Efectos adversos severos del Metimazol. Comunicación de dos casos y revisión de la literatura / Severe adverse effects of Methimazole. Communication of two cases and review of the literature

Los fármacos antitiroideos constituyen uno de los pilares del tratamiento del hipertiroidismo. En nuestro país solo se encuentra disponible el metimazol. Estas drogas han sido asociadas a múltiples reacciones adversas, la mayoría leves. Efectos adversos infrecuentes pero potencialmente letales como la agranulocitosis, hepatitis y el síndrome de artritis por antitiroideos, obligan a suspender el tratamiento. Comunicamos dos casos de complicaciones infrecuentes del tratamiento con metimazol.

Antithyroid drugs are one of the cornerstones in the management of hyperthyroidism. In our country, only methimazole is available. These drugs have been related to a variety of adverse reactions, most of them minor. Infrequent but potentially lethal side effects such as agranulocytosis, hepatitis and the antithyroid arthritis syndrome, demand drug cessation. We report two cases of infrequent complications of methimazole.

Reversible cardiomyopathy.

We report a case of reversible dilated cardiomyopathy, in a middle-aged male. The patient presented with severe left ventricular dysfunction and atrial fibrillation. Inspite of vigorous medical therapy there was only mild clinical improvement. Subsequently laboratory test results diagnosed it as hyperthyroidism and then specific thyrostatic treatment was added. There was a prompt clinical and hemodynamic improvement in the form of reversal of left ventricular dysfunction and achievement of sinus rhythm at the end of two weeks.

Impacto médico-social do tratamento medicamentoso da moléstia de Graves-Basedow em Hospital Público Universitário: avaliação retrospectiva e projeção prospectiva de conduta terapêutica / Cost-effectiveness of the clinical treatment of GraveÆs disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach

O objetivo do presente estudo foi avaliar esquema terapêutico medicamentoso para aumentar a aderência ao tratamento da moléstia de Graves-Basedow (MGB) em Hospital Público Universitário. Os pacientes foram selecionados segundo critérios rigorosos, que incluíam volume glandular inferior a 60cm³, origem da área urbana de São Paulo e não submetidos a terapia prévia da MGB. Receberam gratuitamente a medicação, eram avisados antecipadamente da data da consulta e acompanhados por um único médico durante todo o tratamento. Foram incluídos 229 pacientes, tratados inicialmente com metimazol (MMI - 60mg/dia) em dose única diária, seguindo-se com combinação de MMI (20mg) com LT4 (100æg) em dose única diária por 24 meses. Apenas 83 pacientes (36,2 por cento) completaram o protocolo quando foram subdivididos em 2 grupos, após a suspensão do MMI+LT4: Grupo 1 (n= 34), que permaneceram em remissão por 3 anos, e Grupo 2 (n= 49), que apresentaram recidiva da doença entre 2 e 36 meses. Os fatores preditivos associados à remissão foram: decréscimo do volume glandular, tireoglobulina sérica < 40ng/ml e valores séricos normais de anticorpos anti-receptor de TSH. Constatamos que apesar do planejamento cuidadoso, mais de 60 por cento dos portadores de MGB não completaram o protocolo e foram encaminhados a tratamento com radioiodo. Admitimos que esse baixo êxito terapêutico poderia ser melhorado mediante identificação dos fatores capazes de indicar quais pacientes estariam propensos a seguir um tratamento de longa duração.

Management of a Pregnant Patient with Graves' Disease Complicated by Propylthiouracil induced Agranulocytosis

Relapse and exacerbation of Graves' disease during pregnancy is rare, and thionamide induced agranulocytosis is an uncommon side effect. We report a case of a pregnant woman in her 24th week of gestation that experienced a relapse of Graves' disease that was complicated by propylthiouracil induced agranulocytosis. Following the discontinuation of propylthiouracil and administration of a broad-spectrum of antibiotics, agranulocytosis subsided within 10 days. A total thyroidectomy to avoid any future relapse was planned and a short course of a beta-adrenergic blocker and Lugol solution were prescribed before the operation. At the 28th week of gestation, a total thyroidectomy was performed without complications and thyroxine replacement therapy was commenced. At the 40th week of gestation, labor was induced and a 3, 370 g healthy male infant was born without clinical features of thyrotoxicosis. We report herein on the patient and the treatment options for this rare and complicated case.

Drogas antitiroideanas no tratamento da doença de Graves / Antithyroid agents in the treatment of Graves' disease

Quando prescritas corretamente, as tionamidas, que sao drogas antitiroideanas - no Brasil existem o propilitiouracil (PTU) e o metimazol (MMI) -, sao capazes de controlar o hipertiroidismo em praticamente todos os casos. Ultimamente vem se intensificando a discussao se o tratamento com tionamidas deve ser feito com baixas ou altas doses, levando-se em conta a taxa de remissao a longo prazo e os índices de efeitos colaterais. Contudo nao há consenso em relaçao a baixas e altas doses de tais medicaçoes, bem como a associaçao com hormônio tiroideano na tentativa de diminuir a recidiva da doença. Estes sao os aspectos discutidos no presente artigo.

Predictor of outcome of hyperthyroidism due to Graves disease: serum triiodothyronine/thyroxine ratio.

