O hipertiroidismo em felinos começou a ser diagnosticado a partir de 1979 e atualmente é uma endocrinopatia de grande ocorrência em muitos países. Devido a este fato, foi realizada a determinação dos hormônios tiroidianos (T3 e T4) dos felinos domésticos atendidos no HOVET/USP no período de 2002-2007. Foi utilizada a técnica de radioimunoensaio para a determinação de T4 total, T4 livre e T3 total. A amostragem compôs-se de 234 felinos, dois quais 26 (11,1%) foram diagnosticados com hipertiroidismo, pelo aumento de T4 total. Destes animais, apenas dois (7,7%) apresentavam suspeita para a doença na ocasião da consulta. Dentre as principais manifestações clínicas pôde-se observar: anorexia/disorexia, êmese, perda de peso, poliúria e polidipsia. Os valores de T4 livre e T3 total não foram significativos para o diagnóstico da doença neste estudo. A doença renal crônica foi observada em 46,2% dos felinos que apresentavam hipertiroidismo. Deve-se ter maior atenção ao exame físico do paciente felino idoso em relação à palpação da tiróide. / Recognised with a great occurence nowadays in many countries, hyperthyroidism in cats was first diagnosed in 1979. Due to this fact, thyroid hormones (T3 and T4) were measured in domestic felines assisted on the Veterinary Teaching Hospital of the University of São Paulo - Brazil, during 2002 through 2007. Total T4, free T4 and total T3 values were obtained by a radioimmune assay. Samples of 234 felines were analysed, and 26 (11,1%) were diagnosed with hiperthyroidism, having an increased total T4. Hypethyroidism was suspected in only two (7,7%) animals of this group. Anorexia/disorexia, vomiting, weight loss, polyuria and polydipsia were the main clinical signs observed. In this study, free T4 and total T3 values were not significant in diagnosing the disease. Chronic renal failure was observed in 46,2% of the felines with hyperthyroidism. In conclusion, a low suspicion of hyperthyroidism by the clinitians was noticed and thyroid palpation during the physical exam of the elder feline may be deficient and omissive.

Orientador: Laura Sterian Ward / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T14:43:40Z (GMT). No. of bitstreams: 1 Bufalo_NatassiaElena_D.pdf: 3667340 bytes, checksum: 4934d4d9652dfe1e6d10650634ac9866 (MD5) Previous issue date: 2012 / Resumo: Tanto a Doença de Graves (DG) como o Carcinoma Diferenciado da Tiroide (CDT) são patologias de etiologia multifatorial e envolvem uma interação entre meio ambiente e fatores genéticos de predisposição. Ambas apresentam nítida preferência pelo sexo feminino. Por isso, variações no metabolismo do estrógeno poderiam estar associadas a esta preferência, pois, seus metabólitos podem causar dano ao material genético. Os objetivos foram determinar a influência dos polimorfismos dos genes CYP17A1, HSD-17?1, CYP1A1, CYP1A2, CYP1B1, COMT e SULT1E1 no risco para a DG e para o CDT. Para tanto, foi estudado 282 pacientes com DG (234 mulheres e 48 homens; 39,80±11,69 anos), 292 pacientes com CDT (248 mulheres e 44 homens; 42,23±14,81 anos), comparados com 308 controles (246 mulheres e 62 homens; 36,86±12,95 anos). Para o estudo dos polimorfismos, utilizou-se a técnica TaqMan SNP Genotyping. Alterações polimórficas nos genes CYP17A1 (p=0,0421), CYP1A1 m1 (p=0,0328), CYP1A2*1F (p=0,0085), CYP1B1 códon 119 (p<0,0001) e CYP1B1 códon 432 (p=0,0059) aumentam a suscetibilidade ao CDT. Já as alterações polimórficas nos genes CYP1A1 m1 (p<0,0001), CYP1B1 códon 119 (p<0,0001) e CYP1B1 códon 432 (p=0,0208) aumentam a suscetibilidade à DG. Entre os pacientes com DG, mulheres heterozigotas para CYP1A1 m1 apresentam maior número de gestações (p=0,0071), paridade (p=0,0204) e abortos (p=0,0012), além de bócio mais pesado (gramas) (p=0,0082). Já entre os pacientes com CDT, mulheres heterozigotas para CYP17A1 apresentam maior número de abortos (p=0,0150). A herança heterozigota para o gene CYP1A2*F está relacionada com idade mais precoce (p=0,0073) para o surgimento do CDT. A herança do polimorfismo do gene CYP1B1 códon 119 está associada ao hábito tabagista (p=0,0269), uso de reposição hormonal (p=0,0197) e presença de menopausa (p=0,0317) para pacientes com CDT. Já para pacientes com DG, este polimorfismo se correlaciona com concentrações