Dissertations / Theses on the topic 'Parathyroidectomy'

Background Since the 1850s, parathyroid surgery continues to evolve through improved understanding of the pathophysiology. Dialysis dependant end stage renal failure (ESRF), the major cause of secondary hyperparathyroidism continues to rise in the western world. Other than renal transplantation, parathyroidectomy may provide a substantial cure for longstanding renal hyperparathyroidism in dialysis dependant patients. In 2004, cinacalcet was introduced as an alternative to the surgical management of renal hyperparathyroidism. However, cinacalcet was withdrawn from Australia’s Pharmaceutical Benefits Scheme (PBS) in 2015, as the EVOLVE study failed to demonstrate a statistically significant reduction in the time to death, or non-fatal cardiovascular events in those treated with cinacalcet with renal hyperparathyroidism. This led to a re-emergence in parathyroidectomy. Additionally in our institution, patients who had been on cinacalcet, and subsequently underwent parathyroidectomy because of refractory disease or intolerance to cinacalcet, were noted to experience greater hyperkalaemia and hypocalcaemia in the intraoperative and immediate postoperative period. Aims • To review the engrossing history of the discovery and progression of parathyroid surgery since the 19th century; • To correlate the embryology, anatomy, histology, physiology and pathophysiology of parathyroid glands in end stage renal failure; • To provide up to date review in regards to investigation and the surgical management of renal hyperparathyroidism; • Conduct a cohort study on the association of cinacalcet use with greater likelihood of intraoperative and immediate postoperative hyperkalaemia and hypocalcaemia following parathyroidectomy in renal hyperparathyroidism. Methods Literature reviews utilizing MEDLINE and Cochrane review databases, life science journals and textbooks were utilized. Hospital medical records from The Canberra Hospital were studied to collect data on the cohort case series. Analysis of data was performed using SPSS Statistics and Microsoft Excel. Results Sir Richard Owen is reputed to be the first person to discover the existence of parathyroid glands when examining a rhinoceros in 1852. In the spirit of mortui vivos docent, Captain Charles Martell in the 1930s had significantly increased our understanding of the existence of ectopic locations of parathyroid glands, as well as operative planning. The physiology and pathophysiology of parathyroid glands in chronic renal failure is multifaceted, with a complex interplay between bone, kidneys, intestine, vitamin D, potassium, phosphate and magnesium. There are a range of investigative strategies for localizing parathyroid glands, often yielding greater sensitivity and specificity when utilizing a combination of imaging tools. The choice of operative strategy for parathyroidectomy is often influenced by surgeon’s preference and the institution’s resources, due to paucity of good randomized trials and meta-analysis. Finally, our cohort study has shown that prior cinacalcet use was linked closely with severe intraoperative and immediate postoperative hyperkalaemia, and greater hypocalcaemia compared to control patients who underwent parathyroidectomy for renal hyperparathyroidism. Conclusions The continued inquiry into the basic sciences around renal hyperparathyroidism ensures that we are able to question traditional protocols, and practice the best evidence based medicine. From this, cinacalcet emerged to change the medical and surgical landscape in the treatment of hyperparathyroidism. The results of the cohort study led to development of a protocol for the perioperative management of renal hyperparathyroidism in cinacalcet treated patients requiring parathyroidectomy.

Context: Cardiovascular (CV) complications are a still debated issue in patients with biochemically mild primary hyperparathyroidism (PHPT) and may be related to both the PHPT condition itself and the hypovitaminosis D. Objective: To evaluate the prevalence, nature and reversibility of CV disease and associated risk factors in a large cohort of postmenopausal mild PHPT patients surgically cured (PTx Group) or observed for two years without surgical intervention (no-PTx Group). To preliminarily assess, in both group, if the administration of two different doses (800 UI and 2000 UI) of cholecalciferol (VitD) versus no supplementation could affect the CV disease evolution. Design: Randomized longitudinal prospective open label study. Settings: The study was conducted in the Endocrinology Unit of two university hospitals. Participants: 91 post-menopausal women with PHPT (38 in the PTx Group and 53 in the no-PTx Group) participated in the study. Outcome Measures: Cardiac and vascular damage (blood pressure, transthoracic echocardiography and carotid ultrasonography), lipids and glucose metabolism, renin-angiotensin system (RAAS) activity. Results: Arterial hypertension (AH) was found in 50.5% of patients and was not associated with PHPT after adjusting data for major CV risk factor. Diastolic dysfunction, LV hypertrophy and valve calcifications were diagnosed in 54.9%, 13.2% and 12.1% of patients and were respectively predicted by body mass index (BMI) and advancing age, by the presence of AH and by advancing age and the presence of AH, respectively. Similarly, advancing age was the only significant predictor of the presence of carotid plaque and AH was the only significant predictor of carotid intima-media thickness. We did not find any association between calcium, PTH or 25OHD and all glycemic parameters. No activation of RAAS was found in normotensive mild PHPT patients. All CV complications and risk factors were neither reversed nor significantly improved by surgery and/or VitD administration up to 24 months’ follow-up. Conclusions: The high incidence of CV disease and metabolic derangements reported in mild PHPT may be primarily related to the coexistence of AH, advanced age or increased BMI. Moreover, the administration of VitD supplements would seem to have a neutral effect at least as regards CV complications and CV risk factors in mild PHPT patients.

Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases.

In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated.

In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium.

In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, serum calcium is associated with decreased insulin sensitivity. Parathyroidectomy has positive effects on several, but not all, of the investigated metabolic parameters.

