1. Evaluate the mechanisms by which hyperglycemia and hypothyroidism occur in patients on certain targeted chemotherapy agents.2. Develop treatment recommendations for patients who develop these endocrine toxicities while on therapy.3. Establish appropriate monitoring guidelines for patient receiving certain targeted chemotherapy agents.

Orientador: Danilo Moretti Ferreira / Resumo: As disfunções tireoidianas ocorrem com maior freqüência nos pacientes com Síndrome de Down (SD) do que na população em geral. Os estudos sobre crescimento físico em crianças com SD e disfunção tireoidiana são controversos; alguns autores referem menor crescimento em pacientes com hipotireoidismo compensado, enquanto outros não confirmam estes achados. Portanto, avaliar e monitorizar a função tireoidiana e o crescimento físico de crianças com SD é de extrema importância e foi o que motivou o presente estudo, o qual teve como objetivo investigar a freqüência das disfunções tireoidianas e a evolução das mesmas em pacientes com SD, avaliar o crescimento pondero-estatural das crianças com SD, comparar os percentis de peso e estatura, a velocidade de crescimento e o escore Z E/I e P/I nos pacientes SD com e sem disfunção tireoidiana. CASUÍSTICA E MÉTODO - Estudo envolvendo 43 crianças diagnosticadas como SD no Serviço de Aconselhamento Genético da UNESP - Botucatu, no período de 1996 - 2000. Os pacientes foram estudados por um período mínimo de 9 meses, com avaliação da função tireoidiana pelas dosagens de tiroxina livre e tireotrofina no início e no final do estudo e com avaliação de peso e estatura no início, meio e fim do estudo. Conforme o diagnóstico da função tireoidiana ao final do estudo, foram constituídos 2 grupos: normal ou disfunção. RESULTADOS - A amostra foi homogênea quanto ao sexo, 72% dos pacientes tinham menos de três anos de idade e 23% eram portadores de cardiopatia acianogênica. A trissomia livre do cromossomo 21 ocorreu em 98% dos casos. No início do estudo, 67,4% dos pacientes apresentaram hipotireoidismo compensado, 7% hipotireoidismo adquirido, e um paciente tinha hipertireoidismo. No final do estudo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Thyroid dysfunction occurs more frequently in patients with Down syndrome (DS) than in the general population. Studies on physical growth in children with DS and thyroid dysfunction are controversial; some report lower growth rates in patients with compensated hypothyroidism while others do not confirm these findings. Therefore, the assessment and monitoring of thyroid function and physical growth in children with DS are of great importance. The purpose of the present study was to investigate the frequency and development of thyroid dysfunction, to assess weight/height changes, and compare weight and height percentiles, growth rate and both E/I and P/I Z-scores in DS patients with and without thyroid dysfunction. CASES AND METHODS: This study included 43 children, who were diagnosed as having DS at the Genetic Counseling Service, UNESP-Botucatu, between 1996 and 2000. The patients were followed up from 9 to 36 months. Thyroid function was assessed by measuring the levels of thyroxin and thyrotrophin at the beginning and at the end of the study while weight and height were assessed at the beginning, halfway and at the end of the study. According to the diagnosis of thyroid function at the end of the study, the patients were assigned either to the normal group or the dysfunction group. RESULTS: The study sample was homogeneous regarding sex. Seventy-two percent of the patients were less than 3 years of age and 23% displayed acyanogenic cardiopathy. Free trisomy of chromosome 21 occurred in 98% of the cases. At the beginning of the study, 67.4% of the patients showed compensated hypothyroidism, 7% exhibited acquired hypothyroidism and one had hyperthyroidism. At the end of the study, 53.5% of hypothyroidism was observed while the frequency of the remaining disorders remained unchanged. Of the 29 cases of compensated hypothyroidism... (Complete abstract click electronic address below) / Mestre