mais elevadas de T4livre (p=0,0409) e TRAb (p=0,0465). A herança em heterozigose do gene CYP1B1 códon 432 foi mais frequente em pacientes com carcinoma papilífero do que nos pacientes com carcinoma folicular (p=0,0243), além da herança em homozigose se correlacionar com maior idade (p=0,0204) e com sobrepeso (p=0,0392) em pacientes com DG. Mulheres com o genótipo homozigoto polimórfico para CYP1B1 códon 453 se correlacionam com uso de anticoncepcional (p=0,0332) no CDT. Maior número de gestações (p=0,0256) e de paridade (p=0,0141) se correlacionam com mulheres homozigotas para o gene HSD-17?1 na DG. Concluímos que os fatores exógenos e endógenos ligados aos hormônios sexuais possuem considerável variabilidade individual, devido aos polimorfismos da via de metabolização do estrógeno. As diferentes heranças polimórficas individuais, que são atribuídas aos polimorfismos dos genes codificadores de enzimas envolvidas na produção, metabolização e eliminação do estrógeno devem definir subpopulações de mulheres que são afetadas pela maior exposição aos estrógenos e aos seus metabólitos, os quais afetam o crescimento celular e podem induzir danos celulares carcinogênicos a ativar a resposta imune / Abstract: Graves' disease (GD) and Differentiated Thyroid Carcinoma (DTC) are multifactorial diseases and involved an interaction between environmental factors and genetic predisposition. Both diseases have preference for female. Therefore, variations in estrogen metabolism could be associated with that preference, because its metabolites can cause damage to genetic material. The objectives were to determine the influence of polymorphisms of genes CYP17A1, HSD-17?1, CYP1A1, CYP1A2, CYP1B1, COMT and SULT1E1 at the susceptibility for GD and DTC. We studied 282 patients with GD (234 females and 48 males, 39.80±11.69 years old), 292 patients with DTC (248 women and 44 men, 42.23±14.81 years old), compared with 308 controls (246 women and 62 men, 36.86±12.95 years old). TaqMan SNP genotyping technique was used to study the polymorphisms. Polymorphisms in CYP17A1 (p=0.0421), CYP1A1 m1 (p=0.0328), CYP1A2*1F (p=0.0085), CYP1B1 codon 119 (p<0.0001) and CYP1B1 codon 432 (p=0.0059) increases the susceptibility to DTC. The polymorphisms of CYP1A1 m1 (p<0.0001), CYP1B1 codon 119 (p<0.0001) and CYP1B1 codon 432 (p=0.0208) increases the susceptibility for GD. Women with GD have a higher number of pregnancies (p=0.0071), parity (p=0.0204), abortions (p=0.0012) and goiter heavier (grams) (p=0.0082) when heterozygous for CYP1A1 m1. Among patients with DTC, women heterozygous for CYP17A1 highest number of abortions (p=0.0150). The inheritance in heterozygous for the CYP1A2*F are correlated to younger age (p=0.0073) for the susceptibility to DTC. The inheritance of polymorphism of the CYP1B1 codon 119 gene is associated with smoking (p=0.0269), use of hormone replacement therapy (p = 0.0197) and menopausal status (p=0.0317) for patients with DTC. However, for patients with GD, this polymorphism correlated with higher concentrations of FT4 (p=0.0409) and TRAb (p=0.0465). The inheritance in heterozygous for CYP1B1 codon 432 gene was more frequent in patients with papillary carcinoma than in patients with follicular carcinoma (p=0.0243) and the homozygous inheritance correlate with older (p=0.0204) and overweight (p=0.0392) in patients with GD. Women with the inheritance for polymorphic homozygous for CYP1B1 codon 453 correlated with contraceptive use (p=0.0332) in the DTC. Increased number of pregnancies (p=0.0256) and parity (p=0.0141) correlated with women homozygous for the HSD -17?1 gene in GD. We conclude that exogenous and endogenous factors related to sex hormones have considerable individual variability due to polymorphisms of the estrogen metabolic pathway. The different polymorphic individual heritages, which are attributed to the polymorphisms of genes encoding enzymes involved in the production, metabolism and excretion of estrogen should define subpopulations of women who are affected by increased exposure to estrogens and their metabolites, which affect cell growth and can induce cellular damage carcinogens activate the immune response / Doutorado / Ciencias Basicas / Doutor em Clínica Médica

No description available.