O hiperparatireoidismo (HPT) secundário é uma complicação da doença renal crônica. A paratireoidectomia total com autoimplante proporciona bons resultados no seu tratamento, mas alguns doentes não desenvolvem níveis adequados de hormônio da paratireóide (PTH) após a operação. Os objetivos, do presente estudo, foram analisar fatores que poderiam interferir no funcionamento do autoimplante de glândula paratireóide e quantificar a taxa de hipofunção segundo alguns critérios. Casuística e Métodos: em um estudo prospectivo e observacional, foram analisados a idade, sexo, peso, altura e a etnia. A causa da doença renal crônica (DRC), tempo de DRC antes da paratireoidectomia, tempo de diálise, antecedente de intoxicação por alumínio e tempo de diagnóstico do HPT. Os dados bioquímicos estudados foram os níveis pré-operatórios de fósforo, cálcio total, cálcio iônico, PTH e fosfatase alcalina e aos 6 meses e 1 ano de pós-operatório. Registrada a quantidade de cálcio (gluconato e carbonato) e calcitriol ofertada no pós-operatório sendo realizada durante a primeira semana, no primeiro, terceiro sexto mês de pós-operatório. A histologia da glândula implantada foi analisada. Os pacientes foram divididos, segundo os níveis preconizados de PTH para indivíduos normais e segundo as recomendações da Fundação Nacional do Rim dos Estados Unidos da América (K/DOQI), em grupos hipofuncionante (grupo 1) e funcionante ( grupo 2). Resultados: Entre julho de 2007 e dezembro de 2008, 48 pacientes (18 homens e 30 mulheres) foram submetidos à paratireoidectomia total com autoimplante imediato. A média de idade dos indivíduos foi 44,7 anos (EP: 12,6), a do tempo de diálise foi 9,6 anos (EP: 5,1), a média do tempo de diagnóstico do hiperparatireoidismo de 2,6 anos (EP: 2). A principal causa da doença renal crônica foi a hipertensão arterial em 16 indivíduos (33,3%) seguida de causa indefinida em 12 (25%), GESF em 5 (10,4%), diabetes mellitus em 4 (8,3%). Com relação ao número de fragmentos implantados, houve tendência a uma diferença entre os grupos 1 e 2 (p= 0,14). Houve tendência a uma diferença entre os grupos 1 e 2 (p= 0,1) no que diz respeito a histologia da glândula implantada. O índice de hipofunção do auto implante, em 1 ano, foi de 21,27% no critério do nível de PTH para indivíduos normais e de 72,9% segundo as recomendações do KDOIQ. As complicações e óbitos por causa cardiovascular não diferiram entre os grupos. CONCLUSÃO: a frequência de hipofunção do implante imediato de paratireóide foi de 21,27% e de 72,9% segundo as recomendações do KDOQ e não houve a identificação de fatores preditivos para sua hipofunção.
The secondary hyperparathyroidism (HPT) is a complication of chronic kidney disease. A total parathyroidectomy with autograft provides good results in treatment, but some patients do not develop adequate levels of parathyroid hormone (PTH) after operation. The objectives of study were to analyze factors that could interfere with the function of the parathyroid gland autograft and measure the rate of hypofunction according several criteria. Patients and Methods: a prospective observational study were analyzed age, sex, weight, height and ethnicity. The cause of chronic kidney disease (CKD), duration of CKD prior to parathyroidectomy, duration of dialysis, previous aluminum intoxication and time of diagnosis of HPT. The biochemical data studied : preoperative levels of phosphorus, total calcium, ionized calcium, PTH and alkaline phosphatase and 6 months and 1 year postoperatively. Recorded the amount of calcium (gluconate and carbonate) and calcitriol offered postoperative being held during the first week, the first, third, sixth month postoperatively. Histology of the implanted gland was analyzed. Patients were divided according to the recommended levels of PTH for normal individuals and in accordance with the recommendations of the National Foundation Kidney the United States of America (K / DOQI) in hypofunction groups (group 1) and functional (group 2). Results: Between July 2007 and December 2008, 48 patients (18 men and 30 women) underwent total parathyroidectomy with immediate autograft. The mean age was 44.7 years (SE: 12.6), the duration of dialysis was 9.6 years (SE: 5.1), the average time of diagnosis of hyperparathyroidism 2.6 years (EP: 2). The main cause of chronic renal disease was hypertension in 16 patients (33.3%) followed by unknown cause in 12 (25%), FSGS in 5 (10.4%), diabetes mellitus in 4 (8.3%.). The number of implanted fragments, there was a trend to a difference between groups 1 and 2 (p = 0.14). There was a trend to a difference between groups 1 and 2 (p = 0.1) as regards the histology of the gland implanted. The rate of self hypofunction implant at 1 year was 21.27% at the discretion of the PTH level in normal individuals and 72.9% according to the recommendations of KDOIQ. Complications and deaths from cardiovascular causes did not differ between groups. CONCLUSION: The rate of hypofunction of the parathyroid immediate implant was 21.27% and 72.9% according to the recommendations of KDOIQ and there was no identification of predictive factors for its hypofunction.

