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.

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.

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.

Disfunção tiróidea e amiodarona / Thyroid dysfunction and amiodarone

Apesar de a maioria dos doentes tratados com amiodarona permanecer em eutiroidia, alguns desenvolvem hipertiroidismo (HPEIA) ou hipotiroidismo (HPOIA) induzidos pela amiodarona. Os autores apresentam uma análise retrospectiva dos processos de dez doentes com disfunção tiróidea induzida pela amiodarona. Verificou-se que seis doentes eram mulheres e que o tempo médio de toma da amiodarona foi de 17,7 meses. O HPOIA foi o mais frequente (seis doentes). Dos doentes com HPEIA, dois tinham HPEIA tipo 2, um tipo 1 e um tipo 3. Sintomas sugestivos de disfunção tiróidea ocorreram em cinco doentes, a maioria com HPOIA. No HPEIA, a clínica mais comum foi exacerbação da arritmia de base (três doentes). A interrupção da amiodarona e administração de levotiroxina foi a terapêutica escolhida em 83,3% dos casos de HPOIA, enquanto a tionamida associada a corticoide com suspensão da amiodarona foi opção em 75% dos casos de HPEIA. Registraram-se três óbitos, todos com HPEIA. O HPEIA constituiu uma complicação potencialmente fatal. A clínica pode ser vaga, pelo que a monitorização da função tiróidea é obrigatória.

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.

Icterícia grave e miocardiopatia tireotóxica com trombo atrial / Serious jaundice and thyrotoxic myocardiopathy with atrial thrombus

Icterícia relacionada à tireotoxicose, e não como efeito das drogas antitireoidianas, é uma complicação rara que, em geral, ocorre na presença de insuficiência cardíaca (IC) ou hepatite. Apresentamos o caso de mulher de 54 anos de idade, branca, diagnóstico de hipertireoidismo por doença de Graves com icterícia associada a despeito da suspensão prévia de metimazol. A bilirrubina oscilava em valores elevados entre 30,0 e 52,3 mg/dL, as transaminases eram pouco elevadas com valores de ALT, na admissão, de 46 U/I e AST de 87 U/I; coagulograma e proteínas encontravam-se no limite inferior da normalidade, sendo TAP 68% e albumina = 2,5 g/dL. Sorologias para hepatites foram negativas. Após a primeira dose de radioiodoterapia (RT), a bilirrubina atingiu seu valor máximo, que coincidiu com período de pior exacerbação da IC. A bilirrubina normalizou-se após quatro semanas da segunda dose de RT com a estabilização da IC e a normalização dos hormônios tireoidianos. Discutimos as possíveis etiologias de icterícia severa em pacientes hipertireoideos, assim como a difícil terapia anticoagulante com varfarina.

Jaundice related to thyrotoxicosis and not as an effect of antithyroid drugs is a rare complication that usually occurs in the presence of heart failure (HF) or hepatitis. We report a case of a 54-year-old white woman with hyperthyroidism caused by Graves's disease and jaundice despite methimazole suspension. Bilirubin fluctuated at high values, between 30.0 and 52.3 mg/dL, transaminases were slightly increased, on admission ALT = 46 U/L and AST = 87 U/L; coagulation indices and serum proteins were on the lower limit of the normal range with PT 68% and albumin = 2.5 g/dL. Serology for hepatitis was negative. After the first radioiodine therapy (RT), bilirubin reached its maximum, which coincided with the worst period of HF exacerbation. Bilirubin normalized 4 weeks after the second RT, with the stabilization of HF and normalization of thyroid hormones. We discuss the possible etiologies of severe jaundice in hyperthyroid patients, as well as the difficult anticoagulant therapy with warfarin.