Feline hyperthyroidism is an important disorder in middle-aged and older cats. The cause and pathogenesis of the disease is still unknown and there are few published incidence rates or prevalence estimates. A descriptive cross-sectional study was conducted to determine the prevalence of and potential risk factors for feline hyperthyroidism in Hong Kong. Serum thyroxine (T4) was measured in 305 cats 10 years and older that presented at various veterinary clinics in Hong Kong between June 2006 and August 2007. The veterinarians taking the samples completed a questionnaire regarding the health of each cat. Each owner completed a questionnaire regarding vaccination history, internal and external parasite control, diet and the environment of their cat. Serum total T4 concentration was determined by use of a commercially available radioimmunoassay kit (Coat-a-count®, DPC®). For total T4 the feline reference interval was 12.8-50.0 nmol/L (1.0-3.9 ug/dL). All cats with a serum total T4 concentration of greater than 50.0 nmol/L were classified as hyperthyroid. Alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were measured in all the samples. The prevalence of feline hyperthyroidism in Hong Kong was estimated at 3.93% (95% CI : 2.05-6.77) and there was no significant difference in prevalence between healthy (3.16%) and sick (4.37%) cats. This demonstrates that although this disease is present in Hong Kong, the prevalence is lower than the reported prevalence in other parts of the world. Risk factors that were examined included age, sex, breed, number of cats in household, vaccinations, parasite control, indoor environment, type of diet and type of water. Risk factors for hyperthyroidism identified by multivariate analysis were age and breed. Affected cats were more likely to be older (>15 years) and domestic shorthair cats were less likely to be diagnosed with hyperthyroidism than the other breeds combined. There was no statistically significant relationship between sex, vaccinations, parasite control or indoor environment and the development of hyperthyroidism. There was also no statistically significant relationship between the consumption of a canned food diet by the cats and hyperthyroidism. There were no characteristic clinical features amongst the cats that were hyperthyroid and only one cat exhibited the typical clinical syndrome of ravenous appetite with severe weight loss. The lack of distinctive clinical signs could be due to the presence of a mild or early form of the disease, but can also be due to an atypical form of the disease. This study showed that the disease needs to be considered if any of the following factors are present in an older cat : polyphagia, diarrhoea, and a significant raise in ALT and ALP activities. This study concluded that the prevalence of hyperthyroidism in cats in Hong Kong is less than in most other parts of the world, despite the presence of previously identified risk factors. Comparative epidemiological studies will be necessary to compare the presence of possible risk factors between feline populations in Hong Kong and elsewhere. / Dissertation (MSc)--University of Pretoria, 2008. / Companion Animal Clinical Studies / unrestricted

A 69-year-old man was referred for elevated thyroid hormone levels. He had no symptoms apart from mild hyperhidrosis and heat intolerance with occasional headaches. Past medical history included a right hemithyroidectomy for a multinodular goiter and Hashimoto's disease. At presentation the patient had a firm, slightly enlarged left thyroid lobe. There were no visual abnormalities, and the rest of the physical findings were unremarkable. Laboratory findings included elevated values of free T4, free T3, total T 3, thyrotropin-secreting hormone (TSH), antithyroglobulin, and antimicrosomal antibodies. Normal values were found for cortisol, prolactin, testosterone, follicle-stimulating hormone, luteinizing hormone, a-subunit, and thyroid-stimulating immunoglobulin. Thyroid 123I scan showed an increased 5-hour uptake of 23% and a 24-hour uptake of 53% with a diffuse uniform enlargement of the left side. TSH level did not increase after a thyrotropin-releasing hormone stimulation test. Serum sex hormone binding globulin was elevated. Magnetic