INTRODUÇÃO: Hiperparatireoidismo primário (HPT) é uma doença endócrina relativamente comum, caracterizada por hipercalcemia associada a concentrações de PTH elevadas ou inapropriadamente normais. A maioria dos pacientes (90%-95%) apresenta a forma esporádica da doença, enquanto a forma familiar pode ocorrer associada à neoplasia endócrina múltipla tipo 1 (NEM1) e tipo 2, HPT-tumor de mandíbula, HPT neonatal severo e HPT isolada familiar. HPT associado com NEM1 (HPT/NEM1) difere da forma esporádica em vários aspectos, entre eles: acometimento multiglandular das paratireóides (hiperplasia x adenoma); início da doença mais precoce (20 x 40 anos); afeta homens e mulheres em proporção semelhante (1:1), em contraste a 1:3 no HPT esporádico; diferentes tratamentos cirúrgicos (paratireoidectomia total ou subtotal x adenomectomia); maior taxa de recorrência após paratireoidectomia (PTx); e tende a ser menos agressivo que o HPT esporádico. No HPT esporádico, o perfil da perda mineral óssea e o impacto do tratamento cirúrgico na densidade mineral óssea (DMO) estão bem definidos. Por outro lado, dados sobre perda óssea no HPT/NEM1 e sua potencial recuperação após PTx são escassamente relatados. O objetivo deste estudo é avaliar o perfil densitométrico e o impacto do tratamento cirúrgico na DMO em pacientes com HPT/NEM1. MÉTODOS: Neste estudo, avaliamos inicialmente 36 pacientes (18 homens e 18 mulheres) com diagnóstico de HPT/NEM1 (média de idade ao diagnóstico de HPT de 38,99 ± 14.46 anos, 20-74 anos). Estes pacientes pertenciam a oito famílias não relacionadas previamente caracterizadas clinicamente e portadoras de mutações germinativas MEN1. Avaliamos a DMO no terço proximal do rádio distal (1/3 RD), fêmur (colo do fêmur e fêmur total) e coluna lombar (L1-L4) destes 36 pacientes. A DMO foi medida pela densitometria óssea de dupla emissão com fonte de raios X (DXA) e os valores expressos em índice T, índice Z e em valores absolutos (g/cm2). Após esta avaliação da DMO, vinte e quatro pacientes foram submetidos à paratireoidectomia total seguida por auto-implante em antebraço não dominante. Em um grupo selecionado de 16 pacientes foi avaliada a densidade mineral óssea antes e após (período médio de 15 meses) o tratamento cirúrgico. RESULTADOS: Desmineralização óssea (osteoporose/osteopenia) foi observada no 1/3 RD (28/34, 79,4%); colo do fêmur (26/36, 72,7%) e na coluna lombar (25/36, 69,4%). Osteopenia foi principalmente observada no colo do fêmur (19/36, 52,8%), seguida pelo 1/3 RD (14/34, 41,2%) e coluna lombar (11/36, 30,5%). Osteoporose foi observada principalmente na coluna lombar (14/36, 38,9%) e 1/3 RD (14/34, 41,2%); enquanto no colo do fêmur (7/36, 19,4%) a prevalência foi menor . Valores médios de índice T estavam severamente reduzidos no 1/3 RD (- 2,46±1,436 DP), seguido pela coluna lombar (-2,05±1,539 DP). O colo do fêmur foi o menos afetado (-1,60±1,138 DP). Nos 16 pacientes submetidos ao tratamento cirúrgico, no período médio de 15 meses após PTx, a DMO (g/cm2) aumentou significativamente na coluna lombar de 0,843 para 0,909 g/cm2 (+ 8,4%; p=0,001). A DMO (g/cm2) no colo do fêmur também aumentou significativamente de 0,745 para 0,798 g/cm2 (+ 7,7%; p=0.0001). No 1/3 RD não houve modificação estatisticamente significante da DMO (0,627 ± 0,089 para 0,622 ± 0,075; p=0,76). CONCLUSÃO: Nossos dados demonstraram que o rádio distal é o sítio ósseo preferencial para desmineralização óssea e que a coluna lombar pode não estar relativamente protegida na HPT/MEN1, como descrito no HPT esporádico. Um aumento significante foi observado na coluna lombar e no colo do fêmur em pacientes com HPT/NEM1, em um período médio de 15 meses após paratireoidectomia; enquanto no terço proximal do radio distal, não houve melhora significativa durante este estudo
INTRODUTION: Primary hyperparathyroidism (HPT) is a relatively common endocrine disorder, which is characterized by hypercalcemia and elevated or inappropriately normal levels of PTH. Most patients (90-95%) present with the sporadic form of the disease, whereas familial cases may occur associated with multiple endocrine neoplasias type 1 (MEN1) and type 2, jaw tumours, as well as severe neonatal form and familial isolated HPT. HPT associated with MEN1 (HPT/MEN1) differs from sporadic primary HPT (s- HPT) in the following aspects: it presents as a multiglandular parathyroid neoplasia (hyperplasia vs adenoma); it has an earlier disease onset (20 vs. 40 years of age); there is a sex ratio of 1:1 in contrast to the 1:3 ratio for s- HPT; different surgical treatment (total or subtotal parathyroidectomy x adenomectomy); there are higher recurrence rates after a parathyroidectomy (PTx); and it frequently tends to be less aggressive than s-HPT. In s-HPT, the bone loss profile and the impact of parathyroid surgery are well defined. In contrast, data on bone losses in HPT/MEN1 and the potential bone recovery after PTx have been scarcely reported. The aim of this study is to evaluate the bone mineral status and the impact of surgical treatment on bone mineral density (BMD) in HPT/MEN1 patients. METHODS: We studied 36 cases (18 males and 18 females) diagnosed with HPT/MEN1 (average age at the HPT diagnosis of 38.9 ± 14.46 years; range, 20-74 years). These patients belonged to eight unrelated MEN1 families previously clinically characterized and harboring germline MEN1 mutations. We have assessed the values of BMD in the proximal one third distal radius (1/3 distal radius), femoral (femoral neck and total) and lumbar spine (L1-L4) of these 36 HPT/MEN1 cases. BMD values were measured by dual-energy X-ray absorptiometry and the values expressed in T, Z-score and in absolute values. After BMD analyses, twenty four out of them were submitted to total parathyroidectomy followed by autoimplant in the non-dominant forearm. BMD measurements were evaluated before and in a mean period of 15 months after surgery, in a subset of 16 patients. RESULTS: Bone demineralization (osteoporosis/osteopenia) was seen at the proximal third of distal radius (28/34, 79.4%); femoral neck (26/36, 72.7%) and in the lumbar spine (25/36, 69.4%). Osteopenia was mostly found in femoral neck (19/36, 52.8%), whereas 1/3 distal radius (14/34, 41.2%) and lumbar spine (11/36, 30.5%) were also represented. Osteoporosis was mostly marked at lumbar spine (14/36, 38.9%) and 1/3 DR (14/34, 41.2%), but femoral neck (7/36, 19.4%) was also affected. Mean T score values at the 1/3 DR were severely reduced (-2.46±1.436 SD), followed by lumbar spine (-2.05 ± 1.539 SD). The femoral neck was the least affected site (-1. 60 ± 1.138 SD). In the 16 cases submitted to surgical treatment, in a mean period of 15 months after PTX, BMD (g/cm2) significantly increased at the lumbar spine from 0.843 to 0.909 g/cm2 (+ 8.4%; p=0.001). Femoral neck BMD (g/cm2) also increased significantly from 0.745 to 0.798 g/cm2 (+ 7.7%; p=0.0001). In the proximal one third of distal radius, BMD (g/cm2) remained unchanged (baseline, 0.627 ± 0.089 to 0.622 ± 0.075; p=0.76). CONCLUSION: Our data confirmed distal radius as the preferential site of bone demineralization and that lumbar spine may not be relatively protected in HPT/MEN1, as related in the s-HPT. A significant increase in the BMD has been verified in the lumbar spine and femoral neck BMD in 16 patients with HPT/MEN1, in a mean period of 15 months after parathyroidectomy. However, the proximal one third of distal radius BMD did not present significant improvement during this study