Made available in DSpace on 2014-06-11T19:28:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T18:32:25Z : No. of bitstreams: 1 macedo_ds_me_botfm.pdf: 1047806 bytes, checksum: bcf216c1db1d87e657a075f0c4382ec9 (MD5) / As disfunções tireoidianas ocorrem com maior freqüência nos pacientes com Síndrome de Down (SD) do que na população em geral. Os estudos sobre crescimento físico em crianças com SD e disfunção tireoidiana são controversos; alguns autores referem menor crescimento em pacientes com hipotireoidismo compensado, enquanto outros não confirmam estes achados. Portanto, avaliar e monitorizar a função tireoidiana e o crescimento físico de crianças com SD é de extrema importância e foi o que motivou o presente estudo, o qual teve como objetivo investigar a freqüência das disfunções tireoidianas e a evolução das mesmas em pacientes com SD, avaliar o crescimento pondero-estatural das crianças com SD, comparar os percentis de peso e estatura, a velocidade de crescimento e o escore Z E/I e P/I nos pacientes SD com e sem disfunção tireoidiana. CASUÍSTICA E MÉTODO - Estudo envolvendo 43 crianças diagnosticadas como SD no Serviço de Aconselhamento Genético da UNESP - Botucatu, no período de 1996 - 2000. Os pacientes foram estudados por um período mínimo de 9 meses, com avaliação da função tireoidiana pelas dosagens de tiroxina livre e tireotrofina no início e no final do estudo e com avaliação de peso e estatura no início, meio e fim do estudo. Conforme o diagnóstico da função tireoidiana ao final do estudo, foram constituídos 2 grupos: normal ou disfunção. RESULTADOS - A amostra foi homogênea quanto ao sexo, 72% dos pacientes tinham menos de três anos de idade e 23% eram portadores de cardiopatia acianogênica. A trissomia livre do cromossomo 21 ocorreu em 98% dos casos. No início do estudo, 67,4% dos pacientes apresentaram hipotireoidismo compensado, 7% hipotireoidismo adquirido, e um paciente tinha hipertireoidismo. No final do estudo... / Thyroid dysfunction occurs more frequently in patients with Down syndrome (DS) than in the general population. Studies on physical growth in children with DS and thyroid dysfunction are controversial; some report lower growth rates in patients with compensated hypothyroidism while others do not confirm these findings. Therefore, the assessment and monitoring of thyroid function and physical growth in children with DS are of great importance. The purpose of the present study was to investigate the frequency and development of thyroid dysfunction, to assess weight/height changes, and compare weight and height percentiles, growth rate and both E/I and P/I Z-scores in DS patients with and without thyroid dysfunction. CASES AND METHODS: This study included 43 children, who were diagnosed as having DS at the Genetic Counseling Service, UNESP-Botucatu, between 1996 and 2000. The patients were followed up from 9 to 36 months. Thyroid function was assessed by measuring the levels of thyroxin and thyrotrophin at the beginning and at the end of the study while weight and height were assessed at the beginning, halfway and at the end of the study. According to the diagnosis of thyroid function at the end of the study, the patients were assigned either to the normal group or the dysfunction group. RESULTS: The study sample was homogeneous regarding sex. Seventy-two percent of the patients were less than 3 years of age and 23% displayed acyanogenic cardiopathy. Free trisomy of chromosome 21 occurred in 98% of the cases. At the beginning of the study, 67.4% of the patients showed compensated hypothyroidism, 7% exhibited acquired hypothyroidism and one had hyperthyroidism. At the end of the study, 53.5% of hypothyroidism was observed while the frequency of the remaining disorders remained unchanged. Of the 29 cases of compensated hypothyroidism... (Complete abstract click electronic address below)

ABSTRACT Thyroid disease is one of the most common endocrine disorders in clinical practice. Critical illness is often associated with alterations in thyroid hormone functions. Thyroid dysfunction is a serious matter if managed inaccurately; it may increase morbidity and mortality. The purpose of this Doctor of Nursing Practice project is to identify the knowledge, attitudes, behaviors and practice of advanced practice nurses (acute care nurse practitioners (ACNP) and adult gerontology acute care nurse practitioners (AGACNP)) on current thyroid dysfunction management in the acute care setting. The DNP project demonstrated that most acute care nurse practitioners believe that TD screening, diagnosis and management is important in the acute care setting. The survey results also indicated that most of the AGACNP/ACNPs would initiate treatment while managing patient in an acute care setting and will likely collaborate with endocrinology for overall management or follow ups to ensure quality and comprehensive care in management of TD. Keywords: thyroid disease, thyroid dysfunction, identify, knowledge, attitudes, behaviors, acute care

