Made available in DSpace on 2014-10-09T12:23:50Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:10Z (GMT). No. of bitstreams: 1 01103.pdf: 1172103 bytes, checksum: 91bab2b13d660ec6ae7ebd98dbcc08fa (MD5) / Dissertacao (Mestrado) / IEA/D / Faculdade de Medicina Veterinaria e Zootecnia, Universidade de Sao Paulo - FMVZ/USP

Aim: The aims of this audit were: To determine the proportion of hyperthyroid patients receiving I-131 therapy in whom treatment with a single fixed dose was successful, as defined by the achievement of euthyroidism or hypothyroidism 6-months after the therapy; To identify patients in whom treatment was not successful and a second dose needed; And, if possible, to establish the factors associated with treatment failure. Methods: A single observer reviewed the records of all patients who received I-131 therapy for hyperthyroidism between 23rd April 2010 and 23rd November 2017 in conjunction with their pre and post treatment thyroid function tests. Results of their thyroid ultrasound were retrieved and documented. The images of their Tc-99m sodium pertechnetate thyroid scans were also retrieved and reprocessed. Results: The records of 409 patients treated between April 2010 and November 2017 were retrieved. 223 (63%) patients were referred by the endocrine clinic at Groote Schuur hospital (GSH. Of the 409 patients, 56 (14%) patients that were excluded because their post therapy records were not available for analysis. Majority of our patients were females 310 (88%). Patients between the ages of 15 and 45 years are more likely to present with Grave’s disease while those aged more than 45 years presented with toxic multinodular gland (p=0.000). Patients that presented between the ages of 15 and 45 years are more likely to have moderately increased pretreatment FT4 (12-51 mmol/L) (p=0.002). We administered a radioiodine therapy dose of 456.6±54.8 MBq (Mean ± SD) to these 409 patients. Among the 353 patients, with complete records, 314(89%) achieved cure at some stage after receiving one dose of RAI; 239(76%) achieving cure ≤ 6 months of therapy and 75(24%) patients after 6 months. In our audit the patients who failed to achieve cure following the first RAI therapy appeared to be younger (median(interquartile range) age 39(16), p= 0.03), have severe hyperthyroidism as demonstrated by higher pre-treatment FT4 (median(interquartile range) 27 pmol/L(30.6), p= 0.05) and high pertechnetate uptake (median(interquartile range) uptake 9.9%(14), p= 0.002) on thyroid scintigraphy. CONCLUSION Our audit showed RAI therapy was found to be successful in 68% of patients at 6 month and 89% at a year. A second therapy with radioactive iodine would be indicated in 32% of patients, as these patients have not achieved cure at 6 months. Patients presenting with severe thyrotoxicity are likely to require more than one RAI therapy. Due to major deficiencies in referral, record keeping and follow up, other factors responsible for treatment were not be able to be evaluated. Based on these findings, suggested areas for further research are: should patients with severe hyperthyroidism be considered for pretreatment with antithyroid medication prior to RAI; would a one year follow up after radioiodine therapy be considered before second RAI. Now that the deficiencies in our current practice have been identified and suggestions put forward to address these deficiencies, a follow up audit would be needed.