resonance imaging of the pituitary revealed a pituitary macroadenoma with suprasellar extension to the optic chiasm. Histologic examination of the adenoma after transsphenoidal hypophysectomy showed cells that stained positive for TSH. TSH-secreting pituitary adenomas account for 1% of functioning pituitary tumors and are an exceedingly rare cause of hyperthyroidism. To our knowledge, this is the first report of pituitary tumor inducing hyperthyroidism in the setting of Hashimoto's disease. There is a possibility that TSH elevation related to Hashimoto's disease might have contributed to the development of a TSH-secreting pituitary adenoma.

Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hyperthyroid patients may develop reversible pulmonary hypertension and isolated right heart failure. We report a case of hyperthyroidism presenting with signs and symptoms of isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension, which resolved with treatment of hyperthyroidism.

The thyroid gland secretes hormones that help to govern metabolism and energy expenditure within the body [1]; these hormones also affect growth and development. As a result, the regulation of thyroid hormones is vital for maintaining an individual's well being. Graves' disease is an autoimmune disorder and is a major cause of hyperthyroidism or an overproduction of thyroid hormones. Radioactive iodine (RAI) therapy has become the preferred treatment with typical RAI protocols being based on the Marinelli-Quimby equation to compute the dose; however, up to 90 % of subjects become hypothyroid within the first year after therapy. In this thesis we focus on the development of a new computational protocol for the calculation of RAI in the treatment of Graves' hyperthyroidism. The new protocol implements a two-compartment model to describe RAI kinetics in the body, which accounts for the conversion between different RAI isotopes used in diagnostic and therapeutic applications. Thus, by using the measured response of the subject's thyroid to a test dose of 123I, the model predicts what amount of RAI (131I) will be needed to reduce, through ablation, the functional, thyroid volume/mass to an amount that would result in a normal metabolic balance. A detailed uncertainty analysis was performed using both a standard propagation of error method as well as a simulation method. The simulation method consisted of both parametric and nonparametric bootstrapping techniques. Using clinical data consisting of activity kinetics and mass dynamics of 17 subjects and measured final mass values of 7 of the 17 subjects, we were able to validate the protocol as well as quantify the uncertainty analysis. This protocol is the basis of an ongoing pilot study in conjunction with Cooley Dickinson hospital, Northampton, MA.

Graves’ Disease is an autoimmune disorder represented by the overproduction of thyroid hormones (hyperthyroidism). Graves’ Disease is more common among women of reproductive age, and genetic, endogenous, and environmental factors influence the pathogenesis of Graves’ Disease. Graves’ Disease presents with many clinical manifestations, such as tachycardia, fatigue, heat intolerance, palpitations, weight loss, muscle weakness, alterations in menstrual cycles, insomnia, hair loss, goiter, and others. Currently, there are three main treatment routes for Graves’ Disease: antithyroid drugs, radioactive iodine therapy, and thyroidectomy. Antithyroid drug therapy has a high relapse rate. At the same time, both radioactive iodine and thyroidectomy eradicate or surgically remove the tissue of the thyroid and lead to the consequence of developing another disease, hyperthyroidism, that requires a life-long supplementation of the thyroid replacement hormone, levothyroxine. Presently, investigations are focused on finding new therapeutics that can supplement existing treatments as a combination therapy that can lengthen the remission period after cessation of ATDs or conduction of RAI therapy. Future research is exploring treatment options that target different components of the immune system response pathway, the thyroid stimulating hormone receptor or thyrotropin receptor autoantibodies, that have the potential to cure Graves’ Disease.