Thyroid dysfunction is one of the most common endocrine disorders in women of childbearing age and the obstetric consequences of abnormal thyroid hormone levels during pregnancy have been established. Less understood is the implication of the presence of maternal thyroid autoantibodies on infant outcomes among women who are euthyroid during pregnancy. The objective of this study was two-fold: 1) to examine the influence of antenatal thyroperioxidase (TPO) status on fetal/infant brain and body growth measurements at delivery and 2) to explore the relationship of antenatal TPO status and maternal postpartum thyroid dysfunction (PPTD) on early infant growth and neurocognitive development. Six-hundred thirty-one (631) euthyroid pregnant women were recruited from prenatal clinics in Tampa Bay, Florida and the surrounding area between November 2007 and December 2010. TPO status was determined during pregnancy and fetal/infant brain and body growth variables were assessed at delivery. A subsample of forty-one (41) mother-infant dyads participated in a 6-month longitudinal supplemental study. Infant growth assessments were conducted at 3, 4, 5 and 6 months postpartum. Regression analysis revealed maternal TPO positivity was significantly associated with smaller head circumference, reduced brain weight and lower brain-body-ratio; however maternal race/ethnicity was identified as an effect modifier in the relationship. No significant differences were noted in birth weight, birth length, abdominal circumference or chest circumference measurements among infants born to TPO positive mothers of any racial/ethnic group as compared to their negative counterparts. Mixed model analysis of the smaller subset (n=41) revealed infants of TPO+ mothers were smaller at birth but experienced accelerated growth between birth to 3 months when compared to infants born to TPO- mothers. This acceleration led to their catch-up in growth to their TPO negative counterparts by 3 months of age. No significant differences were noted in neurocognitive outcomes between infants born to TPO+ mothers compared to those born to TPO- mothers. The findings in this dissertation indicate that maternal/race ethnicity modifies the relationship between TPO positivity and reduced fetal/infant brain growth. Additionally, the analyses suggest that maternal autoantibody status could lead to variations in early infant growth and development. The end-result of these variations is unclear. Further research is needed to determine the potential impact of reduced head circumference and accelerated growth as it relates to long-term neurocognitive consequences. Currently, TPO antibody status is not assessed as part of the standard prenatal care laboratory work-up, but findings from this study suggest that fetal brain growth may be impaired by TPO positivity among certain populations, therefore autoantibody screening among high-risk sub-groups may be useful for clinicians to determine whether prenatal thyroid treatment is warranted.

Introduction: Spontaneous abortion (SA) is the most common complication in pregnancy. The aim of the study was to investigate the causality of selected genetic factors - Apolipoprotein E (Apo E) gene polymorphisms, factor V Leiden (FVL), Prothrombin (PT G20210A) and nongenetics factors - Thyroid stimulating hormone (TSH), free thyroxine (fT4), antibodies against thyroid peroxidase (a-TPO) in the role of early SA. Materials and methods: For genotyping of APO E polymorphism was used PCR-RFLP. The detection of mutations in genes FV and FII was performed using by HRM. Laboratory markers of thyroid (TSH, a-TPO and fT4) were determined by an automated analyzer using chemiluminescent immunoassay. Results: APOE genotypes of investigated group of 410 samples abortioned embryonic/ fetal tissues were not significantly different from 2 606 adult controls (P = 0.653). In observed infertile group of 75 women with isolated SA was FVL detected in heterozygous constitution with a prevalence of 12 %. The prevalence of FVL in a group of women with early insulated SA was significantly higher than 76 controls (12 % vs. 2.6 %, P = 0.031). The difference of PTG20210A prevalence between women with isolated SA and controls was not significant (4 % vs. 5.3 %, P = 1). The prevalence of elevated TSH levels (higher than 2.5...

