Evaluation of a coated-tube assay for antithyrotropin receptor antibodies in patients with Graves' disease and other thyroid disorders.

The detection of autoantibodies to the thyrotropin-receptor antibody (TRAb) is commonly used in clinical practice for the diagnostic assessment of Graves' disease (GD) and its differential diagnosis from toxic multinodular goiter (MNG) and autonomous adenoma. Additionally, TRAb assays can be useful during antithyroid drug treatment of GD to evaluate the risk of relapse and/or remission. The detection of TRAb was originally performed using a radioreceptor assay based on detergent-solubilized porcine thyroid membranes (TRAb). More recently new assays using purified porcine or recombinant human thyrotropin (TSH) receptor-coated plastic tubes (CT) have been developed (pCT-TRAb or hCT-TRAb). We have evaluated both assays (TRAb and pCTTRAb) in 300 individuals: healthy controls (n = 51); patients with GD before and after treatment (n = 200), patients with MNG (n = 29), and Hashimoto's thyroiditis [HT; n = 20]). All healthy controls and patients with HT had undetectable TRAb using both methods. Patients with active (not treated) GD had higher pCT-TRAb values (mean +/- standard deviation [SD], 58.2% +/- 20.3%, inhibition of TSH binding) compared to TRAb (41.2% +/- 15.4%, p < 0.01, Wilcoxon test). Results (as percent inhibition for both methods) had a positive and significant correlation (r = 0.68, p < 0.001). Moreover TRAb assay had a 97.3% sensitivity and 96.8% specificity; the pCT-TRAb sensitivity was 96.3% and specificity was 98.4% at a cutoff of 1.51 U/L. During treatment of GD, the TRAb method resulted in significantly lower (p < 0.05) values at 12, 24, and 30 months, while pCT-TRAb only exhibited significancy (compared to basal levels) at 30 months. The percent inhibition after 131I treatment of GD was significantly higher for pCT-TRAb (33.7 +/- 25.7) compared to TRAb (21.9 +/- 17.7, p < 0.01, Wilcoxon test). Only one patient with untreated MNG had a positive pCT-TRAb but negative TRAb value. Patients with MNG treated with 131I were divided into two groups: group 1 (only (131)I) or group 2 (hrTSH preceding (131)I). After MNG radioisotopic ablation, five patients had a positive pCT-TRAb and four had a positive TRAb (group 1) while in group 2, three patients had a positive pCT-TRAb and two had a positive TRAb assay. In conclusion, pCT-TRAb usually had higher percent inhibition values compared to TRAb in untreated GD, had a relatively lower decrease in percent inhibition values during treatment but exhibited a slightly increased sensitivity compared to TRAb. An advantage of the pCT-TRAb assay may be because of the coating system itself that might expose more receptor sites for the antibody.

Cardiovascular assessment of hyperthyroid patients with multinodular goiter before and after radioiodine treatment preceded by stimulation with recombinant human TSH.

Treatment of large multinodular goiter (MNG) with radioiodine preceded by recombinant human thyrotropin (0.1 mg rhTSH) has been shown to be a safe alternative for patients with comorbidities that preclude surgery. However, the increase in serum thyroid hormones that follows both treatments may be harmful for some patients, particularly those with underlying cardiovascular disease. In this study, we evaluated cardiac parameters (clinical, ECG, 24-h Holter, Doppler echocardiogram, treadmill stress test) in 27 of 42 patients (ages 42-80 years) with large MNGs who were treated with rhTSH before receiving 30 mCi radioiodine therapy. At baseline, 18 patients had subclinical and six patients had overt iodine-induced hyperthyroidism. All patients had a transient surge in serum levels of free T4 and total T3 into the hyperthyroid range after therapy. However, repeated cardiac evaluation did not show significant changes as compared with baseline evaluation. In conclusion, rhTSH stimulated RAI treatment of MNG did not affect structural and functional parameters of the heart, despite transient high-serum levels of thyroid hormones.

Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres.

