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The relationship between thyroid status, including subclinical hypothyroidism (SH) and serum leptin is controversial or uncertain. Therefore we evaluated serum leptin in SH and overt hypothyroidism (OH) and determined the effects of levothyroxine (LT(4)) replacement on serum leptin in these disorders.Serum leptin, thyrotropin (TSH), free thyroxine, insulin, glucose, and body composition parameters were compared in 55 SH, 20 OH, and 28 euthyroid (EU) pre- and postmenopausal women. In addition, the effect of LT(4) treatment on serum leptin in SH and OH was assessed.The mean +/- SD (median) serum leptin concentrations in the OH and SH groups were higher than in the EU group (35.1 +/- 27.2 [33.0] and 36.6 +/- 21.9 [30.6] ng/mL, respectively, vs. 23.2 +/- 19.3 [17.9] ng/mL, p = 0.011), but the difference was only significant in postmenopausal women. The body mass index (BMI), fat mass index (FMI), and the homeostasis model assessment-insulin resistance (HOMA-IR) index values were not different among these groups. In premenopausal women there was no correlation between leptin, BMI, or FMI and serum TSH levels (r(s) = 0.009, p = 0.474; r(s) = 0.043, p = 0.367; r(s) = 0.092, p = 0.232). In the postmenopausal women, the partial correlation coefficient between TSH and leptin was present, even when controlling for BMI (r(s) = 0.297, p = 0.042) and FMI (r(s) = 0.275, p = 0.050). LT(4) treatment was associated with a reduction of serum leptin concentrations in the OH group (p = 0.008). In SH group there were no differences between LT(4) replacement or no treatment, since a fall in serum leptin levels was detected in both SH subgroups, despite a more pronounced fall with LT(4) use. Treatment of the SH and OH groups with LT(4) did not influence HOMA-IR index or body composition.Serum leptin concentrations are elevated in postmenopausal women with SH or OH. A relationship between thyroid status and serum leptin is further supported by the fact that LT(4) treatment, to restore the EU status, reduced serum leptin levels in OH in the absence of significant effects on BMI. In women, hypothyroidism influences either leptin secretion or degradation and this effect is more pronounced in postmenopausal than in premenopausal women.

The aim of this study was to evaluate the lipid profile of patients with different degrees of hypothyroidism and the effect of levothyroxine replacement in subclinical hypothyroidism (SH). Initially, a cross-sectional study was performed with 226 participants [SH = 133 participants, manifest hypothyroidism (MH) = 23 participants, and euthyroidism (EU) = 70 participants]. The mean levels of atherogenic lipid variables were greater in MH than in SH and were greater in SH than in EU, although the differences between SH and EU did not reach statistical significance. The SH subgroup with greater serum thyrotropin (TSH) levels and that with positive antithyroperoxidase antibodies (TPO-Ab) had greater levels of triglycerides and of the atherogenic index Apo B/Apo A. A positive correlation exists between serum TSH and total cholesterol (rs = 0.167; P = 0.006), triglycerides (rs = 0.219; P0.001), and ApoB levels (rs = 0.205; P0.001). Eleven patients who received levothyroxine (L-T4) treatment and 15 patients who received placebo were reevaluated 1 year after TSH adjusted intervention. A fall in atherogenic variables was observed in the L-T4-treated group, with significance for total cholesterol (-20.0 vs +16.1 mg/dL in the placebo group) and LDL-c (-21.7 vs +17.2 mg/dL). We concluded that SH leads to an intermediary lipid profile between euthyroid individuals and that found in manifest hypothyroidism and that a significant lipid profile improvement occurred 1 year after L-T4 replacement therapy.

Objective: Treatment of Graves' disease (GD) with antithyroid drugs (ATD) leads to remission of the disease in approximately half of patients treated for at least 6 months. The overall relapse rate is high. Prognostic features that predict a remission after medical treatment are still a matter of controversy in the literature. The aim of this study is to evaluate the uuse of clinical and laboratory data for predicting a remission of GD after 12 months of treatment with ATD. Methods: The study included 46 previously untreated patients who were treated for 12 months and followed for at least 12 months after drug withdrawal. Results: Remission was observed in 25 patients and there was only 1 relapse. Greater duration of symptoms before the beginning of medical treatment, large goiter and high baseline levels of serum free T4, total T3, TRAb, and TPOAb were associated with a decreased remission rate. Individuals who presented a thyroid-stimulating hormone measurement Conclusion: Our results confirm that the rate of lasting remissions of GD treated with ATD is relatively low. Initial goiter size, duration of symptoms and baseline T3, free T4, TRAb, and TPOAb can select a subgroup of patients with GD who will most likely benefit from antithyroid drug treatment as a first choice.

