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1.
Artigo em Inglês | MEDLINE | ID: mdl-31606735

RESUMO

OBJECTIVE: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013. PARTICIPANTS: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration. EVIDENCE: This evidence-based Consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities. CONSENSUS PROCESS: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system. CONCLUSIONS: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31606738

RESUMO

OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: 1) glucose levels < 100 mg/dL and 2) glucose levels > 100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, HOMA-IR, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.

3.
Obes Surg ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31346930

RESUMO

INTRODUCTION: miRNAs are small non-coding RNAs, some of which are expressed in adipose tissues, are present in the circulation, and are regulated in obesity. Bariatric surgery (BS) has been proposed to lead to activation of brown adipose tissue, an effect that may be related to beneficial effects of BS on systemic metabolism. Here, we evaluated circulating levels of miR-92a and miR-99b, two miRNAs proposed as biomarkers of brown fat activity, in a cohort of patients with severe obesity before and after BS, and studied their potential relationship with BS-associated improvements in metabolic parameters. METHODS: Circulating levels of miR-92a and miR-99b were quantified in a cohort of 26 patients (age, 48 ± 10 years; BMI, 45 ± 7 kg/m2) before and 6 months after BS. Clinical parameters were determined at different time points and correlations among them were studied. RESULTS: Basal levels of miR-92a were significantly increased in patients with obesity relative to lean controls. Serum miR-92a levels were strongly reduced at 6 months after BS, reaching levels similar to those in controls. Serum miR-99b levels were unchanged in relation to both the obese condition and BS. Elevated levels of miR-92a were directly correlated with worsened glucose homeostasis parameters and poor BS outcome. CONCLUSIONS: Our findings show that miR-92a is elevated in conditions of obesity, and its reduction after BS correlates with metabolic improvement. Further studies would be necessary to establish miR-92a as serum biomarker and potential predictor of the BS success in improving the metabolic status of patients with obesity.

4.
Cardiovasc Diabetol ; 18(1): 93, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324183

RESUMO

BACKGROUND: Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes. METHODS: We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis. RESULTS: During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7. CONCLUSIONS: The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.

5.
Eur J Endocrinol ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319379

RESUMO

OBJECTIVE: Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. DESIGN: We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. METHODS: We used Sanger sequencing, quantitative real time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. RESULTS: We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro functioning corticotroph tumors (all p<0.05). Moreover, we found a positive correlation between PC2 and CPE gene and protein expression (rho≥0.670, p<0.009) in silent corticotroph tumors compared with functioning ones. CONCLUSIONS: By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro functioning corticotroph tumor behaving as an intermediate state between micro functioning and silent corticotroph tumors.

6.
Clin Nutr ; 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30948220

RESUMO

BACKGROUND & AIMS: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. METHODS: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. RESULTS: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. CONCLUSIONS: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes.

7.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30962160

RESUMO

Although iodine nutrition in Spain has improved in recent years, the problem is not completely resolved. It is necessary that health institutions establish measures to ensure an adequate iodine nutrition of the population, especially among the highest risk groups (children and adolescents, women of childbearing age, pregnant women and nursing mothers). A low salt intake should be advised, but it should be iodized. It is also imperative that food control agencies establish effective control over adequate iodization of salt. Indicators on iodine nutrition should be included in future health surveys. The EUthyroid study and the Krakow Declaration on iodine nutrition provide an opportunity to set up a pan-European plan for the prevention of iodine deficiency that should be considered and used by health authorities.

8.
Clin Nutr ; 38(6): 2740-2746, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30616882

RESUMO

BACKGROUND & AIMS: There is no consensus on the best method for nutritional screening and assessment in patients with heart failure (HF). This study aimed to determine which nutritional assessment method had the highest prognostic significance for patients with HF treated in outpatient clinics. We also aimed to identify a fast, reliable screening method for detecting malnutrition in these patients. METHODS: This prospective study included 151 subjects that attended an outpatient HF clinic at a university hospital. All patients completed three nutritional screening tools: the Malnutrition Universal Screening Tool (MUST), the MNA-short form (MNA-SF), and the Malnutrition Screening Tool (MST), and then, two nutritional assessment questionnaires: the Subjective Global Assessment (SGA) and the Mini Nutritional Assessment®(MNA). Patients were followed-up for 2 years. The primary endpoint was all-cause mortality. RESULTS: Malnutrition or nutritional risk was identified in 15.9% of patients with the SGA and in 25.1% of patients with the MNA. Age, New York Heart Association (NYHA) functional class, and MNA were the only independent all-cause death predictors after adjusting for age, gender, NYHA functional class, body mass index, Barthel index, 25-hydroxyvitamin D concentrations, treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, and treatment with beta-blockers. The SGA could not independently predict all-cause mortality in a multivariate analysis that included the same covariates. The MNA-SF had the best sensitivity, specificity, and kappa coefficient for screening malnutrition, based on the MNA and the SGA as references, compared to the other screening methods. CONCLUSIONS: In our cohort, malnutrition assessed by MNA, but not by SGA, was an independent predictor of mortality. MNA-SF showed remarkable sensitivity and specificity; thus, it might be a valuable tool for rapidly identifying malnutrition risk in outpatients with HF.