Avaliação do peso corporal em pacientes com doença de Graves durante o tratamento com metimazol / Evaluation of body weight in patients with Graves' disease during the treatment with methimazole

OBJETIVO: Avaliar a alteração de peso durante o tratamento do hipertiroidismo e correlacioná-la com IL-6 e TNF-alfa. SUJEITOS E MÉTODOS: Quarenta e dois pacientes foram incluídos. Peso corporal (PC), índice de massa corpórea (IMC), características clínicas e laboratoriais foram registrados. IL-6 e TNF-alfa foram determinados antes do tratamento com metimazol (MMI) e no estado de eutiroidismo. RESULTADOS: O PC foi de 59,62 ± 11,5 kg no estado de hipertiroidismo e de 69,91 ± 14,4 kg no estado de eutiroidismo (p < 0,001). O IMC aumentou de 23,1 ± 3,8 kg/m² para 27 ± 4,7 kg/m² durante o tratamento (p < 0,0001). Antes da terapia, 66,6% tinham IMC < 25 kg/m² e 33,3%, IMC > 25 kg/m². No estado de eutiroidismo, 38% dos pacientes apresentavam IMC < 25 kg/m² e 62%, IMC > 25 kg/m² (p = 0,01). No estado de eutiroidismo, encontrou-se significativa diminuição nos valores de IL-6 e TNF-alfa, mas nenhuma correlação entre IL-6 e TNF-alfa com PC ou IMC. CONCLUSÃO: Um importante aumento no PC e IMC foi observado durante o tratamento do hipertiroidismo e alterações de IL-6 e TNF-alfa relacionam-se somente com o retorno ao eutiroidismo.

OBJECTIVE: To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations. SUBJECTS AND METHODS: Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism. RESULTS: BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m² to 27 kg/m² ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m² and 33.3%, BMI > 25 kg/m². In euthyroidism, 38% of patients had BMI < 25 kg/m² and 62%, BMI > 25 kg/m² (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI. CONCLUSION: An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism.

Vasculitis inducida por metimazol. Reporte de caso / Drug-induced vasculitis by metimazol. A case report

Se reporta el caso de una paciente con enfermedad de Graves, que presentó vasculitis asociada al uso de metimazol. Mujer de 14 años, que acudió a consulta por presentar intolerancia al calor, tremor distal y palpitaciones. El examen físico mostró bocio difuso, y el perfil tiroideo, TSH suprimida y hormonas tiroideas elevadas. Los anticuerpos antiperoxidasa tiroidea fueron positivos. Se inició tratamiento con metimazol y beta bloqueadores. Después de 20 días, la paciente regresó por presentar malestar general, fiebre, poliartralgia, lesiones cutáneas maculopapulares yedema de miembros inferiores. Los anticuerpos antinucleares fueron negativos y los anticuerpos anticitoplasma de los neutrófilos (ANCA), positivos. Se suspendió el metimazol y se inició prednisona. Después de 10 días de tratamiento, las molestias desaparecieron y la paciente recibió I. Las vasculitis asociadas al uso de tionamidas son poco frecuentes, no dependen de la dosis y están asociadas a la presencia de anticuerpos tipo ANCA. Clásicamente, afectan a los vasos pequeños de la piel; sin embargo, también pueden afectar los riñones y pulmones. El cuadro clínico se caracteriza por artralgias y mialgias. En algunos casos puede ocurrir insuficiencia renal de grado variable. En la mayoría de casos, el cuadro remite con la suspensión de la droga; pero, en algunos se requiere el uso de glucocorticoides o inmunosupresores.

A 14-year-old woman presented with recent history of heat intolerance, hand tremor and palpitations. Physical examination showed diffuse thyroid enlargement, and thyroid profile, suppressed TSH and elevated thyroid hormones. Anti-TPO antibodies were positive. Initial treatment included methimazole and beta blockers. After twenty days, patient complained of malaise, fever, polyarthralgia, maculopapular rash, and leg swelling. ANA antibodies were negative; however, ANCA antibodies were positive. Methimazole was stopped and prednisone started. Her clinical evolution was good, and she received I. ANCA associated vasculitis related to thionamides are infrequent. These vasculitis affect small vessels of skin, however they can also affect kidneys and lungs. Arthralgia and myalgia are the classical symptoms. In most patients, symptoms disappear after cessation of drug. In some cases, glucocorticoid or immunosuppressive therapy are also needed.

Interferon-Alpha-Induced Destructive Thyroiditis Followed by Graves' Disease in a Patient with Chronic Hepatitis C: A Case Report

Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-alpha) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-alpha therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-alpha (pegIFN-alpha) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-alpha and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-alpha therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-alpha therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-alpha therapy and remained weakly positive after IFN-alpha therapy was discontinued.