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

INTRODUÇÃO: A criopreservação de tecido paratireóideo é empregada no tratamento cirúrgico do hiperparatireoidismo secundário nos pacientes com doença renal crônica. Entre a captação do tecido e a criopreservação, realizada em laboratório especializado, o tecido é preservado em solução para cultura de células a 4°C (solução para transporte). Não há dados que demonstrem por quanto tempo o tecido paratireóideo humano pode permanecer viável nesta solução, antes de ser criopreservado. Este estudo objetiva avaliar o período de tempo que o tecido da glândula paratireóide hiperplásica de humanos pode permanecer na solução para transporte, sem apresentar danos ultra-estruturais. MÉTODOS: Estudo prospectivo que incluiu 11 pacientes submetidos a paratireoidectomia total com autoimplante heterotópico e criopreservação de fragmentos de tecido paratireóideo. Parte do tecido destinado para exame anatomopatológico foi selecionado para preservação em solução para transporte. Foram definidos 5 períodos relacionados ao tempo de permanência dos fragmentos de paratireóide na solução para transporte. No tempo 1, o material foi fixado a fresco, sem contato com a solução para transporte, este tempo serviu para controle. No tempo 2, os fragmentos de tecido permaneceram imersos na solução para transporte por 2 horas, no tempo 3, este período foi de 6 horas, e os tempos 4 e 5, corresponderam a preservação dos fragmento de paratireóide na solução para transporte por 12 e 24 horas respectivamente. Ao final de cada período os fragmentos foram removidos da solução de transporte e fixados com glutaraldeído a 2%, seguido por preparo do material para cortes ultrafinos. A análise por microscopia eletrônica avaliou a adesão celular e a integridade das membranas plasmáticas, dos núcleos e das mitocôndrias, além da presença de edema celular e de vacúolos. RESULTADOS: Dos 11 casos estudados, 10 apresentaram achados ultraestruturais compatíveis com a normalidade nos fragmentos de tecido que permaneceram na solução para transporte por até 12 horas. Em apenas um destes casos, houve preservação das características morfológicas do tecido por 24 horas, na solução para transporte. Em um caso os achados caracterizaram sinais de dano celular irreversível em todos os períodos, inclusive no tempo inicial, em que o tecido foi fixado a fresco, sem contato com a solução para transporte. As alterações das mitocôndrias representaram os danos ultra-estruturais mais constantes nos casos estudados. CONCLUSÃO: A análise da ultra-estrutura do tecido da glândula paratireoide hiperplásica de humanos permite concluir que ocorre manutenção adequada da integridade estrutural do tecido que permanece na solução com meio de cultura de células a 4°C.até cerca de 12 horas após sua retirada do organismo, na maioria dos casos.
BACKGROUND: The cryopreservation of parathyroid tissue is employed in the surgical treatment of secondary hyperparathyroidism in patients with chronic kidney disease. During the period between surgical resection and cryopreservation of tissue, which requires a specialized laboratory, the tissue is stored in a cell culture solution, at 4 °C (solution for transport from the operating room to the laboratory). There is no data showing for how long the human parathyroid tissue can remain viable in this solution, before being cryopreserved. The present study evaluates the time that the tissue of human hyperplastic parathyroid gland could remain in solution for transportation, without showing ultrastructural damages. METHODS: This prospective study included 11 patients, who underwent total parathyroidectomy with heterotopic autotransplantation and cryopreservation of parathyroid tissue fragments. Part of the tissue intended for pathological examination was selected for storage at solution for transportation. Five periods were defined, related to the storage time of parathyroid fragments at solution for transportation. At time 1, the material was fixed at the time of surgical resection, without contact with the solution for transport, this time was used as control. At time 2, the fragments of tissue remained stored at the solution for transportation for 2 hours, at time 3, this period was 6 hours, and Times 4 and 5, corresponded to the parathyroid fragments stored in the transport solution for 12 and 24 hours, respectively. At the end of each period the fragments were removed from the transport solution and fixed with 2% glutaraldehyde, followed by preparation of material for ultrathin sections. The analysis by electron microscopy was used to evaluate cell adhesion and integrity of plasma membranes, nuclei and mitochondria, and the presence of edema and cell vacuoles. RESULTS: Of the 11 cases studied, 10 showed ultrastructural findings consistent with the normal tissue fragments that remained in the solution to transport up to 12 hours. In only one of these cases, there was preservation of the morphological characteristics of the tissue for 24 hours, at the solution for transportation. In one case, there were findings of marked signs of irreversible cell damage in all periods, including the initial time in which the tissue was fixed at the time of surgical resection, without contact with the solution for transportation. Changes of mitochondria represented the ultrastructural damage more constant in the cases studied. CONCLUSION: The analysis of the ultrastructure of human hyperplastic parathyroid gland tissue shows that, in most cases, ultrastructural integrity is properly maintained in fragments stored up to 12 hours in a solution of cell culture, at 4° C.

