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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Molecular and clinical genetic studies of a novel variant of familial hypercalcemia /

Szabo, Eva. January 2002 (has links)
Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.
12

Metabolic disturbances in relation to serum calcium and primary hyperparathyroidism /

Hagström, Emil, January 2006 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 5 uppsatser.
13

Lamina dura bundle bone or radiographic artifact /

Berenguer, Gaston, January 2005 (has links)
Thesis (M.S.)--University of Florida, 2005. / Typescript. Title from title page of source document. Document formatted into pages; contains 45 pages. Includes Vita. Includes bibliographical references.
14

Scintigrafická detekce funkční tkáně příštítných tělísek při hyperparatyreóze. / Scintigraphicdetection of the parathyroid tissue in hyperparathyroidism.

Chroustová, Daniela January 2017 (has links)
The aim of this work is the assessment of the diagnostic accuracy in parathyroid glands (PG) detection by various scintigraphic methods and to propose the optimal examination procedure for successful localization of hyperfunctional PG. The patients were divided into 3 groups with individual types of hyperparathyroidism (HPT): group I. primary PHPT (253 patients), group II. normocalcemic NPHPT (75 patients) and group III. secondary SHPT (61 patients). For all the patients protocol A was performed: one day a two-phase SPECT/CT scan using 99mTc-MIBI (technetium 2-methoxyisobutylisonitrile) depicted simultaneously thyroid gland and PG, and another day thyroid SPECT using 99mTc-NaTcO4 (pertechnetate) for 3D subtraction analysis. In case of 44 patients from group I with negative or unclear results of the protocol A also protocol B was performed: PET/CT using 18F-FCH (fluorocholine). The results of surgery and histology served as a "gold standard" for the assessment of the accuracy of scintigraphic findings. In group I. 209/253 patients had a positive finding on scintigraphy using protocol A and 44 patients with an unclear or negative finding of protocol A underwent protocol B examination. In total, 253 patients were operated. The results of the diagnostic accuracy: sensitivity, specificity, positive...
15

Caracterização molecular e estudo de expressão de mutações no gene do recptor sensor de calcio / Molecular characterization and expression analysis of mutations in the calcium sensing receptor gene

