Lower proportion of intra-thyroidal B lymphocytes CD20+ associated to methimazole and lack of influence of iodide on lymphocyte subpopulations in Graves' disease.

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD). OBJECTIVE: Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4+, CD8+, CD25+ and CD20+. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood. METHODS: Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4+, CD8+, CD25+ and CD20+ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD25+ (regulatory T lymphocytes) and CD20+ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed. RESULTS: No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20+ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate. CONCLUSION: We found a lower proportion of intrathyroidal CD20+ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.

Acute suppurative thyroiditis with Graves disease - A very rare association.

Acute suppurative thyroiditis is an uncommon disorder caused by a bacterial infection, usually presenting with normal thyroid function. It is a serious condition that requires a prompt diagnosis and treatment with antibiotics and supportive measures. A 62 years-old female presented with a painful cervical induration and odynophagia a week after a fish bone had been removed from her pharynx. She was febrile, and tachycardic and, on physical examination, a painful thyroid mass was detected. High inflammatory parameters and thyrotoxicosis were confirmed: thyroid stimulating hormone (TSH) < 0.01 mIU/L (normal range [NR] 0.27-4.2); free thyroxine (FT4) 3.86 ng/dL (NR 0.9-1.7) and anti-TSH receptor antibodies (TRABs) 5.3 U/L (NR < 1.5). Thyroid scintigraphy showed a diffuse uptake of the thyroid parenchyma suggesting Graves disease. Cervical ultrasonography revealed an abscess of the left thyroid lobe of 36 × 36 mm and fine needle aspiration biopsy (FNAB) with partial drainage was performed. Staphylococcus aureus and Streptococcus viridans were isolated, and directed antibiotic therapy was started. Clinical improvement was observed as well as a decrease of inflammatory parameters and the patient was discharged after 9 days of hospitalization. Eighteen days after discharge, thiamazole was initiated due to persistent thyrotoxicosis. Complete resolution of the abscess was documented within 6 months and the patient became euthyroid under thiamazole one year after initial presentation. To our knowledge, this is the third case reporting an association between acute thyroiditis and Graves disease. Furthermore, this is the first case detailing the simultaneous diagnosis of acute suppurative thyroiditis caused by a foreign body and Graves disease.

Prediction for recurrence following antithyroid drug therapy for Graves' hyperthyroidism.

Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusion: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves' disease.

BACKGROUND: Graves' disease is an autoimmune disorder characterised by excessive production of thyroid hormones, which induces increased cellular metabolism in most tissues and increased production of reactive oxygen species (ROS). The aim of this work was to analyse the effect of ROS on cell viability and the expression of catalase (CAT), glutathione peroxidase-1 (GPx-1), superoxide dismutase (SOD-1) and DNA methyltransferase-1 (DNMT-1) in peripheral blood mononuclear cells (PBMC) from patients with newly diagnosed Graves' disease or treated with methimazole. PATIENTS AND METHODS: For this study, women patients with newly diagnosed Graves' disease (n=18), treated with methimazole (n=6) and healthy subjects (n=15) were recruited. ROS were evaluated by flow cytometry, and the viability/apoptosis of PBMC was analysed by flow cytometry and fluorescence microscopy. Genomic expression of CAT, GPx-1, SOD-1 and DNMT-1 was quantified by real-time PCR. RESULTS: We found high levels of ROS and increased expression of CAT, GPx-1, SOD-1 and DNMT-1 in PBMC from patients with newly diagnosed Graves' disease. Methimazole treatment reversed these parameters. Cell viability was similar in all study groups. CONCLUSIONS: ROS induces the expression of CAT, GPx-1, and SOD-1. The activity of these enzymes may contribute to the protection of PBMC from the harmful effect of free radicals on cell viability. Increased expression of DNMT-1 may be associated with aberrant methylation patterns in immunoregulatory genes contributing to autoimmunity in Graves' disease.

Severe thyrotoxicosis as initial presentation of gastric choriocarcinoma: a case report.