Background: Hyperthyroid cats are predisposed to thrombus formation. The mechanism for thrombogenesis is currently unknown, but could be associated with altered hemostasis as seen in hyperthyroid humans. Objective: The purpose of this study was to evaluate markers of hemostasis in hyperthyroid cats compared to healthy cats, and in hyperthyroid cats before and after treatments with radioactive iodine (RIT). Methods: Twenty-five cats with hyperthyroidism and 13 healthy euthyroid cats > 8 years of age were studied. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin (AT), D-dimers, thrombin-antithrombin complexes (TAT), von Willebrand Factor antigen (vWF:Ag), and activity of factors VIII and IX were measured. An echocardiogram was performed in all cats and healthy cats with abnormal echocardiograms were excluded. Measurements of hemostasis were evaluated again in 7 cats > 6 months after RIT and deemed to have restored euthyroid status. Results: There is a significant likelihood of being in hypercoagulable state based on hyperthyroid state (P = 0.019) and serum T4 level is significantly associated with predicating hypercoagulability (P = 0.043). Hyperthyroidism is associated with significantly higher median fibrinogen concentration (P < 0.0001), higher median AT activity (P < 0.0001), and higher median vWF:Ag level (P = 0.01) with all values decreasing significantly post-RIT. Fibrinogen and AT had a strong positive correlation with serum T4 value (r = 0.79; 95% CI 0.63 - 0.89 and r = 0.70; 95% CI 0.50 - 0.84, respectively). Presence of an abnormal echocardiogram in hyperthyroid cats was associated with a significantly higher median fibrinogen concentration (P = 0.03). Echocardiographic status did not have a significant impact on the remaining hemostatic markers in hyperthyroid cats. Conclusions: These results provide evidence of altered hemostasis and hypercoagulability in hyperthyroid cats that do not appear to be solely attributed to cardiac abnormalities. These differences of altered hemostasis resolved after radioiodine therapy, but further studies are warranted to determine if hypercoagulable state resolves. / Master of Science / In feline hyperthyroidism, there is a predisposition for thrombus formation. An alteration of hemostasis has been documented in hyperthyroid humans, but despite reports of thrombus formation in hyperthyroid cats, the underlying mechanism is currently unknown. Hyperthyroidism can lead to cardiac abnormalities that could possibly contribute thrombus formation, although thrombus formation has occurred in hyperthyroid cats without detected abnormalities. The goal of this study was to evaluate markers of hemostasis in hyperthyroid cats presenting for radioiodine therapy to evaluate for presence of hypercoagulability. Twenty-five hyperthyroid cats were evaluated with hemostasis panels and echocardiograms. The results were compared to a group of 13 healthy cats. Markers of hemostasis and echocardiograms in 7 hyperthyroid cats were also compared to results 6 months or greater post-radioiodine therapy. There was evidence of altered hemostasis and hypercoagulability in hyperthyroid cats. The alterations noted resolved after radioiodine therapy and do not appear to be solely attributed to cardiac abnormalities seen in hyperthyroid cats.

O hipertireoidismo leva o fígado a uma situação de proteção antioxidante limítrofe, que pode aumentar a susceptibilidade do órgão a ações deletérias de xenobióticos ou fenômenos que impliquem em estresse oxidativo. Tal ocorre em ratos Sprague-Dawley tratados simultaneamente com hormônio tireoidiano L-3,3\',5-triiodotironina (T3) e o inseticida lindano (gama-hexaclorociclohexano). Enquanto a dose única de lindano (20 mg/kg peso corpóreo) não alterou a maioria dos parâmetros estudados, a administração de T3 estabeleceu a condição de estresse oxidativo hepático pelo aumento da atividade da NADPH-citocromo c redutase, acompanhado do aumento nos índices de lipoperoxidação e da produção microssomal de ânion superóxido (O2-) e da diminuição da atividade de defesas antioxidantes enzimáticas (superóxido dismutase e catalase) e não-enzimáticas (diminuição dos níveis hepáticos de alfa-tocoferol, beta-caroteno e licopeno). A administração de lindano teve seu efeito potenciado pelo hipertireoidismo, como indicado pelo aumento das razões O2-/SOD e SRAT/GSHT e pela diminuição dos níveis de alfa-tocoferol hepático, ambos efeitos maiores do que a soma dos obtidos nos tratamentos isolados. Devido à importância da atividade dos macrófagos residentes no fígado, observada em vários modelos de dano hepático, a função das células de Kupffer (CK) foi estudada neste modelo. Ao contrário do observado em experimentos no fígado íntegro, a luminescência das CK isoladas sofreu decréscimo nos animais tratados com T3 e lindano separadamente, apresentando uma tendência ao aumento no tratamento conjunto. Todos os tratamentos diminuíram a atividade fungicida das CK. É possível que os tratamentos utilizados estejam prejudicando a ação das CK, sendo restaurada na presença dos dois tratamentos. Por outro lado, a importância das CK no aumento do efeito do lindano no hipertireoidismo experimental foi evidenciada pela supressão dos efeitos acima mencionados após a administração do inativador de CK, o GdCl3. Estudos morfológicos corroboram este dado, mostrando uma supressão de sinais inflamatórios e necróticos nos animais hipertiroídeos tratados com GdCl3. / Hyperthyroidism elicits a borderline antioxidant protection state in the liver, which may increase its susceptibility to deleterious effects of xenobiotics or situations that cause oxidative stress. This happens to Sprague-Dawley rats treated concurrently with thyroid hormone L-3,3\',5-triiodothyronine (T3) and the pesticide lindane (gama-hexachlorocyclohexane). While a single dose of 20 mg/kg body weight of lindane did not alter most of the assessed parameters, T3 administration established a hepatic oxidative stress condition by means of an increase in NADPH-cytochrome c reductase activity, with a concomitant increase in lipoperoxidation (increase of thiobarbituric acid reactants) and microsomal generation of superoxide anion (O2-) and lower enzymatic (decreased activities of superoxide dismutase (SOD) and catalase) and non-enzymatic antioxidant defenses (decreased hepatic levels of alpha-tocopherol, beta-carotene, and lycopene). Lindane administration had potentiated effects on hyperthyroid animals, as indicated by the increased O2-/SOD ratio and further lowering of alpha-tocopherol levels in the liver; both effects greater than the sum of the ones observed after isolated treatments. As liver resident macrophages have been shown to play an important role in several hepatic damage models, Kupffer cell (KC) function was also studied in this model. Contrary to what was observed in experiments in the whole liver, Kupffer cell (KC) luminescence was diminished in separately T3 and lindane treated rats, revealing a tendency to increase after joint treatment. All treatments decreased KC fungicidal activity. It is possible that the separate treatments impair KC function, which is restored after the joint treatment. KC role in the potentiation of lindane-induced oxidative stress was evidenced by the suppression of this effect after KC inactivator, gadolinium chloride, administration. Morphological aspects of liver corroborate these data, showing a suppression of inflammatory and necrotic signals, present in hyperthyroid animals treated with lindane.