Andrade, Simone Caixeta de, 1977- 21 February 2006 (has links)
Orientador: Lilia F. R. de Souza Li / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T01:59:33Z (GMT). No. of bitstreams: 1 Andrade_SimoneCaixetade_M.pdf: 1991149 bytes, checksum: 4c5b783ab7776886c12977300fbb6af7 (MD5) Previous issue date: 2006 / Resumo: O CASR pertence à família C dos receptores que se acoplam à proteína G e é ativado quando interage com o cálcio extracelular, sendo responsável pelo ajuste do ¿set point¿ do cálcio extracelular por meio da regulação da secreção de PTH e excreção de cálcio. Mutações no Receptor Sensor de Cálcio (CASR) estão associadas a FHH (Hipercalcemia Hipocalciúrica Familiar) e NSHTP (Hiperparatireoidismo Neonatal Grave) quando inativadoras do receptor e ADH (Hipoparatireoidismo Autossômico Dominante) quando ativadoras. O Hiperparatireoidismo Neonatal Grave (NSHPT) é uma doença rara caracterizada por calcemias elevadas, próximas às consideradas incompatíveis à vida, associada ao aumento da concentração de PTH, desmineralização óssea grave e sintomas neonatais como hipotonia e baixo ganho ponderal. Trata-se de uma doença familiar, com pais portadores de Hipercalcemia Hipocalciúrica Familiar (FHH), uma doença autossômica dominante, geralmente assintomática, com calcemias elevadas ou no limite superior da normalidade, associada a concentrações de PTH normais, porém não suprimidas e hipocalciúria. ADH, por sua vez, cursam com desregulação no ajuste da concentração de cálcio extracelular, onde baixas concentrações de cálcio ativam o receptor e inibem a secreção de PTH pelas paratireóides e aumentam a excreção de cálcio pelos rins. Indivíduos afetados apresentam hipocalcemia, PTH no limite inferior ou abaixo do normal, hiperfosfatemia e hipercalciúria. O objetivo desse trabalho foi estudar duas famílias portadoras de NSHPT e FHH, identificar novas mutações e analisar o grau de expressão dos receptores mutados. Identificamos três mutações pontuais, nas posições c.1913.G>T, c.2.T>G e c.2244.C>G. Na família S encontramos a mutação c.1913.G>T que resulta em mudança de aminoácido Arginina por Leucina na posição 638 e a mutação silenciosa c.2244.C>G que não altera o aminoácido Prolina da posição 748. Na família J encontramos a mutação c.2.T>G que resulta em mudança do primeiro aminoácido Metionina e em perda da seqüência Kozak (AXXATGG). Um programa de análise para a previsão de seqüências utilizadas para início da tradução protéica, indicou que, na presença da mutação, o ATG com maior probabilidade de ser utilizado como o novo sítio de início de tradução localiza-se no exon 3, na mesma matriz de leitura original. Para análise da expressão do receptor, com a mutação no códon inicial de transcrição do receptor (p.M1?), inserimos no cDNA do CASR um fragmento correspondente à região -226 a 66 do CASR, contendo cinco potenciais seqüências Kozak. Para o estudo da expressão dos receptores mutados da família S inserimos as mutações no cDNA do CASR através de mutagênese sítio dirigida. Analisamos a expressão dos receptores mutados através do Western Blot. O receptor mutado p.R638L apresentou uma expressão similar ao receptor nativo e foram visualizadas as formas monoméricas correspondentes às bandas de 140kDa (forma imatura, parcialmente glicosilada) e 160kDa (forma madura e glicosilada) e bandas superiores maiores que 220kDa. A mutação c.2244.C>G é silenciosa e apresentou expressão similar à do receptor nativo. Em contraste, a expressão do receptor mutado p.M1? através do Western blot estava consideravelmente reduzida. Nos experimentos de imunocitoquímica, observamos que o receptor nativo foi bem expresso na superfície celular tanto em células não permeabilizadas, quanto permeabilizadas. Padrão semelhante foi observado para o receptor mutado p.R638L, indicando maturação e processamento apropriado no retículo endoplasmático enquanto que o receptor com a mutação p.M1? não foi visualizado na superfície celular de células não permeabilizadas e só foi identificado no interior de células permeabilizadas, sugerindo que o receptor mutado era retido no retículo endoplasmático não conseguindo se expressar na membrana plasmática / Abstract: The CASR belongs to family C of the G protein coupled receptors and it is activated by the interaction with extracellular calcium, which is responsible for adjusting extracellular calcium set point adjusting PTH and calcium excretion. Calcium Sensing Receptor mutations are related to Familial Hypocalciuric Hypercalcemia (FHH) and Neonatal Severe Hyperparathyroidism (NSHPT) when inactivating and to Autosomal Dominant Hypocalcemia (ADH) when activating. Neonatal Severe Hyperparathyroidism (NSHPT) is a rare disease characterized by hypercalcemia, calcium levels close to those incompatible with life, markedly elevated PTH levels, severe bone demineralization and neonatal symptoms as hypotonia and poor weight gain. Familial Hypocalciuric Hypercalcemia is a familial disease with Autosomal dominant inheritance, in which parents are usually affected, generally asymptomatic, mild ¿ to ¿ moderate hypercalcemia and normal PTH levels (but not suppressed) and hypocalciuria. In ADH, affected individuals¿ present hypocalcemia, PTH at the lower limit or normal range, hyperphosphatemia and hypercalciuria. The objective of this work was study of two families (S and J) with Neonatal Severe Hyperparathyroidism and Familial Hypocalciuric Hypercalcemia, search for new mutations and analyze the expression pattern of mutated receptors. Three new missense mutations were found: c.1913.G>T, c.2.T>G and c.2244.C>G. The mutation c.1913.G>T was identified at family S. and resulted in Arginine to Leucine change at codon 638. The silent mutation c.2244.C>G didn¿t change the amino acid Proline at codon 748. A novel mutation in exon 2, T to G transition at nucleotide 2, changing Metionine to Arginine was identified at family M. The mutation disrupts the original Kozak sequence (AXXATGG), altering the protein start site. Computational analysis using a program that predicts start sites showed that the putative new translation start site was in the exon 3 in frame. A portion of the gene containing the mutation and five cryptic Kozak sequences (-226 to 66) was used to analyze the expression of the mutant receptor (p.M1?). To analyze the expression pattern of Family S, the mutated cDNAs was inserted in a vector, using site direct mutagenesis. Western blot was performed to analyze the expression analysis of the mutated receptors. The p.R638L receptor showed similar expression pattern compared with the wild type receptor, presenting the monomeric forms of 140 (immature, partial glycosylated) and 160kDa (mature, glycosylated) and other forms higher than 200kDa. The mutation c.2244.C>G showed similar expression pattern compared with the wild type receptor. In contrast, Western blot expression levels of the mutant receptor p.M1? was dramatically reduced. Immunocytochemistry experiments showed strong staining at the cell surface of nonpermeabilized and permeabilized HEK293 cells expressing the wild type receptor. The same pattern was observed for the mutant receptor p.R638L, suggesting correct maturation and trafficking. While the mutant receptor p.M1? was not expressed on the cell surface and the staining was only identified inside permeabilized cells, suggesting that the mutant receptor was trapped within the endoplasmatic reticulum and was not expressed at the plasmatic membrane / Mestrado / Mestre em Farmacologia
16