11.
Endocrinol. diabetes nutr. (Ed. impr.) ; 65(8): 428-437, oct. 2018.
Artigo em Espanhol | IBECS | ID: ibc-176283

RESUMO

Objetivos: Buscar consenso sobre cuestiones que pueden generar dudas en el manejo de la acromegalia en España. Método: Grupos nominales y Delphi. Se seleccionaron 4 expertos que definieron cuestiones relevantes en el manejo de la acromegalia sobre las que se formularon distintas aseveraciones y recomendaciones. Posteriormente, se eligió un grupo de 30 expertos adicionales con el que se determinó el grado de acuerdo con las mismas en 2 rondas Delphi. Se establecieron las siguientes categorías de respuesta: 1) totalmente en desacuerdo; 2) básicamente en desacuerdo; 3) básicamente de acuerdo; y 4) totalmente de acuerdo. Se definió acuerdo si, en la segunda ronda Delphi≥70% de las respuestas estaban en las categorías 1 y 2 (consenso con el desacuerdo) o 3 y 4 (consenso con el acuerdo). Resultados: Se generaron aseveraciones y recomendaciones sobre diversos aspectos de la práctica clínica incluyendo: 1) instrumentos de utilidad en la individualización del tratamiento (marcadores predictivos de respuesta, técnicas de imagen, etc.); 2) perfiles clínicos y comorbilidades en la individualización del tratamiento; 3) papel del paciente en la toma de decisiones terapéuticas; y 4) acceso al tratamiento (accesibilidad y equidad). La primera ronda Delphi incluyó 35 aseveraciones, en 6 se alcanzó consenso, 2 fueron eliminadas y 2 reformuladas. En la segunda se incluyeron 27 y se alcanzó consenso en 24 (22 en el acuerdo, 2 en el desacuerdo) y 3 se eliminaron. Conclusiones: Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones en el manejo de la acromegalia


Objectives: To seek a consensus on issues that may generate doubts in management of acromegaly in Spain. Method: Nominal groups and Delphi. Four experts defined relevant issues in management of acromegaly and generated different assertions and recommendations. Subsequently, a group of 30 additional experts was selected to test agreement with the assertions through two Delphi rounds. The following response categories were established: 1) Totally disagree; 2) Basically disagree; 3) Basically agree; 4) Totally agree. Agreement was defined as ≥70% of answers in categories 1 and 2 (consensus with the disagreement) or 3 and 4 (consensus with the agreement) in the second Delphi round. Results: Assertions covers various aspects of clinical practice, including: 1) Useful instruments in individualization of treatment (response predictive markers, imaging techniques, etc.); 2) Clinical profiles and relevant comorbidities in treatment individualization; 3) Role of patient in treatment decision-making; 4) Access to treatments (accessibility and equity). The first Delphi round included 35 assertions. Consensus was reached on six of these assertions, two were eliminated, and two were reformulated. Of the 27 assertions included in the second round, consensus was reached on 24 (22 in the agreement, two in the disagreement) and three were eliminated. Conclusions: This document is intended to solve some common clinical questions and to facilitate decision making in the management of patients with acromegaly


Assuntos
Humanos , Acromegalia/tratamento farmacológico , Tomada de Decisão Clínica , Somatostatina/uso terapêutico , Acromegalia/fisiopatologia , Biomarcadores , Comorbidade , Participação do Paciente , Pesquisa Qualitativa , Conferências de Consenso como Assunto
12.
Endocrinol Diabetes Nutr ; 65(8): 428-437, 2018 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30244765