O hipotireoidismo subclínico (HS) já foi associado a aumento do risco cardiovascular. Na avaliação desse risco, a medida da espessura íntima-média (EIM) carotídea por ultra-sonografia é capaz de detectar alterações iniciais da aterosclerose. O objetivo deste estudo foi avaliar a EIM carotídea em pacientes com HS e sua associação com um provável aumento do risco cardiovascular. Não foi encontrada diferença significativa nas medidas da EIM das pacientes com HS e das controles. Os resultados encontrados nos dois grupos estudados foram, respectivamente: 0,573 ± 0,070 mm vs. 0,576 ± 0,068 mm para as carótidas comuns (p= 0,904) e 0,602 ± 0,079 mm vs. 0,617 ± 0,102 mm para as bifurcações (p= 0,714). Mesmo após estratificação das pacientes de acordo com o TSH e com a presença ou não de auto-imunidade, a diferença entre os sub-grupos permaneceu sem significância estatística. As medidas da EIM nesses grupos nos sítios avaliados foram: TSH 4-8 mUI/L: 0,579 ± 0,070 mm e 0,586 ± 0,063 mm; TSH > 8 mUI/L: 0,569 ± 0,073 mm e 0,616 ± 0,091 mm; anti-TPO+: 0,585 ± 0,070 mm e 0,621 ± 0,085 mm; anti-TPO-: 0,554 ± 0,072 mm e 0,571 ± 0,066 mm. Também não houve diferença no lipidograma e nas dosagens de apoproteína B e de lipoproteína (a). Este fato sugere que o HS, quando leve, sem alterações metabólicas associadas, não promove aumento do risco cardiovascular.

Treatment of Graves disease (GD) with antithyroid drugs (ATD) leads to remission of the disease in approximately half of patients treated for at least 6 months and the overall relapse rate is high. A few small prospective trials have considered methimazole (MMI) somewhat more effective and safer in lower doses than propylthiouracil (PTU), but the choice between the drugs has been a matter of personal preference. The aim of this clinical trial is to evaluate the effect of different ATD regimens on remission rates of GD and on the side effect profiles. The study included 55 previously untreated patients with GD who were randomized in 2 groups: 40 to 60 mg methimazole daily was prescribed to 30 patients and 200 to 300 mg propylthiouracil every 12 hours was prescribed to 25. The patients were treated for 12 months and followed for 12 to 38 months after drug withdrawal. Fifteen patients of 21 in the PTU group (71.4%) and 10 of 25 in the MMI group (40.0%) reached 1-year remission of GD (P 0.04), but there was no statistical difference between the drug regimes after adjusting for antithyroid- stimulating hormone receptor antibody (TRAb) levels. Among the 25 patients who reached 1-year remission, relapse occurred in one case at 18 months after drug withdrawal. All patients presented good compliance and only 2 patients developed minor side effects. During the treatment, both drug groups showed a significant fall in serum TRAb and thyroid peroxidase autoantibody titers, and the TRAb levels observed in the MMI group were consistently higher. There- fore, in our study, there were no significant differences between PTU and MMI groups in relation to remission rate, side effect profiles, and compliance rates. Furthermore, individuals with higher baseline antibody titers presented a lower probability of long term remission of GD.

Objectives: Recently, studies have shown an association between antiperoxidase for the detection of thyroid autoimmunity (TAI) and abortion. Another point to be considered is the association of high risk of abortion and maternal age. The aim of the present study was to evaluate if the association between TAI and miscarriage could also be verified whether a population of unselected pregnant young women who normally present a low risk of miscarriage. Materials and methods: We studied 534 pregnant women, by determining their serum thyroid antiperoxidase antibodies (TPO-Abs), thyrotropin (TSH) and free thyroxine (fT4) levels. Our end point was the pregnancy loss or live birth. Results: Age ranged from 12 to 49 years (mean ± S.D.; 23.5 ± 5.9). Of 534 women, 29 (5.4%) were TPO-Ab positive. TSH levels were significantly higher in TPO-Ab-positive women compared with TPO-Ab negative women (median; 1.9 versus 1.1; P = 0.001). Elevated TSH levels were found in 13.8% (4 of 29) of the TPO-Ab-positive women compared with only 2.4% (12 of 505) in the TPO-Ab-negative women. There were no significant differences in fT4 levels in relation with autoimmunity and risk of miscarriage. The overall risk of miscarriage was 2.4% (13 of 534). Risk of miscarriage was significantly higher among women older than 35 years (7.7%), TPO-Ab positive (10.3%) and presenting high levels of TSH (12.5%). These factors remained independently associated with the risk of miscarriage in full multivariate analysis. Conclusions: We conclude that TAI is independently associated with is a higher risk of miscarriage in a population of unselected pregnant presenting a low risk of miscarriage.