Efeito da associação do carbonato de magnésio com acetato de cálcio (OSVAREN®) no controle do fósforo, no hiperparatireoidismo secundário e no remodelamento ósseo em ratos urêmicos / Magnesium carbonate/calcium acetate (Osvaren®) association effects in phosphorus, secondary hyperparathyroidism and bone turnover in uremic rats

Guaraciaba Oliveira Ferrari 27 July 2012 (has links)
Introdução: O quelante de fósforo (P) Osvaren® foi lançado recentemente no mercado internacional para tratamento da hiperfosfatemia nos pacientes com Doença Renal Crônica (DRC). Não existem estudos experimentais com esta medicação. Objetivo: Avaliar a ação deste quelante no tratamento do Distúrbio Mineral e Ósseo (DMO) de ratos com DRC induzida por adenina e por nefrectomia 5/6 (NX5/6). Métodos: Experimento 1: Durante 4 semanas, ratos Wistar receberam dieta com adenina [2 semanas (0,75%); 2 semanas (0,50%)] e então foram divididos em 3 grupos para receber dieta padrão (grupo DRC); dieta padrão com 3% de Acetato de Cálcio (grupo Ca); e dieta padrão com 3% de Osvaren® (grupo CaMg). Um grupo Controle (função renal normal) recebeu a dieta padrão durante todo o estudo. Ao final de cinco semanas de tratamento os animais foram sacrificados. Experimento 2: ratos da mesma espécie foram submetidos à NX5/6, divididos em grupos como no experimento 1 para receberem os quelantes de P imediatamente após a nefrectomia, e sacrificados após 9 semanas. Nos dois experimentos foram coletados soro, fêmures, aortas e paratireóides para análise bioquímica, histomorfometria óssea, pesquisa de calcificação vascular (CV) e imunohistoquímica de paratireóides, respectivamente. Resultados: Experimento 1: Os animais que receberam adenina apresentaram níveis maiores de creatinina, PTH, P e magnésio (Mg) que os do grupo Controle. Os quelantes de P reduziram a fração de excreção de P (FeP), mas não o P sérico, enquanto os níveis de PTH, FGF23 e calcitriol diminuíram de forma não significativa nos grupos tratados. O Mg sérico foi significativamente maior no grupo CaMg, enquanto maior calciúria, mais CV e menor marcação pelo PCNA nas paratireóides foram observadas no grupo Ca. Os animais que receberam adenina apresentaram doença óssea mista e ambos os quelantes de P melhoraram a remodelação, mas favoreceram a um acúmulo ainda maior de osteóide. Experimento 2: Da mesma forma que no experimento 1, o animais submetidos à NX5/6 evoluíram com uremia, e os efeitos dos quelantes no PTH, na CV e nas paratireóides foram similares. No entanto, o grupo CaMg apresentou mortalidade de 54% (vs 20% no grupo Ca), além de retardo na mineralização óssea. Conclusão: O tipo de nefropatia pode ter influência no efeito do quelante de P Osvaren®, já que o acúmulo de Mg provavelmente foi o responsável pela maior mortalidade e déficit de mineralização observados no experimento 2. Em relação ao efeito como quelante de P, o Osvaren® foi equivalente ao acetato de cálcio, mas este último está associado a maior sobrecarga de cálcio e a CV. O acúmulo de osteóide observado em ambos os experimentos parece ser o preço pago pela reduzida absorção intestinal de P favorecida pelos quelantes no hiperpatireoidismo secundário severo e esse efeito deveria ser avaliado em pacientes em diálise / Introduction: Osvaren® is a phosphate (P) binder that has been recently introduced for Chronic Kidney Disease (CKD) patients therapy. However, it has not been tested in experimental models yet. Aims: To study Osvaren® effects on mineral and bone metabolism in CKD experiment models. Methods: Experiment 1: For 4 weeks (wk), rats were fed normal chow or an adenine-enriched diet (0,75% for 2 wks; 0,50% for 2 wks). After that, adenine was discontinued and rats were divided into 3 groups: Ca (3% calcium acetate); CaMg (3% Osvaren®) and CKD (normal diet/untreated). A control group, with normal renal function was also studied. After 5 wks of therapy, animals were sacrificed. Experiment 2: Animals underwent 5/6 nephrectomy, and were submitted to different P binders treatment as in experiment 1 and then sacrificed 9 weeks after surgery. We performed biochemical and histomorphometric analyses, parathyroid PCNA imunohistochemistry, as well as Von Kossa staining and calcium content of aortic sections. Results: Experiment 1: Higher creatinine, PTH, FGF-23, P and Mg were found in all adenine-fed rats. P binders did not reduce serum P but decreased fractional excretion of P (FeP) and tended to reduce PTH, FGF23 and calcitriol levels. In the CaMg group, Mg was slightly elevated, whereas Ca group had greater urinary calcium as well as vascular calcification and smaller parathyroid PCNA staining. Adenine-fed rats presented features of mixed bone disease and P binders therapy was able to decrease bone resorption, but was associated with an osteoid accumulation. Experiment 2: As in experiment 1, nephrectomized rats were uremic and P binder effects on PTH, vascular calcification and parathyroid were very similar, except for the mortality rate, that was higher in CaMg group (54% vs 20% in Ca group). An increase in mineralization lag time was also found in CaMg group. Conclusions: Osvaren® may cause different effects on different types of nephropathy, as in experiment 2 the Mg was probably the responsible for higher mortality as well as for bone mineralization defect. In terms of P binding efficacy, Osvaren® was equivalent to calcium acetate, but the last one caused calcium overload and vascular calcification. The osteoid accumulation is probably related to the decrease in intestinal P absorption caused by the P binders in these models of secondary hyperparathyroidism. These effects should also be evaluated in dialysis patients
17