OBJECTIVE: Patients with very large multinodular goitres, frequently found among elderly people, often suffering from cardiovascular or other disabling disorders, may be considered as unsuitable for surgery. We have evaluated the feasibility of relatively high-dose 131I therapy in such patients. As subclinical or clinical hyperthyroidism is commonly found in these patients, associated with a low radioiodine (RAI) uptake at 24 h, we pretreated a group of patients with a single intramuscular injection of recombinant human TSH (rhTSH 0.45 mg) in order to increase the uptake of the therapeutic dose of RAI. DESIGN AND PATIENTS: Forty-one patients with large, long-standing multinodular goitres, were recruited for this study. After a careful and detailed clinical and laboratory evaluation, 34 patients (28 women, six men) were included and randomly assigned to group 1 (control, n = 17, 15 women, two men, age 63.1 +/- 11.2 years) receiving only RAI. Patients in group 2 (n = 17, 13 women, four men, age 63.6 +/- 12.3 years) received the therapeutic dose of RAI, having been pretreated (24 h) with 0.45 mg of rhTSH. Both groups of patients were submitted to a low iodine diet, 4-6 months before RAI treatment, while seven thyrotoxic patients also received methimazole (40 mg/day) until they reached euthyroidism. Ultrasonographic studies were performed for all patients and fine-needle aspiration biopsy (FNAB) were performed on one or two nodules before RAI treatment. RAI was given as a single oral dose to the hospitalized isolated patients. Blood samples for thyroid function tests and serum thyroglobulin (Tg) were collected daily during the first week following RAI treatment, and at 1, 3, 6, 9 and 12 months thereafter. MEASUREMENTS: Goitre volume was estimated by computed tomography scan. Thyroid function tests (total T3, free T4, TSH and serum Tg) were assayed with commercial kits. Urinary excretion of iodine was assayed by the Sandell-Kolthoff method. RESULTS: After the RAI therapeutic dose, serum thyroid function tests were carried out daily for the first week and then on a monthly basis (1, 3, 6, 9 and 12 months). Serum TSH levels rose to a peak level of 45.9 +/- 19.1 mU/l (24 h) in group 2 returning to normal at 72 h. Free T4 serum concentrations rose significantly to 59.35 +/- 21.61 pmol/l at 48 h (in group 2) returning to normal at 7 days. Similarly, serum TT3 also peaked above normal levels only in group 2 (6.12 +/- 1.89 nmol/l) at 24 h. Serum Tg increased in both groups (significantly higher in group 2) and remained elevated during the following 12 months. Both groups had a significant reduction in goitre volume at 12 months (group 2: 57.8%vs. group 1: 39.7%, P < 0.05). Hypothyroidism was detected after RAI treatment, respectively, in 21.4% (group 1) and 64.7% (group 2), of the patients at 12 months. CONCLUSIONS: Our results indicate that the use of hTSH increased the efficacy of the RAI therapeutic dose. This was basically due to an increased uptake of the radionuclide (as a consequence of the higher serum TSH levels) and a more extensive distribution of 131I within the nodules of the multinodular goitre. A more intense radiation effect was reflected in there being a higher output of serum Tg and thyroid hormones (group 2). As a consequence this group had a significantly higher reduction of the goitre volume. Also incidence of hypothyroidism post-RAI was significantly higher in group 2. We concluded that pretreatment with rhTSH in elderly patients with large multinodular goitres increases the uptake of the RAI therapeutic dose, thereby significantly reducing the multinodular goitre volume and relieving the compressive symptoms with relatively few side-effects.