De-differentiated thyroid carcinoma is characterized by loss of thyroid-specific functions and properties. The therapeutic options for this type of thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte and tumor regression after 131I therapy. The aim of the present study was to assess the effects of RA therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. A total of 5 patients (1 follicular carcinoma, 3 papillary carcinomas and 1 poorly differentiated carcinoma) were treated with isotretinoin (1.0 to 1.5 mg/kg/day) for 5 weeks and then submitted to radioiodine therapy. Three parameters for assessment of RA effects were established: a) reduction of serum thyroglobulin levels; b) increment of the post-therapeutic dose radioiodine uptake; c) tumor size regression after therapy. All patients completed the treatment and the most frequent side effects were dry skin and lips and hypertriglyceridemia. One patient showed satisfactory response (2 or more of the 3 criteria were reached) and a new cycle of RA was given. In two, just a partial response (1 criterion) was seen and the other patients did not respond. Based on these results, isotretinoin might be an option for de-differentiated thyroid cancer, with low rate of severe side effects, especially when compared with cytotoxic drugs. Aggressive thyroid cancer frequently needs multimodal adjuvant therapy.

O presente trabalho objetiva verificar a presença de alterações músculo-esqueléticas em pacientes com HS. Avaliados 31 pacientes acompanhados no ambulatório de endocrinologia do HUCFF-UFRJ (27 mulheres e 2 homens com idade entre 18 e 75 anos) com pelo menos duas dosagens elevadas de TSH. Todos receberam uma pontuação (score) baseada na escala de Billewicz modificada por Zulewski. Foram aplicados testes musculares manuais (TMM) para as cinturas escapular e pelvica; medida a força muscular de quadríceps em dinamômetro de cadeira eletromecânico; e estimada a força dos músculos inspiratórios através do registro da pressão inspiratória máxima com manovacuômetro. Score < 3 (normal) foi observado em 11 pacientes (35,5%); entre 3 e 5 (disfunção subclínica) em 14 (45,1%) e superior a 5 (hipotireoidismo) em 6 (19,4%). Fadiga foi uma queixa freqüente (45%) e apresentou associação positiva com score maior que 2. O comprometimento da força muscular periférica (alteração no TMM) foi encontrado em 14% dos pacientes. Diminuição grave da força inspiratória (< 60% do previsto) estava presente em 28 participantes (51,6%). Nenhuma das demais alterações encontradas mostraram associação com o escore ou níveis de TSH. A redução da força muscular inspiratória e proximal pode contribuir para a referida fadiga. A ausência de associação estatística entre essas variáveis deverá ser melhor esclarecida com o aumento da amostra e com a inclusão de um grupo controle pareado além do desenvolvimento de um estudo prospectivo com utilização de levotiroxina e placebo.

Carcinoma tireoideano é a neoplasia endócrina maligna mais freqüente. Aproximadamente 90% dos cânceres não-medulares da tireóide são classificados como diferenciados e apresentam em geral bom prognóstico após tratamento adequado. Entretanto, recidiva tumoral ocorre em cerca de 20 a 40% e perda da diferenciação celular em até 30%. O carcinoma desdiferenciado é caracterizado pela perda da função e propriedades tireóide-específicas e as opções terapêuticas são limitadas e pouco eficazes. Em estudos recentes in vitro, tem sido mostrado que o acido retinóico (AR) pode ser útil em induzir rediferenciação da célula tireoideana, como evidenciado pela maior expressão de tireoglobulina, 5' desiodase tipo I e co-transportador sódio-iodeto, além do incremento da captação de iodo pela célula tumoral. Além dos estudos experimentais, estudos clínicos demonstram efeito benéfico do AR, com aumento da captação de iodo em 40% e regressão tumoral em 20% dos pacientes com carcinoma não captante de iodo submetidos ao tratamento. Thyroid carcinoma is the most common endocrine malignancy. Approximately 90% of non-medullary thyroid malignancies are classified as well-differentiated thyroid carcinomas. Even though this type of tumor is not aggressive and usually curable after therapy, recurrence develops in 20-40% and progression to cellular de-differentiation occurs in up to 30% of patients. Poorly differentiated cancers are characterized by loss of thyroid-specific functions and properties, such as the capacity to concentrate radioiodide. Therapeutic options for de-differentiated thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte in vitro, as suggested by increased expression of thyroglobulin, type I iodothyronine 5'-deiodinase and the sodium/iodide symporter, and by the increment of cellular iodide uptake. Clinical research demonstrated beneficial effects of RA, with 40% of patients with radioiodine non-responsive tumor showing increase of iodide uptake and 20% tumor regression, after RA treatment.

Pulse therapy with steroids has been advocated as an effective therapy for Graves’ ophthalmopathy, followed or not by external radiotherapy, if more than one course fails or when side effects are not tolerated. Nineteen patients with Graves’ ophthalmopathy were treated with methylprednisolone IV pulses and a maintenance oral prednisone dose between pulses. Ten patients subsequently were sub-mitted to orbital radiotherapy because of recurrence of inflammatory signs and symptoms. Eight patients exhibited significant improvement after pulse therapy, and seven patients had a lesser response; inflammation showed significant regression in most patients, and proptosis improved in eight. Radiotherapy resulted in slight improvement in three patients and significant improvement in the other four. Proptosis regressed partially in three patients and completely in two. Diplopia disappeared in one patient, and visual acuity improved in five. Our results with steroid pulse therapy are comparable with other series reported in the literature, while other results with radiotherapy are less favorable.