A comparison between 11C-methionine PET/CT and MIBI SPECT/CT for localization of parathyroid adenomas/hyperplasia / 副甲状腺腺腫/過形成の局在診断における11C-メチオニン PET/CTとMIBI SPECT/CTの比較

Hayakawa, Nobuyuki 23 March 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18866号 / 医博第3977号 / 新制||医||1008(附属図書館) / 31817 / 京都大学大学院医学研究科医学専攻 / (主査)教授 戸井 雅和, 教授 平岡 眞寛, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
18

Riziko osteoporózy u postmenopauzálních žen, které prodělaly úspěšnou chirurgickou léčbu primární hyperparatyreózy: nutriční faktory / Risk of osteoporosis in postmenopausal women after successful surgical intervention for primary hyperparathyroidism: nutritional factors

Vokounová, Kateřina January 2020 (has links)
Introduction: Osteoporosis is a chronical systemic metabolic disease of bone tissue, which is manifested by a decrease in the amount of bone mass and/or a decrease in its quality and may result in a fracture. Fractures are also common for primary hyperparathyroidism due to increased parathyroid hormone secretion. Surgical treatment will help increase bone density in most cases, nevertheless emphasis is placed on reducing risk factors for osteoporosis and fractures. Objective: Purpose of this thesis is to map the nutrition condition with focus on calcium and protein intake of postmenopausal women after successful surgical intervention for primary hyperparathyroidism (PHPT group), and to evaluate the results in relation with osteoporosis and fractures. Methods: Nutritional status was assessed using questionnaires of eating habits and analysis of three-day menus. Intakes of energy, protein, fat, sugar, fiber, free sugar, vitamin C, sodium, calcium nad phosphorus intake were calculated using Nutriservis PROFI program (and other nutritional databases). The degree of vitamin D saturation was obtained from serum calcidiol concentrations. Body composition and bone mineral density parametres were measured using dual energy X-ray absorptiometry. Results: Nutritional analysis of diets showed no statically...
19

