Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Results of a nationwide survey on multidisciplinary teams on thyroid cancer in Spain.

AIM: There is an important lack of knowledge as to the functioning of multidisciplinary teams on thyroid cancer in current clinical practice. We aimed to retrieve data on the composition, structure, and procedures developed by the multidisciplinary units of thyroid cancer in Spain. METHODS: A nationwide survey consisting of questions about composition, structure, and functioning of multidisciplinary teams was designed. It was available online from November 15, 2017 to February 15, 2018. RESULTS: Seventy-two multidisciplinary units responded to our survey. Of these, 15 (20.8%) focused only in thyroid cancer, while 57 (79.2%) included other endocrine disorders or non-endocrine tumors. The median (interquartile range) of members of the teams was 11 (9-14). The most frequent medical specialties in the units were endocrinology (100%), surgery (94.4%), pathology (80.6%), radiology (75.0%), nuclear medicine (73.6%), and medical oncology (55.6%). The annual number of patients reviewed by the teams was 40 (20-74). 56.9% of the multidisciplinary teams have elaborated clinical protocols for local use. Apart from clinical case discussions in the meetings, 45.8% of the units included educational activities and 36.1% research subjects. Quality indicators were developed by 22% of the teams. CONCLUSIONS: These results suggest that there are some hopeful signs that international recommendations of having multidisciplinary approach to patients with thyroid cancer are being followed in Spain. This gives us the opportunity to proceed with further studies to analyze the real impact of this high standard of care on patient outcomes.

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years.

Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI).

Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.

Consensus on management of advanced medullary thyroid carcinoma on behalf of the Working Group of Thyroid Cancer of the Spanish Society of Endocrinology (SEEN) and the Spanish Task Force Group for Orphan and Infrequent Tumors (GETHI).

BACKGROUND: Of all thyroid cancers, <5 % are medullary (MTC). It is a well-characterized neuroendocrine tumor arising from calcitonin-secreting C cells, and RET gene plays a central role on its pathogeny. METHODS: The electronic search was conducted using MEDLINE (PubMed), EMBASE and Cochrane Central Register of Controlled Trials. Quality assessments of selected current articles, guidelines and reviews of MTC were performed. RESULTS: This consensus updates and summarizes biology, treatment and prognostic considerations of MTC. CONCLUSIONS: Multidisciplinary teams and specialized centers are recommended for the management of MTC patients. In the metastatic setting, those patients with large volume of disease are candidates to start systemic treatment mainly if they are symptomatic and the tumor has progressed in the last 12-14 months. Wait and see strategy should be offered to patients with: disseminated disease with only high levels of calcitonin and no macroscopic structural disease, low burden and absence of progression.

Comments to SEOM clinical guidelines for the treatment of thyroid cancer

No disponible

Body mass index classification misses subjects with increased cardiometabolic risk factors related to elevated adiposity.

CONTEXT: Body mass index (BMI) is widely used as a measure of overweight and obesity, but underestimates the prevalence of both conditions, defined as an excess of body fat. OBJECTIVE: We assessed the degree of misclassification on the diagnosis of obesity using BMI as compared with direct body fat percentage (BF%) determination and compared the cardiovascular and metabolic risk of non-obese and obese BMI-classified subjects with similar BF%. DESIGN: We performed a cross-sectional study. SUBJECTS: A total of 6123 (924 lean, 1637 overweight and 3562 obese classified according to BMI) Caucasian subjects (69% females), aged 18-80 years. METHODS: BMI, BF% determined by air displacement plethysmography and well-established blood markers of insulin sensitivity, lipid profile and cardiovascular risk were measured. RESULTS: We found that 29% of subjects classified as lean and 80% of individuals classified as overweight according to BMI had a BF% within the obesity range. Importantly, the levels of cardiometabolic risk factors, such as C-reactive protein, were higher in lean and overweight BMI-classified subjects with BF% within the obesity range (men 4.3 ± 9.2, women 4.9 ± 19.5 mg l(-1)) as well as in obese BMI-classified individuals (men 4.2 ± 5.5, women 5.1 ± 13.2 mg l(-1)) compared with lean volunteers with normal body fat amounts (men 0.9 ± 0.5, women 2.1 ± 2.6 mg l(-1); P<0.001 for both genders). CONCLUSION: Given the elevated concentrations of cardiometabolic risk factors reported herein in non-obese individuals according to BMI but obese based on body fat, the inclusion of body composition measurements together with morbidity evaluation in the routine medical practice both for the diagnosis and the decision-making for instauration of the most appropriate treatment of obesity is desirable.