Hipertiroidismo en niños y adolescentes / Hyperthyroidism in children and adolescents

Background: Hyperthyroidism (HT) prevalence is 0.1/100,000 children and 1/100,000 adolescents and Graves Disease is the most frequent etiology. Objective: To evaluate the clinical presentation, etiology and treatment in hyperthyroid children. Method: Retrospective review of clinical charts of children under 15 years-old, between June 2004 and August 2005. Hyperthyroidism diagnosis was performed with suppressed TSH and increased thyroid hormones levels. Etiological study was done by TRAb, ATPO, ATG, thyroid echotomography and I131 capture. Results: 26 patients were evaluated; 84.6 percent females and age at diagnosis was 9.8 +/- 3,5 years-old (range: 3,8 - 14,5). Goiter was the most frequent clinical sign (96,2 percent), tachicardy and swelling. Etiology: Graves Disease (73 percent),Hashitoxicosis (15,3 percent) and unknown etiology (11,5 percent). Treatment: 88,4 percent began with anti-thyroid drugs (DAT): 78 percent PTU and 22 percent Tiamazol. 62.5 percent became euthyroid after 6 months and 79.1 percent after 12 months. 31.5 percent of GD presented hypothyroidism at 6.3 +/- 4 months of DAT, requiring LT4 substitution. I131 was applied to 4 children (16.6 percent); 3 due to hepatic compromise pre or post PTU use and 1 girl for missing treatment, developing a thyrotoxic torment. Thyroidectomy was done in 2 patients (8.3 percent), both with GD; 1 for giant goiter without DAT response at 19 months and 1 for persistant hyperthyroidism after 25 months of DAT. 92 percent received (3-blockers (Propanolol) for adrenergic symptoms for 5 +/- 4 months. Conclusions: Goiter was the most frequent pediatric HT symptom and Graves disease the main etiology. DAT treatment control HT in 76.9 percent patients and no adverse reactions with I131 were observed. These resUIts promote DAT treatment as first line in HT management, prefering Tiamazol for its better adherence and less adverse reactions. Radioiodide therapy and thyroidectomy are alternatives if treatment fails...

El hipertiroidismo (HT) tiene una prevalencia de 0,1/100 000 en niños y 1/100 000 en adolescentes, siendo la enfermedad de Graves (EG) la etiología más frecuente. Objetivo: Revisar presentación clínica, etiología y manejo de niños con HT. Método: Estudio retrospectivo de fichas clínicas de niños con HT menores de 15 años, evaluados entre Junio/04 y Agosto/05. El diagnóstico de HT se hizo con TSH suprimida y hormonas tiroideas elevadas. El estudio etiológico se realizó en base a anticuerpos TRAb, ATPO, ATG; Ecotomograña tiroidea, y captación de I131. Resultados: Se evaluaron 26 pacientes; 84,6 por ciento fueron mujeres. Edad promedio al diagnóstico fue 9,8 +/- 3,5 años (rango 3,8 a 14,5). La presentación clínica más frecuente fue bocio (96,2 por ciento), seguidos por taquicardia y sudoración. Etiología: Enfermedad de Graves 73 por ciento, Hashitoxicosis 15,3 por ciento y etiología no precisada 11,5 por ciento. Manejo: 88,4 por ciento inician con drogas antitiroideas (DAT); 78 por ciento PTU y 22 por ciento con Tiamazol. 62,5 por ciento se hizo eutiroideo a los 6 meses y 79,1 por ciento a los 12 meses. El 31,5 por ciento de EG presentó hipotiroidismo a los 6,3 +/- 4 meses de uso de DAT, requiriendo sustitución con LT4. El I131 fue indicado a 4 niños (16,6 por ciento): en 3 casos por compromiso hepático importante pre o post uso de PTU y 1 niña por abandono de tratamiento y reingreso con tormenta tiroidea. Tiroidectomía: se indicó a 2 pacientes (8,3 por ciento), ambos con EG; uno por bocio gigante, sin respuesta a DAT después de 19 meses de uso y el otro por persistir hipertiroideo después de 25 meses de uso de DAT. El 92 por ciento recibió (3 bloqueador (propanolol) para manejo de los síntomas adrenérgicos, (5 +/- 4 meses). Discusión y conclusiones: El bocio es el síntoma principal en pediatría. La etiología más frecuente es la Enf de Graves. Las DAT permitieron controlar el HT en 76,9 por ciento de los pacientes, no observamos complicaciones con el uso de I131...