Imaging of renal hyperparathyroidism using SPECT/CT with low-dose localizing CT

Doruyter, Alexander Govert George 12 1900 (has links)
Thesis (MMed)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Background: Hybrid imaging using single photon emission computed tomography/low dose (x-ray) computed tomography (SPECT/LDCT) is of benefit in preoperative scintigraphy of primary hyperparathyroidism. The role of SPECT/LDCT in preoperative assessment of renal hyperparathyroidism has not yet been examined. The aim of the study was to determine whether SPECT/LDCT conferred any benefit over SPECT alone in terms of detection and/or localization of hyperfunctioning parathyroid tissue in this patient group. Methods: A retrospective study of patients with renal hyperparathyroidism and positive planar and SPECT scintigraphy was undertaken. All patients underwent planar scintigraphy using 99mTc-pertechnetate immediately followed by 99mTc-sestamibi as well as SPECT/LDCT 60 min after sestamibi injection and a delayed static image to assess for differential washout at 2-3 hours. Planar subtraction images were generated. For each patient, two nuclear physicians reported on planar+ SPECT images followed by planar + SPECT/LDCT images (assisted by a radiologist). Confidence for the presence of hyperfunctioning parathyroid tissue as well as confidence of location was scored on a Likert-type scale. Interpretation of planar + SPECT was compared with interpretation of planar + SPECT/LDCT. The impact of LDCT on equivocal lesions and number of ectopic lesions detected was also assessed. Results: Twenty patients (M:13; F:7) imaged between February 2008 and June 2011 were included [mean age: 40 years (24 – 55)]. Mean creatinine was 687 μmol/l (169-1213), mean corrected calcium: 2.55 mmol/l (1.95-3.33) and median PTH 167 pmol/l (2.4 - >201). Thirty-five lesions were detected on planar and SPECT and this was unchanged after assessment of the LDCT data. Confidence for the presence of parathyroid pathology changed in 5 patients (5 lesions) with the addition of LDCT. LDCT changed the mean confidence of parathyroid pathology from 3.17 to 3.29 (p=0.16). Addition of LDCT reduced the number of equivocal lesions from 18 (14 patients) to 14 (10 patients) (p=0.13). The addition of LDCT changed localization in 4 lesions (3 patients). Confidence in localization of pathology changed in 9 lesions (7 patients) and the mean localization confidence score was improved from 4.2 to 4.46 (p=0.002) with LDCT. The number of lesions classified as ectopic increased from 5 (on planar+SPECT) to 8 (with addition of LDCT) (p=0.25). Conclusion: In renal hyperparathyroidism SPECT/LDCT altered localization of lesions detected on planar and SPECT alone and improved reader confidence of localization accuracy. SPECT/LDCT conferred no additional benefit over SPECT in terms of detection, confidence of parathyroid pathology or ability to distinguish equivocal from non-equivocal parathyroid lesions. The addition of LDCT did not detect significantly more ectopic lesions. Whereas the minor improvement in reader confidence of localization (with addition of LDCT) was of questionable clinical significance, we speculate that the changed and presumably improved localization of lesions on SPECT/LDCT had potential clinical impact in a significant proportion of patients. On this basis we recommend the use of hybrid SPECT/LDCT in imaging of renal hyperparathyroidism when surgery is