Manejo de los corticoides en la práctica clínica / No disponible

Los corticoides son ampliamente utilizados por muy diversas especialidades.Sin embargo su uso no está exento de complejidad. Elmanejo adecuado de estos fármacos requiere tener nociones básicasde fi siopatología y conocer bien las características del corticoide que sepretende emplear: sus equivalencias, vida media en sangre, potenciaglucocorticoide y mineralcorticoide relativa o tipo de acción tisular delpreparado. Los efectos secundarios son frecuentes y pueden llegar a sergraves, por lo que con frecuencia deben tomarse medidas para minimizarlos.En los casos en los que se administren dosis suprafi siológicasdebe evaluarse adecuadamente el estado del eje hipofi so-adrenal altérmino del tratamiento(AU)

Corticoids are massively utilised by specialists in different areas. However,their use is not free of complexity. The adequate management ofthese compounds involves having basic notions of pathophysiology andfamiliarity with the characteristics of the particular corticoid that is goingto be used. This knowledge should include the equivalences between thedifferent corticoids, their plasma half life, the relative biological activityor their mineral- or gluco- corticoid action. Corticoid-related side effectsare a frequent complication and may be severe; therefore it is usuallynecessary to associate prophylactic measures in order to minimize them.The pituitary-adrenal axis should be adequately assessed at the end ofthe treatment when supra-physiologic doses are used(AU)

Relationship between thyroid-stimulating hormone and insulin in euthyroid obese men.

BACKGROUND/AIMS: Obesity has been associated with hypothyroidism and impaired insulin sensitivity. However, few studies have specifically addressed the association between insulin sensitivity and thyroid function. Our aim was to look for a relation between these 2 factors in a sample of obese males. METHODS: One hundred and forty-four euthyroid male obese patients--mean age 42.6 years, mean body mass index (BMI) 41.8--were enrolled in this cross-sectional study. The hospital study protocol at entrance included baseline serum thyroid-stimulating hormone (TSH), insulin and glucose concentrations. Data were studied using an age-adjusted simple and multivariate linear regression analysis with TSH as the dependent and insulin and BMI as the independent variables. RESULTS: Mean TSH and insulin were 1.6 and 21.2 mU/l, respectively. It was found that their relationship follows a regression model: TSH=1.725-0.019 (age) + 0.003 (insulin) + 0.017 (BMI). Further data showed a positive correlation between BMI and TSH (r= 0.22; p<0.05), as well as between serum baseline insulin (>10 mU/l) and TSH concentration (r=0.27; p<0.05). This association was stronger in patients with higher insulin values (>21.2 mU/l; r=0.40; p<0.01). However, negative correlations between age and insulin (r= -0.14; not significant) and age and TSH (r= -0.35; p<0.05) were observed. CONCLUSIONS: In obese males, insulin resistance is significantly related with impairment of thyroid function, and this situation seems to be attenuated with age.