Cardiac manifestations in hyperthyroidism (HT) are very common and have varied clinical aspects. Reports of tricuspid regurgitation (TR) and pulmonary arterial hypertension (PAH) are, however, infrequent because neither is often symptomatic. TR in HT is functional and secondary to the right ventricle (RV) dilatation as a result of the increased venous return. The exact mechanism of the PAH in HT is not known but could be related to the hyperkinetic state of thyrotoxicosis or an autoimmune phenomenon. Four cases of PAH and TR occurring in association with HT are described.

OBJECTIVES: Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. SUBJECTS AND METHODS: We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. RESULTS: Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. CONCLUSIONS: Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.

OBJECTIVE: To evaluate the effects of levothyroxine (L-T4) replacement in echocardiographic parameters of middle-aged women with subclinical hypothyroidism (SH). SUBJECTS AND METHODS: This was a randomized, double-blind, placebo-controlled study. Echocardiographic evaluation was carried out at baseline and one year after restoration of euthyroidism. Thirty-three women with SH were assigned to one of two groups (L-T4 or placebo). RESULTS: The two groups had similar basal characteristics. There was a significant deterioration of left ventricular Tei index after one year of placebo use, which differed from the effect of L-T4 replacement (+0.086 ± 0.092 vs. -0.014 ± 0.012; p = 0.047). There was also a slight reduction in cardiac output and cardiac index with placebo use, which was not different from L-T4 effect. CONCLUSION: Results suggest a positive impact of L-T4 replacement in cardiac function of middle-aged women with SH. OBJETIVO: Avaliar os efeitos da reposição de levotiroxina (L-T4) nos parâmetros ecocardiográficos em mulheres de meia-idade com hipotireoidismo subclínico (HS). SUJEITOS E MÉTODOS: Realizado estudo duplo-cego, controlado com placebo com avaliação dos parâmetros ecocardiográficos no início e um ano após o restabelecimento do eutireoidismo. Trinta e três mulheres foram incluídas em dois grupos (uso de L-T4 ou placebo). RESULTADOS: Os dois grupos tinham características basais similares. Houve uma significativa piora do índice TEI do ventrículo esquerdo no grupo que usou placebo por um ano. Já no grupo em reposição com L-T4 observou-se uma leve melhora desse índice (+0,086 ± 0,092 vs. -0,014 ± 0,012; p = 0,047). Ocorreu também uma leve redução no débito cardíaco e no índice cardíaco com placebo, os quais não diferiram do efeito da reposição de L-T4. CONCLUSÃO: Os resultados sugerem um impacto positivo com a reposição de L-T4, na função cardíaca de mulheres de meia-idade, com HS.

Objective To describe a case of bilateral orbital lymphoma mistakenly diagnosed as Graves’ ophthalmopathy. Methods We present a case report, with laboratory data and photographic documentation, and discuss the differential diagnosis in patients with orbital masses. Results A 65-year-old man with bilateral exophthalmos and substantial weight loss was referred to the Endocrine Clinic for evaluation of possible Graves’ disease. A 6-cm mass was detected in the left axilla. Biopsy of this mass revealed the histopathologic diagnosis of anaplastic B-cell lymphoma. Treatment with intrathecally administered methotrexate and orally administered dexamethasone promptly resulted in decreased proptosis. Conclusion The most frequent cause of bilateral proptosis is Graves’ ophthalmopathy, and when it is associated with weight loss in an elderly patient, the initial diagnostic consideration is thyrotoxic Graves’ disease. This case should remind physicians that bilateral orbital lymphoma, although uncommon, may mimic Graves’ ophthalmopathy. (Endocr Pract. 2001;7:110-112)

OBJECTIVE: To evaluate the frequency of thyroid cancer and thyroid dysfunction in first-degree relatives of thyroid cancer patients, and to determine if there is a difference between familial and sporadic thyroid cancer. SUBJECTS AND METHODS: Fifteen first-degree relatives of seven families with at least two family members with thyroid cancer (TC) were compared with 128 first-degree relatives of 45 families with only one family member affected. Laboratory and ultrasound evaluation, fine-needle aspiration biopsy and thyroid surgery were used as normally done in clinical practice. RESULTS: Thyroid dysfunction was similar between the two groups. The frequency of TC and autoimmunity in the group that had two relatives with known thyroid cancer was higher, compared with the families that had sporadic thyroid cancer among their family members (40% vs. 2%, p = 0.0001). CONCLUSION: Frequency of TC increases when more than one member of the family is affected. These findings suggest that these relatives should be screened more frequently than individuals in families in which only one case of TC is observed.