considered. / AFRIKAANSE OPSOMMING: Agtergrond: Hibriedbeelding met enkelfoton emissie rekenaartomografie / lae dosis rekenaartomografie (EFERT/LDRT) is voordelig in pre-operatiewe beelding van primêre hiperparatiroïedisme. Die rol van EFERT/RT in pre-operatiewe evaluering van renale hiperparatiroïedisme is nog nie ondersoek nie. Die doel van hierdie studie was om in hierdie pasiëntgroep te bepaal of EFERT/RT 'n voordeel bo EFERT alleen verleen. Metode: 'n Retrospektiewe studie van pasiënte met renale hiperparatiroïedisme en positiewe planare en EFERT flikkergrafie is onderneem. Na die toediening van 99mTc-pertegnetaat is planare beelding op alle pasiënte gedoen, onmiddellik gevolg deur 99mTc-sestamibi sowel as EFERT/RT beelding 60 min na sestamibi inspuiting en 'n laat statiese beeld vir differensiële uitwas op 2-3 uur. Planare subtraksiebeelde is verkry. Twee kerngeneeskundiges het die planare + EFERT beelde van elke pasiënt gerapporteer, waarna die planare + EFERT/RT beelde met die hulp van 'n radioloog gerapporteer is. Sekerheid oor die teenwoordigheid van hiperfunksionerende paratiroïedweefsel sowel as die sekerheid oor die lokalisering daarvan, is op 'n Likert-tipe skaal verkry. Interpretasie van planare + EFERT is vergelyk met die interpretasie van planare + EFERT/RT. Die impak van LDRT op twyfelagtige letsels en die aantal ektopiese letsels waargeneem, is ook bepaal. Resultate: Twintig pasiënte (M:13; F:7) met beelding tussen Februarie 2008 en Junie 2011 is ingesluit [gemiddelde ouderdom: 40 jaar (24-55)] . Die gemiddelde kreatinien was 687 μmol/l (169-1213), gemiddelde gekorrigeerde kalsium 2.55 mmol/l (1.95-3.33) en mediaan PTH 167 pmol/l (2.4->201). Vyf en dertig letsels is op planare en EFERT beelde waargeneem en was onveranderd na assessering van die LDRT-data. Sekerheid oor die teenwoordigheid van paratiroïedpatologie het verander in 5 pasiënte (5 letsels) met die toevoeging van LDRT. LDRT het die gemiddelde sekerheid van paratiroïedpatologie van 3.17 tot 3.29 verander (p = 0.16). Toevoeging van LDRT het die aantal twyfelagtige letsels van 18 (14 pasiënte) tot 14 (10 pasiënte) verminder (p = 0.13). Die byvoeging van LDRT het die lokalisering in 4 letsels (3 pasiënte) verander. Sekerheid oor die lokalisering van patologie is in 9 letsels (7 pasiënte) verander en die gemiddelde lokalisering betroubaarheidswaarde is verbeter van 4.2 tot 4.46 (p = 0.002) met LDRT. Met die byvoeging van LDRT het die aantal letsels geklassifiseer as ektopies van 5 tot 8 (p = 0.25) toegeneem. Gevolgtrekking: In renale hiperparatiroïedisme het EFERT/RT die lokalisering van letsels wat op planare + EFERT beelding alleen waargeneem is, verander en die leser se vertroue om akkuraat te lokaliseer verbeter. EFERT/LDRT het geen bykomende voordeel bo EFERT in terme van die opsporing, sekerheid van paratiroïedpatologie of onderskeidingsvermoë tussen twyfelagtige teenoor nie-twyfelagtige paratiroïedletsels verleen nie. Met die byvoeging van LDRT is nie beduidend meer ektopiese letsels gevind nie. Terwyl die geringe verbetering in die sekerheid van lokalisering (met die byvoeging van LDRT) van twyfelagtige kliniese betekenis was, spekuleer ons dat die verandering en vermoedelik verbeterde lokalisering van letsels op EFERT/LDRT ʼn potensiële kliniese impak het in 'n beduidende aantal pasiënte. Die gebruik van EFERT/LDRT in die beelding van renale hiperparatiroïedisme wanneer chirurgie oorweeg word, word dus vir bogenoemde rede aanbeveel.
20