Objective: To determine the efficacy and safety of iopanoic acid for the treatment of experimentally-induced hyperthyroidism in cats. Animals: 15 healthy adult domestic short hair cats Procedures: Hyperthyroidism was induced by daily subcutaneous administration of levothyroxine for 42 days. On day 28, cats were randomized to a control group receiving a placebo PO every 12 hours, a low dose group receiving 50 mg iopanoic acid PO every 12 hours, and a high dose group receiving 100 mg iopanoic acid PO every 12 hours. Cats were treated for 14 days. Weight and heart rates were obtained on days -8, 0, 28, 35, and 42. Blood was collected for CBC and biochemical analysis and for T4, T3, and rT3 measurement on days -8, 28, 35, and 42. Results: Two cats were removed prior to day 28 due to prolonged anorexia and another on day 36 because of heart failure. The low dose and high dose groups had significantly lower T3 concentrations on days 35 and 42 compared to the control group and to their own T3 concentrations on day 28. The T3 concentrations in cats administered iopanoic acid were not different from those obtained prior to induction of hyperthyroidism. Body weight and food consumption were not altered by iopanoic acid treatment, while heart rate was decreased in the low dose group on day 35 when compared to day 28. Conclusions and clinical relevance: Iopanoic acid was effective in decreasing T3 concentrations, but its effect on clinical signs of hyperthyroidism was less apparent. Studies evaluating the long-term efficacy in cats with naturally-occurring hyperthyroidism are warranted. / Master of Science

INTRODUÇÃO: No Brasil, são poucos os estudos sobre a freqüência das doenças tireoidianas e a maioria limita-se a populações específicas. OBJETIVOS: O objetivo principal deste estudo é correlacionar função tireoidiana subclínica a aspectos ultra-sonográficos em mulheres que realizaram rastreamento para função tireoidiana em local de trabalho. MÉTODOS: Estudo transversal de rastreamento com 135 mulheres de 40 anos ou mais, funcionárias da Universidade de São Paulo. Todas as participantes responderam a questionário específico, foram submetidas à mensuração de medidas antropométricas e da pressão arterial, tiveram uma amostra de sangue colhida para avaliação de função tireoidiana e anticorpos anti-tireoperoxidase, glicemia de jejum, colesterol total, HDL-colesterol, triglicérides e a proteína C ultra-sensível e foram submetidas à ultrasonografia da tireóide. Em uma subamostra do estudo foi realizada punção aspirativa por agulha fina guiada por ultra-sonografia de nódulos tireoidianos que preenchiam critérios de punção. RESULTADOS: As freqüências de hipotireoidismo e hipertireoidismo subclínico foram, respectivamente, 7,4% e 2,2%. A frequência de função tireoidiana normal foi 90,4%. Os valores médios de TSH foram diferentes nestes três grupos (P < 0,0001). Os níveis de anti-TPO foram significativamente diferentes entre os grupos, sendo mais elevados nos dois grupos de doença subclínica (P < 0,0001). O volume médio da tireóide no grupo do hipotireoidismo subclínico foi 8,9 ± 5,2 cm3, seguido pelo grupo do hipertireoidismo subclínico (8,9 ± 1,9 cm3) e pelo grupo das mulheres com função tireoidiana normal (7,7 ± 2,5 cm3) (P= 0,32). Não houve diferenças significativas entre os três grupos quanto à hipoecogenicidade da tireóide (P = 0,64). Entretanto, a ecotextura tireoidiana foi significativamente diferente entre os grupos (P = 0,02). Não foram encontradas diferenças significativas entre os grupos quanto à presença de nódulos císticos, sólidos ou mistos, nem quanto ao número médio de nódulos nas participantes que tinham algum nódulo à ultra-sonografia. Em 14% das mulheres houve indicação de biópsia dos nódulos e em duas foi diagnosticado carcinoma papilífero (1,4% da amostra). Houve uma associação entre ecotextura heterogênea e aumento dos níveis de anti-TPO (P < 0,0001) e uma associação limítrofe entre hipoecogenicidade e presença de anti-TPO (P = 0,051). O volume médio da tireóide no grupo das pacientes com anti-TPO elevado foi