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40% of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (131I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg-1·day-1 for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8%, a stable disease rate in 25% and a progression disease rate in 56.2%. Five patients died (62.5%) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

OBJETIVO: Avaliar a mudança no perfil e abordagem dos pacientes com doença de Graves submetidos a dose terapêutica de radioiodo. MATERIAIS E MÉTODOS: Avaliamos, retrospectivamente, 226 pacientes portadores de doença de Graves submetidos a dose terapêutica de radioiodo entre janeiro de 1990 e dezembro de 2001. O período de 12 anos foi dividido em três períodos de 4 anos para fins de análise estatística, sendo comparadas variáveis clínicas e laboratoriais nos períodos descritos. RESULTADOS: Constatamos que o número de pacientes encaminhados para a dose terapêutica, assim como o percentual de pacientes do sexo feminino (de 62% para 86%; p = 0,005), tiveram incremento significativo. Houve aumento significativo no percentual de pacientes em uso de metimazol previamente à dose terapêutica (de 9,1% para 35,6%; p = 0,03). A dose média de iodo administrada também teve incremento significativo (de 7,6 mCi para 12,7 mCi; p = 0,000003), com reflexo direto em um maior percentual de pacientes curados (de 55,6% para 83,7%; p = 0,004) um ano pós-dose terapêutica. CONCLUSÃO: A dose terapêutica de radioiodo tem sido um método cada vez mais aceito nos pacientes com doença de Graves e a dose administrada tem sido cada vez maior, no intuito de cura permanente e diminuição das chances de recidiva. OBJECTIVE: To evaluate the changes in clinical parameters and in the approach to patients submitted to radioiodine therapy for Graves' disease. MATERIALS AND METHODS: Dossiers of 226 patients submitted to radioiodine therapy for Graves' disease in the period between January 1990 and December 2001 were retrospectively evaluated. For the purposes of statistical analysis, the 12-year period was subdivided into three periods of 4 years, with a comparison of clinical and laboratory variables in these periods. RESULTS: The authors have observed that the total number of patients referred for radioiodine therapy as well as the percentage of female patients presented a significant increase (from 62% to 86%; p = 0.005). The percentage of patients pretreated with methimazole before radioiodine therapy increased significantly (from 9.1% to 35.6%; p = 0.03). The mean radioiodine dose delivered has also presented a significant increase (from 7.6 mCi to 12.7 mCi; p = 0.000003) with a direct reflection on a higher percentage of patients cured one year after the radioiodine therapy (from 55.6% to 83.7%; p = 0.004). CONCLUSION: Radioiodine therapy has increasingly been accepted for treatment of patients with Graves' disease and the doses delivered have increased to achieve a permanent cure as well as a reduction of the chances of recurrence.

Problem To investigate the utility of thyroid peroxidase antibodies (TPOAb) in early pregnancy combined with clinical information for prediction of postpartum thyroid dysfunction (PPTD) within 1 year postpartum. Method of study We studied 98 pregnant women by determining their TPOAb levels in early pregnancy, as well as their serum thyrotropin and free thyroid (fT4) levels at 6 and 12 months postpartum. Furthermore, they answered a questionnaire and physical examination was performed by only one examiner. Results Of the 98 women, 10 were positive TPOAb in early pregnancy. The overall risk of PPTD within 1 year of follow-up was 10.2% (95% CI 4.1–16.3). Risk of PPTD was significantly higher among women with a family history of thyroid disease, TPOAb positive and presenting goiter in early pregnancy. The sensitivity, specificity and positive predictive value of TPOAb in PPTD prediction were 60.0%, 95.5% and 60%. Restricting screening to women with a family history of thyroid disease or presenting goiter increases the positive predictive value from 60% to 82.4%. Conclusion Our results suggest that TPOAb could be used as a screening test for PPTD prediction at least among women who present a high risk of developing PPTD.

A classificação TNM segundo a UICC é usada para avaliar os resultados do acompanhamento do carcinoma de tireóide. A 6ª edição modificou a descrição do tumor primário (T), dos linfonodos regionais (N) e dos grupos de estadiamento. O objetivo deste estudo foi comparar a habilidade das 5ª e 6ª edições em predizer resultados. As duas classificações foram aplicadas em uma análise retrospectiva de 90 pacientes do HUCFF. Sessenta e nove pacientes apresentavam carcinoma papilífero, 14 folicular, 4 células de Hürthle e 3 misto. Os pacientes foram acompanhados por um período médio de 58,3 meses. Ao final do acompanhamento, 49 pacientes estavam em remissão, 23 com doença persistente, 4 com recorrência tumoral, 11 com metástases e 3 evoluíram para o óbito. De acordo com a 6ª edição, 19 pacientes foram classificados como T1, comparado com 7 pela 5ª edição; 19 pacientes T2 comparado com 30; 14 classificados como T3 comparado com 10; 22 como T4 comparado com 27, e 16 pacientes como Tx. Ambas as edições mostraram remissões comparáveis para os estágios I, II e III. Para o estágio IV houve uma mudança significativa na remissão, entretanto não houve diferença comparando IV e IV C.