Utilidad clínica de los anticuerpos antitiroideos / No disponible

La determinación de anticuerpos antitiroideos es parte importante dela evaluación del paciente con enfermedad tiroidea y su presencia seasocia con la reacción infl amatoria del tiroides. La mayor utilidad demedir anticuerpos anti-peroxidasa (TPO) es el diagnóstico de enfermedadautoinmune del tiroides, concretamente tiroiditis de Hashimoto.Los anticuerpos contra TPO también son una herramienta importanteen la evaluación de la mujer antes y después de la gestación. Los anticuerposcontra la tiroglobulina (Tg) deben determinarse a la par quelas mediciones de Tg en el seguimiento de los pacientes con cáncerdiferenciado de tiroides. Los anticuerpos contra el receptor de TSH puedenser estimuladores o bloqueadores. Los primeros son característicosde la enfermedad de Graves. Concentraciones elevadas de anticuerposcontra TSH después del tratamiento con fármacos antitiroideos indicanun alto riesgo de recidiva(AU)

Measurement of thyroid autoantibodies is an important component inevaluating patients with thyroid disease, since their presence is associatedwith infl ammatory thyroid reaction. The main utility of measuringanti-peroxidase (TPO) antibodies is to diagnose autoimmune thyroiddisease, specifi cally Hashimoto’s thyroiditis. TPO antibodies are alsoa useful tool in the evaluation and assessment of women before andafter pregnancy. Thyroglobulin (Tg) antibodies should be determinedwith every serum Tg measurement during the follow-up of patients withdifferentiated thyroid carcinoma. Antibodies against the TSH receptor(TSHR) may be stimulating or blocking. The former are characteristicof Graves’ disease. High TSHR antibody levels after antithyroid drugtreatment indicate a high risk of relapse(AU)

Utilidad clínica de los anticuerpos antitiroideos / Clinical utility of thyroid autoantibodies

La determinación de anticuerpos antitiroideos es parte importante de la evaluación del paciente con enfermedad tiroidea y su presencia se asocia con la reacción infl amatoria del tiroides. La mayor utilidad demedir anticuerpos anti-peroxidasa (TPO) es el diagnóstico de enfermedad autoinmune del tiroides, concretamente tiroiditis de Hashimoto. Los anticuerpos contra TPO también son una herramienta importanteen la evaluación de la mujer antes y después de la gestación. Los anticuerpos contra la tiroglobulina (Tg) deben determinarse a la par que las mediciones de Tg en el seguimiento de los pacientes con cáncerdiferenciado de tiroides. Los anticuerpos contra el receptor de TSH pueden ser estimuladores o bloqueadores. Los primeros son característicos de la enfermedad de Graves. Concentraciones elevadas de anticuerposcontra TSH después del tratamiento con fármacos antitiroideos indican un alto riesgo de recidiva

Measurement of thyroid autoantibodies is an important component in evaluating patients with thyroid disease, since their presence is associated with infl ammatory thyroid reaction. The main utility of measuringanti-peroxidase (TPO) antibodies is to diagnose autoimmune thyroid disease, specifi cally Hashimoto’s thyroiditis. TPO antibodies are also a useful tool in the evaluation and assessment of women before andafter pregnancy. Thyroglobulin (Tg) antibodies should be determined with every serum Tg measurement during the follow-up of patients with differentiated thyroid carcinoma. Antibodies against the TSH receptor(TSHR) may be stimulating or blocking. The former are characteristic of Graves’ disease. High TSHR antibody levels after antithyroid drug treatment indicate a high risk of relapse

Advantage of salivary cortisol measurements in the diagnosis of glucocorticoid related disorders.

