by Judy, Po-shan Lai. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references(leaves 83-87). / Abbreviations --- p.iii / List of Tables --- p.iv / List of Figures --- p.v / Acknowledgements --- p.vi / SUMMARY --- p.1 / Chapter 1. --- INTRODUCTION --- p.2 / Chapter 2. --- BACKGROUND --- p.4 / Chapter 2.1 --- PROBLEMS ENCOUNTERED IN THYROID FUNCTION TESTS --- p.4 / Chapter 2.2 --- A NEED FOR TISSUE MARKER VERSUS EXISTING THYROID FUNCTION TESTS --- p.8 / Chapter 2.3 --- CHOICE OF TISSUE MARKER AS AN ADJUNCT TO THYROID FUNCTION TESTS --- p.10 / Chapter 2.3.1 --- ERYTHROCYTE ZINC --- p.10 / Chapter 2.3.2 --- ERYTHROCYTE CARBONIC ANHYDRASE ISOENZYME --- p.11 / Chapter 3. --- CARBONIC ANHYDRASE --- p.14 / Chapter 3.1 --- HISTORY AND BACKGROUND --- p.14 / Chapter 3.2 --- CARBONIC ANHYDRASE ISOENZYMES --- p.15 / Chapter 3.2.1 --- STRUCTURE AND DISTRIBUTION --- p.15 / Chapter 3.2.2 --- GENERAL MECHANISMS --- p.18 / Chapter 3.2.3 --- GENETICS AND REGULATION --- p.18 / Chapter 3.2.4 --- PHYSIOLOGICAL AND CLINICAL ASPECTS --- p.20 / Chapter 4. --- ANALYTICAL METHODS FOR MEASUREMENT OF ERYTHROCYTE CARBONIC ANHYDRASE --- p.22 / Chapter 4.1 --- DETERMINATION OF ECAI USING IMMUNOTURBIDIMETRIC ASSAY --- p.23 / Chapter 4.1.1 --- PRINCIPLE OF TECHNIQUE --- p.23 / Chapter 4.1.2 --- COLLECTION AND HANDLING OF BLOOD SPECIMENS --- p.29 / Chapter 4.1.3 --- PREPARATION OF HAEMOLYSATE --- p.31 / Chapter 4.1.4 --- MEASUREMENT OF HAEMOLYSATE CAI --- p.32 / Chapter 4.1.5 --- OPTIMIZATION PROCEDURE --- p.34 / Chapter 4.1.6 --- EVALUATION EXPERIMENTS --- p.36 / Chapter 4.1.7 --- DETERMINATION OF HAEMOGLOBIN CONCENTRATION IN HAEMOLYSATE --- p.39 / Chapter 4.1.8 --- DETERMINATION OF MEAN CELL HAEMOGLOBIN CONCENTRATION --- p.41 / Chapter 4.1.9 --- CALCULATION OF ERYTHROCYTE CARBONIC ANHYDRASE I CONCENTRATION --- p.43 / Chapter 4.2 --- DETERMINATION OF ECAI USING RADIAL IMMUNODIFFUSION METHOD --- p.43 / Chapter 5. --- RESULTS OF OPTIMIZATION AND EVALUATION EXPERIMENTS --- p.46 / Chapter 5.1 --- OPTIMIZATION RESULTS --- p.46 / Chapter 5.1.1 --- WAVELENGTH --- p.46 / Chapter 5.1.2 --- PEG CONCENTRATION --- p.49 / Chapter 5.1.3 --- SAMPLE VOLUME --- p.52 / Chapter 5.1.4 --- ANTIBODY DILUTION --- p.52 / Chapter 5.1.5 --- TEMPERATURE --- p.54 / Chapter 5.1.6 --- TIME OF INCUBATION --- p.54 / Chapter 5.1.7 --- OPTIMIZED TEST PROTOCOL --- p.56 / Chapter 5.2 --- EVALUATION RESULTS --- p.56 / Chapter 5.2.1 --- STABILITY --- p.56 / Chapter 5.2.2 --- LINEARITY --- p.58 / Chapter 5.2.3 --- PRECISION --- p.62 / Chapter 5.2.3.1 --- WITHIN-RUN --- p.62 / Chapter 5.2.3.2. --- BETWEEN-RUN --- p.62 / Chapter 5.2.4 --- CROSS-REACTIVITY --- p.62 / Chapter 5.2.5 --- RECOVERY --- p.62 / Chapter 5.2.6 --- COMPARISON WITH COMPARATIVE METHOD --- p.64 / Chapter 5.3 --- DISCUSSION --- p.64 / Chapter 6. --- ECAI IN NORMAL SUBJECTS --- p.67 / Chapter 6.1 --- SUBJECTS AND METHOD --- p.67 / Chapter 6.2 --- RESULTS --- p.67 / Chapter 6.3 --- DISCUSSION --- p.67 / Chapter 7. --- PATIENT STUDY --- p.69 / Chapter 7.1 --- SUBJECTS AND METHOD --- p.69 / Chapter 7.2 --- RESULTS --- p.70 / Chapter 7.2.1 --- DEMOGRAPHIC AND BIOCHEMICAL PARAMETERS --- p.70 / Chapter 7.2.2 --- CORRELATION BETWEEN ECAI AND FT3 RESULTS OF THYROTOXIC PATIENTS BEFORE TREATMENT --- p.71 / Chapter 7.2.3 --- CORRELATION BETWEEN ECAI AND EZN RESULTS OF THYROTOXIC PATIENTS --- p.71 / Chapter 7.2.4 --- RELATIONSHIP BETWEEN THE CHANGES IN ECAI AND FT3 RESULTS IN THYROTOXIC PATIENT ON TREATMENT --- p.71 / Chapter 7.3 --- DISCUSSION --- p.76 / Chapter 8. --- GENERAL DISCUSSION --- p.79 / Chapter 9. --- REFERENCES --- p.83

Ho Sin Yee, Stella. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 94-105). / Background --- p.1 / Chapter Chapter 1 --- Introduction / Thyrotoxicosis --- p.3 / Graves' Disease --- p.5 / Laboratory Assessment of the Mothers --- p.7 / Placental Transfer --- p.10 / Effects of Maternal Thyroid and Antithyroid Agents on the Fetus --- p.13 / Diagnostic and Screening Tests for Fetal Thyroid Dysfunction --- p.19 / Fetal Treatment --- p.21 / Aims and Objectives of the Research --- p.24 / Chapter Chapter 2 --- Subjects and Methods / Patients' Profile --- p.26 / Categorization of the Thyrotoxic Population --- p.28 / Intraobserver Error --- p.30 / Pilot Study --- p.31 / Equipment --- p.31 / Measurements --- p.32 / Growth Charts employed --- p.32 / Imaging Technique --- p.33 / Calculations --- p.39 / Gestational Age of the Fetus --- p.41 / Analytical Methods --- p.43 / Chapter Chapter 3 --- Results / Intraobserver Error --- p.45 / Pilot Study --- p.45 / Maternal Thyroid Status (Thyrotoxic Population) --- p.48 / Fetal Thyroid Volume --- p.49 / Rate of Fetal Thyroid Growth --- p.59 / Fetal Thyroid Volume to Estimated Fetal Weight Ratios (V/W) --- p.60 / Birthweight of the Infants --- p.63 / Chapter Chapter 4 --- Discussion / Methodology --- p.64 / Findings and Observations --- p.71 / Chapter Chapter 5 --- Conclusions --- p.92 / References --- p.94 / Appendix I --- p.106

O hipertireoidismo é a endocrinopatia mais prevalente em felinos. Sua incidência vem aumentando nos últimos anos em todo mundo embora ainda seja pouco frequente no Brasil. Estudos evidenciam que gatos com manifestações clínicas da endocrinopatia têm baixa suspeição da doença pelos clínicos comparado a prevalência da mesma. Assim, este trabalho objetivou avaliar as opiniões e experiências de médicos veterinários brasileiros acerca da abordagem e manejo de felinos com hipertireoidismo por meio de um questionário com 22 perguntas sobre o tema. Foram respondidos 1113 questionários, onde 535 (48%) dos veterinários disseram realizar a palpação da tireoide em todos os gatos que atendem. Perda de peso (89,2%), hiperatividade (82,8%) e polifagia (81,6%) foram as manifestações clínicas mais reconhecidos pelos clínicos. E, 747 (61,1%) solicitam o T4 total como exame endocrinológico de triagem para realizar o diagnostico. Houve associação (p<0,001) entre frequência de palpação, nível de conhecimento, ter curso de especialização e tempo de formação com a quantidade de casos atendidos e o tempo para realizar o diagnostico. A radioiodoterapia foi o tratamento escolhido como padrão ouro por 619 (55,6%), seguido do tratamento medicamentoso 385 (34,6%) e cirúrgico 66 (5,9%). Porém, no momento de indicar, 642 (57,7%) escolhem o medicamentoso, 340 (30,5%) a radioiodoterapia e 84 (7,5%) o cirúrgico. A principal limitação para a escolha da radioiodoterapia foi o custo, por 825 (74,1%) dos clínicos. Pôde-se observar que os veterinarios que consideram conhecer bem a doença e aqueles especilizados em felinos são os que agem em maior compatibilidade com a literatura; e, portanto, o conhecimento sobre a doença pode ser um importante fator limitante na prevalência da doença no Brasil. / Hyperthyroidism is the most prevalent endocrinopathy in felines. Its incidence has been increasing in the world in the last years. Although it is still uncommon in Brazil. Studies show that cats with clinical signs of the endocrinopathy have low suspicion of the disease by the clinicians compared the prevalence of the same. Thus, this study aimed to evaluate the opinions and experiences of Brazilian veterinarians about the approach and management of cats with hyperthyroidism through a questionnaire with 22 questions on the subject. A total of 1113 questionnaires were answered, where 535 (48%) of the veterinarians said to perform the thyroid palpation on all the cats they attend. Weight loss (89.2%), hyperactivity (82.8%) and polyphagia (81.6%) were the clinical signs most recognized by clinicians. And, 747 (61.1%) requested the total T4 as screening test to perform the diagnosis. There was an association (p<0.001) between palpation frequency, knowledge level, specialization course and graduation time with the number of cases attended and the time to perform the diagnosis. Radioiodinetherapy was chosen as the gold standard for 619 (55.6%), followed by drug treatment 385 (34.6%) and surgery 66 (5.9%). However, 642 (57.7%) indicate the drug, 340 (30.5%) radioiodinetherapy and 84 (7.5%) the surgical. The main limitation for the choice of radioiodinetherapy was the cost, for 825 (74.1%) of clinicians. Veterinarians who consider knowing the disease well and those specialized in felines are those that act in greater compatibility with the literature; and therefore, knowledge about a disease may be an important limiting factor in the prevalence of the disease in Brazil.