INTRODUÇÃO: O hiperparatireoidismo primário (HPTP) é uma doença endócrina cuja prevalência aumentou muito nas últimas décadas. Descobriu-se grande contingente de portadores de formas leves e assintomáticos. Foi observado que esses pacientes apresentam alta morbidade e mortalidade por causas cardiovasculares. O estudo da pressão arterial revelou alta incidência de hipertensão arterial e descenso atenuado. A reversibilidade destes efeitos após a paratireoidectomia, entretanto é controversa. MÉTODO: Estudo prospectivo observacional com pacientes portadores de HPTP esporádico submetidos a paratireoidectomia para verificar as alterações dos parâmetros relativos à pressão arterial após a resolução do HPTP. Os pacientes realizaram monitorização ambulatorial de 24 horas da pressão arterial antes e após cirurgia curativa para HPTP, no 3º pós-operatório, 3 meses, 6 meses e 12 meses. RESULTADOS: Em 7 casos (6 mulheres, idade média 65,7 anos), houve aumento do descenso da pressão arterial sistólica e diastólica. As médias (desvio padrão) da pressão arterial sistólica (PAS) e da pressão arterial diastólica (PAD) foram 124,0mmHg (10,6) e 78,7mmHg (10,4). Não foi observada alteração significativa após a operação. As médias de PAS foram 129,4 mmHg (3 PO), 130,4 mmHg (3 meses) 125,4 mmHg(6 meses) e 131,1 mmHg (12 meses). As médias de PAD foram 73,7 mmHg (3 PO), 78,6 mmHg 75,4 mmHg (6 meses) e 78,0 MMhg (12 meses). Por outro lado, o descenso noturno sistólico e diastólico da pressão arterial apresentaram melhora significativa aos 6 meses e sustentada aos 12 meses. As médias do descenso da PAS foram de 4,3% no pré-operatório; 1,2% no 3o pós-operatório; 10,7% após 6 meses (p=0,002) e de 10,5% 12 meses depois da operação (p=0,008). As médias do descenso da PAD foram de 7,1% no pré-operatório, 4,0% no 3o pós-operatório, 13,3%; aos 6 meses (p=0,02) e de 14,7% depois de 12 meses da paratireoidectomia (p=0,03). CONCLUSÃO: A paratireoidectomia melhora o descenso noturno da pressão arterial em pacientes com HPTP esporádico
INTRODUCTION: Primary hyperparathyroidism is an endocrine disease and its prevalence has increased dramatically in the last decades. There is a great number of individuals with mild or asymptomatic forms of the disease. There is evidence of cardiovascular complications and mortality in these patients. The study of blood pressure showed high prevalence of hypertension and decreased dipping. The reversibility of these effects on blood pressure after curative parathyroidectomy is debatable. METHODS: Prospective study to evaluate the changes in blood pressure measurements of patients undergoing curative parathyroidectomy for sporadic PHPT with 24-hour ambulatory blood pressure monitoring before (PRE) and after curative surgery, during hospital stay (PO3), three months (3 mo), six months (6 mo) and at 12 months (12 mo). RESULTS: In 7 cases (6 female, mean age 65.7 years), there was an improvement of the nocturnal dipping of the systolic and diastolic arterial pressure. Mean (standard deviation) preoperative Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were 124.0 mmHg (10.6) and 78.7 mmHg (10.4). No significant change in blood pressure was observed after the operation. Mean SBP values were 129.4 mmHg (PO 3), 130.4 mmHg (3 mo), 125.4 mmHg (6 mo) and 131.1 mmHg (12 mo). Mean DBP measures were 73.7 mmHg (PO 3), 78.6 mmHg (3 mo), 75.4 mmHg (6 mo) and 78.0 mmHg (12 mo). Conversely, nocturnal systolic and diastolic dipping presented a small nonsignificant decrease immediately after the operation, but a statistically significant and sustained improvement at 6 months and 12 months. Mean systolic nocturnal dipping was 4.3% (PRE), 1.2% (PO 3); 10.7% (6 mo) (p=0,002) and 10.5% (12 mo) (p=0.008). Mean diastolic nocturnal dipping was 7.1% (PRE), 4.0% (PO 3), 13.3% (6 mo) (p=0,01) and 14.7% (12 mo) (p=0.03). Conclusions: In sporadic PHPT, parathyroidectomy improves nocturnal dipping of blood pressure