de 9,5 ± 4,5 cm3 e no grupo das pacientes com anti-TPO normal foi de 7,5 ± 2,5 cm3 (P = 0,02). A função tireoidiana e os aspectos ultra-sonográficos das mulheres procedentes de zona de bócio endêmico na infância não foram estatisticamente diferentes dos resultados encontrados em mulheres procedentes de zonas iodo-suficientes. CONCLUSÃO: O estudo mostrou associação entre função tireoidianasubclínica e alteração da ecotextura da tireóide em amostra de funcionárias da Universidade de São Paulo submetidas a rastreamento de função tireoidiana em local de trabalho. Níveis elevados de anti-TPO se associaram à alteração da ecotextura e ecogenicidade. Não houve diferenças em relação ao perfil de função tireoidiana ou aos achados ultra-sonográficos nas mulheres quando estratificadas de acordo com a procedência remota. / INTRODUCTION: In Brazil, there are few studies on the frequency of thyroid diseases and the majority is limited to specific populations. OBJECTIVE: The goal of this study is to correlate subclinical thyroid function to ultrasound characteristics in a sample of women submitted to screening of thyroid function at worksite. METHODS: Cross-sectional screening study with 135 women aged 40 years or older, all of them civil servants, working at Universidade de São Paulo. All the women answered specific questionnaires, had anthropometric variables and blood pressure measured, blood analyzed for total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting glucose, thyroid-stimulating hormone (TSH), free-thyroxine (free-T4), antithyreoperoxidase antibodies (anti-TPO), high-sensitive C reactive protein (hsCRP) and they underwent a thyroid ultrasound. An ultrasound-guided fine needle aspiration biopsy of thyroid nodules was performed in a sub-sample of this group. RESULTS: The frequency of subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, 7,4% e 2,2%. The frequency of normal thyroid function was 90,4%. The mean values of TSH were different among the three groups (P < 0,0001). The levels of anti-TPO were significantly different among the groups, with higher levels within the two subclinical disease groups (P < 0,0001). The average thyroid volume within the subclinical hypothyroidism group was 8,9 ± 5,2 cm3, followed by the subclinical hyperthyroidism group with 8,9 ± 1,9 cm3 average volume and lastly by the normal thyroid function group with 7,7 ± 2,5 cm3 average volume (P= 0,32). There were no significant differences among the three groups regarding thyroid hypoechogenicity (P = 0,64). However, thyroid echotexture was significantly different among the groups (P = 0,02). There were no meaningful differences among the groups neither for the presence of cystic lesions, solid or mixed nodules nor for the average number of nodules of any kind within the group of women with thyroid nodules. Fourteen percent of the women had a nodule biopsy indication and 2 were diagnosed with papillary carcinoma (1,4% of the sample). There was an association between heterogeneous echotexture and high levels of anti-TPO (P < 0,0001) and a borderline association between hypoechogenicity and the presence of anti- TPO (P=0,051). The group with the high levels of anti-TPO showed a mean thyroid volume of 9,5 ± 4,5 cm3 and the group with normal levels of anti-TPO showed a mean thyroid volume of 7,5 ± 2,5 cm3 (P = 0,02). The thyroid function and the ultrasonographic aspects of the women from endemic areas in childhood were not statistically different from the results found in women from iodine sufficient areas. CONCLUSION: This study demonstrated the association between subclinical thyroid function and altered thyroid echotexture in a sample of female civil servants working at Universidade de São Paulo submitted to screening of thyroid function at worksite. It was demonstrated that high levels of anti-TPO were associated with thyroid echotexture and echogenicity alterations. There were no differences relating to the thyroid function profile or regarding the ultrasonographic findings among the women when classified according to their origin.