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O diabetes mellitus(DM) e as disfunções tireoidianas(DT) são as duas desordens endocrinológicas mais comuns na prática clínica. A DT não reconhecida pode interferir no controle metabólico e adicionar mais risco a um cenário predisponente à doença cardiovascular. O objetivo deste estudo foi avaliar a prevalência da DT em pacientes com diabetes mellitus tipo 1 e tipo 2 (DM1 e DM2) e avaliar o risco cardiovascular em pacientes com DM2 com e sem DT utilizando parâmetros clínicos e laboratoriais. Trata-se de um estudo observacional de corte transversal. Foram avaliados 304 pacientes com DM2 e 82 pacientes com DM1. Os pacientes foram submetidos a um inquérito clínico-demográfico e avaliação laboratorial para determinação do perfil lipídico, glicídico e da função tireoidiana. Os pacientes com DM2 tiveram seus escores de risco cardiovascular em 10 anos determinados pelas equações de Framingham e do UKPDS risk engine. A frequência de disfunção tireoidiana entre os 386 pacientes foi de 14,7%, sendo de 13% nos que não possuíam disfunção prévia. A disfunção mais frequente encontrada foi de hipotireoidismo subclínico, com 13% no DM1 e de 12% no DM2. A prevalência de anticorpos anti-tireoperoxidase (TPO) positivos foi de 10,8%, sendo de14,6% em pacientes com DM1.Foram diagnosticados 44 (11,2%) novos casos de disfunção tireoidiana em pacientes que negavam ou desconheciam terem DT prévia.Destes novos casos, 12,8% em DM1 e 13,1% em DM2.Dos 49 pacientes com DT prévia, 50% dos DM1e 76% dos DM2 estavam compensados. Não foi observada diferença entre as médias do escore de risco de Framingham entre os pacientes DM2 com eutireoidismo e com hipotireoidismo subclínico. Observou-se uma associação entre o hipotireoidismo subclínico e risco cardiovascular nos pacientes com DM2 demonstrado pela diferença estatisticamente significativa entre as médias do escore UKPDS para doença coronariana não-fatal e fatal, acidente vascular cerebral fatal entre os dois grupos (p=0,007; 0,005;0,027 respectivamente). As demais funções tireodianas (hipotireoidismo clínico, hipertireoidismo clínico e subclínico) encontradas não foram analisadas devido ao pequeno número de pacientes em cada grupo.Concluímos que o rastreio da doença tireoidiana entre os pacientes com diabetes mellitus deve ser realizado rotineiramente considerando-se a prevalência de novos casos de DT diagnosticados e o fato de que os pacientes com DM2 e com hipotireoidismo subclínico avaliados possuírem um risco cardiovascular maior. Todavia, concluímos que estudos prospectivos e com maior número de pacientes são necessários para o esclarecimento do impacto da doença tireoidiana no risco cardiovascular do paciente com DM. / Diabetes mellitus and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The unrecognized TD may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective of this study was to evaluate the prevalence of TD in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM) and to evaluate the cardiovascular risk of patients with T2DM with and without thyroid dysfunction using clinical and laboratory parameters. This is an observational cross-sectional study. We evaluated 304 patients with T2DM and 82 patients with T1DM. The patients underwent a clinical-demographic survey and laboratory evaluation to determine the lipid and glycemic profile and thyroid function. Patients with T2DM had their 10 years cardiovascular risk scores determined by Framingham equations and the UKPDS risk engine. The frequency of TD among the 386 patients was 14.7% and 13% who denied previous TD. The most frequently TD was subclinical hypothyroidism, in 13% of patients with T1DM and in 12% of patients with T2DM.The prevalence of anti-TPO antibodies was 10.8%, being more frequently among patients with T1DM (14.6%). Forty-four (11.2%) new cases of TD were diagnosed during the study in patients who denied or were unaware of this clinical condition. Of the 49 patients with prior TD,50% of the T1DM and 76% of T2DM were compensated. No differencies were observed between the mean scores of the Framingham risk among patients with T2DM who had normal thyroid function compared to those with subclinical hypothyroidism. An association between subclinical hypothyroidism and cardiovascular risk in T2DM patients was found by statistically significant difference between the mean UKPDS scores for non-fatal and fatal CHD and fatal stroke between the two groups (p = 0,007;0,005;0027; respectively). The other TD (clinical hypothyroidism, clinical and subclinical hyperthyroidism) found were not analyzed due to the small number of patients in each group.We conclude that screening for thyroid disease among patients with diabetes mellitus should be routinely performed considering the prevalence of new cases diagnosed and the fact that patients with DM2 and subclinical hypothyroidism evaluated had a higher cardiovascular risk. However, prospective studies and with more patients are warranted to determine the impact of thyroid dysfunction in the cardiovascular risk of patients with diabetes.