RESUMO

OBJECTIVES: To seek a consensus on issues that may generate doubts in management of acromegaly in Spain. METHOD: Nominal groups and Delphi. Four experts defined relevant issues in management of acromegaly and generated different assertions and recommendations. Subsequently, a group of 30 additional experts was selected to test agreement with the assertions through two Delphi rounds. The following response categories were established: 1) Totally disagree; 2) Basically disagree; 3) Basically agree; 4) Totally agree. Agreement was defined as ≥70% of answers in categories 1 and 2 (consensus with the disagreement) or 3 and 4 (consensus with the agreement) in the second Delphi round. RESULTS: Assertions covers various aspects of clinical practice, including: 1) Useful instruments in individualization of treatment (response predictive markers, imaging techniques, etc.); 2) Clinical profiles and relevant comorbidities in treatment individualization; 3) Role of patient in treatment decision-making; 4) Access to treatments (accessibility and equity). The first Delphi round included 35 assertions. Consensus was reached on six of these assertions, two were eliminated, and two were reformulated. Of the 27 assertions included in the second round, consensus was reached on 24 (22 in the agreement, two in the disagreement) and three were eliminated. CONCLUSIONS: This document is intended to solve some common clinical questions and to facilitate decision making in the management of patients with acromegaly.

13.
Nutrients ; 10(9)2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158448

RESUMO

Medical nutrition therapy is an important part of the management of type 1 diabetes mellitus (T1DM). Proper adherence to a healthy diet may have a favorable impact on diabetes management and its diabetic complications. Our aim was to assess differences in food and nutrient intake of type 1 diabetic patients with and without diabetic retinopathy (DR). This was a two-center, cross-sectional study in patients with T1DM, with and without DR. Subjects were recruited from the outpatient clinic of the two participating centers. A validated food frequency questionnaire was administered. A total of 103 T1DM patients with DR and 140 T1DM patient without DR were recruited. Subjects with DR showed a lower intake of total fat (p = 0.036) than that of their non-DR counterparts. DR was associated with increasing age (p = 0.004), hypertension (p < 0.001), and diabetes duration (p < 0.001), however there was a negative association with high educational level (p = 0.018). The multivariate-adjusted analysis showed that the intake of complex carbohydrates was positively related to the presence of DR (p = 0.031). In contrast, the intakes of total fat (p = 0.009), monounsaturated fatty acids (MUFAs) (p = 0.012), oleic acid (p = 0.012), and vitamin E (p = 0.006) were associated with the absence of DR. As conclusions, the intake of total MUFAs, oleic acid, and vitamin E is associated with a lower frequency of DR in patients with T1DM. These results suggest a potential protective effect of these lipid components for DR.

14.
Eur J Nutr ; 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30019088

RESUMO

PURPOSE: We aimed to assess food intake and adherence to the Mediterranean Diet in patients with T1D compared with nondiabetic individuals. METHODS: This was an observational, multicenter study in 262 T1D subjects and 254 age- and sex-matched nondiabetic subjects. A validated food-frequency questionnaire was administered. The alternate Mediterranean Diet Score (aMED) and alternate Healthy Eating Index (aHEI) were assessed. The clinical variables were also collected. The analysis of data included comparisons between groups and multivariate models. RESULTS: Compared to the controls, the patients with T1D had a higher intake of dairy products (p < 0.001), processed meat (p = 0.001), fatty fish (p = 0.009), fruits and vegetables (p < 0.001), nuts (p = 0.011), legumes (p < 0.001), potatoes (p = 0.045), and bread (p = 0.045), and a lower intake of seafood (p = 0.011), sweets (p < 0.001), and alcohol drinks (p = 0.025). This intake pattern resulted in a higher consumption of complex carbohydrates (p = 0.049), fiber (p < 0.001), protein (p < 0.001), polyunsaturated fatty acids (PUFA) (p = 0.007), antioxidants (p < 0.001), vitamins (p < 0.001), and minerals (p < 0.001). The frequency of patients with T1D and low aMED score (23.2%) was lower than that of the controls (35.4%; p = 0.019). The overall multivariate analysis showed that, among other factors, being a T1D subject was associated with improved aMED and aHEI scores (p = 0.006 and p < 0.001). In patients with T1D, residing in a nonurban area was associated with improved aMED and aHEI scores (p = 0.001 and p < 0.001). CONCLUSIONS: Adult patients with T1D showed healthier dietary habits and a higher adherence to the Mediterranean Diet than nondiabetic subjects. Residing in a nonurban area is associated with an improved dietary pattern.