As doenças renais crônicas (DRC) evoluem com distúrbios na homeostase do cálcio e do fósforo, diminuição na produção de vitamina D e aumento na secreção de PTH. Osteodistrofia renal (OR) é o termo usado para definir as alterações ósseas dos pacientes com DRC e classifica-se em doença de alta remodelação representada pela osteíte fibrosa (OF) e doença mista (DM); e de baixa remodelação representada pela osteomalácia (OM) e pela doença adinâmica (DOA). Pacientes com DRC apresentam elevada incidência de fraturas e recentemente demonstrou-se que a hiperfosfatemia leva a diminuição do volume ósseo. Estudamos o efeito isolado do fósforo no tecido ósseo de animais com insuficiência renal mantidos com infusão fixa de PTH variando o conteúdo de fósforo na dieta. Cinqüenta e cinco ratos Wistar foram submetidos à paratireoidectomia (PTX) e nefrectomia (Nx) com reposição de PTH em diferentes concentrações ou foram sham operados e recebiam infusão de veículo. Todos os animais receberam a mesma dieta variando apenas a concentração de P (pobre em P (pP): 0,2% e rico em P (rP):1,2%). Dividimos os grupos em: Sham (N=8); Sham-pP (N=8); Sham-rP (N=7); NxPTHn-pP (N=8); NxPTHn-rP (N=8); NxPTHe-pP (N=9); NxPTHe-rP (N=7). Após 2 meses, realizamos análises bioquímicas e histomorfometria do fêmur proximal. Os animais que ingeriram dieta rica em fósforo apresentaram hiperfosfatemia assim como menor valor de cálcio sérico. A reposição de PTH foi efetiva e proporcional às concentrações infundidas. A histomorfometria óssea mostrou que os ratos que ingeriram dieta rica em fósforo independente da uremia tinham diminuição do volume ósseo (BV/TV), e que este efeito foi amenizado pela reposição do PTH em concentrações elevadas. Nossos resultados demonstram que o fósforo é deletério para o tecido ósseo e que na uremia são necessários níveis mais elevados de PTH para manter a integridade óssea.
Chronic kidney disease (CKD) involves disturbances in calcium and phosphorus metabolism, reduced vitamin D production and increased parathormone (PTH) secretion. Renal osteodistrophy (RO) is a term used to define bone disease complications of patients with CKD, and is classified in high turnover disease represented by osteitis fibrosa (OF) and mixed bone disease; and low turnover disease represented by osteomalacia (OM) and adynamic bone disease (ABD). It is already known that patients with CKD have high incidence of bone fractures, and it has been demonstrated that hyperphosphatemia results in to decreased trabecular bone volume (BV/TV). We evaluated the effect of phosphorus (P) in rats? bone tissue submitted to experimental uremia that received continuous infusion of 1-34 rat PTH in physiologic or five times the normal values. Fifty five Wistar rats were submitted to parathyroidectomy (PTX), nephrectomy (Nx) and received PTH in different concentrations or some were PTX and NX controls (Sham) that received only vehicle. Rats received identical diets, excepted for the P content which was different according to the group [Low P (LP): 0,2% and high P (HP): 1,2%]. Groups were divided as follow: Sham (N=8), Sham LP (N=8), Sham-HP (N=7), NxPTHn-LP (N=8), NxPTHn-HP (N=8), NxPTHh-LP (N=9), NxPTHh-HP (N=7). After two months, animals were sacrificed and biochemical and bone histomorphometry were performed. Rats who received high P diet developed hyperphosphatemia and hypocalcemia. PTH replacement was effective and in accordance with infusion concentration. Bone histomorphometric analysis showed that HP rats presented low trabecular bone volume (BV/TV) independently of the uremia. BV/TV decreased slightly in the group where PTH continuous infusion was five times the physiologic values. Our results demonstrated that P has a deleterious action on bone tissue and in uremia it is necessary high levels of PTH to maintain bone integrity.

ABSTRACT Background and aim of the study We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, and for its clinical impact in sporadic parathyroid carcinoma and atypical parathyroid adenoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism - hyperparathyroidism-jaw tumor (HPT-JT) syndrome – that carries an increased risk of aggressive parathyroid cancer. Methods We investigated every patient with a diagnosis of parathyroid carcinoma or atypical parathyroid adenoma, who had undergone surgery by one surgeon from 1975 to May 2012 at our Department. Genetic studies were performed from genomic DNA isolated from peripheral blood leukocytes and parathyroid tissue. Preoperative (symptoms, biochemical analysis, imaging), operative (surgery, histological analysis) and post-operative (follow-up) data have been collected in a database and statistically processed. The genetic analysis results have been correlated with the clinical course. Results The study involved 70 patients (group 1: 39 carcinomas, group 2: 31 atypical adenoma). Until now, we investigated 18 patients with parathyroid carcinoma and 8 patients with atypical adenoma. We detected HRPT2 mutation in two patients with carcinoma that died for rapid tumor progression. Conclusions HRPT2 status would be a piece of information to add to the conventional clinical parameters: it correlates with a more aggressive disease. The diagnostic utility of the HRPT2 screening might provide grounds for more aggressive follow-up and family screening. This test will be especially helpful if it directs us to an aggressive surgical approach because that is ultimately the only cure for this devastating disease.
RIASSUNTO Presupposti e scopo dello studio La nostra ricerca è finalizzata all’analisi di mutazione del gene HRPT2, che codifica per la proteina Parafibromina, e alla valutazione del suo impatto clinico nelle forme sporadiche di carcinoma delle paratiroidi e negli adenomi paratiroidei atipici, in quanto mutazioni inattivanti il gene HRPT2 sono emerse in una forma famigliare di iperparatiroidismo- la sindrome iperparatiroidismo associato a tumore della mandibola (HPT-JT)- che comporta un aumentato rischio di carcinoma delle paratiroidi clinicamente aggressivo. Materiali e Metodi Lo studio ha arruolato tutti i pazienti affetti da carcinoma o adenoma atipico delle paratiroidi che sono stati sottoposti ad intervento chirurgico presso il nostro reparto dal 1975 a maggio 2012. Lo studio genetico è stato eseguito su DNA isolato dal tessuto patologico e dai leucociti ottenuti da sangue periferico. Sono stati raccolti in un database e analizzati statisticamente i dati clinici preoperatori (sintomi, dati di laboratorio, dati radiologici), operatori (tipo di intervento chirurgico, esame istologico, paratormone rapido intraoperatorio-IOPTH) e postoperatori (dati di laboratorio, follow-up). I risultati dello studio genetico sono stati correlati con i dati clinici. Risultati Lo studio ha compreso 75 pazienti (gruppo 1: 41 carcinomi; gruppo 2: 34 adenomi atipici) di età media 59 anni. I pazienti con adenoma atipico e carcinoma non differivano statisticamente per sintomi, calcemia media preoperatoria (3,2 mMol/L), dimensione della lesione , ma i carcinomi presentavano valori medi di PTH più elevati (477,8 vs 931,8 ng/L). La sopravvivenza è risultata dell’88,13% a cinque anni e del 79,74% a dieci anni. Costituiscono fattori di rischio per lo sviluppo di recidiva: valori elevati di calcemia preoperatoria (3,4 mMol/L), l’esecuzione di paratiroidectomia semplice, la mancata riduzione dello IO-PTH, il reperto istologico di infiltrazione dei tessuti limitrofi. Fattore prognostico negativo è risultata la presenza di mutazione HRPT2, riscontrata in tre pazienti affetti da carcinoma, i quali hanno avuto decorso rapidamente infausto. Nessun adenoma atipico ha presentato mutazione HRPT2. Conclusioni Nei carcinomi delle paratiroidi, la genetica HRPT2 dovrebbe essere considerata parte delle analisi da valutare assieme ai parametri convenzionali in quanto correla con una forma di malattia più aggressiva. L’utilità dello screening genetico HRPT2 dovrebbe presupporre un follow-up più intenso e uno screening famigliare. Lo studio genetico è sicuramente utile nell’indirizzare ad un approccio chirurgico più aggressivo che a tutt’oggi rimane il solo trattamento più efficace.