Made available in DSpace on 2014-06-11T19:35:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2006Bitstream added on 2014-06-13T19:05:26Z : No. of bitstreams: 1 costa_fs_dr_botfmvz.pdf: 709206 bytes, checksum: 01f8884968e3a8e1c302fe031542bffb (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O hipertiroidismo felino é caracterizado pela presença de excessivas concentrações plasmáticas dos hormônios tiroidianos. Para melhor caracterizar os efeitos da tirotoxicose, 16 gatos foram submetidos experimentalmente ao estado hipertiroídico a partir de uma dose de 150µg/kg de levotiroxina sódica a cada 24 horas durante 42 dias. Foram analisados os níveis séricos dos hormônios tiroidianos pela técnica de radioimunoensaio e a densidade mineral óssea da extremidade distal do rádio direito pela metodologia de densitometria óptica em imagens radiográficas. As metaloproteinases de matriz –2 e –9 foram avaliadas pela técnica de zimografia a partir de amostras séricas de um grupo de cinco animais que apresentaram-se com marcante desmineralização óssea. Adicionalmente, foi analisado o perfil plasmático das enzimas fosfatase alcalina, ALT, AST e GGT, assim como avaliação das isoenzimas de origem óssea e hepática da fosfatase alcalina. Os resultados demonstraram haver uma elevação dos níveis séricos dos hormônios tiroidianos acompanhada de significativa desmineralização óssea e hiperfosfatasemia. As formas ativas das MMPs –2 e –9 apresentaram uma forte correlação negativa com os valores densitométricos da extremidade distal do rádio dos animais. A avaliação da bioquímica sérica revelou marcante hiperfosfatasemia e níveis normais das enzimas ALT, AST e GGT entre os momentos avaliados. A eletroforese revelou maior elevação da isoenzima óssea ao final do protocolo experimental. Conclui-se que a tirotoxicose promovida proporciona desmineralização óssea em felinos domésticos e este evento é acompanhado de um aumento da atividade das metaloproteinases de matriz. A isoenzima originária do tecido ósseo é a principal responsável pela hiperfosfatasemia promovida / Hyperthyroidism is characterized by excessive plasmatic concentrations of thyroid gland hormones. For a better characterization of thyrotoxicosis effects, 16 cats were induced into hyperthyroid state by intaking a dose of 150µg/kg of sodium L-thyroxine every 24 hours during 42 days. The thyroid hormones serum levels were evaluated through radioimmunoassay technique and the bone mineral density of the right distal radius extremity was measured through radiographic optical densitometry technique. The matrix metalloproteinases –2 and –9 were evaluated through gelatin zymography of serum of five animals who presented considerable bone demineralization at densitometric evaluation. In addition, total alkaline phosphatase, bone and hepatic alkaline phosphatases isoenzymes, ALT, AST, and GGT plasmatic profile were evaluated during this experimental period. Results show a raise of serum thyroid hormones associated with significant bone demineralization and hiperphosphatasemia. The active forms of MMPs –2 and –9 demonstrated a strong negative correlation with bone density of right distal radius extremity. The evaluation of serum biochemical show considerable hiperfosfatasemia and normal levels of ALT, AST e GGT during the experiment. Electrophoresis revealed greater elevation of bone isoenzyme at the final of experimental protocol. It was possible to conclude that thyrotoxicosis induced promoted bone demineralization in domestic cats and this event was associated with an increasing of matrix metalloproteinases activity. Bone isoenzyme is the main responsible for hiperfosfatasemia found in this study