Summary Objective Subclinical hyperthyroidism (SH) has been associated with exercise intolerance, changes in cardiac morphology, atrial arrhythmias and sympathovagal imbalance. The aim of this study was to evaluate the vagal reserve and modulation by a sympathetic stimulus in nonelderly patients with SH without cardiovascular problems. Design We carried out a cross-sectional study, comparing data of the heart rate variability (HRV) of SH patients and healthy controls at rest and after vagal and sympathetic stimulation. Patients We studied 16 female patients with at least 6 months of SH and 16 healthy female controls with the same median age (40 vs. 34·5 years). Measurements We used the tilt test, with electrocardiographic record at rest, during the respiratory sinus arrhythmia (RSA) manoeuvre and after tilting, in order to analyse HRV in the frequency domain (%high frequency (HF) and low/high frequency ratio (LF/HF) using Biopotentials Captation System software. Results The median TSH level was 0·03 mU/l in patients and 1·37 mUI/l in controls. The median free T4 was 1·37 ng/dl in patients and 1·20 ng/dl in controls. Patients demonstrated a significantly smaller difference between %HF during the RSA and %HF at rest than controls (median –7·5 vs. 36·6, P

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% (84/119), enquanto nos pacientes em uso de MMI foi de 85,7% (42/49), e de 84,5% (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).

Subclinical hyperthyroidism (SH) may be responsible for many cardiovascular changes, including an impaired exercise performance. The aim of our study was to evaluate the response to the treadmill cardiopulmonary test in patients with SH. We studied 14 female patients from our endocrine clinic with exogenous SH, free from cardiovascular diseases, with mean age of 38.6 +/- 10.2 years, body mass index (BMI) of 24.4 +/- 4.0 kg/m(2), and disease duration of 4.9 +/- 4.9 years. The mean serum thyrotropin (TSH) was 0.03 +/- 0.03 mU/L, serum free thyroxine (FT(4)), 1.72 +/- 0.21 ng/dL, and serum triiodothyronine level, 137 +/- 32 ng/dL. The control group comprised 15 euthyroid, healthy women, with mean age of 35.4 +/- 7.4 years and BMI of 27.3 +/- 5.9 kg/m(2). Both groups had a sedentary lifestyle and underwent the cardiopulmonary test using a treadmill with the Balke protocol. Gas concentrations and the respiratory outflow were measured and the electrocardiogram (ECG) was registered in real time. We calculated the minute ventilation (V(E)), the oxygen consumption (peak VO(2)), the carbonic gas exhalation (peak VCO(2)) and the anaerobic threshold (AT). The heart rate (HR) at rest (90.9 +/- 15.7 versus 78.9 +/- 8.7 beats per minute; p = 0.03) was higher in the patients from our clinic. There was no difference between groups regarding age, BMI, fat percentage, blood pressure, peak HR, exercise duration, mean treadmill peak inclination, V(E), peak VO(2), peak VCO(2), and AT. There was no correlation between peak VO(2) and FT(4), TSH, or disease duration. Our results show that exercise capacity in young and middle-aged female patients is not significantly affected by exogenous SH.