INTRODUÇÃO: A paratireoidectomia total com auto-enxerto imediato heterotópico (PTH+AE) é uma das técnicas cirúrgicas hoje usadas no tratamento do hiperparatireoidismo secundário à doença renal crônica e do hiperparatireoidismo persistente após o transplante renal. Os níveis adequados de paratormônio sistêmico (PTHs) no pós-operatório ainda são controversos e o perfil funcional do auto-enxerto de tecido paratireóideo, pouco esclarecido. No presente estudo, nós analisamos a função do tecido paratireóideo implantado pacientes com hiperparatireoidismo secundário e terciário. MÉTODO E CASUÍSTICA: Em um estudo prospectivo observacional, 19 pacientes portadores de doença renal crônica (PDRC) e quatro pacientes transplantados renais (PTR) foram submetidos à PTX+AE com e seguidos por um ano. Todos os pacientes apresentaram PTHs indetectável no pós-operatório imediato (POi). Os níveis séricos de PTH em ambos os membros superiores, cálcio, fósforo, fosfatase alcalina e reposição de cálcio elementar e calcitriol foram verificados com um mês, dois, três, quatro, seis, nove e 12 meses após a cirurgia. A 25-Hidroxivitamina D (25OHD) foi medida no POi, seis e 12 meses após a cirurgia. A função do auto-enxerto foi classificada em estados funcionais (EF) de acordo com os níveis de PTHs. RESULTADOS: A maioria dos PDRC e PTR mostraram níveis detectáveis de PTHs já no primeiro mês. No segundo mês pósoperatório, todos os pacientes apresentaram níveis detectáveis de PTHs quando também houve estabilização dos níveis séricos em ambos os grupos. Os gradientes de concentração de PTH não mostraram correlação com o PTHs. No pós-operatório, a hipercalcemia foi observada em 73,7% dos PDRC em pelo menos um episódio, reduzindo ou inibindo a secreção de paratormônio em oito pacientes. Não houve melhora dos níveis de 25OHD em ambos os grupos, permanecendo com níveis insuficientes. Oito PDRC regrediram de EF ao final do estudo. CONCLUSÃO: O perfil funcional do AE é semelhante entre os PDRC e PTR. A função do AE, inicia-se no primeiro mês pós-operatório, atingindo um maior EF até o quarto mês pós-operatório na maioria dos pacientes, porém pode haver declínio da função ao longo do tempo
BACKGROUND: Total parathyroidectomy with immediate forearm transplantation (PTX+AT) is employed in renal hyperparathyroidism. Appropriate postoperative systemic parathyroid hormone (sPTH) levels are still controversial and autograft functional behavior is unclear. In the present study, we analyzed the function of autotransplanted parathyroid tissue in secondary and tertiary hyperparathyroidism. METHODS: In a prospective observational study, 19 dialysis patients (DPs) and 4 kidney transplant patients (KTPs) who underwent PTX+AT were followed. All patients had undetectable PTH in the early postoperative period (ePO). Autograft function and the following biochemical variables were assessed at one, two, three, four, six, nine and 12 months following the operation: serum calcium, phosphorus, alkaline phosphatase, and intact PTH before and after the operation. 25-Hidroxyvitamin D levels (25OHD) were measured in the ePO, six and twelve months. Oral doses of calcium and calcitriol were recorded. Autograft function was stratified into four functional status (FS) according to sPTH. RESULTS: All functioning grafts presented sPTH until the second month. On the second postoperative month, all patients had sPTH detectable levels also when serum levels were steady in both groups. PTH gradients showed no significant correlation with sPTH levels. In at least one occasion in the postoperative period, hypercalcemia was observed in 73.7% of DPs, and it reduced or inhibited PTH secretion in 8 patients. There was no improvement in levels of 25OHD in both groups, resulting in insufficient levels. Eight DPs changed to a lower FS at the end of the study. CONCLUSION: The function of the autotransplanted parathyroid tissue usually initiates during the first month following operation and is similar in patients. The most of the patients reachs FS2 during the fourth month but autograft function can decrease over time

