RESUMO
OBJECTIVE: We aimed to determine outcome predictors of papillary thyroid cancer (PTC) persistence and recurrence, separately. CONTEXT: The factors contributing to either persistence or recurrence of PTC are poorly defined, as both outcomes are usually evaluated together. DESIGN AND PATIENTS: In this 10-year follow-up cohort study, 190 PTC patients were evaluated (18-85 years old; registered from 1 January 1990 to31 December 1999 at a Brazilian Cancer Care referral Hospital). After initial surgery, we examined persistence (disease detected up to 1 year), recurrence (disease detected after 1 year) and PTC-free status (disease absence during follow-up). MEASUREMENTS: Outcome predictors were modelled using multinomial logit regression analysis. RESULTS: The univariate analysis showed that persistence and recurrence were significantly associated with lymph node metastasis (OR = 12·33; OR = 2·84, respectively), local aggressiveness (OR = 5·22; OR = 3·35) and extrathyroidal extension (OR = 5·07; OR = 7·11). Persistence was associated with male sex (OR = 3·49), age above 45 years old at diagnosis (OR = 1·03), macroscopic lymph node metastasis (OR = 5·85), local aggressiveness (OR = 5·22), each 1-cm tumour size increase (OR = 1·34), a cancer care referral hospital as the place of initial surgery (OR = 2·3), thyroidectomy or near total thyroidectomy(OR = 3·03) and neck dissection (OR = 3·19). Recurrence was associated with the time of radioactive iodine ((131) I) therapy (OR = 3·71). After data modelling, persistence was associated with macroscopic lymph node metastasis (OR = 6·17), 1-cm increases in tumour size (OR = 1·30) and thyroidectomy or near total thyroidectomy (OR = 3·82), while recurrence was associated with surgery at referral hospital (OR = 3·79). CONCLUSIONS: The best predictors of persistence were tumour size and macroscopic lymph node metastasis; when the initial surgery is of quality, the recurrence depends more on tumour's biology aspects.
Assuntos
Carcinoma/patologia , Carcinoma/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Carcinoma Papilar , Estudos de Coortes , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Metástase Linfática , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia , Adulto JovemRESUMO
BACKGROUND: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.
Assuntos
Bócio Nodular/terapia , Tireotropina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anatomia Transversal , Terapia Combinada , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Bócio Nodular/tratamento farmacológico , Bócio Nodular/radioterapia , Humanos , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Testes de Função Tireóidea , Hormônios Tireóideos/sangue , Tireoidectomia , Tireotropina/administração & dosagem , Tireotropina/efeitos adversos , Traqueia/anatomia & histologiaRESUMO
Several methods can be used to determine the activity of (131)I in the treatment of hyperthyroidism. However, many of them do not consider all the parameters necessary for optimum dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: organ mass, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with (131)I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the IRD was used to calibrate a scintillation camera and a uptake probe SCT-13004 at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and a uptake probe SCT-13002, available at the Nuclear Medicine Institute in Goiânia. The biokinetic parameters were determined based on measurements performed in eight voluntary patients. It is concluded that the use of the equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable and feasible procedure for dose optimization in terms of effectiveness, simplicity and cost.
