Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers.

BACKGROUND: Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. METHODS AND RESULTS: In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. CONCLUSIONS: Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study.

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.

Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Thyroid lobectomy in patients with differentiated thyroid cancer: an analysis of the clinical outcomes in a nationwide multicenter study.

BACKGROUND: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcinoma (DTC), but the extent of the thyroidectomy remains controversial. Thyroid lobectomy (TL) has been widely used in eastern countries; however, its use has not been generalized in western countries, including Spain. Our aims were to analyse the clinical outcome of a multicentre nation-wide cohort of DTC patients treated by TL and to assess the proportion of patients who required completion of the thyroidectomy and who presented disease recurrence. METHODS: We retrospectively analyzed patients who underwent TL for DTC and were followed-up for ≥12 months. We collected demographic, clinical, and histopathological data. Dynamic risk stratification (DRS) was performed at 12 months and at last visit. RESULTS: One hundred and sixty-four patients (128 women, mean age 50.8 years, median follow-up 45.4 months) from 9 hospitals were included. There were 158 cases of papillary and 6 of follicular thyroid carcinoma (FTC). Remission of the disease (excellent response) was shown in 71.6% of the patients at 12 months and in 74.4% at the end of follow-up. At that time, there were 34 patients (20.7%) with indeterminate response, 6 (3.7%) with biochemical incomplete response, and 2 (1.2%) with structural incomplete response. Completion of the thyroidectomy was necessary in 8 patients (4.9%), but only 3 of them (1.8%) had disease recurrence. CONCLUSIONS: These results, obtained in real clinical practice, suggest that TL is a safe operative option for selected patients with DTC and that the intensity of the treatment must be tailored according to the presurgical tumor-associated risk, in line with a personalized medicine.

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

INTRODUCCIÓN: El nódulo tiroideo (NT) es un motivo de consulta frecuente en la práctica diaria. El objetivo de este estudio es conocer el proceso diagnóstico y terapéutico del NT en nuestro medio y evaluar el estado actual sobre la existencia y estructura de las consultas de alta resolución de NT. MATERIAL Y MÉTODOS: Los miembros de la Sociedad Española de Endocrinología y Nutrición fueron invitados en el año 2018 a participar en una encuesta online sobre los procesos diagnósticos y terapéuticos del NT. RESULTADOS: Se recibieron 211 encuestas válidas. El 30,8% de los encuestados indicaron que existía consulta de alta resolución de NT en su medio, siendo el endocrinólogo el responsable mayoritario de realizar la ecografía (87,7%) y la punción-aspiración con aguja fina (PAAF) (69,2%). Respecto a la clasificación ecográfica, el 32,7% utilizaban criterios ATA y el 32,2% criterios TI-RADS (el 22,7% no utilizaba ninguna clasificación). El 35,5% comprobaban in situ la idoneidad de la muestra y el análisis molecular en el 8,1%. El 65,4% plantearían alta del NT tras 5 años de seguimiento y PAAF benigna. Ante un Bethesda III, el 50,2% de los encuestados repetirían la PAAF y un 35,5% optarían por cirugía; ante un Bethesda IV, el 95,8% optarían por cirugía. CONCLUSIONES: La consulta de alta resolución de NT es una estructura con una creciente introducción en nuestro medio, siendo el endocrinólogo el responsable fundamental de realizar la ecografía y la PAAF. La práctica clínica habitual en nuestro medio es concordante con la mayoría de las recomendaciones de las guías de práctica clínica de NT

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

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.

La nutrición de yodo en España. Necesidades para el futuro / Iodine nutrition status in Spain Needs for the future

Aunque la nutrición de yodo en España ha mejorado en los últimos años, el problema no está resuelto del todo. Es preciso que las Instituciones sanitarias establezcan medidas para garantizar que la nutrición de yodo de toda la población sea la adecuada, especialmente entre los colectivos de mayor riesgo (niños y adolescentes, mujeres en edad fértil, mujeres embarazadas y madres lactantes). Debe aconsejarse un bajo consumo de sal, pero que esta sea yodada. También es imprescindible que las agencias de control alimentario establezcan un control efectivo sobre una adecuada yodación de la sal. En las futuras encuestas de salud debería incluirse indicadores sobre la nutrición de yodo. El estudio EUthyroid y la Declaración de Cracovia sobre la nutrición de yodo brindan una oportunidad para establecer un plan paneuropeo para la prevención de la deficiencia de yodo que debería ser considerada y aprovechada por las autoridades sanitarias

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

Iodine nutrition status in Spain Needs for the future. / La nutrición de yodo en España. Necesidades para el futuro.

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.

Utility of recombinant human TSH stimulation test in the follow-up of patients with differentiated thyroid cancer depending on basal thyroglobulin results.

Background: Thyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay. Methods: We retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays. Results: rhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85 ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2 ng/mL. Conclusions: Patients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.