OBJECTIVE: Salivary cortisol in the assessment of glucocorticoid related disorders. DESIGN-METHODS: Serum and salivary cortisol were measured in 189 patients (22 Cushing's syndrome, 67 pseudo-Cushing, 11 Addison's disease, 89 controls) at 8:00 and 24:00 h. RESULTS: Serum and salivary cortisol correlated in the whole study population (r=0.62, p=0.000). Morning serum and saliva cortisol in Addison's disease were lower than in controls (6.74+/-1.69 vs 22.58+/-1.78 microg/dL, and 0.15+/-0.25 vs 0.67+/-0.12 microg/dL) (p<0.001). Morning serum cortisol was similar in controls and patients with Cushing's syndrome or pseudo-Cushing (22.58+/-1.78 vs 13.96+/-6.02 vs 16.13+/-1.69 microg/dL). Morning serum and salivary cortisol at 8:00 had the same sensitivity to distinguish patients with Addison's disease from healthy controls. 24:00 am serum cortisol in controls (2.61+/-0.20 microg/dL) was lower than in the pseudo-Cushing group (6.53+/-0.77 microg/dL, p<0.001) and in Cushing's syndrome (10.90+/-2.36 microg/dL, p=0.003). 24:00 am salivary cortisol in controls (0.0025+/-0.001 microg/dL) was lower than in patients with Cushing's syndrome (0.58+/-0.11 microg/dL, p<0.001) and those higher than in patient with pseudo-Cushing (0.10+/-0.06 microg/dL, p=0.001). Both salivary cortisol and serum cortisol presented high specificity (82% and 100%) to detect Cushing's syndrome but salivary cortisol higher sensitivity (saliva 88% and serum 50%). CONCLUSION: Morning salivary cortisol is as good as serum as screening test for patients with Addison's disease and nighttime salivary cortisol is more adequate than serum in the screening of Cushing's syndrome.

[Markers of thyroid function (I). Assessment of glandular activity]. / Marcadores de función tiroidea (I). Evaluación de la actividad glandular.

Thyroid hormones have a fundamental role in the metabolism, and are active in all organs and systems. Thyroid dysfunction (TD) is an important public health problem that concerns 10% of the general population. Diagnosis of TD is currently carried out on the basis of serum hormone levels determined by laboratory analysis. The results are classified into clinical (TSH and thyroid hormones out of normal range) and subclinical (isolated TSH disorder) dysfunction. The development of third generation assays in the TSH test represents a great step forward in the diagnosis of TD. However, the debate about the pathological significance of subclinical TD has intensified. There is as yet no agreement on the best approach for diagnosis and treatment of this common condition. It is currently impossible to know which subjects with subclinical TD will develop the typical complications of clinical dysfunction. In this setting, it is feasible that a number of subclinical hypothyroid subjects may in some cases be overtreated with thyroxin, while others remain undertreated with increased iatrogenic morbidity as a consequence.

[Markers of thyroid function (II). Assessment of tissue action]. / Marcadores de función tiroidea (II). Evaluación de la acción tisular.

Advances in molecular medicine have increased our knowledge of the consequences of hormone action in target cells. We are currently able to determine to some extent the molecular thyroid hormone activity in different organs. The effects are related with a variety of factors, but their association with plasmatic hormone levels is only partially correlated. Recent advances indicate that there are several intermediate factors in thyroid tissue activity. The iodothyronine selenodeiodinases have a relevant role in this context. The clinical and biochemical methods currently available for thyroid function assessment do not permit us to explore many of these new elements. However, it is well known that thyroid hormones enhance the expression of a number of proteins, and some of these can be measured by simple methods. Accordingly, the plasmatic value of these proteins may be related with the effect of thyroid hormones in the target tissues, which is the result of thyroid function. The ability to determine the tissue activity of thyroid hormones will enable us to administrate the treatment dose more accurately, only to patients who require it, avoiding iatrogenism.

Marcadores de función tiroidea (I). Evaluación de la actividad glandular / Markers of thyroid function (I). Assessment of glandular activity