Assuntos
Hipertireoidismo/tratamento farmacológico , Radioisótopos do Iodo/uso terapêutico , Medicina Nuclear , Câmaras gama , Doença de Graves/tratamento farmacológico , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/metabolismo , Medicina Nuclear/instrumentação , Medicina Nuclear/métodos , Dosagem RadioterapêuticaRESUMO
The manipulation of a wide variety of unsealed sources in Nuclear Medicine results in a significant risk of internal exposure of the workers. 131I should be highlighted among the most frequently used radionuclides because of its large application for diagnosis and therapy of thyroid diseases. The increasing use of radionuclides for medical purposes creates a demand for feasible methodologies to perform occupational control of internal contamination. Currently in Brazil, there are approximately 300 nuclear medicine centres in operation but individual monitoring is still restricted to the control of external exposure. This work presents the development of in vivo and in vitro bioassay techniques aimed to quantify incorporation of radionuclides used in Nuclear Medicine. It is also presented the results of a preliminary survey of internal exposure of a group of workers involved in the preparation of therapeutic doses of 131I. Workers were monitored with a gamma camera available in the Nuclear Medicine Service of the University Hospital of Rio de Janeiro and at the Institute of Radiation Protection and Dosimetry Whole-Body Counter (IRD-WBC). The in vivo detection systems were calibrated with a neck-thyroid phantom developed in IRD. Urine samples from radiopharmacy workers were collected after preparation and administration of therapeutic doses (10-250 mCi) of 131I and measured with a HPGe detection system available in the Bioassay Laboratory of IRD. The results show that the bioassay methods developed in this work present enough sensitivity for routine monitoring of nuclear medicine workers. All workers monitored in this survey presented positive results for 131I in urine samples and two workers presented detectable activities in thyroid when measured at the IRD-WBC. The highest committed effective dose per preparation was estimated to be 17 microSv.
Assuntos
Bioensaio/métodos , Carga Corporal (Radioterapia) , Pessoal de Saúde , Modelos Biológicos , Radiometria/métodos , Brasil , Simulação por Computador , Humanos , Medicina Nuclear , Doses de Radiação , Eficiência Biológica Relativa , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The estrogen receptor (ER) plays an important role in mediating estrogen action on target tissues. ER-alpha, the most abundant, is found in all human reproductive tissues and studies on alpha-ER knockout mice have highlighted its role in reproduction. ER-alpha gene (ESR1) polymorphisms have been associated with a variety of disorders including human infertility. In this study, we examined the association of ESR1 PvuII and XbaI polymorphisms with fertility in two populations with different reproductive patterns and precisely in a sample of healthy Italian men and women (n=178) and in a sample of healthy African-Ecuadorian women (n=57). ESR1 xx and ppxx genotypes among the Italian men were found to be associated with an above-median number of children (P=0.01 and P=0.004, respectively). ESR1 pp genotype among the Italian women showed a tendency to be associated with a lower number of abortions (P=0.04), whereas ESR1 pp and ppxx genotypes among African-Ecuadorian women were associated with a higher number of children (P=0.02 and P=0.03, respectively). These results are consistent with previous observations indicating a role of ESR1 genotypes in human infertility and give insight into the complex interactions between genotypes and reproductive behaviours in human populations.
Assuntos
Receptor alfa de Estrogênio/genética , Fertilidade/genética , Polimorfismo Genético , População/genética , Comportamento Sexual , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra/genética , Equador/etnologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIM: The human peroxisome proliferator-activated receptor gamma (PPAR-gamma) is involved in lipid storage, glucose homeostasis and adipocyte differentiation. The Ala allele of the Pro12Ala polymorphism has been associated with a protective effect against T2DM. Ala allele frequencies are known for many populations, but data are absent for other interesting human groups. METHODS AND RESULTS: We examined samples from Ethiopia, Benin, Ecuador and Italy. In addition, we performed an analysis of the Pro12Ala polymorphism distribution in world populations, also in relation to T2DM prevalence and the diet lipid content. In the European populations, the Ala allele frequencies are distributed according to a latitudinal trend, with the highest in the northern and central European populations and the lowest in the Mediterranean populations. Considering the world populations, a significant inverse relationship between Ala frequency and T2DM prevalence was observed mainly in populations where energy from lipids exceeded 30% of the total energy intake. CONCLUSION: Northern Europe's cold climate has been hypothesised to have played a role in contributing to the present pattern. Moreover our analysis appears to confirm, at a population level, the protective effect of Ala allele against T2DM, already observed in case-control studies, but only in populations with a diet rich in lipids.