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Resumen Introduccion El hiperaldosteronismo primario (HAP) es la causa mas frecuente de hipertension endocrina, con una prevalencia del 6-12% en pacientes hipertensos. El cociente aldosterona/renina es el metodo de cribado de eleccion. Dada la variabilidad de sus puntos de corte, se sugiere contar con valores de referencia propios. Objetivos 1) Optimizar los puntos de corte del cociente aldosterona/renina para el cribado de hiperaldosteronismo con la metodologia actual; 2) evaluar la correlacion y la sensibilidad diagnostica de los cocientes aldosterona/actividad de renina plasmatica (RAA) y aldosterona/concentracion de renina (RAC) para el cribado de hiperaldosteronismo, y 3) determinar la prevalencia de hiperaldosteronismo en nuestra poblacion. Materiales y metodos Se determinaron los niveles de aldosterona (RIA competitivo en fase solida RIAZENco Zentech), actividad de renina plasmatica (RIA en fase solida DiaSorin) y concentracion de renina (quimioluminiscencia Liaison DiaSorin) en 345 sujetos (136 controles y 209 hipertensos). Se calcularon los cocientes RAA y RAC. Resultados La prevalencia de HAP, tras confirmacion diagnostica, fue del 5,9% de los hipertensos. El valor de corte para sospecha de HAP determinado por curvas ROC fue 48,9 (ng/dl)/(ng/ml/h) para RAA (sensibilidad 100% y especificidad 93,6%) y 2,3 (ng/dl)/(μUI/ml) para RAC (sensibilidad 100% y especificidad 90,9%). Se observo buena correlacion entre RAA y RAC (ρ = 0,83; p Conclusiones Hemos determinado en nuestra poblacion nuevos valores de corte de RAA y RAC para el cribado de HAP, con buena sensibilidad y concordancia como metodos de cribado. Es importante contar con rangos de normalidad propios para evitar errores diagnosticos.

Introduction Primary aldosteronism (PA) is the most common cause of endocrine hypertension, with a prevalence rate of 6–12% in hypertensive patients. Aldosterone/renin ratio (ARR) is the screening test of choice for PA. Because of the variable cut-off points of ARR, reference values related to the populations and methods considered are recommended. Objectives (i) To optimize the ARR cut-off points for PA screening with current methods; (ii) to assess the correlation and diagnostic sensitivity of the plasma aldosterone concentration/plasma renin activity (ARR) ratio and the aldosterone concentration/renin concentration (ARC) ratios for PA screening, and (iii) to determine the prevalence of PA in our population. Materials and methods Plasma aldosterone concentration and plasma renin activity levels were measured using radioimmunoassays (RIAZENco Zentech and RIA DiaSorin respectively), while a chemiluminescence assay (Liaison Diasorin) was used to test renin concentration. ARR and ARC ratios were calculated in 345 subjects (136 healthy subjects and 209 hypertensive patients). Results Prevalence of PA was 5.9% after diagnostic confirmation. ROC curve analysis suggested an ARR threshold of 48.9 (ng/dL)/(ng/mL/h) (100% sensitivity, 93.6% specificity) and an ARC threshold of 2.3 (ng/dL)/(μIU/mL) (100% sensitivity, 90.9% specificity). Good correlation was seen between ARR and ARC (ρ = 0.83, p Conclusions New cut-off values of ARR and ARC for screening of PA, with high sensitivity and good diagnostic concordance, were determined in the study population. It is important to have valid normal ranges to avoid diagnostic errors.

Purpose: Inflammation plays a critical role in the progression of COVID-19. Nonthyroidal illness syndrome (NTIS) has been increasingly recognized in affected patients. We aim to evaluate the correlation of thyroid hormones with markers of inflammation and association with disease outcome in hospitalized patients with COVID-19, and in two profiles of NTIS (low T3-normal/low FT4 vs low T3-high FT4). Methods: prospective study of 55 patients (50.9% men, median age 56 years) admitted to a non-intensive care unit for COVID-19. Infection was mild in 22%, moderate in 27.1% and severe in 50.8%; 7.41% died. T4, T3, FT4, FT3 and their ratios (T3/T4, FT3/FT4) were correlated with albumin, ferritin, fibrinogen, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], lactate dehydrogenase [LDH] and D-dimer. Results: Albumin correlated positively with T3 and hormones ratios, but negatively with FT4. T3, FT3, T3/T4 and FT3/FT4 ratios correlated inversely with ferritin, fibrinogen, ESR, CRP, LDH and D-dimer. FT4 showed direct correlation with fibrinogen and ESR. T3/T4 ratio was lower in severe compared to mild/moderate disease [7.5 (4.5-15.5) vs 9.2 (5.8-18.1); p=0.04], and lower in patients who died than in those discharged [5 (4.53-5.6) vs 8.1 (4.7-18.1); p=0.03]. A lowT3/high FT4 profile was associated with lower albumin, higher ferritin, and severity. Conclusion: In this cohort, thyroid hormones correlated with inflammation and outcome. T3 and T3/T4 ratio correlated inversely with inflammatory markers; a low T3/T4 ratio was associated with severity and poor prognosis. Patients with low T3 but high FT4 had higher ferritin, lower albumin, and more severe disease at presentation.