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.

O hipertireoidismo leva o fígado a uma situação de proteção antioxidante limítrofe, que pode aumentar a susceptibilidade do órgão a ações deletérias de xenobióticos ou fenômenos que impliquem em estresse oxidativo. Tal ocorre em ratos Sprague-Dawley tratados simultaneamente com hormônio tireoidiano L-3,3\',5-triiodotironina (T3) e o inseticida lindano (gama-hexaclorociclohexano). Enquanto a dose única de lindano (20 mg/kg peso corpóreo) não alterou a maioria dos parâmetros estudados, a administração de T3 estabeleceu a condição de estresse oxidativo hepático pelo aumento da atividade da NADPH-citocromo c redutase, acompanhado do aumento nos índices de lipoperoxidação e da produção microssomal de ânion superóxido (O2-) e da diminuição da atividade de defesas antioxidantes enzimáticas (superóxido dismutase e catalase) e não-enzimáticas (diminuição dos níveis hepáticos de alfa-tocoferol, beta-caroteno e licopeno). A administração de lindano teve seu efeito potenciado pelo hipertireoidismo, como indicado pelo aumento das razões O2-/SOD e SRAT/GSHT e pela diminuição dos níveis de alfa-tocoferol hepático, ambos efeitos maiores do que a soma dos obtidos nos tratamentos isolados. Devido à importância da atividade dos macrófagos residentes no fígado, observada em vários modelos de dano hepático, a função das células de Kupffer (CK) foi estudada neste modelo. Ao contrário do observado em experimentos no fígado íntegro, a luminescência das CK isoladas sofreu decréscimo nos animais tratados com T3 e lindano separadamente, apresentando uma tendência ao aumento no tratamento conjunto. Todos os tratamentos diminuíram a atividade fungicida das CK. É possível que os tratamentos utilizados estejam prejudicando a ação das CK, sendo restaurada na presença dos dois tratamentos. Por outro lado, a importância das CK no aumento do efeito do lindano no hipertireoidismo experimental foi evidenciada pela supressão dos efeitos acima mencionados após a administração do inativador de CK, o GdCl3. Estudos morfológicos corroboram este dado, mostrando uma supressão de sinais inflamatórios e necróticos nos animais hipertiroídeos tratados com GdCl3. / Hyperthyroidism elicits a borderline antioxidant protection state in the liver, which may increase its susceptibility to deleterious effects of xenobiotics or situations that cause oxidative stress. This happens to Sprague-Dawley rats treated concurrently with thyroid hormone L-3,3\',5-triiodothyronine (T3) and the pesticide lindane (gama-hexachlorocyclohexane). While a single dose of 20 mg/kg body weight of lindane did not alter most of the assessed parameters, T3 administration established a hepatic oxidative stress condition by means of an increase in NADPH-cytochrome c reductase activity, with a concomitant increase in lipoperoxidation (increase of thiobarbituric acid reactants) and microsomal generation of superoxide anion (O2-) and lower enzymatic (decreased activities of superoxide dismutase (SOD) and catalase) and non-enzymatic antioxidant defenses (decreased hepatic levels of alpha-tocopherol, beta-carotene, and lycopene). Lindane administration had potentiated effects on hyperthyroid animals, as indicated by the increased O2-/SOD ratio and further lowering of alpha-tocopherol levels in the liver; both effects greater than the sum of the ones observed after isolated treatments. As liver resident macrophages have been shown to play an important role in several hepatic damage models, Kupffer cell (KC) function was also studied in this model. Contrary to what was observed in experiments in the whole liver, Kupffer cell (KC) luminescence was diminished in separately T3 and lindane treated rats, revealing a tendency to increase after joint treatment. All treatments decreased KC fungicidal activity. It is possible that the separate treatments impair KC function, which is restored after the joint treatment. KC role in the potentiation of lindane-induced oxidative stress was evidenced by the suppression of this effect after KC inactivator, gadolinium chloride, administration. Morphological aspects of liver corroborate these data, showing a suppression of inflammatory and necrotic signals, present in hyperthyroid animals treated with lindane.