Orientador: Lucy Marie Ribeiro Muniz / Banca: Luiz Carlos Vulcano / Banca: Paulo Roberto Rodrigues Ramos / Banca: Paulo Ricardo de Oliveira Paes / Banca: Archivaldo Reche Junior / Resumo: O hipertiroidismo felino é caracterizado pela presença de excessivas concentrações plasmáticas dos hormônios tiroidianos. Para melhor caracterizar os efeitos da tirotoxicose, 16 gatos foram submetidos experimentalmente ao estado hipertiroídico a partir de uma dose de 150µg/kg de levotiroxina sódica a cada 24 horas durante 42 dias. Foram analisados os níveis séricos dos hormônios tiroidianos pela técnica de radioimunoensaio e a densidade mineral óssea da extremidade distal do rádio direito pela metodologia de densitometria óptica em imagens radiográficas. As metaloproteinases de matriz -2 e -9 foram avaliadas pela técnica de zimografia a partir de amostras séricas de um grupo de cinco animais que apresentaram-se com marcante desmineralização óssea. Adicionalmente, foi analisado o perfil plasmático das enzimas fosfatase alcalina, ALT, AST e GGT, assim como avaliação das isoenzimas de origem óssea e hepática da fosfatase alcalina. Os resultados demonstraram haver uma elevação dos níveis séricos dos hormônios tiroidianos acompanhada de significativa desmineralização óssea e hiperfosfatasemia. As formas ativas das MMPs -2 e -9 apresentaram uma forte correlação negativa com os valores densitométricos da extremidade distal do rádio dos animais. A avaliação da bioquímica sérica revelou marcante hiperfosfatasemia e níveis normais das enzimas ALT, AST e GGT entre os momentos avaliados. A eletroforese revelou maior elevação da isoenzima óssea ao final do protocolo experimental. Conclui-se que a tirotoxicose promovida proporciona desmineralização óssea em felinos domésticos e este evento é acompanhado de um aumento da atividade das metaloproteinases de matriz. A isoenzima originária do tecido ósseo é a principal responsável pela hiperfosfatasemia promovida / Abstract: Hyperthyroidism is characterized by excessive plasmatic concentrations of thyroid gland hormones. For a better characterization of thyrotoxicosis effects, 16 cats were induced into hyperthyroid state by intaking a dose of 150µg/kg of sodium L-thyroxine every 24 hours during 42 days. The thyroid hormones serum levels were evaluated through radioimmunoassay technique and the bone mineral density of the right distal radius extremity was measured through radiographic optical densitometry technique. The matrix metalloproteinases -2 and -9 were evaluated through gelatin zymography of serum of five animals who presented considerable bone demineralization at densitometric evaluation. In addition, total alkaline phosphatase, bone and hepatic alkaline phosphatases isoenzymes, ALT, AST, and GGT plasmatic profile were evaluated during this experimental period. Results show a raise of serum thyroid hormones associated with significant bone demineralization and hiperphosphatasemia. The active forms of MMPs -2 and -9 demonstrated a strong negative correlation with bone density of right distal radius extremity. The evaluation of serum biochemical show considerable hiperfosfatasemia and normal levels of ALT, AST e GGT during the experiment. Electrophoresis revealed greater elevation of bone isoenzyme at the final of experimental protocol. It was possible to conclude that thyrotoxicosis induced promoted bone demineralization in domestic cats and this event was associated with an increasing of matrix metalloproteinases activity. Bone isoenzyme is the main responsible for hiperfosfatasemia found in this study / Doutor

O hipertireoidismo é a endocrinopatia mais prevalente em felinos. Sua incidência vem aumentando nos últimos anos em todo mundo embora ainda seja pouco frequente no Brasil. Estudos evidenciam que gatos com manifestações clínicas da endocrinopatia têm baixa suspeição da doença pelos clínicos comparado a prevalência da mesma. Assim, este trabalho objetivou avaliar as opiniões e experiências de médicos veterinários brasileiros acerca da abordagem e manejo de felinos com hipertireoidismo por meio de um questionário com 22 perguntas sobre o tema. Foram respondidos 1113 questionários, onde 535 (48%) dos veterinários disseram realizar a palpação da tireoide em todos os gatos que atendem. Perda de peso (89,2%), hiperatividade (82,8%) e polifagia (81,6%) foram as manifestações clínicas mais reconhecidos pelos clínicos. E, 747 (61,1%) solicitam o T4 total como exame endocrinológico de triagem para realizar o diagnostico. Houve associação (p<0,001) entre frequência de palpação, nível de conhecimento, ter curso de especialização e tempo de formação com a quantidade de casos atendidos e o tempo para realizar o diagnostico. A radioiodoterapia foi o tratamento escolhido como padrão ouro por 619 (55,6%), seguido do tratamento medicamentoso 385 (34,6%) e cirúrgico 66 (5,9%). Porém, no momento de indicar, 642 (57,7%) escolhem o medicamentoso, 340 (30,5%) a