Aspectos ultra-sonográficos e prevalência da tireoidite pós-parto em gestantes sem disfunçäo tireóidea atendidas em hospital público de Säo Paulo / Ultrasonographic aspects and prevalence of thyroiditis postpartum in pregnant without thyroid dysfunction attended in public hospital at Säo Paulo

Avaliamos prospectivamente a funçäo, as imagens ultra-sonográficas e a auto-imunidade tireóidea em grupo racial heterogêneo de 800 mulhres grávidas, primíparas ou multíparas (1 a 7 gestaçöes prévias) atendidas em hospital universitário de Säo Paulo durante o pré-natal. Quarenta e seis pacientes foram excluídas do estudo por apresentarem diagnóstico confirmado de doença tireóidea antrior; das 754 restantes, 386 abandonaram o seguimento antes ou após o parto. Assim, a coorte avaliada no puerpério constituiu-se de 368 puérperas, examinadas aos 3, 6, 12 meses e no 2§ ano pós-parto. Embora 29 pacientes tenham tido aumento transitório daqueles anticorpos antitireóideos, caracterizando reaçäo de auto-imunidade, estes progressivamente declinaram ou tornaram-se negativos durante o puerpério. Entretanto, nenhuma destas evolui com disfunçäo tireóidea durante o acompanhamento. Quarenta e nove pacientes (13,3 por cento) desenvolveram progressivamente alteraçäo funcionais da tireóide (principalmente hipotireoidismo), provavelmente devido à TPP. Além disso, a continuaçäo do seguimento mostrou que em 18 a 24 meses, 42 mostraram níveis séricos de anti-TPO mais elevados, em comparaçäo aos valores do primeiro ano. Os fatores de risco para o desenvolvimento da TPP, presentes durante a gravidez, foram: (1) níveis relativamente baixos de anti-TPO, entre 60 e 100U/ml (risco relativo ou odds ratio de 3,1) e (2) alteraçöes estruturais ultra-sonográficas da tireóide no primeiro trimestre (odds ratiode 6,4). Concluímos que a prevalência de TPP em hospital público de Säo Paulo foi de 13,3 por cento, considerando as 368 pacientes seguidas. Em 29 puérperas foi diagnosticada forma transitória de reaçäo tireóidea auto-imune, caracterizada por elevaçäo dos níveis séricos de anti-TPO, que posteriormente regrediram.

Comparaçäo entre diferentes métodos para avaliar a presença de auto-anticorpos dirigidos ao receptor de TSH em pacientes com moléstia de Graves-Basedow / Comparison between different methods for evaluate the presence of autoantibodies against TSH receptor in patients with Graves-Basedow'disease

Auto-anticorpos anti-receptores de TSH (TSHRAbs) foram avaliados por dois diferentes métodos [TRAb, como porcentagem de inibiçäo de ligaçäo do TSH por anticorpos séricos e produçäo de AMP cíclico em cultura de células CHO expressando o receptor de TSH humano recombinante (CHO-rhT-SHR)] em 52 pacientes (36F/16M) com moléstia de Graves-Basedow (DGB), tanto antes do tratamento como aos 6 e 12 meses de terapia contínua com metimazol (40-60mg/dia) e L-tiroxina (100pg/dia); outros 20 pacientes tireotóxicos (12F/8M) foram tratados com doses individualizadas de radioiodo. Os TSHRAbs determinados pelo radioreceptorensaio foram positivos em 47/52 pacientes (90,4 por cento) com valor médioñEPM de 56,7ñ3,9 por cento, diminuindo significantemente aos 6 (40,5ñ3,2 por cento) e 12 meses (43,5ñ4,7 por cento) de terapêutica, bem como após radioiodo (30,7ñ4,5 por cento). Os TSHRAbs foram discriminados pelo bioensaio em todos os 52 pacientes com DGB ativa (1122ñ409 por cento). Após 6 e 12 meses de terapêutica houve decréscimo (näo significante) dos valores iniciais. Nenhum indivíduo do grupo controle normal (n= 80) apresentou TSHRAbs detectado por qualquer dos métodos. Portanto, a sensibilidade da pesquisa dos anticorpos pelo bioensaio, nos 52 pacientes com DGB ativa, foi maior que nos mesmos indivíduos avaliados pelo radioreceptorensaio. Houve correlaçäo positiva (r= 0,59; p<0,001) entre TRAb e CHO-rhTSHR. Concluímos que a pesquisa dos TSHRAbs, realizada quer pelo radioreceptorensaio como pelo bioensaio, constitui recurso útil para se avaliar a atividade autoimune na DGB.