Purpose Inflammation plays a critical role in the progression of COVID-19. Nonthyroidal illness syndrome (NTIS) has been increasingly recognized in affected patients. We aim to evaluate the correlation of thyroid hormones with markers of inflammation and association with disease outcome in hospitalized patients with COVID-19, and in two profiles of NTIS (low T3-normal/low FT4 vs. low T3-high FT4). Methods consecutive patients admitted to a nonintensive care unit for COVID-19 were recruited. Infection was mild in 22%, moderate in 27.1% and severe in 50.8%; 7.41% died. T4, T3, FT4, FT3, and their ratios (T3/T4, FT3/FT4) were correlated with albumin, ferritin, fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer. Results Fifty five patients (50.9% men, median age 56 years) were included. Albumin correlated positively with T3 and hormones ratios, but negatively with FT4. T3, FT3, T3/T4, and FT3/FT4 correlated inversely with ferritin, fibrinogen, ESR, CRP, LDH, and D-dimer. FT4 showed direct correlation with fibrinogen and ESR. T3/T4 was lower in severe compared to mild/moderate disease [7.5 (4.5–15.5) vs. 9.2 (5.8–18.1); p = 0.04], and lower in patients who died than in those discharged [5 (4.53–5.6) vs. 8.1 (4.7–18.1); p = 0.03]. A low T3/high FT4 profile was associated with lower albumin, higher ferritin, and severity. Conclusion In this cohort, thyroid hormones correlated with inflammation and outcome. T3 and T3/T4 correlated inversely with inflammatory markers; a low T3/T4 ratio was associated with severity and poor prognosis. Patients with low T3 but high FT4 had higher ferritin, lower albumin, and more severe disease at presentation.

Objective The aim of this study was to measure quality of life (QOL) impairment in individuals currently suffering from Graves’ ophthalmopathy (GO) and to determine the correlation of GO-specific QOL scores with disease severity and activity. Subjects and methods Seventy three GO-specific QOL surveys were prospectively analysed and compared with GO status. The GO-specific QOL survey was translated into Spanish and applied to Argentine patients with Graves’ disease (GD). Results were compared with presence or absence of GO, Clinical Activity Score (CAS), severity score, age, gender and thyroid function. Results Fifty-six patients answered the survey and underwent complete ophthalmic evaluation, 15 did not have GO and were considered to be a control group. Appearance QOL score for patients with GO (53 ± 31.4) was lower than the control group (88.3 ± 17) (p < 0,000), no difference was observed in functional QOL score. There was a negative correlation between GO severity and both functional (r = -0.575; p < 0.000) and appearance QOL (r = -0.577; p < 0.000). Functional QOL differed between patients with active GO vs control group (p = 0.043). Patients with active and inactive GO had lower appearance QOL scores than control group (p < 0.000, p < 0.001 respectively). Conclusions GO has significant impact on the life of these Argentine patients. QOL was worse in GO patients than in control group, functional QOL was mostly affected by the activity and appearance QOL was mainly altered by the effects of the disease. Patients with more severe GO had lower scores on both QOL scales.

Resumen Las metastasis ganglionares regionales del cuello estan presentes en un gran porcentaje de los casos con CPT. Sin embargo, en varios trabajos se pudo observar como no todo compromiso ganglionar tiene igual impacto en la evolucion de dicha patologia. Recientemente en Argentina, Chile y Brasil se modificaron las guias del manejo del CDT y estas recomiendan una estratificacion de riesgo y abordaje terapeutico diferente segun el numero, el tamano y la extension del compromiso ganglionar. En esta monografia se analizaron las caracteristicas de las metastasis ganglionares y su impacto en la evolucion del CDT y esto fue realizado previamente a la reciente publicacion de las nuevas guias de la ATA. Dada esta situacion, se incorporaron a la monografia original algunos aspectos de las guias de ATA.