Osteoporosis transitoria de cadera en el embarazo / Transient osteoporosis of the hip during pregnancy

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Correction to: Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Réplica: Sobre la profesionalidad en el manejo de los tumores del tiroides y los grupos de trabajo multidisciplinares / Reply letter: On professionalism in the management of thyroid tumors and multidisciplinary working groups

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Características de profesionalidad de los especialistas y ventajas de los equipos multidisciplinares en cáncer de tiroides: resultados de una encuesta de opinión nacional / Characteristics of professionalism of specialists and advantages of multidisciplinary teams in thyroid cancer: results of a national opinion survey

Introducción: En nuestro país no se ha estudiado la opinión de los profesionales sobre los equipos multidisciplinares en cáncer de tiroides. El objetivo de este estudio ha sido conocer la opinión de los especialistas sobre las características de los profesionales y las ventajas que aportan estos estos equipos. Métodos: Se diseñó una encuesta para valorar la opinión sobre las características de profesionalidad y las ventajas de los equipos multidisciplinares para pacientes, profesionales y sistema sanitario. La encuesta se mantuvo activa online del 15 de noviembre de 2017 al 15 de febrero de 2018. Resultados: Se recibieron 226 encuestas. La capacidad para trabajar en equipo fue considerada la característica más importante que deben cumplir los profesionales por el 37,2% de los encuestados, mientras que la competencia científica fue el indicador de profesionalidad más importante para el 37,6%. Más de 2/3 de los especialistas opinan que los equipos multidisciplinares mejoran la elección de tratamientos y procedimientos diagnósticos, reducen la variabilidad clínica, facilitan la implementación de las guías clínicas, mejoran la formación continuada y aumentan la satisfacción de los pacientes, así como el prestigio del hospital. El grado de acuerdo con las ventajas de los EMD fue significativamente superior entre los especialistas que contaban con un EMD en su hospital. Conclusiones: Estos resultados muestran una opinión globalmente muy favorable de los profesionales hacia el modelo de trabajo multidisciplinar. Los responsables de los hospitales y las autoridades sanitarias deberían tener en cuenta estos hechos para favorecer y apoyar la implantación de estos equipos

Introduction: The opinion of professionals about multidisciplinary teams (MDT) in thyroid cancer has not been studied in Spain. This study was intended to ascertain the opinion of specialists about the characteristics of the professionals and the advantages provided by these teams. Methods: A survey was designed to assess the opinion about the characteristics of professionalism and the advantages of MDT for patients, professionals, and the health care system. The survey was posted online from November 15, 2017 to February 15, 2018. Results: A total of 226 surveys were evaluated. The ability for teamwork was considered the most important characteristic to be met by professionals by 37.2% of respondents, while scientific competence was the most important indicator of professionalism for 37.6%. More than two thirds of specialists felt that MDTs improve the choice of treatments and diagnostic procedures, decrease clinical variability, facilitate implementation of clinical guidelines, improve ongoing training, and increase patient satisfaction and hospital prestige. The degree of agreement with the advantages of MDTs was significantly higher among specialists who had a MDT at their hospitals. Conclusions: The overall opinion of professionals on the MDT model is highly favorable. Hospital managers and health care authorities should take these facts into account in order to encourage and support implementation of these teams

Characteristics of professionalism of specialists and advantages of multidisciplinary teams in thyroid cancer: results of a national opinion survey. / Características de profesionalidad de los especialistas y ventajas de los equipos multidisciplinares en cáncer de tiroides: resultados de una encuesta de opinión nacional.

INTRODUCTION: The opinion of professionals about multidisciplinary teams (MDT) in thyroid cancer has not been studied in Spain. This study was intended to ascertain the opinion of specialists about the characteristics of the professionals and the advantages provided by these teams. METHODS: A survey was designed to assess the opinion about the characteristics of professionalism and the advantages of MDT for patients, professionals, and the health care system. The survey was posted online from November 15, 2017 to February 15, 2018. RESULTS: A total of 226 surveys were evaluated. The ability for teamwork was considered the most important characteristic to be met by professionals by 37.2% of respondents, while scientific competence was the most important indicator of professionalism for 37.6%. More than two thirds of specialists felt that MDTs improve the choice of treatments and diagnostic procedures, decrease clinical variability, facilitate implementation of clinical guidelines, improve ongoing training, and increase patient satisfaction and hospital prestige. The degree of agreement with the advantages of MDTs was significantly higher among specialists who had a MDT at their hospitals. CONCLUSIONS: The overall opinion of professionals on the MDT model is highly favorable. Hospital managers and health care authorities should take these facts into account in order to encourage and support implementation of these teams.

Consensus statement for use and technical requirements of thyroid ultrasound in endocrinology units. / Criterios sobre la utilización y requerimientos técnicos de la ecografía tiroidea en los servicios de endocrinología y nutrición.

Thyroid nodule detection has increased with widespread use of ultrasound, which is currently the main tool for detection, monitoring, diagnosis and, in some instances, treatment of thyroid nodules. Knowledge of ultrasound and adequate instruction on its use require a position statement by the scientific societies concerned. The working groups on thyroid cancer and ultrasound techniques of the Spanish Society of Endocrinology and Nutrition have promoted this document, based on a thorough analysis of the current literature, the results of multicenter studies and expert consensus, in order to set the requirements for the best use of ultrasound in clinical practice. The objectives include the adequate framework for use of thyroid ultrasound, the technical and legal requirements, the clinical situations in which it is recommended, the levels of knowledge and learning processes, the associated responsibility, and the establishment of a standardized reporting of results and integration into hospital information systems and endocrinology units.