published_or_final_version / Medicine / Master / Doctor of Medicine

O hipertireoidismo da doença de Graves é a forma mais comum de hipertireoidismo em pacientes entre 20-50 anos. Três abordagens terapêuticas são atualmente utilizadas, drogas antitireoidiana, cirurgia e iodo radioativo (131I). O iodo radioativo tem sido cada vez mais aceito como primeira escolha terapêutica, porque é um tratamento seguro, definitivo e de fácil administração. O risco de piora do quadro de tireotoxicose após administração do 131I, os fatores prognósticos de falência e o cálculo da dose administrada têm sido alguns dos aspectos discutidos na literatura recentemente, e constituem o foco desta artigo. Em pacientes com bócios pequenos (<30g), crianças e adolescentes, e em situações especiais como na gravidez, as drogas antitireoidianas ainda é a primeira escolha no tratamento para a maioria dos autores. O tratamento cirúrgico é, atualmente, quase um tratamento de exceção, com indicação restrita para os casos em que as terapias anteriores não possam ser utilizadas. / Graves’ disease is the most frequent cause of hyperthyroidism and current treatment options are antithyroid drugs, radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, cheap and effective treatment. The risk of exacerbation of hyperthyroidism after 131I administration, factors that may predict the response to radioiodine and the dose to be administrated have been discussed in the literature and we comment the controversies in this review. In patients with mild disease, small goiters, children, adolescents and in special situations, as pregnancy, antityhyroid drugs are still the first choice of treatment for most authors. Surgery is rarely employed, and it is indicated only in cases where antithyroid drugs have not been effective and radioiodine is contraindicated or not acceptable by the patients.

O hipertireoidismo da doença de Graves é a forma mais comum de hipertireoidismo em pacientes entre 20-50 anos. Três abordagens terapêuticas são atualmente utilizadas, drogas antitireoidiana, cirurgia e iodo radioativo (131I). O iodo radioativo tem sido cada vez mais aceito como primeira escolha terapêutica, porque é um tratamento seguro, definitivo e de fácil administração. O risco de piora do quadro de tireotoxicose após administração do 131I, os fatores prognósticos de falência e o cálculo da dose administrada têm sido alguns dos aspectos discutidos na literatura recentemente, e constituem o foco desta artigo. Em pacientes com bócios pequenos (<30g), crianças e adolescentes, e em situações especiais como na gravidez, as drogas antitireoidianas ainda é a primeira escolha no tratamento para a maioria dos autores. O tratamento cirúrgico é, atualmente, quase um tratamento de exceção, com indicação restrita para os casos em que as terapias anteriores não possam ser utilizadas. / Graves’ disease is the most frequent cause of hyperthyroidism and current treatment options are antithyroid drugs, radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, cheap and effective treatment. The risk of exacerbation of hyperthyroidism after 131I administration, factors that may predict the response to radioiodine and the dose to be administrated have been discussed in the literature and we comment the controversies in this review. In patients with mild disease, small goiters, children, adolescents and in special situations, as pregnancy, antityhyroid drugs are still the first choice of treatment for most authors. Surgery is rarely employed, and it is indicated only in cases where antithyroid drugs have not been effective and radioiodine is contraindicated or not acceptable by the patients.