Análise crítica do decaimento no nível do paratormônio intra-operatório para prognóstico de sucesso da paratireoidectomia no controle precoce do hiperparatireoidismo secundário e terciário / Critical analysis of the decrease in the level of intraoperative parathyroid hormone for the prognosis of successful parathyroidectomy in the early control of secondary and tertiary hyperparathyroidism

Silveira, André Albuquerque 12 December 2018 (has links)
INTRODUÇÃO: A monitorização do paratormônio rápido (PTHr) é padrão no tratamento cirúrgico do hiperparatireoidismo primário, para garantir a retirada da paratireoide doente e preservação das saudáveis. Sua utilidade no tratamento cirúrgico do hiperparatireoidismo secundário à doença renal crônica é controversa. Esse estudo tem como objetivo verificar: 1) se a medida PTHr auxilia na predição do resultado cirúrgico precoce; 2) se existem diferenças de comportamento do PTHr entre pacientes dialíticos e transplantados; 3) se existem diferenças de comportamento do PTHr entre modalidades de operações distintas; 4) a acurácia do método em predizer controle do hiperparatireoidismo renal. MÉTODOS: Trata-se de estudo de coorte retrospectiva e prospectiva observacional, de pacientes com diagnóstico de HPTr, dialítico ou persistência após transplante renal, submetidos a paratireoidectomia total ou subtotal em único centro, no período de 2011 a 2016. Durante a cirurgia, realizamos coletas seriadas do PTHr, sendo três dessas amostras antes da exérese das glândulas paratireoides (basal periférico, basal central e pré-retirada), e duas após ressecção (10 min e 15 min). O critério de queda porcentual igual ou maior a 80% do maior valor entre as amostras basais, em 10 minutos, foi arbitrado preditor de êxito intra-operatório. Os pacientes foram seguidos durante intervalos regulares (15 dias, 3, 6 e 12 meses). Foram divididos em dois grupos (sucesso e falha da operação) de acordo com o controle dos níveis de PTH, cálcio e fósforo conforme consensos internacionais, ao término do seguimento de 1 ano. RESULTADOS: Duzentos e vinte e oito pacientes foram elegíveis, sendo 186 (81,6%) dialíticos e 42 (18,4%) transplantados. A paratireoidectomia alcançou sucesso em 92,1% (210/228) e falha em 7,9% (18/228) dos pacientes, sem diferenças de resultados entre grupos de diagnósticos diferentes e/ou tipos de operações distintas. O principal motivo de falha foi presença de glândula supranumerária, em 61,1% dos casos (11/18). A amostra basal central (BC) representou o real maior valor basal do PTHr para ambos os diagnósticos, porém com maior chance de picos do PTHr na amostra pré-retirada (PRE) nos pacientes transplantados. Após remoção da massa de tecido paratireóideo doente, os níveis de PTHr foram menores em 10 minutos quando comparados com as amostras basais (resultado estatisticamente significativo) para todos diagnósticos, tipos de operações e desfechos terapêuticos. No grupo sucesso, houve diferença estatisticamente significativa, entre as medidas de 10 e 15 minutos entre si, com valores menores em 15 minutos, enquanto que no grupo falha, sem distinção de 10 e 15 minutos entre si e com valores médios maiores em 15 min. Os valores do PTHr foram maiores no paciente dialítico quando comparados com transplantado, em todas as amostras (p < 0,001). No grupo sucesso, os pacientes dialíticos e transplantados, e os pacientes dialíticos submetidos a exérese total e subtotal apresentaram porcentual de queda do PTHr semelhantes em 10 e 15 minutos para as amostras BC e PRE; o paciente transplantado obteve decaimentos porcentuais menores quando houve ressecção subtotal. O grupo falha apresentou queda porcentual nitidamente menor e com significância estatística (p < 0,001), para todas amostra basais e em qualquer momento, quando comparado ao grupo sucesso. A função renal pré-operatória dos transplantados não influenciou a cinética de decaimento do PTHr (não teve correlação, p=0,09). A monitorização do PTHr influenciou a conduta cirúrgica em 7% (16/228) da casuística; o principal motivo foi a ocorrência de localização ectópica de umas das quatros paratireoides, responsável por 75% (12/16) dos casos. A paratireiodectomia bem sucedida exibiu impacto negativo na função do enxerto renal no pós-operatório, porém com posterior recuperação ao término de 1 ano. O método da dosagem do PTHr com o critério de 80% de queda, apresentou acurácia de 87%, sensibilidade de 88% e especificidade de 67% para a amostra BC em 15 minutos, e melhor especificidade (74%) na amostra PRE em 10 min. CONCLUSÕES: Em pacientes com hiperparatireoidismo renal, uso de medidas intra-operatórias do PTHr apresenta alta sensibilidade para indicar o sucesso da operação quando há redução de 80% dos valores iniciais. Apesar de valores absolutos diferentes, as taxas de redução desse hormônio após uma paratireoidectomia bem sucedida não são significativamente diferentes em pacientes dialíticos e transplantados, em operação total com auto-enxerto ou subtotal, com efetiva queda em 10 minutos de amostragem. A utilização