There is a proportionally greater increase in the serum T3 than Serum T4 concentration in patients with hyperthyroidism due to Grave's disease which results in an elevation of serum T3 to T4 ratio. The study was undertaken to investigate the alteration of serum T3 to T4 ratio in relation to the outcome of antithyroid drug therapy. 98 patients of hyperthyroid Grave's disease were studied and 78 patients had T3 to T4 ratio greater than 20 ng/microgram before therapy (normal range 14-20; mean 16.0) In 16 out of 78 patient T3 to T4 ratio remained high during a 18 months course of antithyroid drug therapy and in 13 of them (81%) hyperthyroidism recurred after stoppage of treatment. In the remaining 62 patients, the initial high T3 to T4 ratio became normal (< 20) during treatment and 34 of them (54.9%) had a remission of the disease after stoppage of the drug. Of the 20 patients in whom the initial T3 to T4 ratios were within normal range, the ratio remained normal during treatment and 16(80%) had a remission. Goiter size was larger in patients with high serum T3 to T4 ratio and reduction of goiter size occurred in some patients (59%) with decreasing T3 to T4 ratios. It is concluded that serum T3 to T4 ratio is a single and a useful predictor of the outcome of antithyroid drug therapy in patients with hyperthyroidism due to Grave's disease. A ratio greater than 20 throughout therapy indicates that the chances of relapse is high and a ratio below 20 either initially or during therapy is an indication of prolonged remission.

Role of goitrogens in iodine deficiency disorders & brain development.

Although iodine deficiency has primarily been implicated in the causation of goitre, the significant role played by food goitrogens in the etiology of iodine deficiency disorder (IDD) is being increasingly recognized. Impaired brain development is the major cause of concern in IDD. Detailed experimental studies were undertaken to ascertain various biochemical changes associated with developing brain in response to treatment with a goitrogens--thiocyanate. Addition of thiocyanate to food deprived of KI brought down significantly the circulating levels of thyroxine (T4) in rats. Nucleic acids and protein content in different regions of brain were significantly lowered in rat pups exposed to thiocyanate. The rate of microtubule assembly, which is detrimental for neurite growth was considerably lowered, thereby influencing both myelin deposition and synaptogenesis in developing brain. Goitrogen intake not only caused an adaptive increase in the activity of type II 5'-deiodinase, which governs availability of triiodothyronine (T3) in brain, it also increased the latter's binding to brain nuclear receptors under conditions of thiocyanate induced hypothyroid state. Addition of adequate quantities of KI mitigated thiocyanate induced alterations by restoring circulating level of thyroxine. These investigations suggest that goitrogens play a significant role in influencing biochemical events unique to developing brain.

Maladie de Basedow: Utilisation de doses elevees d'antithyroidiens de synthese dans la preparation a la chirurgie

With the intention to abridge the duration of the hospitalization for preparing Grave's disease to surgery, we have conduct a study about 30 patients. In 21 cases taken haphazardly without modification of the associate treatment, a treatment by 16 tab/day of antithyroid drugs was used that is to say the double of the habitual do sage. The normal rate of thyroid hormons was obtained after an average delay of 17 days under high quantities of antithyroid drugs against 29-46 days in the 9 patients under 8 tab/day that is to say one reduction of the hospitalization duration of 50%. We didn't note a singnificant difference for the undesirable effects of antithyroid drugs or the complications per and post surgery

Empleo del yodato sódico (Biloptin) en el tratamiento agudo de las complicaciones cardiovasculares severas del hipertiroidismo / Acute treatment of severe cardiovascular complications of thyrotoxic patients by sodium ipodate

Los cambios hemodinámicos del hipertiroidismo son atríbuidos al efecto cronotropo e inotropo cardíaco directo del exceso de T3, así como a cambios en la resistencia periférica. Recientes estudios han demostrado que el yopodato sódico disminuye rápidamente los niveles de T3 en más del 50 por ciento de los valores basales dentro de las 24 horas, al bloquear la conversión de T4 a T3. Este estudio muestra su utilidad en controlar las manifestaciones cardiovasculares severas del hipertiroidismo, en 5 casos de Enfermedad de Graves,evaluados en la Unidad de Cuidados Intensivos mediante cateterismo cardíaco con catéter Swan-Ganz, conectado a un computador Edward de gasto cardíaco y a un medidor de presión Twinbbean-Sanborn. A cada paciente se le administró una dosis de 3 gr. de yopodato p.o más Tapazol 45 mg/d 2 días antes, y se evaluó antes y durante 24 hrs post-yopodato la frecuencia cardíaca ( FC ), presión arterial diferencial ( PAdif ), presiones de aurícula derecha, ventrículo derecho, arteria pulmonar y capilar pulmonar, calculándose índice cardiáco ( IC ), resistencia sistémica total ( RST ) Y trabajo ventricular izquierdo ( TVI ), así como fracción de e yección ventricular izquierda ( FEVI ) mediante un ecocardiógrafo modo M y bidimencional. T3 se midió por radioinmunoensayo ( RIA ). Todos, excepto RST Y FEVI, estuvieron elevados basalmente, y disminuyeron significativamente desde las 3 hrs. después del yopodato, mientras RST se elevó a normal a 6 hrs. FEVI se mantuvo bajo, evidenciando compromiso ventricular izquierdo. Los cambios fueron paralelos a la caída de T3