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O diabetes mellitus(DM) e as disfunções tireoidianas(DT) são as duas desordens endocrinológicas mais comuns na prática clínica. A DT não reconhecida pode interferir no controle metabólico e adicionar mais risco a um cenário predisponente à doença cardiovascular. O objetivo deste estudo foi avaliar a prevalência da DT em pacientes com diabetes mellitus tipo 1 e tipo 2 (DM1 e DM2) e avaliar o risco cardiovascular em pacientes com DM2 com e sem DT utilizando parâmetros clínicos e laboratoriais. Trata-se de um estudo observacional de corte transversal. Foram avaliados 304 pacientes com DM2 e 82 pacientes com DM1. Os pacientes foram submetidos a um inquérito clínico-demográfico e avaliação laboratorial para determinação do perfil lipídico, glicídico e da função tireoidiana. Os pacientes com DM2 tiveram seus escores de risco cardiovascular em 10 anos determinados pelas equações de Framingham e do UKPDS risk engine. A frequência de disfunção tireoidiana entre os 386 pacientes foi de 14,7%, sendo de 13% nos que não possuíam disfunção prévia. A disfunção mais frequente encontrada foi de hipotireoidismo subclínico, com 13% no DM1 e de 12% no DM2. A prevalência de anticorpos anti-tireoperoxidase (TPO) positivos foi de 10,8%, sendo de14,6% em pacientes com DM1.Foram diagnosticados 44 (11,2%) novos casos de disfunção tireoidiana em pacientes que negavam ou desconheciam terem DT prévia.Destes novos casos, 12,8% em DM1 e 13,1% em DM2.Dos 49 pacientes com DT prévia, 50% dos DM1e 76% dos DM2 estavam compensados. Não foi observada diferença entre as médias do escore de risco de Framingham entre os pacientes DM2 com eutireoidismo e com hipotireoidismo subclínico. Observou-se uma associação entre o hipotireoidismo subclínico e risco cardiovascular nos pacientes com DM2 demonstrado pela diferença estatisticamente significativa entre as médias do escore UKPDS para doença coronariana não-fatal e fatal, acidente vascular cerebral fatal entre os dois grupos (p=0,007; 0,005;0,027 respectivamente). As demais funções tireodianas (hipotireoidismo clínico, hipertireoidismo clínico e subclínico) encontradas não foram analisadas devido ao pequeno número de pacientes em cada grupo.Concluímos que o rastreio da doença tireoidiana entre os pacientes com diabetes mellitus deve ser realizado rotineiramente considerando-se a prevalência de novos casos de DT diagnosticados e o fato de que os pacientes com DM2 e com hipotireoidismo subclínico avaliados possuírem um risco cardiovascular maior. Todavia, concluímos que estudos prospectivos e com maior número de pacientes são necessários para o esclarecimento do impacto da doença tireoidiana no risco cardiovascular do paciente com DM. / Diabetes mellitus and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The unrecognized TD may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective of this study was to evaluate the prevalence of TD in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM) and to evaluate the cardiovascular risk of patients with T2DM with and without thyroid dysfunction using clinical and laboratory parameters. This is an observational cross-sectional study. We evaluated 304 patients with T2DM and 82 patients with T1DM. The patients underwent a clinical-demographic survey and laboratory evaluation to determine the lipid and glycemic profile and thyroid function. Patients with T2DM had their 10 years cardiovascular risk scores determined by Framingham equations and the UKPDS risk engine. The frequency of TD among the 386 patients was 14.7% and 13% who denied previous TD. The most frequently TD was subclinical hypothyroidism, in 13% of patients with T1DM and in 12% of patients with T2DM.The prevalence of anti-TPO antibodies was 10.8%, being more frequently among patients with T1DM (14.6%). Forty-four (11.2%) new cases of TD were diagnosed during the study in patients who denied or were unaware of this clinical condition. Of the 49 patients with prior TD,50% of the T1DM and 76% of T2DM were compensated. No differencies were observed between the mean scores of the Framingham risk among patients with T2DM who had normal thyroid function compared to those with subclinical hypothyroidism. An association between subclinical hypothyroidism and cardiovascular risk in T2DM patients was found by statistically significant difference between the mean UKPDS scores for non-fatal and fatal CHD and fatal stroke between the two groups (p = 0,007;0,005;0027; respectively). The other TD (clinical hypothyroidism, clinical and subclinical hyperthyroidism) found were not analyzed due to the small number of patients in each group.We conclude that screening for thyroid disease among patients with diabetes mellitus should be routinely performed considering the prevalence of new cases diagnosed and the fact that patients with DM2 and subclinical hypothyroidism evaluated had a higher cardiovascular risk. However, prospective studies and with more patients are warranted to determine the impact of thyroid dysfunction in the cardiovascular risk of patients with diabetes.