Las hormonas tiroideas desempeñan un papel fundamental en el metabolismode todos los órganos y sistemas. La disfunción tiroidea (DT) esun importante problema de salud pública que afecta al 10% de la poblacióngeneral. El diagnóstico actual de la DT se realiza de acuerdocon la concentración plasmática de hormonas determinadas en el laboratorio.El resultado permite clasificarla en clínica (TSH y hormonastiroideas fuera del rango de normalidad) y subclínica (TSH alterada deforma aislada). El desarrollo de ensayos de tercera generación para ladeterminación de TSH ha supuesto un gran avance en el diagnóstico dela DT. Sin embargo ha aumentado el debate sobre el significado patológicode la morbilidad asociada a la DT subclínica, hasta el punto de quelos expertos mantienen posturas divergentes sobre el mejor métododiagnóstico y las necesidades terapéuticas de esta situación tan prevalente1-3.Ello es así porque carecemos de la capacidad de conocer cuales son lospacientes con enfermedad tiroidea subclínica que desarrollarán las complicacionespropias de la disfunción clínica4-7. La consecuencia prácticade todo ello es que con toda probabilidad estamos tratando de formainadecuada a pacientes con hipotiroidismo subclínico: en algunos casoslos sobretratamos, mientras que en otros no les proporcionamos lahormona que necesitan

Thyroid hormones have a fundamental role in the metabolism, and areactive in all organs and systems. Thyroid dysfunction (TD) is an importantpublic health problem that concerns 10% of the general population.Diagnosis of TD is currently carried out on the basis of serum hormonelevels determined by laboratory analysis. The results are classified intoclinical (TSH and thyroid hormones out of normal range) and subclinical(isolated TSH disorder) dysfunction. The development of third generationassays in the TSH test represents a great step forward in the diagnosisof TD. However, the debate about the pathological significance ofsubclinical TD has intensified. There is as yet no agreement on the bestapproach for diagnosis and treatment of this common condition1-3. It iscurrently impossible to know which subjects with subclinical TD willdevelop the typical complications of clinical dysfunction4-7. In this setting,it is feasible that a number of subclinical hypothyroid subjects may insome cases be overtreated with thyroxin, while others remainundertreated with increased iatrogenic morbidity as a consequence

Marcadores de función tiroidea (II). Evaluación de la acción tisular / Markers of thyroid function (II). Assessment of glandular activity

Los avances en el campo de la medicina molecular nos han permitidocomenzar a descubrir las consecuencias de la acción de las hormonasen las diferentes células diana. Hoy en día conocemos en parte losefectos de la actividad molecular de las hormonas tiroideas en diversostejidos. Sus efectos se vinculan con múltiples factores, pero la correspondenciacon la concentración plasmática de hormona es solo relativa.Hoy en día sabemos que existen varios elementos intermedios entrelos que destacan la acción de las desyodasas. Los métodos de estudioclínicos y bioquímicos disponibles en la práctica hospitalaria habitualno permiten abordar estos aspectos. Sin embargo se conoce que lashormonas tiroideas aumentan la expresión de varias proteínas y variasde ellas sí que pueden ser medidas por medios sencillos. Por ello, ladeterminación de estas proteínas podría mostrar el efecto de las hormonastiroideas en los tejidos diana, lo que constituye, en último término,el resultado de la función tiroidea. La capacidad para determinar laactividad tisular de las hormonas tiroideas ayudará a administrar ladosis adecuada de tratamiento únicamente a los sujetos que lo requieran,evitando el iatrogenismo

Advances in molecular medicine have increased our knowledge of theconsequences of hormone action in target cells. We are currently able todetermine to some extent the molecular thyroid hormone activity indifferent organs. The effects are related with a variety of factors, buttheir association with plasmatic hormone levels is only partiallycorrelated. Recent advances indicate that there are several intermediatefactors in thyroid tissue activity. The iodothyronine selenodeiodinaseshave a relevant role in this context. The clinical and biochemical methodscurrently available for thyroid function assessment do not permit us toexplore many of these new elements. However, it is well known thatthyroid hormones enhance the expression of a number of proteins, andsome of these can be measured by simple methods. Accordingly, theplasmatic value of these proteins may be related with the effect of thyroidhormones in the target tissues, which is the result of thyroid function.The ability to determine the tissue activity of thyroid hormones willenable us to administrate the treatment dose more accurately, only topatients who require it, avoiding iatrogenism