OBJETIVO: avaliar a influência do hipertiroidismo na evolução da gravidez e a necessidade de ajustes na dose de antitiroidianos neste período e no pós-parto. MÉTODOS: avaliação prospectiva de dados clínicos e laboratoriais de treze gestações em onze mulheres com hipertiroidismo devido à doença de Graves, com dosagem de TSH e T4 livre a cada trimestre ou quatro semanas após ajuste do antitiroidiano. O objetivo foi manter o T4 livre no terço superior da normalidade usando a menor dose possível de antitiroidiano. RESULTADOS: a média de idade no início da gravidez foi de 31,1 anos (23 a 41). Houve redução da dose de antitiroidiano em oito gestações (69,5%) e, em duas, a droga foi suspensa. Antes da gravidez, a dose média de propiltiouracil era de 400 mg/dia (200 a 900) e a de metimazol, 45 mg/dia (20 a 60). Após o parto, a dose dos antitiroidianos foi reduzida para 200 e 30 mg/dia, respectivamente. Uma paciente apresentou parto prematuro (36ª semana de gestação) e outra, recém-nato pequeno para a idade gestacional (2.000 g com 38 semanas de gestação). Houve um caso de natimortalidade. Não houve abortamentos ou anomalias congênitas. Após o parto, a dose de antitiroidiano foi aumentada em sete pacientes e mantida nas demais. CONCLUSÕES: recomendamos acompanhamento rigoroso de gestantes hipertiroidianas e titulação decrescente da dose dos antitiroidianos no decorrer da gestação, com o intuito de evitar o hipotiroidismo materno e suas conseqüências no desenvolvimento fetal. O acompanhamento após o parto dever ser cuidadoso, já que há a possibilidade de nova exacerbação do hipertiroidismo. O uso dos antitiroidianos foi seguro para as pacientes e sua prole. PURPOSE: to evaluate the influence of hyperthyroidism during pregnancy and the necessity of changing antithyroid drug dose in this period and after delivery. METHODS: prospective evaluation of clinical and laboratorial findings of thirteen pregnancies in eleven pregnant women with hyperthyroidism due to Graves' disease. These women were evaluated through TSH and serum free T4 at each trimester or four weeks after setting thionamide dosage. The goal was to maintain free T4 in the superior third of the normal range using the lowest possible thionamide dose. RESULTS: the mean age at the beginning of the pregnancy was 31.1 years (23 to 41). The mean dosage of thionamide was reduced in eight pregnancies (69.5%) and, in two, the drug was discontinued. Before pregnancy, mean propylthiouracil dose was 400 mg/day (200-900) and mean methimazole dose was 45 mg/day (20-60). After delivery, antithyroid drug dose was 200 and 30 mg/day, respectively. One patient presented premature labor (at 36 weeks) and another, a newborn small for gestational age (2.000 g at 38 weeks). There was one stillborn. There were no miscarriages or congenital anomalies. After labor, antithyroid drug dose was increased in seven patients and in the others the dose was maintained. CONCLUSIONS: we suggest close follow-up of pregnant women with hyperthyroidism and progressive reduction of thionamide dose during pregnancy to avoid maternal hypothyroidism and its consequences to fetal development. After labor, these women must be evaluated regarding their thyroid function because hyperthyroidism can worsen. Thionamide use is safe for the patients and their offspring.

A tireóide sofre importantes modificações durante a gravidez. Visando mostrar as modificações no eixo hipófise-tireóide ao longo deste período, estudamos a função tireoidiana de 587 mulheres, com dosagens de TSH, T4 livre, anti-TPO, betahCG no 1º. trimestre e TSH, T4 livre e anti-TPO no 2º. e 3º. trimestres. Observamos aumento progressivo do TSH no 2º. (média: 2,14mU/L) e 3º. (média: 2,76mU/L) trimestres, em relação ao 1º. (média: 1,39mU/L). No grupo com TSH abaixo do valor de referência (0,4mU/L) no 1º. trimestre, a média de bhCG foi de 129.200UI/L, enquanto no grupo que apresentou níveis normais de TSH, a média foi de 34.200UI/L. Observamos, também, uma ligeira diminuição do T4 livre no 2º. e 3º. trimestres em relação ao 1º. (médias: 1º: 1,15; 2º: 0,99; 3º: 0,94ng/dl). A presença de anti-TPO positivo ocorreu em 13,9% das mulheres. Não foram observadas alterações significativas nos valores médios de TSH e T4 livres naquelas com ou sem auto-imunidade. Entretanto, proporções significativamente maiores de gestantes apresentaram valores hormonais fora da faixa da normalidade em todos os trimestres da gestação. Concluímos que a função tireoidiana é afetada pela gravidez, com tendência ao declínio durante seu progresso, sendo este fenômeno mais marcante no grupo de gestantes anti-TPO positivas. The thyroid undergoes important changes during pregnancy. In order to evaluate changes of the hypophyseal-thyroid axis during this period we studied the thyroid function in 587 pregnants by determining serum TSH, free T4, TPO antibodies and betahCG in the 1st trimester and serum TSH, free T4 and TPOAb in to 2nd and 3rd. We observed a progressive rise in average serum TSH in the 2nd (2.14mU/L) and 3rd (2.96mU/L) trimesters when compared to the 1st (1.39mU/L). Serum TSH values in the 1st trimester were inversely correlated with betahCG levels in as much as TSH levels below 0.4mU/L corresponded to average betahCG levels of 129,000UI/L whereas these were 34,200UI/L in the normal TSH group. A slight decrease in free T4 levels was also observed in the 2nd and 3rd trimesters (averages 1st: 1.15; 2nd: 0.99; 3rd: 0.94ng/dl). Thyroid autoimmunity defined as positive TPOAb occurred in 13.9% of our patients during pregnancy. No significant differences in TSH and free T4 medium values were found between patients with positive TPOAb and those without. However, a significantly higher proportion of pregnants had abnormal hormonal values throughout the trimesters. We conclude that thyroid function is affected by pregnancy with a tendency for decline as it progresses, a feature more easily observed in positive TPOAb group.