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Gorduras na Dieta/administração & dosagem , Meio Ambiente , PPAR gama/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina , Benin/epidemiologia , Clima , Gorduras na Dieta/efeitos adversos , Equador/epidemiologia , Etiópia/epidemiologia , Comportamento Alimentar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , ProlinaRESUMO
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.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Isotretinoína/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/terapia , Adulto , Idoso , Carcinoma/patologia , Carcinoma/terapia , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Feminino , Humanos , Isotretinoína/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cintilografia , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
Human apolipoprotein E is the most important supplier of the cholesterol precursor for steroid hormone production in steroidogenic tissues and therefore could play a role in the regulation of steroid hormone function and influence human reproduction. This hypothesis has been confirmed by studies describing a differential fertility associated with common apolipoprotein (APOE) genotypes in two European populations. In the present investigation the impact of APOE genetic variation on fertility was studied in two Ecuadorian populations, African-Ecuadorians (57 women) and Cayapa Indians (27 women). In addition some biodemographic variables concerning women's fertility were investigated (124 African-Ecuadorian women; 40 Cayapa women) to better understand the APOE-fertility relationships in these pre-industrial populations. General fertility rates in both populations were very high (6.5 and 6.2 for the African-Ecuadorians and for the Cayapa respectively). When considering only women near the end of reproductive life (>/=40 years), a more marked difference was observed between the two groups (9.1 versus 7.7, P=0.09). In both communities, the highest number of children was found to be associated with the e*4/e*3 genotype; the e*4/e*3 genotype frequency (0.50) in the African-Ecuadorian women with 9-17 children was about three times that of the women with 0-8 children (0.14) (P=0.02). The present findings are at variance with those observed in European populations, where e*3/e*3 was the genotype associated with the highest reproductive efficiency. A possible explanation for this inconsistency could be due to the different functional properties associated with the e*3 and e*4 alleles and to genotype interactions with environmental factors including reproductive strategies.
Assuntos
Apolipoproteínas E/genética , Fertilidade/fisiologia , Indústrias , Polimorfismo Genético , Adulto , Coeficiente de Natalidade , Equador , Etnicidade , Europa (Continente) , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Gravidez , Resultado da GravidezRESUMO
We report herein the study of two siblings (DESM and DSM) with hypothyroidism, goiter, and positive perchlorate discharge tests (50% and 70%) in a family (M) with no history of consanguinity. Thyroid gland histology showed a predominance of hyperactive follicles, with high epithelial cells and variable colloid content. Thyroid peroxidase iodide oxidation (DESM, 1034; DSM, 1064 U/g protein) and albumin iodination (DESM, 16; DSM, 8 nmol I/mg protein) activities were within the normal range. Tg content was normal in both glands compared with that in diffuse toxic goiter (DESM, 28; DSM, 17; diffuse toxic goiter, 19 mg/g tissue), and Tg could be normally iodinated by thyroid peroxidase in vitro (DESM, 3.4; DSM, 4.3; diffuse toxic goiter, 6.3 nmol I/mg Tg). Thyroid cytochrome c reductase activities in these goiters were higher than that in paranodular tissues (DESM, 473; DSM, 567; paranodular tissues, 78 nmol NADP(+)/h/mg protein). However, thyroid NADPH oxidase activities were very low both in the particulate 3,000 x g (DESM, 4.8; DSM, 44; paranodular tissues, 224 nmol H(2)O(2)/h/mg protein) and in the particulate 100,000 x g fractions (DESM, 40; DSM, 47; paranodular tissues, 200 nmol H(2)O(2)/h/mg protein). Thus, a decreased Ca(2+)/NAD(P)H-dependent H(2)O(2) generation is the probable cause of the organification defect in these goiters.