BACKGROUND: Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin. CASE PRESENTATION: A 62-year-old Hispanic female presented with a 3-week history of shortness of breath, palpitations, extreme weakness, new-onset hot flashes, and right flank pain. Her physical examination was remarkable for tachycardia, hepatomegaly, hyperreflexia, and tremor; goiter was absent. Laboratory studies revealed increased lactate dehydrogenase, alkaline phosphatase, suppressed thyroid stimulating hormone, very elevated T4, and absent thyroid stimulating immunoglobulin. 18F-fluorodeoxyglucose positron emission tomography-computed tomography exhibited hepatomegaly with multiple large fluorodeoxyglucose-avid liver masses and a focus of fluorodeoxyglucose avidity in the stomach with no structural correlate. A thyroid scan (99mTcO 4 - ) showed diffusely increased tracer uptake. She was started on propranolol and methimazole. Upon stabilization of severe thyrotoxicosis, upper endoscopy was performed, showing a ~ 5 cm bleeding lesion in the greater stomach curvature body; biopsy was consistent with choriocarcinoma; beta-human chorionic gonadotropin hormone was 2,408,171 mIU/mL. The patient received methotrexate followed by etoposide and cisplatin. Methimazole was titrated down, and upon liver failure the medication was stopped. The thyrotoxicosis was effectively controlled with antithyroid drug and concurrent chemotherapy. At ~ 1.5 months after initial diagnosis, the patient died due to bleeding/acute liver failure with coagulation defects followed by multiple organ failure. CONCLUSIONS: Severe thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options.

Graves' disease inducing a massive cardiac tamponade.

A 23-year-old woman was diagnosed with Graves' disease 5 months ago with decompensated thyroid function, for which she is taking thiamazole and propranolol. She developed progressive respiratory dyspnoea [New York Heart Association (NYHA) class III] and frequent palpitations. On emergency admission, the patient was tachypnoeic, hypotensive (77/54 mm Hg) and tachycardic (120 beats per minute), with an oxygen saturation of 94%. She also presented with cold, swollen and shaky extremities, with extended capillary filling time, and a significant reduction in heart sounds. Echocardiogram showed massive pericardial effusion compatible with cardiac tamponade. Pericardiocentesis was performed, with a drainage of 1420 mL serosanguinolent fluid, with prompt haemodynamic recovery. Analysis of the pericardial fluid showed exudates. A diagnosis of pericardial effusion secondary to Graves' disease was determined and corticotherapy, lithium carbonate, cholestyramine and phenobarbital were prescribed. An oral iodine-131 was performed and the patient showed reasonable control of the clinical manifestations of hyperthyroidism. After 3 months, the patient showed no symptoms of hyperthyroidism and a new echocardiogram revealed a significant reduction in pericardial effusion.

Endocrinopatías por inmunoterapia oncológica / Endocrinopathies by oncological immunotherapy

La relación entre inmunidad y cáncer es compleja. Las células tumorales desarrollan mecanismos de evasión a las respuestas del sistema inmunitario. Esta capacidad permite su supervivencia y crecimiento. La inmunoterapia ha transformado el tratamiento oncológico mejorando la respuesta inmunitaria contra la célula tumoral. Esta se basa en el bloqueo de los puntos de control inmunitario mediante anticuerpos monoclonales contra la molécula inhibidora CTLA-4 (antígeno 4 del linfocito T citotóxico [CTLA-4]) y la proteína 1 de muerte celular programada y su ligando (PD-1/PD-L1). Aunque los inhibidores de los puntos de control inmunitario (ICIs) son fármacos bien tolerados, tienen un perfil de efectos adversos conocido como eventos adversos inmunorrelacionados (EAI). Estos afectan varios sistemas, incluyendo las glándulas endocrinas. Los eventos adversos endocrinos más frecuentes son la disfunción tiroidea, la insuficiencia hipofisaria, la diabetes mellitus autoinmune y la insuficiencia suprarrenal primaria. El creciente conocimiento de estos efectos adversos endocrinos ha llevado a estrategias de tratamiento efectivo con el reemplazo hormonal correspondiente. El objetivo de esta revisión es reconocer la incidencia de estas nuevas endocrinopatías, la fisiopatología, su valoración clínica y el manejo terapéutico. (AU)

The relationship between immunity and cancer is complex. Tumor cells develop evasion mechanisms to the immune system responses. This ability allows their survival and progression. Immunotherapy has transformed cancer treatment by improving the immune response against tumor cells. This is achieved by blocking immune checkpoints with monoclonal antibodies against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 and its ligand (PD-1 / PD-L1). Although the immune checkpoint inhibitors (ICIs) are well tolerated drugs, they have a profile of adverse effects known as immune-related adverse events (irAES). These involve diverse systems, including the endocrine glands. The most frequent endocrine immune-related adverse events are thyroid and pituitary dysfunction, autoimmune diabetes mellitus and primary adrenal insufficiency. The increasing knowledge of these irAES has led to effective treatment strategies with the corresponding hormonal replacement. The objective of this review is to recognize the incidence of these new endocrinopathies, the physiopathology, their clinical evaluation, and therapeutic management. (AU)

