RESUMO
Thyroid malignancy has been induced by long-term endogenous thyrotropin (TSH) stimulation in experimental animals, leading to local and distant metastasis. It has been postulated that constant and prolonged endogenous TSH stimulation in dyshormonogenetic thyroid tissues could result in thyroid neoplasia. The possible role of growth factors and oncogenes in goitrogenesis and favoring neoplasia has also been mentioned. Overexpression of certain growth factors and/or their receptors, and of oncogenes implicated in growth promotion may play a significant role in the relatively frequent finding of thyroid malignancy in congenital goiters. In this study the expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGF-R), transforming growth factor-beta (TGF-beta), c-myc, and p53 mRNAs was determined in 14 thyroid tissue samples: 6 from patients with thyroid peroxidase (TPO) gene mutations, 4 with thyroglobulin (Tg) gene defects and 4 normal thyroid tissues. EGF mRNA overexpression was seen in 7 of 10 dyshormonogenetic tissues (3.5 to 12.0 arbitrary optical densitometry units [AODU]) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.25 to 0.32 AODU). Moreover, overexpression of EGF-R mRNA was present in 6 of 10 dyshormonogenetic tissues (2.23 to 13.03 AODU) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.42 to 0.65 AODU). There was no difference in c-myc, p53, and TGF-beta mRNAs expression between dyshormonogenetic and normal tissues. The overexpression of EGF and EGF-R mRNAs found in dyshormonogenetic tissues may suggest that this growth factor may play a role in cellular proliferation and contribute to goiter formation.
Assuntos
Fator de Crescimento Epidérmico/genética , Receptores ErbB/genética , Expressão Gênica , Bócio/metabolismo , RNA Mensageiro/análise , Hormônios Tireóideos/sangue , Divisão Celular , Bócio/patologia , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genéticaRESUMO
Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n = 13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n = 20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean +/- SEM 6.2 +/- 2.8 kg and Group II 13.4 +/- 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m2. However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.
Assuntos
Fenfluramina/uso terapêutico , Fluoxetina/uso terapêutico , Obesidade Mórbida/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Serotoninérgicos/uso terapêutico , Redução de Peso/efeitos dos fármacos , Adulto , Idoso , Índice de Massa Corporal , Quimioterapia Combinada , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/fisiopatologia , Resultado do TratamentoRESUMO
An ultrasonographic survey of thyroid abnormalities was conducted in 547 consecutive apparently normal overweight subjects (380 females and 167 males), aged 27-58 years in an urban area with relatively low iodine intake (mean daily urinary iodine excretion: 10.6 micrograms/dL). Individuals with any previous thyroid disease or familial thyroid pathology were excluded. In 240 subjects (44%) high resolution ultrasonography of the thyroid was considered normal. In 307 individuals (56%) abnormalities of the echo structure (39%) or thyroid nodular disease (17%) were detected by ultrasonography. Marked heterogeneity of the echo structure that was considered suggestive of chronic autoimmune thyroiditis was present in 81 subjects (15%). In 72 of these patients the serum anti-TPO levels were positive by a sensitive RIA. Thyroid nodules either solid or predominantly cystic were present in 90 subjects (17%). Eighteen patients had a relatively large nodule (diameter 15-18 mm). Eleven of these nodules were missed at clinical examination. Fine needle aspiration cytology was performed in 14 patients and 7 individuals underwent thyroid surgery. In 6 subjects the pathologic diagnosis was benign adenomatous goiter and one patient had a follicular carcinoma. Thyroid function studies confirmed subclinical hypothyroidism in 27 patients (4.9%), all of them with elevated serum anti-TPO autoantibodies levels. It was concluded that the overall occurrence of thyroid disease is more common than suspected by clinical examination.
Assuntos
Iodo/administração & dosagem , Doenças da Glândula Tireoide/epidemiologia , Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Biópsia por Agulha , Brasil/epidemiologia , Feminino , Humanos , Iodeto Peroxidase/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças da Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/patologia , Tireoidite Autoimune/diagnóstico por imagem , Tireoidite Autoimune/epidemiologia , Tireoidite Autoimune/imunologia , UltrassonografiaRESUMO
We evaluated the prevalence of antithyroid peroxidase antibodies (anti-TP0 Ab) in 402 patients with thyroid disease and 30 healthy controls by a commercial radioimmunoassay (RIA) and compared the results with the passive hemagglutination (HA) method. The patients in the study had autoimmune thyroid disorders (AITD) such as Graves' disease and Hashimoto's disease or had nonautoimmune thyroid diseases (NAITD) such as thyroid cancer, congenital goiter, endemic goiter, and nodular goiter. Subjects were recruited from a population with a mild iodine deficiency (Sao Paulo, Brazil). The effect of specific therapy (for either thyrotoxicosis or chronic thyroiditis) on the circulating anti-TPO levels was also investigated. Positive anti-TPO Ab was detected in 89.9% of the patients with AITD as compared with a prevalence of positive tests of only 4.8% in patients with NAITD. Positive microsomal antibody (M Ab) was found in 68.4% of the patients with AITD and in 6.4% of the patients with NAITD. A positive and significant correlation was obtained between M Ab and anti-TPO Ab. A positive anti-TPO test with negative anti-M was found in 14.1% of the patients with AITD but in only 4.3% of the patients with NAITD and normal controls. These results suggest that anti-TPO Ab by RIA is more sensitive and specific than M Ab by HA. In patients with AITD, anti-TPO Ab levels usually decreased after treatment, suggesting that this parameter could be used in the follow-up of these thyroid disorders.
