysis, we included significant data in the univariate analysis, excluding those from the end of the follow-up with the aim of having some predictive meaning in our results. RESULTS: New episodes of CVD were detected in 28 patients (15.9%). These events were statistically related with baseline diagnosed hypertension, presence of diabetic nephropathy and retinopathy, HbA(1C), and total cholesterol. Among mean values during follow-up, the association was with HbA(1C), cholesterol, urinary albumin excretion rate (UAER), glomerular filtration rate (GFR), and systolic arterial pressure. There was also a relationship of CVD events with the new appearance or worsening of diabetic retinopathy or nephropathy, creatinine and UAER increase and the decrease of GFR and effective renal plasma flow (ERPF), during follow-up. In the multivariate analysis, we found an independent association with the appearance of CVD and mean HbA(1C), mean UAER and the presence of proliferative diabetic retinopathy at baseline. CONCLUSIONS: We have a rather low incidence of CVD in our patients with DM-2. The appearance of CVD is independently related with HbA(1C), the level of UAER, and the presence at baseline of diabetic retinopathy.