Encefalopatía asociada a enfermedad tiroídea, un diagnóstico a tener en mente / Encephalopathy associated with thyroid disease, a diagnosis to take into account

Mujer de 54 años con antecedentes de Hipertensión arterial e Hipotiroidismo. Historia de aproximadamente 3 meses de evolución caracterizado al inicio por ánimo bajo, cambios en el comportamiento con aparición progresiva de conductas extraña, ideas delirantes y alucinaciones visuales y auditivas, junto con disminución en requerimientos de hormonas tiroídeas hasta la suspensión. Consulta en varios centros donde se cataloga como Trastorno depresivo severo con síntomas psicóticos, Síndrome confusional, Síndrome Psicótico. En este contexto se pesquisa Hipertiroidismo con títulos elevados de Anticuerpos Antitiroídeos e inicia tratamiento con Metimazol y Betabloqueo. Tras extenso estudio que descartan causas infecciosas, neoplásicas y autoinmunes; se inicia tratamiento con pulsos de Metilprednisolona con excelente y rápida respuesta clínica, la cual mantiene durante el curso del seguimiento con dosis decrecientes de corticoides.

A 54-year-old woman with a history of arterial hypertension and hypothyroidism. History of approximately 3 months of evolution characterized at the beginning by low mood, changes in behavior with progressive appearance of bizarre behaviors, delusional ideas and visual and auditory hallucinations. Consultation in several centers where it is classified as severe Depressive disorder with psychotic symptoms, Confusional syndrome, Psychotic syndrome. Hyperthyroidism is investigated with high titers of Antithyroid Antibodies and initiates treatment with Methimazole and Betablock. After extensive study that ruled out infectious, neoplastic and autoimmune causes; Treatment with Methylprednisolone pulses is initiated with excellent and rapid clinical response, which is maintained during the course of follow-up with decreasing doses of corticosteroid.

Diabetic Ketoacidosis Associated with Thyroxine (T4) Toxicosis and Thyrotoxic Cardiomyopathy.

Thyrotoxicosis and diabetic ketoacidosis (DKA) both may present as endocrine emergencies and may have devastating consequences if not diagnosed and managed promptly and effectively. The combination of diabetes mellitus (DM) with thyrotoxicosis is well known, and one condition usually precedes the other. Furthermore, thyrotoxicosis is complicated by some degree of cardiomyopathy in at least 5% de patients; but the coexistence of DKA, thyroxin (T4) toxicosis, and acute cardiomyopathy is extremely rare. We describe a case of a man, previously diagnosed with DM but with no past history of thyroid disease, who presented with shock and severe DKA that did not improve despite optimal therapy. The patient evolved with acute pulmonary edema, elevated troponin levels, severe left ventricular systolic dysfunction, and clinical and laboratory evidence of thyroxin (T4) toxicosis and thyrotoxic cardiomyopathy. Subsequently, the patient evolved favorably with general support and appropriate therapy for DKA and thyrotoxicosis (hydrocortisone, methimazole, Lugol's solution) and was discharged a few days later.

TeleCondutas: hipertireoidismo / TeleGuides: hyperthyroidism

Hipertireoidismo é o excesso de função da glândula tireoide. É a principal causa de tireotoxicose, que, por sua vez, é a manifestação clínica do excesso de hormônios tireoidianos. O hipertireoidismo é mais comum em mulheres do que em homens (razão de 5:1), tendo como principais causas a Doença de Graves (60 % a 80% dos casos), etiologia típica em mulheres jovens com idade entre 20 a 40 anos, e o bócio multinodular tóxico (10 % a 30% dos casos), mais frequente em idosos. O adenoma tóxico e as tireoidites são menos comuns (1%). Hipertireoidismo e tireotoxicose também podem ser induzidos por medicamentos como amiodarona, interferon, levotiroxina e lítio. A doença deve ser investigada em pacientes com manifestações clínicas, não havendo recomendação para rastreamento populacional. Informações sobre tireotoxicose induzida por levotiroxina (TSH reduzido em paciente que faz uso de levotiroxina) podem ser obtidas no material TeleCondutas Hipotireoidismo. Esta guia apresenta informação que orienta a conduta para casos de hipertiroidismo no contexto da Atenção Primária à Saúde, incluindo: sinais e sintomas, diagnóstico do hipertireoidismo, tratamento do hipertireoidismo, tratamento do hipertireoidismo subclínico, hipertireoidismo na gestação, encaminhamento para serviço especializado.

Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

Objective Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. Materials and methods Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. Results From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. Conclusions We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes?

Serum thyroid stimulating hormone (TSH) levels increase with age. This elevation has been associated with better outcomes in very elderly subjects; however, little is known about the relationship between TSH below the lower limit of the reference range and health-related outcomes. Here, we investigated the association between cognitive impairment or depressive symptoms and low-normal serum TSH (<1.0 µIU/mL, in the reference range) in elderly subjects and whether the use of methimazole in subjects without dementia but with low-normal TSH could affect cognition or depressive symptoms. From 293 healthy adults ≥65 years old with normal TSH included in the sectional phase, only subjects without dementia were prospectively analyzed: 1) TSH ≥1.0 µIU/mL (observation; untreated); 2) TSH <1.0 µIU/mL (observation; untreated); and 3) TSH <1.0 µIU/mL (methimazole therapy). Cognition was assessed, using the Mini Mental State Examination (MMSE) and depressive symptoms (at MMSE ≥ 13) by the Geriatric Depression Scale (GDS). Age >80 years was the sole independent factor associated with dementia (OR=2.89; confidence interval [CI] 1.72-4.86; p<0.01). Prospectively, 93 completed follow-up, with 7.5% (7) receiving methimazole intervention. Untreated subjects with lower TSH showed the greatest declines in MMSE scores during follow-up that was not observed in those with serum TSH ≥1.0 µIU/mL. Lower MMSE score reductions were associated with elderly subjects receiving methimazole. There were no significant changes in depressive symptoms and GDS scores among those with serum TSH <1.0 µIU/mL. In this study, low-normal TSH was not associated with higher prevalence of dementia. However, in elderly subjects without dementia, low TSH was associated with worsening cognition.

Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

OBJECTIVE: Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 µIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. MATERIALS AND METHODS: Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 µIU/mL vs. TSH ≥1.0 µIU/mL. In the second phase, participants with TSH < 1.0 µIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. RESULTS: From 89 elderly evaluated, 75 had TSH ≥ 1 µIU/mL and 14 TSH < 1 µIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 µIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. CONCLUSIONS: We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Abrupt onset of muscle dysfunction after treatment for Grave's disease: a case report.

Myopathy is a known complication of hypothyroidism, commonly characterized by an elevation in Creatine Kinase (CPK) due to increase capillary permeability proportional to the hypothyroid state. Thyroid hormone is important for the expression of fast myofibrillar proteins in the muscle. In hypothyroidism the expression of these proteins are deficient and there is an increase accumulation of slow myofibrillar proteins. A rapid or abrupt descend in thyroid hormones caused by radioiodine therapy after prolonged hyperthyroidism can lead to local hypothyroid state within the muscle tissue, resulting in CPK elevation and hypothyroid myopathy. Hormone replacement leads to resolution of symptoms and normalization of muscle enzymes serum levels.

Falla cardíaca como manifestación temprana de hipertiroidismo neonatal: caso clínico / Heart failure as early manifestation of neonatal hyperthyroidism: case report

Introducción: Hipertiroidismo neonatal es una condición usualmente autolimitada, generalmente asociada al paso transplacentario de anticuerpos estimulantes de tiroides, secundario a enfermedades autoinmunes maternas. Detectar oportunamente a las madres con estos antecedentes, permitirá disminuir el riesgo de eventos adversos fetales. Objetivo: Presentar un caso de hipertiroidismo neonatal, asociado a falla cardíaca y restricción del crecimiento intrauterino, Caso clínico: Recién nacido de 36 semanas, peso de nacimiento 1.240 g. Evolucionó con taquicardia, frialdad distal, exoftalmos, hepatomegalia y temblores. Ecocardiograma descartó alteración cardíaca estructural. Por hallazgos maternos sugerentes de hipertiroidismo, se realizaron exámenes encontrando TSH de 0,01 uUI/ml, T4 libre de 7,7 ng/dl, con lo que se confirmó el diagnóstico de hipertiroidismo neonatal. Se manejó con metimazol y propanolol con resolución de los síntomas y descenso de los niveles de T4 libre. Conclusiones: Conocer los antecedentes maternos permite identificar y manejar las complicaciones neonatales del hipertiroidismo. La falla cardíaca y otras alteraciones cardiopulmonares son los factores determinantes de la mortalidad en el período neonatal temprano. Debe haber un seguimiento a los recién nacidos de riesgo.