de uma medida adicional 15 minutos após a retirada das glândulas aumenta a acurácia do método. A medida intra-operatória do PTHr pode auxiliar na tomada de decisões durante a operação desses pacientes / INTRODUCTION: Rapid Parathyroid Monitoring (rPTH) is standard in the surgical treatment of primary hyperparathyroidism, to ensure the excision of the diseased parathyroid and preservation of healthy parathyroid glands. Its usefulness in the surgical treatment of hyperparathyroidism secondary to chronic kidney disease is controversial. This study aims to verify: 1) whether the rPTH measure assists in the prediction of the early surgical outcome; 2) whether there are differences in rPTH pattern between dialytic and transplanted patients; 3) if there are differences in the decay of the rPTH between different operations modalities; 4) the accuracy of the method in predicting control of renal hyperparathyroidism. METHODS: This is a retrospective and prospective observational cohort study of patients with a diagnosis of PTH, dialysis or persistence after renal transplantation, who underwent total or subtotal parathyroidectomy in a single center from 2011 to 2016. During surgery, we performed serial samples of the rPTH, three of these were before excision of the parathyroid glands (peripheral basal, central basal and pre-withdrawal), and two after resection (10 min and 15 min). The criterion of percentage drop equal to or greater than 80% of the highest value of the basal samples, in 10 minutes, was arbitrated predictor of intraoperative success. Patients were followed at regular intervals (15 days, 3, 6 and 12 months). They were divided into two groups (success and failure of the operation) according to the control of the levels of PTH, calcium and phosphorus according to international consensus, at the end of the 1 year follow-up. RESULTS: Two hundred and twenty-eight patients were eligible, being 186 (81.6%) dialytic and 42 (18.4%) transplanted. Parathyroidectomy achieved success in 92.1% (210/228) and failure in 7.9% (18/228) of the patients, with no differences in results between groups of different diagnoses and/or different types of operations. The main reason for failure was the presence of supernumerary glands, 61.1% of the cases (11/18). The central basal (CB) sample represented the actual higher baseline PTHr for both diagnoses, but with a higher chance of rPTH peaks in the pre-withdrawal sample (PRE) in the transplanted patients. After removal of the diseased parathyroid tissue mass, rPTH levels were lower in 10 minutes compared to baseline (statistically significant) for all diagnoses, types of operations and therapeutic outcomes. In the success group, there was a statistically significant difference between the 10 and 15 minutes measurements, with smaller values in 15 minutes, while in the failure group, there was no distinction of 10 and 15 minutes between them and with mean values greater in 15 min. The rPTH values were higher in the dialytic patient when compared to transplanted in all samples (p < 0.001). In the success group, dialytic and transplanted patients, and dialytic patients submitted to total and subtotal excision, presented similar percent drop in rPTH at 10 and 15 minutes for CB and PRE samples; the transplanted patient had lower percentage decreases when subtotal resection. The failure group had a significantly lower percentage drop and with statistical significance (p < 0.001), for all baseline and at any time, when compared to the success group. The preoperative renal function of the transplanted patients did not influence the kinetics of rPTH decay (had no correlation, p=0.09). The rPTH monitoring influenced the surgical management in 7% (16/228) of the series; the main reason was the occurrence of ectopic localization of one of the four parathyroid glands, responsible for 75% (12/16) of the cases. In transplanted patients, successful parathyroidectomy had a negative impact on renal graft function in the postoperative period, but with a subsequent recovery at the end of 1 year. The rPTH dosage method with the 80% drop criterion showed an accuracy of 87%, a sensitivity of 88% and specificity of 67% for the CB sample in 15 minutes and a better specificity (74%) in the PRE sample in 10 min. CONCLUSION: In patients with renal hyperparathyroidism, the use of intraoperative measurements of rPTH has a high sensitivity to indicate the success of the operation when there is a reduction of 80% of the initial values. In spite of different absolute values, the rates of reduction of this hormone after successful parathyroidectomy are not significantly different in dialytic and transplant patients, in total autograft or subtotal operation, with an effective drop in 10 minutes of sampling. The use of an additional measurement 15 minutes after removal of the glands increases the accuracy of the method. The intraoperative measurement of rPTH may aid in decision making during the operation of these patients

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