OBJETIVO: Determinar a prevalencia de disfuncao tireoidiana em pacientes usando amiodarona e os possiveis fatores associados. Verificar atraves de questionario aplicado a cardiologistas, a importância do farmaco causar alteracoes na funcao tireoidiana. METODO: Avaliados 56 pacientes em uso cronico (> 3 meses) de amiodarona com dosagens sericas de TSH, T4 livre, T3 total e Anti-TPO e definidos como portadores de disfuncao tireoidiana (DT) pacientes com TSH alterado. RESULTADOS: A prevalencia de disfuncao tireoidiana foi de 33,9%. Nao houve diferenca entre este grupo e os pacientes sem disfuncao, exceto em relacao a prevalencia de anti-TPO positivo maior nos pacientes com DT (p=0,02). Hipotireoidismo subclinico foi diagnosticado em 10 (17,9%) pacientes e hipotireoidismo clinico em 6 (10,7%). A prevalencia de hipertireoidismo subclinico foi de 3,6% e de hipertireoidismo clinico de 1,8%. Anticorpos anti-TPO foram positivos em 5 (8%) pacientes (dos quais 4 apresentavam disfuncao). Quando comparados aos doentes sem anti-TPO positivo este grupo teve maior prevalencia de disfuncao (80% vs 29,4%; p=0,04). Verificado que apenas 49,2% dos cardiologistas faziam acompanhamento da funcao tireoidiana rotineiramente e a prevalencia de disfuncao referida na experiencia da maioria era de 1 a 10%. CONCLUSAO: A prevalencia de disfuncao tireoidiana na nossa populacao foi elevada, mostrando a necessidade de implementacao de uma rotina laboratorial. Houve grande divergencia entre os cardiologistas em relacao ao tipo de acompanhamento utilizado nos pacientes em uso de amiodarona.

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 +/- 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p0.01). IGF-1 concentrations were higher in men than women (p0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p0.01). At the end of the study the mean GH dose was lower in men than in women (p0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.

We describe the case of a 41-year-old man with hoarseness and a hard, fixed mass in the anterior cervical region. He was referred to our endocrinology service for evaluation of possible thyroid cancer. The results of laboratory tests of thyroid function were normal. Indirect laryngoscopy revealed paralysis of the left hemilarynx and the presence of a large vegetating lesion. Computed tomography of the neck disclosed the presence of a mass in the anterior region, along with invasion and destruction of the adjacent structures. The cytologic diagnosis was established by analysis of a fine-needle aspiration biopsy specimen, which revealed a squamous cell carcinoma. The final diagnosis was carcinoma of the larynx.

The amplification of thyroglobulin (TG) mRNA in peripheral blood of patients with thyroid cancer has been studied for almost one decade, but its real contribution for diagnosis of cancer relapse has not yet been established. In the present paper we report the case of a patient with papillary thyroid cancer with undetectable stimulated serum thyrogobulin levels after thyroid ablation. Follow-up showed the presence of high titers of anti-thyroglobulin antibodies and the presence of TG mRNA in a peripheral blood sample, while cervical ultrasound and thorax and cervical computerized tomography were negative. Reinvestigation confirmed lymph node metastases. Anti-TG antibodies progressively decreased after surgery for metastatic lymph nodes resection followed by radioiodine therapy. Although our recent findings show that patients with positive TG mRNA do not have increased risk of cancer recurrence after 24 months of follow-up, the presence of TG mRNA along with high anti-TG antibodies were important indicators that determined further extensive investigation of tumour relapse in this patient, since positron emission tomography scan was not available at our Institution. A methodological standardization that can distinguish specific from non-specific TG mRNA amplification might be of great interest for the follow-up of differentiated thyroid cancer, especially in patients with high levels of anti-TG antibodies. A amplificação de mRNA de tireoglobulina (TG) no sangue periférico de pacientes com câncer de tireóide tem sido estudada por quase uma década, mas a sua real contribuição para o diagnóstico do câncer ainda não foi estabelecida. No presente trabalho, relatamos o caso de uma paciente com carcinoma papilífero de tireóide com níveis séricos de TG indetectáveis após ablação com radioiodo. No seguimento apresentou títulos elevados de anticorpos anti-TG e a presença de mRNA TG em uma amostra de sangue periférico, enquanto a ultra-sonografia e as tomografias computorizadas de tórax e cervical foram negativas. Os níveis de anticorpos anti-TG diminuíram progressivamente após ressecção cirúrgica dos linfonodos seguida de terapia com radioiodo. Embora nossos achados recentes mostrem que pacientes com mRNA TG não apresentam risco aumentado de recorrência do câncer após 24 meses de seguimento, a presença de mRNA TG associada a altos títulos de anticorpos anti-TG foram importantes indicadores que determinaram o prosseguimento da investigação para recorrência tumoral nesta paciente, uma vez que não dispunhamos, na ocasião, e PET-Scan em nossa instituição. Uma padronização metodológica que permita distinguir entre amplificação de mRNA TG específica e inespecífica poderá ser de grande interesse no seguimento do carcinoma diferenciado da tireóide, especialmente naqueles com títulos elevados de anticorpos anti-TG.