This prospective study analyzed the frequency of V600E mutation of oncogene BRAF in patients operated for benign thyroid nodules and for papillary thyroid cancer in an Argentine population. In patients with papillary thyroid cancer we compared clinicopathological characteristics between those harboring BRAF mutation and those without it. Twenty five consecutive patients operated for benign nodules and for papillary carcinoma were prospectively included. Fresh tissue samples of thyroid nodules and of adjacent thyroid parenchyma were obtained. DNA was extracted and amplified by amplification refractory mutation system polymerase chain reaction (ARMS PCR). Direct sequencing was performed in four samples. Of those patients operated for papillary thyroid cancer, 77% harbored BRAF mutation. All samples from adjacent thyroid parenchyma and from patients operated for benign nodules tested negative for the mutation. Direct sequencing confirmed the results obtained by ARMS PCR. Patients with BRAF mutation were significantly older at the time of diagnosis (BRAF+ 47.7 ± 12.7 years vs. BRAF- 24.7 ± 8.1 years, p0.01). Nine out of ten papillary carcinomas with BRAF mutation corresponded to the classic histological subtype, which was not observed in BRAF negative tumors (p0.02). In conclusion, we found a high frequency of BRAF V600E mutation in this population of patients operated for papillary thyroid carcinoma in Argentina. These results are consistent with those reported in the literature.

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries. Estas recomendações tiveram por objetivo o desenvolvimento de diretrizes para avaliação e manejo de pacientes com câncer diferenciado da tiroide em países latino-americanos. Um painel composto por 13 membros da Sociedade Latino-Americana de Tireoide (SLAT) - que estavam envolvidos em pesquisas, e eram peritos no cuidado do paciente com câncer da tiroide e provenientes de diferentes centros médicos latino-americanos - utilizou os princípios da Medicina Baseada em Evidências para produzir esse consenso. Após uma primeira reunião, um texto inicial foi elaborado, baseado em evidências e opiniões dos especialistas do painel e, posteriormente, circulado entre os membros do painel, para revisão. Após a revisão, o documento foi enviado aos membros da SLAT para comentários e considerações e, finalmente, revisado e refinado pelos autores. As recomendações finais aqui apresentadas demonstram o estado da arte no manejo do câncer diferenciado da tireoide aplicadas aos países latino-americanos.

Thyroid Hormone Receptor β (THRB) defects, typically transmitted as autosomal dominant traits, cause Resistance to Thyroid Hormone (RTH). We analyzed the THRB gene in thirteen South American patients with clinical evidence RTH from eleven unrelated families. Sequence analysis revealed seven novel missense mutations. Four novel mutations were identified in exon 9. The first, a c.991A>G transition which originates a substitution of asparagine by aspartic acid (p.N331D). The second nucleotide alteration consists of a guanine to cytosine transversion at position 1003 (c.1003G>C) and results in substitution of the alanine at codon 335 by proline (p.A335P). The third mutation, a c.1022T>C transition produces a change of leucine by proline (p.L341P). The fourth mutation detected in exon 9 was a c.1036C>T transition which replaces the leucine at codon 346 by phenylalanine (p.L346F). The sequencing of the exon 10 detected three novel missense mutations. The first, a c.1293A>G transition changing isoleucine 431 for methionine (p.I431M). The second, the cytosine at position 1339 was replaced by adenine (c.1339C>A) resulting in the replacement of proline by threonine (p.P447T). The third mutation detected in exon 10 was a c.1358C>T transition resulting in the substitution of proline at codon 453 by leucine (p.P453L). Finally, sequencing analysis of the THRB gene revealed three substitutions previously described (p.A268G, p.P453T and p.F459C). The p.P453T was found in two patients. In conclusion, we report thirteen patients with RTH caused by heterozygous mutations of the THRB gene. Seven of the identified mutations correspond to novel substitutions. Fil: Rivolta, Carina Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Salamanca; España Fil: Olcese, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Belforte, Fiorella Sabrina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Gruñeiro Papendieck, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Iorcansky, Sonia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Herzovich, Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Cassorla, Fernando. Universidad de Santiago de Chile. Hospital Clinico San Borja Arriaran. Instituto de Investigaciones Materno Infantil; Chile Fil: Gauna, Alicia Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Gonzalez Sarmiento, Rogelio. Universidad de Salamanca; España Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.

The water diffusional permeability, its activation energy and the lipid composition were studied in urinary bladders from toads adapted to different temperatures. It was observed that the unidirectional water flux greatly depends on the temperature at which the experiments are performed. This dependence is greater in the animals adapted to higher temperatures. Toads adapted to cold show strong reduction in the activation energy for water diffusion permeability (from 11.4+/-1.9 kcal-mol-1 to 4.4+/-1.1kcal-mol-1) and an increase of 30% in the amount of total lipids from bladder epithelial cells. There were no significant changes in the phospholipid/cholesterol ratio, composition of the parafinic chains or protein concentration between toads adapted to both temperatures. The possibility that water translocates through the mucosal border of the toad bladder by partitioning in the polar zone and diffusioning between the hydrocarbon chains of the membrane lipids and that cold adaptation would induce a stronger "packing" of lipids in the membrane is discussed.

Background: Thyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves’ disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over. The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves’ disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb. Methods: Cross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves’ disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured. Results: Only euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves’ disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves’ disease. In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = �0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01). Conclusions: In euthyroid women with a history of Graves’ hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this antibody may affect the bone metabolism.