15.
Atherosclerosis ; 276: 50-57, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30032025

RESUMO

BACKGROUND AND AIMS: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) and diabetes. Traditional cardiovascular risk factors fail to fully account for the increase in cardiovascular risk in these patients. This study aims to analyse the prevalence and progression of subclinical atherosclerosis in CKD patients with and without diabetes. METHODS: We included data from CKD patients with and without diabetes free from previous cardiovascular events from the NEFRONA cohort. Patients underwent baseline and 24-month follow-up carotid and femoral ultrasound examinations. Multivariable models were used to assess the contribution of diabetes to the presence and plaque progression. RESULTS: A total of 419 patients with diabetes and 1129 without diabetes were included. Diabetic patients were older, had higher BMIs, more hypertension and dyslipidaemia. At baseline, the proportion of patients with plaque was higher among diabetic patients (81.4% vs. 64.1%, p < 0.001). Diabetic patients more frequently had more than two vascular territories with plaque (64.4% vs. 48.4%, p < 0.001). Multivariable analysis indicated that plaque at baseline was significantly associated with age, gender, smoking and renal replacement therapy (RRT) in the non-diabetic patients, but only with age and male gender in diabetic patients. Plaque progression was significantly associated with age, number of territories with basal plaque, smoking and RRT in both groups. CONCLUSIONS: Subclinical atherosclerosis is more prevalent, carries a higher plaque burden and is more rapidly progressive in renal patients with diabetes. In these patients, diabetes outweighs other described risk factors associated with the presence of subclinical atherosclerosis.

16.
Cardiovasc Diabetol ; 17(1): 66, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728117

RESUMO

BACKGROUND: Cardiovascular (CV) disease due to atherosclerosis is a major cause of morbidity and mortality in adult patients with diabetes, either type 1 or type 2 diabetes. The aim of the study was to assess the association of the frequency and the burden of subclinical carotid atherosclerotic disease in patients with type 1 diabetes according to the presence and severity of diabetic retinopathy (DR). METHODS: A cross-sectional study was conducted in 340 patients with type 1 diabetes (41.5% with DR), and in 304 non-diabetic individuals. All participants were free from previous CV disease and chronic kidney disease (CKD). B-mode carotid ultrasound imaging was performed in all the study subjects. Patients with type 1 diabetes underwent a full eye examination, and DR patients were divided into two groups: mild disease and advanced disease. RESULTS: In the group of patients with type 1 diabetes, the percentage of patients with carotid plaques was higher in those with DR compared with those without DR (44.7% vs. 24.1%, p < 0.001). Patients with DR also presented a higher incidence of ≥ 2 carotid plaques (25.5% vs. 11.1%, p < 0.001). Apart from other traditional cardiovascular risk factors, the presence of advanced stages of DR was independently associated with the presence (p = 0.044) and the burden (≥ 2 carotid plaques; p = 0.009) of subclinical carotid atherosclerosis. CONCLUSIONS: In patients with type 1 diabetes without previous CV disease or established CKD, the presence of advanced stages of DR is associated with a higher atherosclerotic burden in the carotid arteries. The presence of DR identifies patients at risk for carotid atherosclerotic disease.

17.
Thyroid ; 28(5): 601-612, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29635968

RESUMO

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Unlike most cancers, its incidence has dramatically increased in the last decades mainly due to increased diagnosis of indolent PTCs. Adequate risk stratification is crucial to avoid the over-treatment of low-risk patients, as well as the under-treatment of high-risk patients, but the currently available markers are still insufficient. Kallikreins (KLKs) are emergent biomarkers in cancer, but their involvement in PTC is unknown. METHODS: This study analyzed DNA methylation (HumanMethylation arrays) and gene expression (RNA-Seq) of KLKs, BRAF and RAS mutations, and clinical data from four published thyroid cancer data sets including normal and tumor tissues (n = 73, n = 475, n = 20, and n = 82) as discovery, training, and validation series. The C4.5 classification algorithm was used to generate a decision tree. Disease-free survival was estimated using Kaplan-Meier and Cox approaches. Specific analyses were performed using real-time polymerase chain reaction and immunohistochemistry. RESULTS: The entire KLK family was deregulated in PTC, displaying a specific epigenetic and transcriptional profile strongly associated with BRAFV600E or RAS mutations. Thus, a decision-tree algorithm was developed based on three KLKs with >80% sensitivity and >95% specificity, identifying BRAF- and RAS-mutated tumors. Notably, tumors lacking these mutations were classified as BRAF- or RAS-like. Most importantly, the KLK algorithm uncovered a novel PTC subtype showing favorable prognostic features. CONCLUSIONS: The KLK algorithm could lead to a new clinically applicable strategy with important implications for the risk stratification of PTC and the management of patients.