Assuntos
Autoanticorpos/análise , Iodeto Peroxidase/imunologia , Iodo/deficiência , Doenças da Glândula Tireoide/imunologia , Tireoidite Autoimune/imunologia , Especificidade de Anticorpos , Autoanticorpos/imunologia , Brasil/epidemiologia , Bócio/congênito , Bócio/epidemiologia , Bócio/imunologia , Bócio Endêmico/epidemiologia , Bócio Endêmico/imunologia , Bócio Nodular/epidemiologia , Bócio Nodular/imunologia , Doença de Graves/epidemiologia , Doença de Graves/imunologia , Testes de Hemaglutinação , Humanos , Radioimunoensaio , Doenças da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/imunologia , Tireoidite Autoimune/epidemiologiaRESUMO
Basal and stimulated growth hormone (GH) secretions are impaired in obesity, and partial restoration of the GH response to various stimuli is observed after weight loss. The aim of the present study was to investigate whether D-fenfluramine, a serotoninergic agent, would increase the GH response to growth hormone-releasing factor (GRF) as compared with placebo in obese android patients. The subjects were 17 patients with android obesity (four men and 13 women) aged 21 to 58 years with a body mass index (BMI) ranging from 32.0 to 52.2 kg/m2 and an abdominal-gluteal ratio greater than 1.0. The following four GRF (1-44) tests were performed: T-30 (control), T0 (after 30 days of a hypocaloric diet), T1 (after 30 days of either placebo or D-fenfluramine 15 mg twice daily), and T2 (after 30 additional days of placebo or D-fenfluramine). The hypocaloric diet was maintained during the T1 and T2 periods. At each test, the serum GH response to GRF was measured at frequent intervals, and the peak GH response and the GH area under the curve were calculated. Serum insulin concentrations were also assayed before GRF stimulation, and the insulin to GH ratio was obtained. The D-fenfluramine-treated group had a mean +/- SEM GH peak level after GRF significantly higher at T1 (43.3 +/- 8.2 micrograms/L) and T2 (50.9 +/- 9.2 micrograms/L) compared with the placebo group. Likewise, the mean integrated areas of GH response were significantly higher for the D-fenfluramine-treated group as compared with the placebo group at both T1 and T2 of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Dieta Redutora , Fenfluramina/uso terapêutico , Hormônio Liberador de Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Obesidade/terapia , Adulto , Análise de Variância , Antropometria , Terapia Combinada , Feminino , Fenfluramina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/tratamento farmacológico , Obesidade/fisiopatologiaRESUMO
We have studied the therapeutic effects of two different doses (30 mg and 60 mg, twice daily) of DL-fenfluramine (DL-F) in, respectively, prepuberal (11-13 years old) and adolescent subjects (14-17 years old). Sixty-eight obese subjects were recruited for this study (22 boys, 36 girls, aged 10-17 years old) with body mass index ranging from 24.5 to 44.0 kg/m2, absolute weight ranging from 37.0 to 119.5 kg and % over IBW ranging from 122% to 260%. Results were compared to a placebo treated group of obese adolescent patients (n = 17), 6 boys and 11 girls, aged 10-17 years old, BMI ranging from 26-44 kg/m2, absolute weight 53.1 to 96.5 kg, and with 129% to 253% over IBW. In the DL-F-treated subjects most patients (n = 41) had a continuous weight loss during 12 months but 27 individuals were unable to lose any additional weight after the initial 6 months of the trial. Taken together 65% of all patients lost weight during DL-F treatment (12 months) whereas only 17.4% of the placebo group lost a significant (> 10% BMI) amount of excess weight. Also the placebo group had a higher withdrawal rate (57%) as compared with the DL-F-treated group (24%). There was a significant (p < 0.05) decrease of the mean +/- SD of the BMI (at 6 and 12 months of therapy). No significant change of the BMI was observed for control group. Minor adverse side effects consisted of a brief period of drowsiness and dry mouth. Our findings indicated that the continuous administration of DL-Fenfluramine might help obese adolescent subjects adhere to a diet and to maintain the weight loss achieved without major or harmful adverse effects.