radioiodoterapia e 84 (7,5%) o cirúrgico. A principal limitação para a escolha da radioiodoterapia foi o custo, por 825 (74,1%) dos clínicos. Pôde-se observar que os veterinarios que consideram conhecer bem a doença e aqueles especilizados em felinos são os que agem em maior compatibilidade com a literatura; e, portanto, o conhecimento sobre a doença pode ser um importante fator limitante na prevalência da doença no Brasil. / Hyperthyroidism is the most prevalent endocrinopathy in felines. Its incidence has been increasing in the world in the last years. Although it is still uncommon in Brazil. Studies show that cats with clinical signs of the endocrinopathy have low suspicion of the disease by the clinicians compared the prevalence of the same. Thus, this study aimed to evaluate the opinions and experiences of Brazilian veterinarians about the approach and management of cats with hyperthyroidism through a questionnaire with 22 questions on the subject. A total of 1113 questionnaires were answered, where 535 (48%) of the veterinarians said to perform the thyroid palpation on all the cats they attend. Weight loss (89.2%), hyperactivity (82.8%) and polyphagia (81.6%) were the clinical signs most recognized by clinicians. And, 747 (61.1%) requested the total T4 as screening test to perform the diagnosis. There was an association (p<0.001) between palpation frequency, knowledge level, specialization course and graduation time with the number of cases attended and the time to perform the diagnosis. Radioiodinetherapy was chosen as the gold standard for 619 (55.6%), followed by drug treatment 385 (34.6%) and surgery 66 (5.9%). However, 642 (57.7%) indicate the drug, 340 (30.5%) radioiodinetherapy and 84 (7.5%) the surgical. The main limitation for the choice of radioiodinetherapy was the cost, for 825 (74.1%) of clinicians. Veterinarians who consider knowing the disease well and those specialized in felines are those that act in greater compatibility with the literature; and therefore, knowledge about a disease may be an important limiting factor in the prevalence of the disease in Brazil.

<p>Iodine is considered an essential nutrient as lack can cause severe metabolic and neurological issues in adults, with the added consequence of permanent developmental damage in children and infants. However, excessive iodine intake can result in similar symptoms, with a wide variance in adverse health outcomes. The safe range of iodine intake may be relatively low, with some studies suggesting the possibility of a high frequency of subclinical cases of iodine poisoning going unnoticed or misdiagnosed. </p> <p>In this study, the zebrafish model was tested as an integrative whole animal model to demonstrate behavioral, morphological, and genetic responses to overt and subclinical iodine poisoning in developing humans. Zebrafish embryos were treated with sodium iodide (NaI) immediately after fertilization. Survivability was monitored every 24 hours until 120 hours post fertilization (hpf). Concentrations with no statistical significance on survival, plus the smallest dose of significant lethality were then examined using behavioral analysis at 120 hpf to compare both overt and subclinical outcomes. Morphology measurements of body length, head length, head width, brain length, swim bladder volume, jaw length, and ventral dissension were also recorded at 120 hpf. Gene expression of <i>slc5a5</i>, <i>tpo</i>, and <i>tshba</i> at 72 hpf was also measured using quantitative PCR (qPCR). </p> <p>A significant decrease in survival rates were observed at 24 hpf for 25, 37.5, and 50 mM NaI treatments (p<0.0001). Morphological measurements taken at 120 hpf showed a significant increase in body length, head length, head width, jaw length, and swim bladder volume in the 10 mM NaI treatment group (p<0.0001) and a significant decrease in body length, head length, jaw length, and swim bladder volume in the 25 mM treatment group (p<0.0001). A ventral distension also developed near the location of the thyroid gland exclusively in the 25 mM group. </p> <p>Behavioral analysis showed significant increases in movement for both the 10 mM and 25 mM treatment groups during dark phases (p<0.0001). The 25 mM treatment group had an increase in movement during dark phases for standard well