Made available in DSpace on 2014-06-11T19:31:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-05-12Bitstream added on 2014-06-13T19:41:12Z : No. of bitstreams: 1 cardoso_mjl_dr_botfmvz.pdf: 248290 bytes, checksum: 9109a7b559aa1fe60811340d1a417214 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os efeitos do hipertireoidismo experimental (150 g/kg/dia/42 dias) na homeostase do cálcio e nos marcadores do metabolismo ósseo foram estudados em 14 gatos sem raça definida, com idade entre um e três anos. Houve uma clara tendência de aumento das concentrações séricas de PTH intacto a partir do momento inicial com diferença significativa entre este e os demais momentos. O cálcio ionizado demonstrou uma diminuição significativa aos 14 dias em relação ao momento inicial e aos 42 dias em relação aos 14 dias. Os hormônios tireoidianos apresentaram correlação positiva com o PTH e negativa com o cálcio ionizado. Já a densidade mineral óssea (DMO) apresentou tendência de correlação negativa com o PTH a partir dos 28 dias. Observou-se correlação negativa do PTH com o cálcio ionizado aos 14, 28 e 42 dias. Conclui-se que o hipertireoidismo em gatos adultos jovens sem doenças concomitantes apresenta hiperparatireoidismo secundário. As concentrações séricas da OC apresentaram diferença significativa (p<0,05) entre si, nos quatro momentos. O ICTP, um marcador específico da reabsorção óssea, não apresentou diferença significativa entre os momentos. Provavelmente o remodelamento ósseo foi provocado pelo estado hipertireóideo, visto que tanto a OC como o ICTP apresentou forte correlação positiva com a TT4 e um pouco inferior com a FT4. A FT4 não apresentou correlação positiva com o ICTP, excetuando-se aos 28 dias. Observou-se baixa correlação, em todos os momentos, entre os marcadores do metabolismo ósseo e a densidade mineral óssea. Conclui-se que o excesso dos hormônios tireoidianos em gatos provocou aumento do remodelamento ósseo visto que ocorreu alta correlação entre estes hormônios e os marcadores do metabolismo ósseo. O hipertireoidismo provocou diminuição da DMO óssea, porém a OC e o ICTP apresentaram baixa correlação com esta variável. / The effect of experimental hyperthyroidism (150 g/kg/day/42 days) on calcium homeostasis and markers of bone metabolism was studied in fourteen shorthair cats from one to three years of age. Serum concentrations of unbroken PTH had a clear tendency to increase from beginning with significant differences from the initial to other moments. The ionized calcium significantly decreased at the 14 days in comparison to the initial moment and at the 42 days in comparison to the 14 days. The thyroid hormones showed positive correlation with PTH and negative with ionized calcium. In contrast, bone mineral density had a tendency of negative correlation with the PTH from the 28 days. Negative correlation of the PTH and calcium ionized was observed at 14, 28 and 42 days. In the present study, hyperthyroidism in young adult cats without concomitant illnesses did not present secondary hyperparathyroidism. However, increase of PTH and reduction of ionized calcium were observed. Serum concentrations of osteocalcin (OC) were significantly different among all four moments. The carboxi-terminal telopeptides of collagen type I (ICTP), a specific marker of the bone reabsorption, did not significantly differ (p<0.05) between moments. Bone turnover was probably caused by the hyperthyroid state, since OC and ICTP presented strong positive correlation with TT4 and a little less with free T4 (FT4). The FT4 did not present positive correlation with the ICTP, excepting at the 28 days. Positive correlation in all the moments between markers of bone metabolism and bone mineral density was very low. In conclusion, the high correlation between thyroid hormones and markers of bone metabolism indicates that the excess of thyroid hormones in cats may cause an increase of the bone turnover. Moreover, hyperthyroidism may cause reduction of the bone DMO, although OC and the ICTP had low correlation with DMO.