Neonatal hyperthyroidism is usually a self-limited condition frequently associated with transplacental passage of thyroid stimulating antibodies secondary to maternal autoimmune disorders. To timely detect mothers with this medical antecedents decreases the risk for fetal adverse events. Objective: To report a case of neonatal hyperthyroidism associated with intrauterine growth restriction and heart failure. Case report: A 36 week-old newborn with birth weight of 1,240 g. Symptoms were tachycardia, distal coldness, exophthalmos, hepatomegaly and tremors. Echocardiogram ruled out structural heart disorders. Due to maternal symptoms suggestive of hyperthyroidism, TSH tests were performed showing 0.01 ulU/ml, free T4 7.7 ng/dl, so the diagnosis of neonatal hyperthyroidism was confirmed. It was treated with methimazole and propanol, alleviating the symptoms and decreasing the levels of free T4. Conclusions: To know the maternal history helps identify and manage neonatal complications of hyperthyroidism. Heart failure and other cardiopulmonary disorders are determinants of mortality during early neonatal period. High-risk newborns should receive follow up assessments.

Graves disease in children: thyroid-stimulating hormone receptor antibodies as remission markers.

OBJECTIVE: To evaluate clinical and biochemical features of 115 children (98 female, mean age 11.3 ± 3.5 years) with Graves disease to identify possible determinants of remission. STUDY DESIGN: We defined as positive outcome the improvement of clinical features and restoration of euthyroidism or induction of hypothyroidism after antithyroid drug (ATD) therapy and as negative outcome hyperthyroidism persistent over 2 years of ATD therapy or relapsed after ATD withdrawal. RESULTS: Thirty-eight children (33%) had remission after 2 years of ATD therapy. The absence of goiter at diagnosis was correlated with a better outcome. Median thyroid-stimulating hormone receptor antibody (TRAb) values at diagnosis were significantly lower in patients with a positive outcome (P = .031). We found a significant relationship between the time required for TRAb normalization and the patient outcome; TRAb normalization within 1 year from time of Graves disease diagnosis was significantly more common among patients with a positive outcome (P < .0001), and the mean time for TRAb normalization was significantly shorter in patients with a positive outcome (1.3 ± 0.8 years) compared with that observed in patients with a negative outcome (2.5 ± 2.7 years, P = .026). CONCLUSIONS: Although no clinical variable investigated is constantly associated with a definite outcome, the absence of goiter at the diagnosis may be associated with a better outcome. The most relevant predictor of Graves disease outcome was serum level; TRAb at time of Graves disease diagnosis less than 2.5 times the upper reference limit, TRAb normalization during ATD, and TRAb normalization timing each may predict positive outcomes. These results may have a role in the empiric clinical management of pediatric patients with Graves disease.

[Heart failure as early manifestation of neonatal hyperthyroidism. Case report]. / Falla cardíaca como manifestación temprana de hipertiroidismo neonatal. Caso clínico.

UNLABELLED: Neonatal hyperthyroidism is usually a self-limited condition frequently associated with transplacental passage of thyroid stimulating antibodies secondary to maternal autoimmune disorders. To timely detect mothers with this medical antecedents decreases the risk for fetal adverse events. OBJECTIVE: To report a case of neonatal hyperthyroidism associated with intrauterine growth restriction and heart failure. CASE REPORT: A 36 week-old newborn with birth weight of 1,240 g. Symptoms were tachycardia, distal coldness, exophthalmos, hepatomegaly and tremors. Echocardiogram ruled out structural heart disorders. Due to maternal symptoms suggestive of hyperthyroidism, TSH tests were performed showing 0.01 ulU/ml, free T4 7.7 ng/dl, so the diagnosis of neonatal hyperthyroidism was confirmed. It was treated with methimazole and propanol, alleviating the symptoms and decreasing the levels of free T4. CONCLUSIONS: To know the maternal history helps identify and manage neonatal complications of hyperthyroidism. Heart failure and other cardiopulmonary disorders are determinants of mortality during early neonatal period. High-risk newborns should receive follow up assessments.

[Thyroid dysfunction and amiodarone]. / Disfunção tiróidea e amiodarona.

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.