environments (p<0.0001), but this did not hold true for larger well environments, instead trending towards a non-significant decrease (p>0.05). The 10 mM group had a significant decrease during the first light phase in standard wells (p=0.002), with a significant increase in the second light phase for large wells (p=0.005). There were no significant changes in the expression of selected genes associated with the thyroid pathway (<i>slc5a5</i>, <i>tpo</i>, or <i>tshba</i>) across all treatment groups (p>0.05). </p><p><br></p> <p>Overall, the results suggest zebrafish larvae exhibit both overt and subclinical symptoms of excess iodine intake. Future studies are needed to determine internalization, biodistribution, clearance, and further characterization of adverse outcomes along the thyroid pathway for additional exploration into subclinical thyrotoxicosis due to excess iodine intake. Researchers should express caution with time points, as the Wolff-Chaikoff effect may influence exposure windows in zebrafish. </p>

Yes / The most commonly reported symptom of hyperthyroidism is weight loss; successful treatment increases weight. Weight gain faced by patients with hyperthyroidism is widely considered a simple reaccumulation of premorbid weight, whereas many patients feel there is a significant weight “overshoot” attributable to the treatment. We aimed to establish if weight gain seen following treatment for hyperthyroidism represents replenishment of premorbid weight or “overshoot” beyond expected regain and, if there is excessive weight gain, whether this is associated with the applied treatment modality. Methods: We calculated the risk of becoming obese (body mass index [BMI] >30 kg/m2) following treatment for hyperthyroidism by comparing BMI of 1373 patients with overt hyperthyroidism seen in a secondary care setting with the age- and sex-matched population (Health Survey for England, 2007–2009). Next, we investigated the effect of treatment with an antithyroid drug (ATD) alone in regard to ATD with radioactive iodine (131I) therapy. We modeled the longitudinal weight data in relation to the treatment pathway to thyroid function and the need for long-term thyroxine replacement. Results: During treatment of hyperthyroidism, men gained 8.0 kg (standard deviation ±7.5) and women 5.5 kg (±6.8). At discharge, there was a significantly increased risk of obesity in male (odds ratio = 1.7 [95% confidence interval 1.3–2.2], p < 0.001) and female (1.3, 1.2–1.5, p < 0.001) patients with hyperthyroidism compared with the population. Treatment with 131I was associated with additional weight gain (0.6 kg, 0.4–0.8, p < 0.001), compared with ATD treatment alone. More weight gain was seen if serum thyrotropin (TSH) was markedly increased (TSH >10 mIU/L; 0.5 kg, 0.3–0.7, p < 0.001) or free thyroxine (fT4) was reduced (fT4 ≤ 10 pmol/L (0.8 ng/dL); 0.3 kg, 0.1–0.4, p < 0.001) during follow-up. Initiation of levothyroxine was associated with further weight gain (0.4 kg, 0.2–0.6, p < 0.001) and the predicted excess weight gain in 131I-induced hypothyroidism was 1.8 kg. Conclusions: Treatment for hyperthyroidism is associated with significant risks of becoming obese. 131I treatment and subsequent development of hypothyroidism were associated with small but significant amounts of excess weight gain compared with ATD alone. We advocate that the discussion over the weight “overshoot” risk forms part of the individualized treatment decision-making process.

by Albert Yan Wo Chan. / Thesis (M.D.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 203-242). / Chapter CHAPTER1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Brief History of thyroid diseases --- p.2 / Chapter 1.2 --- Thyrotoxicosis and muscle diseases --- p.7 / Chapter 1.2.1 --- Thyrotoxic myopathy --- p.8 / Chapter 1.2.2 --- Exophthalmic ophthalmoplegia (Grave's ophthalmopathy) --- p.10 / Chapter 1.2.3 --- Myasthenia gravis --- p.10 / Chapter 1.2.4 --- Thyrotoxic periodic paralysis (TPP) --- p.11 / Chapter 1.2.4.1 --- Overview --- p.11 / Chapter 1.2.4.2 --- Prevalence --- p.13 / Chapter 1.3 --- Periodic paralysis syndromes in the Chinese --- p.16 / Chapter 1.4 --- Potassium homeostasis in TPP --- p.19 / Chapter 1.5 --- Cellular potassium transport --- p.24 / Chapter 1.5.1 --- Role of the sodium pump --- p.24 / Chapter 1.5.2 --- Hormonal control of the sodium pump --- p.26 / Chapter 1.5.3 --- Molecular biology of the sodium pump --- p.27 / Chapter 1.5.4 --- Na-K-Cl transporter --- p.30 / Chapter 1.5.5 --- Summary --- p.32 / Chapter 1.6 --- Mechanism of paralysis --- p.33 / Chapter 1.7 --- Aetiology of TPP --- p.37 / Chapter 1.7.1 --- Genetic predisposition --- p.37 / Chapter 1.7.2 --- Possible membrane defect --- p.38 / Chapter 1.7.3 --- The central role of the sodium pump in the pathogenesis of TPP --- p.39 / Chapter 1.7.4 --- Environmental factor --- p.40 / Chapter 1.7.5 --- Summary --- p.40 / Chapter 1.8 --- Aims of the thesis --- p.41 / Chapter CHAPTER2 --- A PILOT STUDY ON THE PATHOPHYSIOLOGY OF TPP --- p.44 / Chapter 2.1 --- Aim --- p.45 / Chapter 2.2 --- Background --- p.45 / Chapter 2.2.1 --- The measurement of Na-K ATPase/ sodium pump activity --- p.45 / Chapter 2.2.2 --- In vitro decline in plasma potassium concentration --- p.48 / Chapter 2.2.3 --- Catecholamines --- p.49 / Chapter 2.3 --- Subjects & methods --- p.50 / Chapter 2.4 --- Results --- p.51 / Chapter 2.5 --- Discussion --- p.56 / Chapter 2.6 --- Conclusion --- p.58 / Chapter CHAPTER3 --- PLATELET NA-K ATPASE AS A TISSUE MARKER OF HYPERTHYROIDISM --- p.59 / Chapter 3.1 --- Aim --- p.60 / Chapter 3.2 --- Background --- p.60 / Chapter 3.2.1 --- Thyroid function tests (TFTs) --- p.60 / Chapter 3.2.2 --- TFTs vs tissue markers as an index of hyperthyroidism --- p.61 / Chapter 3.2.3 --- Sodium pump activity as a tissue marker and TPP --- p.63 / Chapter 3.2.4 --- Choice of tissue for sodium pump study --- p.64 / Chapter 3.2.5 --- Rationale behind the aim of study --- p.65 / Chapter 3.3 --- Subjects & methods --- p.68 / Chapter 3.3.1 --- Chemicals --- p.68 / Chapter 3.3.2 --- Subjects --- p.68 / Chapter 3.3.3 --- Plasma thyroid hormones analysis --- p.69 / Chapter 3.3.4 --- Determination of platelet Na-K ATPase activity --- p.71 / Chapter 3.3.4.1 --- Principle --- p.71 / Chapter 3.3.4.2 --- Preparation of platelets --- p.73 / Chapter 3.3.4.3 --- Preparation of platelet lysate --- p.73 / Chapter 3.3.4.4 --- Measurement of Na-K ATPase activity --- p.74 / Chapter 3.3.4.5 --- Measurement of Pi --- p.76 / Chapter 3.3.4.6 --- Measurement of protein --- p.78 / Chapter 3.4 --- Statistics & data handling --- p.80 / Chapter 3.5 --- Results --- p.81 / Chapter 3.5.1 --- Development of the platelet Na-K ATPase assay --- p.81 / Chapter 3.5.1.1 --- Introduction --- p.81 / Chapter 3.5.1.2 --- Effect of saponin concentration on the Na-K ATPase activity --- p.81 / Chapter 3.5.1.3 --- Linearity of the Na-K ATPase assay --- p.83 / Chapter 3.5.1.4 --- Imprecision of the Na-K ATPase assay --- p.83 / Chapter 3.5.1.5 --- Linearity of the Pi assay --- p.86 / Chapter 3.5.1.6 --- Linearity of the protein assay --- p.86 / Chapter 3.5.2 --- Thyroid function tests --- p.89 / Chapter 3.5.3 --- Platelet Na-K ATPase activity --- p.92 / Chapter 3.5.4 --- Correlation between thyroid hormones concentrations and platelet Na-K ATPase activity --- p.95 / Chapter 3.5.5 --- Correlation between age and platelet Na-K ATPase activity --- p.95 / Chapter 3.5.6 --- Performance of platelet ATPase as an indicator of hyperthyroidism --- p.99 / Chapter 3.6 --- Discussion --- p.102 / Chapter CHAPTER4 --- BASAL NA-K ATPASE ACTIVITY IN THYROTOXIC SUBJECTS WITH AND WITHOUT HYPOKALAEMIC PERIODIC PARALYSIS --- p.107 / Chapter 4.1 --- Aim --- p.108 / Chapter 4.2 --- Introduction --- p.108 / Chapter 4.2.1 --- Background --- p.108 / Chapter 4.2.2 --- Difficulties and limitations in TPP study --- p.109 / Chapter 4.3 --- Subjects & methods --- p.112 / Chapter 4.3.1 --- Platelet Na-K ATPase --- p.112 / Chapter 4.3.2 --- Rubidium loading test --- p.114 / Chapter 4.4 --- Statistics & data handling --- p.115 / Chapter 4.5 --- Results --- p.117 / Chapter 4.5.1 --- Platelet Na-K ATPase activity --- p.117 / Chapter 4.5.1a --- Thyrotoxic vs TPP --- p.121 / Chapter 4.5.1b --- Thyrotoxic vs euthyroid and TPP vs EuTPP --- p.124 / Chapter 4.5.1c --- Control vs euthyroid and EuTPP --- p.126 / Chapter 4.5.2 --- Rubidium loading test --- p.127 / Chapter 4.6 --- Discussion --- p.129 / Chapter 4.6.1 --- Clinical marker of TPP --- p.129 / Chapter 4.6.2 --- RBC/ lymphocyte sodium pump activity --- p.130 / Chapter 4.6.3 --- Platelet Na-K ATPase activity --- p.135 / Chapter