Bioequivalência de preparaçòes comerciais de L-tiroxina (100 e 200µg): avaliação em pacientes hipotereóideos previamente tireoidectomizados / Bioequivalence of commercial formulations of L-thyroxine (100 and 200µg): evaluation in previously thyroidectomized hypothyroid patients

A bioequivaléncia e biodisponibilidade das preparações comerciais de L-tiroxina podem apresentar diferenças significativas entre si. O objeto do presente trabalho foi comparar variáveis séricas tireóideas (T4 e T3 totais, T4 livre e TSH endógeno) em pacientes previamente tireoidectomizados (há mais de 5 anos) e sem evidência clínica ou ecográfica de tecido glandular cervical remanescente. Os referidos parâmetros foram medidos, por 15 dias, a intervalos de tempo regulares, durante administração de solução oral de L-tiroxina (100pg), presumivelmente de absorção e biodisponibilidade ideais. Comparou-se, em seguida, a oscilação das mesmas variáveis com duas outras preparações comerciais, sob forma de comprimidos de L-tiroxina (LT4A e LT4B) nas doses de 100pg/dia e a seguir 200Ng/dia. Não se observou diferença significativa entre a solução oral e as duas preparações comerciais nos vários tempos de medida. Tampouco houve diferença significativa entre os comprimidos de L-T4A e L-T4B em doses de 100pg ou de 200pg/dia. Concluí-mos que ambas as preparações apresentam biodisponibilidade e bioe-quivaléncia adequadas nas condições utilizadas neste estudo.

Clinical evaluation of serum thyroglobulin measurements in the follow-up of patients with differentiated thyroid carcinoma

As concentraçöes séricas de tireoglobulina (Tg), T3, T4 e TSH foram analisadas em 52 pacientes com carcinoma diferenciado de tireóide após tireoidectomia total, enquanto a medicaçäo supressiva por L-tiroxina havia sido suspensa. Mapeamento ósseo, radiografia torácica e mapeamento radioisotópico de corpo inteiro (MRCI) foram igualmente solicitados. Os pacientes foram divididos em três grupos: G1) sem remanescente tissular tireóideo na área cervical (n=12); G2) com remanescente tissular tireóideo cervical mas sem metástases locais ou distantes (n=27); e G3) com a presença de metástases pulmonares, ósseas ou cervicais (n=13). As concentraçöes de Tg séricas foram, respectivamente (média DP): 99 + ou - 5,7 µg/L (G1), 29,9 + ou - 22,9 µg/L (G2) e 564,8 + ou - 833,4 µg/L (G3). Observou-se correlaçäo significativa entre os achados clínicos, a presença de MRCI positivo ou negativo e o nível de Tg sérica. As concentraçöes séricas de Tg revelaram-se mais sensíveis que o MRCI para detecçäo de eventual metástase, apesar de haver certo grau de superposiçäo de valores de Tg sérica entre os pacientes dos grupos 2 e 3. Em outro grupo de pacientes (n=141) com diagnóstico prévio de câncer de tireóide diferenciado, analisou-se a Tg sérica por método imunorradiométrico (IRMA), enquanto os indivíduos se achavam sob a açäo de doses supressivas de L-tiroxina. A Tg sérica mostrou-se näo detectável (<1,0 µg/L) em 94 por cento dos pacientes do grupo 1 (sem remanescente tireóideo) e em 75 por cento dos indivíduos do grupo 2. A Tg sérica variou de <1,0 µg/L até 88 µg/L nos pacientes dos grupos 3 e 4. Concluímos que o método IRMA usando dois anticorpos monoclonais é mais sensível e permite melhor acompanhamento, com mais segurança, do paciente com diagnóstico prévio de câncer de tireóide. Recomenda-se que a verificaçäo da Tg sérica seja realizada com um MRCI em pacientes tireoidectomizados, pelo menos na fase inicial.