Efeito do propiltiouracil sobre a eficácia da dose terapêutica de iodo radioativo (I-131) no hipertiroidismo por doença de graves / The effect of propylthiouracil on the efficacy of radioiodine (I-131) therapy in gravesÆ hyperthyroidism / The effect of propylthiouracil on the efficacy of radioiodine (I-131) therapy in gravesÆ hyperthyroidism

Com objetivo de avaliar a influência das drogas antitiroidianas (AT) sobre a eficácia da dose terapêutica de iodo radioativo (DT), avaliamos retrospectivamente 226 prontuários de pacientes portadores de doença de Graves submetidos à DT no período entre 1990 e 2001: 58 pacientes sem antitiroidiano (AT), 119 em uso de propiltiouracil (PTU) e 49 em uso de metimazol (MMI). O estado funcional tiroidiano 9-12 meses pós-DT dividia os pacientes entre curados e não curados. Níveis elevados de T4 livre, captação de 131I em 24 h tiveram influência negativa sobre a taxa de cura, assim como menor dose de iodo administrada e maior volume do bócio (p< 0,05). O percentual de pacientes curados em uso de PTU previamente à DT foi de 70,2 por cento (84/119), enquanto nos pacientes em uso de MMI foi de 85,7 por cento (42/49), e de 84,5 por cento (49/58) nos pacientes sem AT pré-DT (p= 0,034). Em modelo de regressão multivariado, T4 livre > 4 ng/dl, maior volume do bócio, dose terapêutica < 10 mCi e o uso prévio de PTU tiveram relação com menores taxas de cura. Quando comparado ao grupo sem AT, concluímos que PTU implica em maior risco de falência pós-DT (OR= 3,13), o mesmo não ocorrendo com MMI (OR= 1,28).

Aiming at evaluating the effect of antithyroid drugs on the efficacy of radioiodine treatment (RAI) we retrospectively analyzed 226 patients with GravesÆ disease hyperthyroidism submitted to RAI between 1990 and 2001: 58 patients without any antithyroid drug (ATD) prior to RAI, 119 patients using propylthiouracil (PTU) and 49 patients using methimazole (MMI) prior to RAI. Clinical and laboratory parameters 1 year after RAI defined their clinical status (cured or not cured). High serum free T4 and 131-iodine uptake were negatively related with cure as well as lower RAI doses (mCi) and larger goiters (p< 0.05). The percentage of cured patients on PTU prior to RAI was 70.2 percent (84/119), while those on MMI was 85.7 percent (42/49), and 84.5 percent (49/58) of those without ATD prior to RAI (p= 0.034). On logistic regression analysis, free T4 > 4 ng/dl, large goiter, RAI dose < 10 mCi and PTU prior to RAI were related to lower cure rates. Compared to patients with no ATD prior to RAI, we concluded that the previous use of PTU implies in higher failure rates after RAI (OR= 3.13), an effect not observed in patients on MMI (OR= 1.28).

Tratamento clínico com drogas antitireoidianas ou dose terapêutica de iodo-131 no controle do hipertireoidismo na doença de graves: avaliação dos custos e benefícios / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis

Com o objetivo de avaliar os custos e a efetividade das 2 formas de tratamento mais utilizadas em nosso meio para a Doença de Graves, iodo radioativo e tratamento clínico prolongado, analisamos pacientes submetidos a essas terapias na região de Maringá, PR. Foram estudados 23 pacientes, 7 homens e 16 mulheres, com idade média de 35,4 anos, submetidos ao tratamento clínico, e 34 pacientes, 5 homens e 29 mulheres, com idade média de 39,4 anos, submetidos à dose terapêutica com iodeto de sódio (iodo-131). Após 2 anos de tratamento clínico com tiamazol (Tapazol®), 21 pacientes atingiram o eutireoidismo e dois permaneceram hipertireóideos. No grupo da dose terapêutica com iodeto de sódio (iodo-131), 21 pacientes evoluíram para o hipotireoidismo, enquanto que 13 atingiram o eutireoidismo. Para o cálculo do custo de cada modalidade de tratamento, analisamos o número de consultas necessárias durante o seguimento, exames complementares solicitados e medicações utilizadas, como tiamazol e/ou tiroxina. O grupo submetido ao tratamento clínico necessitou de maior número de consultas e exames, sendo que o custo médio foi de R$ 1.345,81 neste período de dois anos, enquanto que no grupo com iodeto de sódio (iodo-131) o valor médio foi de R$ 622,94. Assim, os custos da dose terapêutica com iodeto de sódio (iodo-131) foram 53,7 por cento menores do que o tratamento clínico com drogas antitireoidianas. Este trabalho demonstra que o tratamento com dose terapêutica com iodeto de sódio (iodo-131) apresenta um menor custo, sendo bastante efetivo no controle do hipertireoidismo na doença de Graves.

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5 percent lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

Thyrotoxicosis in children: treatment and outcome.

OBJECTIVES: To study the treatment modalities and the outcome of treatments of children with thyrotoxicosis or Graves' disease. MATERIAL AND METHOD: A retrospective study of 56 patients diagnosed with thyrotoxicosis from January 1992 to December 2004 was conducted. There were 44 girls and 12 boys (female to male ratio 3.7:1). The average age at diagnosis was 11.9 +/- 3.4 years. RESULTS: All patients were initially treated with antithyroid drugs, either propylthiouracil (n = 53) or methimazole (n = 3). All patients achieved euthyroidism within 8.4 +/- 3.3 weeks. Eleven patients are still on the treatment, and 45 patients have completed the treatment. Of these 45 patients, 38 (84.4%) remitted after antithyroid drug treatment of an average duration of 37.4 +/- 16.5 months (range 12-90), 4 patients (8.9%) chose radioactive iodine treatment and three patients (6.7%) underwent thyroidectomy. Of the 38 patients remitted with antithyroid drugs, eleven (28.9%) relapsed within 4-24 months. The relapsed patients remitted with a second course of antithyroid drugs in three patients, underwent radioactive iodine in seven patients, and thyroidectomy in one patient. Therefore, of the total 45 patients who had completed the treatment, 30 patients (66.7%) remitted with antithyroid drugs, eleven patients (24.4%) received radioactive iodine, and four patients (8.9%) underwent thyroidectomy. Using stepwise multivariate logistic regression, the authors could not identify any factors (including age, gender, family history of thyroid diseases, size of goiter, level of free T4, dosage and duration of antithyroid drugs) that would predict the remission of thyrotoxicosis with antithyroid drugs. CONCLUSION: Antithyroid drugs should remain the first-line therapy for treatment of thyrotoxicosis in children with a remission rate of 66.7%. The patients who are noncompliant or relapse after treatment with antithyroid drugs should be treated with radioactive iodine.

A Case of Hyperglycemic Hyperosmolar State Associated with Graves' Hyperthyroidism: A Case Report

Hyperglycemic hyperosmolar state (HHS) is an acute complication mostly occurring in elderly type 2 diabetes mellitus (DM). Thyrotoxicosis causes dramatic increase of glycogen degradation and/or gluconeogenesis and enhances breakdown of triglyc-erides. Thus, in general, it augments glucose intolerance in diabetic patients. A 23-yr-old female patient with Graves' disease and type 2 DM, complying with methimazole and insulin injection, had symptoms of nausea, polyuria and generalized weakness. Her serum glucose and osmolarity were 32.7 mM/L, and 321 mosm/kg, respectively. Thyroid function tests revealed that she had more aggravated hyperthyroid status; 0.01 mU/L TSH and 2.78 pM/L free T3 (reference range, 0.17-4.05, 0.31-0.62, respectively) than when she was discharged two weeks before (0.12 mU/L TSH and 1.41 pM/L free T3). Being diagnosed as HHS and refractory Graves' hyperthyroidism, she was treated successfully with intravenous fluids, insulin and high doses of methimazole (90 mg daily). Here, we described the case of a woman with Graves' disease and type 2 DM developing to HHS.