CHAPTER5 --- VALIDATION OF THE ORAL GLUCOSE TOLERANCE TEST --- p.142 / Chapter 5.1 --- Aim --- p.143 / Chapter 5.2 --- Background --- p.143 / Chapter 5.2.1 --- Need for a validated protocol for OGTT --- p.143 / Chapter 5.2.2 --- Effectiveness of sodium fluoride as a preservative of glucose in blood sample --- p.144 / Chapter 5.2.3 --- Effect of delay in sample handling --- p.146 / Chapter 5.2.4 --- Ideal concentration of NaF --- p.147 / Chapter 5.2.5 --- D-mannose as a preservative of blood glucose --- p.147 / Chapter 5.2.6 --- Rationale behind the aim of study --- p.148 / Chapter 5.3 --- Subjects & methods --- p.149 / Chapter 5.3.1 --- Effectiveness of NaF --- p.149 / Chapter 5.3.2 --- Effect of delay in sample handling --- p.150 / Chapter 5.3.3 --- Ideal concentration of NaF --- p.151 / Chapter 5.3.4 --- Evaluation of D-mannose as a preservative of blood glucose --- p.151 / Chapter 5.4 --- Results and discussion --- p.153 / Chapter 5.4.1 --- Effectiveness of NaF --- p.153 / Chapter 5.4.2 --- Effect of delay in sample handling --- p.157 / Chapter 5.4.3 --- Ideal concentration of NaF --- p.159 / Chapter 5.4.4 --- D-mannose as a preservative of glucosein blood --- p.161 / Chapter 5.4.5 --- Summary --- p.167 / Chapter CHAPTER6 --- HYPERINSULINAEMIA AND NA-K ATPASE ACTIVITY IN TPP --- p.168 / Chapter 6.1 --- Aim --- p.169 / Chapter 6.2 --- Background --- p.169 / Chapter 6.2.1 --- "Insulin, hypokalaemia and sodium pump" --- p.169 / Chapter 6.2.2 --- Insulin and skeletal muscle membrane potential --- p.170 / Chapter 6.2.3 --- Potential role of insulin in the pathogenesis of TPP --- p.172 / Chapter 6.2.4 --- Hyperinsulinaemia and thyrotoxicosis --- p.173 / Chapter 6.2.5 --- TPP vs uncomplicating thyrotoxic patients --- p.173 / Chapter 6.2.6 --- Catecholamines and insulin secretion --- p.175 / Chapter 6.3 --- Subjects and methods --- p.177 / Chapter 6.4 --- Statistics and data handling --- p.179 / Chapter 6.5 --- Results --- p.180 / Chapter 6.6 --- Discussion --- p.187 / Chapter CHAPTER7 --- OVERALL DISCUSSION AND CONCLUSION --- p.192 / Chapter 7.1 --- General discussion --- p.193 / Chapter 7.2 --- Role of sodium pump in the pathogenesis of TPP --- p.196 / Chapter 7.3 --- Strategy for further study --- p.201 / Chapter 7.4 --- Conclusion --- p.202 / REFERENCES --- p.203 / APPENDIX --- p.239 / (Selected publications)

In this study the volume determination which is a part of the doseplanning for patients with thyrotoxicosis was investigated. The aim was to find an accurate method to determine the active volume with single photon emission tomography (SPECT) which in several studies have shown better results than with the currently used method planar scintigraphy (PS). This was implemented on the Xeleris 3.1 by General Electric (GE) at the University Hospital of Umeå (NUS). The examination time with SPECT is required not to be significantly longer than the examination time with PS. Despite the relatively short examination time, the accuracy of the volume determination should be more accurate. This was analyzed with a true value of the volume, conducted with Monte Carlo simulations of digital anthropomorphic phantoms. It is also important that the developed method is user friendly. The study included ten patients with thyrotoxicosis from which, relative activity uptakes were measured. These uptakes were specified in 22 digital XCAT phantoms which were random sampled with respect to phantom mass. The Monte Carlo program "simulating medical imaging nuclear detectors" (simind) was used to simulate the SPECT-system. The projection images were ordered subset expectation maximization (OSEM) reconstructed and Butterworth filtered. Unfiltered images were used to compare volume calculations with filtered ones. The volume of the thyroid was segmented using threshold values applied to all voxels in the image-sets and the optimization of the thresholds was conducted by numerical calculations. The results in this study shows that the best choice of intensity threshold value is 21.1(24)% of the maximum voxel value for all phantoms. The threshold is valid for OSEM iteration number five and unfiltered image-sets. Butterworth filtered images were less suitable to use than unfiltered images when the thyroid volume was calculated with data from SPECT-simulations of phantoms.