Assuntos
Cálcio/fisiologia , Bócio/metabolismo , Peróxido de Hidrogênio/metabolismo , Hipotireoidismo/metabolismo , NADPH Oxidases/metabolismo , Adolescente , Adulto , Feminino , Bócio/genética , Humanos , Hipotireoidismo/genética , Iodeto Peroxidase/metabolismo , Masculino , NADH Desidrogenase/metabolismo , Tireoglobulina/metabolismoRESUMO
The genetic structure of two African-Ecuadorian communities, Rio Cayapas and Viche (Esmeraldas province, northwest Ecuador), was studied on the basis of ACP1, ADA, AK1, CA2, ESD, GLO1, G6PD, PGD, and PGM1 subtypes and thermostability, PGM2, HBbeta, F13A, F13B, ORM1, AHSG, C6, C7, and APOC2 gene frequency, and migration data on 255 individuals. The fixation index of Wright (F(ST)), correspondence, and genetic distance analysis were applied to compare the genetic relationships between these communities and other American populations of African ancestry. F(ST) values from the migration data and surname origins suggest that Rio Cayapas is genetically more isolated and shows less mobility and admixture than does Viche. The genetic admixture estimates indicate a large contribution of African genes to the gene pool of both communities (74.3% to 58.4%), whereas the proportion of the Amerindian component differs significantly (14.5% in Rio Cayapas to 27.6% in Viche).
Assuntos
População Negra/genética , Frequência do Gene , Pool Gênico , África/etnologia , Demografia , Equador , Emigração e Imigração , Enzimas/genética , Etnicidade/genética , Feminino , Humanos , Masculino , Fenótipo , Filogenia , Proteínas/genéticaRESUMO
Three DNA polymorphisms (XbaI, EcoRI, and Ins/Del) of the apolipoprotein B (APOB) gene and the CfoI polymorphism of the APOE gene were investigated in a sample of 96 Cayapa Indians from Ecuador. The frequencies of the X+ (0.182), R+ (1.000), and Del alleles (0.432) at the three APOB sites were found to be higher than and to differ significantly from those reported for East Asians. No comparisons could be made between the Cayapa and other native Americans because of the lack of data on these sites. We observed in our sample that, like native American populations but unlike East Asians, the APOE allele frequencies were characterized by the absence of the APOE*2 allele and by a high frequency of the APOE*4 allele (0.280). Besides a probable drift effect, the high APOE*4 value was tentatively attributed to an effect of selection. Because this allele enhances the absorption of cholesterol by the intestine, it could confer an advantage to carriers in an unfavorable environment (i.e., diet poor in cholesterol).
Assuntos
Apolipoproteínas B/genética , Apolipoproteínas E/genética , Frequência do Gene/genética , Indígenas Sul-Americanos/genética , Polimorfismo Genético/genética , Adulto , Mapeamento Cromossômico , Dieta , Equador , Feminino , Humanos , Estilo de Vida , MasculinoRESUMO
The Cayapa Indians are a population of 3600 individuals living in Ecuador, along the Cayapas River and its tributaries. They are thought to have migrated from the Andes, north of Quito, and settled in the Cayapas area five centuries ago as a consequence of Inca expansion and of the Spanish conquest. In order to study the genetic structure of the Cayapa and their relationships with other native American peoples, and to enquire on the possibility of admixture from nearby Black communities, we have investigated a sample of 139 individuals for seven plasma genetic markers (F13A, F13B, ORM1, AHSG, C6, C7 and APOC2) by isoelectric focusing and immunoblotting. The following gene frequencies have been found: F13A*1 = 0.824, F13A*2 = 0.176; F13B*1 = 0.126, F13B*3 = 0.874; ORM1*1 = 0.554, ORM1*2 = 0.446; AHSG*1 = 0.275, AHSG*2 = 0.725; C6*A = 0.131, C6*B = 0.814, C6*A21 = 0.055; C7*1 = 1.000; APOC2*1 = 1.000. The findings confirm, whenever the comparison was possible, quite a good resemblance of the Cayapa with other Native American populations.