Plasmacitosis reactiva severa y agranulocitosis debido a metimazol / Severe reactive plasmocytosis and agranulocytosis associated with methimazol

El presente reporte muestra un efecto tóxico inusual asociado al uso de metimazol en el tratamiento de hipertiroidismo. Una niña de 14 años se presentó con fiebre, compromiso general y una tumoración eritematosa en el muslo izquierdo. Dos meses antes había sido diagnosticada de hipertiroidismo e iniciado metimazol a razón de 30mg/d. El laboratorio mostró: leucocitos en 1200/mm3 con 25 por ciento de neutrófilos, hematocrito en 31 por ciento y plaquetas en 350000/mm3. Se inició antibióticos y filgastrim y se debridó el abceso. Nueve días después los leucocitos estaban en 9200/mm3 con 55 por ciento de neutrófilos. La MO mostró una celularidad baja pero representada en un 80 por ciento por células plasmáticas, muchas de ellas atípicas. En resumen una mujer con enfermedad de Graves estando con metimazol desarrolló una severa agranulocitosis con plasmacitosis medular que simula mieloma múltiple y que mejoró con tratamiento.

Avaliação do tratamento clínico da doença de Graves / Evaluation of the medical treatment of Graves' disease (GD)

O tratamento da doença de Graves (DG) com drogas antitireoidianas (DAT) associa-se à remissão da doença em metade dos indivíduos tratados por no mínimo 6 meses, e o índice de recidiva é alto, variando de 60 a 80 por cento. A presença de fatores prognósticos de sucesso do tratamento medicamentoso da DG é tema de discussão na literatura. Neste estudo avaliamos a incidência de remissão e recidiva em resposta ao tratamento clínico da DG com diferentes esquemas de tratamento com as duas DAT disponíveis no Brasil (propiltiouracil - PTU e metimazol - MMI), bem como determinar a presença de possíveis fatores preditivos de remissão e recidiva da doença e o perfil de efeitos colaterais. Revimos, no Hospital Universitário Clementino Fraga Filho (HUCFF), prontuários de todos os pacientes submetidos ao tratamento clínico da DG (sem história de tratamento prévio) por pelo menos 6 meses e seguidos após a suspensão da DAT por no mínimo 12 meses. Foram identificados 127 pacientes (idades de 18 a 88 anos; média 39,3±12,8), nos quais remissão da doença foi observada em 58 (45,7 por cento) e recidiva em 31 deles (53,4 por cento), num período médio de 14,5±16,1 meses. Sexo, idade e tempo de duração dos sintomas antes do tratamento clínico não interferiram significativamente sobre as taxas de remissão e recidiva, enquanto a presença de bócio >40 gramas, oftalmopatia de Graves (OG) e uso de doses diárias de DAT >600mg de PTU / 60mg de MMI influenciaram negativamente a taxa de remissão. Além disso, pacientes que apresentaram níveis de TSH <0,4æIU/mL entre 4 e 5 semanas após a suspensão da DAT apresentaram maior probabilidade cumulativa de recidiva da doença. Nossos resultados confirmam que a taxa de remissão em longo prazo da DG tratada com DAT é relativamente baixa. Concluímos que a combinação de oftalmopatia, bócio >40g e uso de dose diária de PTU >600mg ou MMI >60mg relacionou-se fortemente ã341; ausência de remissão da DG. Ademais, observamos que a dosagem de TSH entre 4 e 5 semanas após a suspensão da DAT parece ser uma ferramenta útil na determinação da chance de remissão ou recidiva da doença.

Bloqueo auriculo-ventricular de primer grado en tirotoxicosis aguda / First degree atrio-ventricular block in acute thyrotoxicosis

El cuadro clínico de la tirotoxicosis incluye síntomas cardiovasculares variados. La taquicardia sinusal es el trastorno electrocardiográfico más frecuente y los trastornos de conducción son extremadamente raros como modo de presentación. Comunicamos un caso de bloqueo aurículo-ventricular de primer grado en una paciente con hipertiroidismo recién diagnosticado y que comenzó días antes de la consulta con un cuadro general inespecífico. Su evaluación ulterior demostró que se trataba de una tirotoxicosis aguda autoinmune, y su tratamiento con metimazol corrigió el trastorno totalmente. Se discuten los mecanismos fisiopatológicos involucrados y las implicancias clínicas desde el punto de vista del internista.