18.
Endocrinol Diabetes Nutr ; 65(2): 107-113, 2018 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29396214

RESUMO

There is currently no consensus among the different scientific societies on screening for thyroid dysfunction in the first trimester of pregnancy. Indeed, diagnosis and treatment of subclinical hypothyroidism during pregnancy are controversial, as no cut-off value for thyrotropin (TSH) is universally accepted. TSH measurement may be influenced by different factors throughout pregnancy, but especially during the first trimester. The association between overt hypothyroidism during pregnancy and obstetric and perinatal complications is well established. It is also accepted that thyroid hormones are important for neurodevelopment of the offspring. However, there is no scientific evidence available about the impact of subclinical hypothyroidism and its treatment during the first trimester of pregnancy on children's neurodevelopment. In recent years, studies conducted in the offspring of mothers with subclinical hypothyroidism have reported new biochemical parameters which may eventually serve as biomarkers of offspring neurodevelopment and which are more reproducible and are measured at an earlier time than the conventional clinical tests.

19.
Clin Endocrinol (Oxf) ; 88(5): 728-734, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29453792

RESUMO

OBJECTIVE: An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal-maternal complications with first trimester maternal Thyrotropin (TSH) values. DESIGN: A retrospective study in a single tertiary care hospital was performed. PATIENTS: A total of 1981 pregnant women were studied during 2012. MEASUREMENTS: Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal-maternal complications and newborn health parameters. RESULTS: Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10 (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR 1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by mother's age. There was no association with the other outcomes analysed. CONCLUSIONS: There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.

20.
Endocrinol. diabetes nutr. (Ed. impr.) ; 65(2): 107-113, feb. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-171952

RESUMO

There is currently no consensus among the different scientific societies on screening for thyroid dysfunction in the first trimester of pregnancy. Indeed, diagnosis and treatment of subclinical hypothyroidism during pregnancy are controversial, as no cut-off value for thyrotropin (TSH) is universally accepted. TSH measurement may be influenced by different factors throughout pregnancy, but especially during the first trimester. The association between overt hypothyroidism during pregnancy and obstetric and perinatal complications is well established. It is also accepted that thyroid hormones are important for neurodevelopment of the offspring. However, there is no scientific evidence available about the impact of subclinical hypothyroidism and its treatment during the first trimester of pregnancy on children's neurodevelopment. In recent years, studies conducted in the offspring of mothers with subclinical hypothyroidism have reported new biochemical parameters which may eventually serve as biomarkers of offspring neurodevelopment and which are more reproducible and are measured at an earlier time than the conventional clinical tests (AU)


En la actualidad no existe un consenso entre las diferentes sociedades científicas para la detección de la disfunción tiroidea en el primer trimestre del embarazo. De hecho, el diagnóstico y tratamiento del hipotiroidismo subclínico durante el embarazo es controvertido, ya que no se acepta universalmente el valor límite para la tirotropina (TSH). La determinación de TSH puede estar influenciada por diferentes factores durante todo el embarazo, pero especialmente durante el primer trimestre. La asociación entre el hipotiroidismo clínico durante el embarazo y las complicaciones obstétricas y perinatales está bien establecida. También se acepta que las hormonas tiroideas son importantes para el desarrollo neurológico del feto. Sin embargo, falta evidencia científica sobre el impacto en el neurodesarrollo infantil del tratamiento del hipotiroidismo subclínico en el primer trimestre de gestación. En los últimos años, los estudios realizados en hijos de madres con hipotiroidismo subclínico han descrito nuevos parámetros bioquímicos que eventualmente pueden servir como biomarcadores del neurodesarrollo fetal, siendo más reproducibles y pudiendo determinarse en un período anterior al de las pruebas clínicas clásicas (AU)


Assuntos
Humanos , Feminino , Gravidez , Hipotireoidismo/terapia , Hipotireoidismo/diagnóstico , Primeiro Trimestre da Gravidez , Tireotropina , Mortalidade Perinatal , Sociedades Científicas/normas , Biomarcadores , Período Pós-Parto/metabolismo
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