O hiperparatireoidismo secundário à doença renal crônica (HPS) acomete inúmeros pacientes. Não existe consenso sobre qual tipo de paratireoidectomia (PTx) se associa com melhores resultados. Na PTx total com autoimplante (PTx-AI) especula-se se o número de fragmentos implantados melhora desfechos clínicos. Trinta e seis (36) pacientes com HPS foram randomizados para PTx-AI com 45 ou 90 fragmentos de paratireoide. Prospectivamente, avaliamos os fatores clínicos, bioquímicos e anatomopatológicos que influenciaram a função do AI. No início do estudo (t0), o Grupo-45 (N = 28) e Grupo-90 (N = 8) eram semelhantes, com exceção dos níveis séricos de fosfato. Após 12 meses (t12), os níveis séricos de PTH do enxerto e sistêmico correlacionaram-se com o cálcio iônico (Cai)-t0 (r2 = 0,442, p = 0,016; r2= 0,450, p = 0,008, respectivamente). A duração da fome óssea correlacionou-se com fosfatase alcalina (FA)-t0 (r2 = 0,593, p = 0,001). Nas células paratireoideanas, a expressão de PCNA correlacionou-se com o tempo em hemodiálise (r2 = 0,437, p = 0,016); a expressão do receptor-1 do fator de crescimento de fibroblastos (FGFR1) com FA-t0 (r2 = -0,758; p = 0,0001); o receptor de vitamina-D (VDR) com Cai-t0 (r2 = -0,464, p = 0,007) e carga cumulativa de Ca elemento (r2 = - 0,359, p = 0,04); o receptor sensível ao Ca (CaSR) com menor uso de calcitriol (r2 = -0,445, p = 0,049); e o Klotho com a dose de vitamina D pré- PTx (r2 = 0,811, p = 0,027) e com fosfato-t0 (r2= -0,528, p = 0,017). Houve progressão do escore de calcificação vascular [0,53 (0 - 4) vs. 1,1 (0 - 8); p = 0,04], que se correlacionou com a carga cumulativa de Ca elemento (r2 = 0,605, p = 0,006) e com o fosfato-t0 (r2 = 0,503; p = 0,028). Em conclusão, a PTx independentemente do número de AI controlou o HPS; porém parece piorar a calcificação vascular. Os níveis séricos de PTH pós-PTx ou evolução para hipo- ou normoparatireoidismo não foram influenciados pelo número de AI, nem por outros parâmetros bioquímicos e tão pouco pela densidade de expressão de PCNA, CaSR, VDR, FGFR1 ou Klotho nas células paratireoideanas
Hyperparathyroidism secondary to chronic kidney disease (SHP) affects many patients. There is no consensus about what kind of parathyroidectomy (PTx) is associated with better results. In total PTx with auto transplant (PTx- AT) it is speculated that the number of implanted fragments improves clinical outcomes. Third six (36) patients with refractory SHP were randomized to PTx-AT with 45 or 90 parathyroid fragments. We prospectively evaluated the clinical, biochemical and pathological factors influencing AT function. At baseline (t0) Group-45 (N = 28) and Group-90 (N = 8) were similar, except for serum phosphate levels. After 12 months (t12), PTH levels of graft and systemic correlated with ionic calcium (Cai) t0 (r2 = 0.442, p = 0.016; r2 = 0.450, p = 0.008, respectively). The duration of hungry bone syndrome correlated with alkaline phosphatase (AP) -t0 (r2 = 0.593, p = 0.001). In parathyroid cells, PCNA expression correlated with time on hemodialysis (r2 = 0.437, p = 0.016), expression of receptor-1 of fibroblast growth factor (FGFR1) with AP-t0 (r2 = -0.758; p = 0.0001), vitamin D receptor (VDR) with Cai t0 (r2 = -0.464, p = 0.007) and cumulative elemental Ca load (r2 = -0.359, p = 0.04), Ca sensing receptor (CaSR) with less use of calcitriol (r2 = -0.445, p = 0.049), and Klotho with the dose of vitamin D pre-PTx (r2 = 0.811, p = 0.027) and phophate-t0 (r2 = -0.528, p = 0.017). There was progression of vascular calcification score [0.53 (0 to 4) vs. 1.1 (0 to 8); p = 0.04] which correlated with cumulative elemental Ca load (r2 = 0.605, p = 0.006) and with phosphate-t0 (r2 = 0.503; p = 0.028). In conclusion, PTx controlled refractory SHP regardless of the number of AT; however, it seems to worsening vascular calcification. Serum levels of PTH or post-PTx evolution of hypo- or normoparathyroidism were not influenced by the number of AT or other biochemical parameters, nor by the density of PCNA expression, CaSR, VDR, FGFR1 or Klotho in parathyroid cells

INTRODUÇÃO: Em pacientes transplantados renais, a paratireoidectomia está associada à piora aguda da função renal. Os efeitos agudos e crônicos da paratireoidectomia sobre a filtração glomerular foram pouco estudados em Hiperparatireoidismo Primário (HPTP). MÉTODO E CASUÍSTICA: Neste estudo retrospectivo de coorte, foram estudados 494 pacientes submetidos a paratireoidectomia por HPTP, entre os anos de 2007 e 2016. Variações agudas da creatinina foram aferidas diariamente na internação, até o 4o pós-operatório, sendo classificados conforme os critérios de KDIGO para IRA. Dados bioquímicos incluíram dosagem sérica de creatinina, cálcio iônico e total, paratormônio (PTH) e 25-OH vitamina D. A taxa de filtração glomerular foi estimada a partir da equação CKD-EPI. Foram comparados dados de função renal pré e pós-operatórios até 5 anos de seguimento. RESULTADOS: Dos 494 pacientes, 391 (79,1%) eram mulheres e 422 (85,4%) de cor branca. A causa mais comum de HPTP foi adenoma de paratireóide (351, 71,1%) e a mediana de idade foi de 58 anos. As medianas (Q1-Q3) de creatinina, PTH e cálcio total séricos foram de: 0,81 mg/dL (0,68-1,01), 154,5 pg/mL (106-238,5) e 10,9 mg/dL (10,3-11,5) respectivamente. A mediana de eGFR préoperatória foi de 86 mL/min x 1,73m2. No período agudo, houve redução mediana de 26 mL/min x 1,73m2 na eGFR (p < 0,0001), que representou -27,44% (±19,12%) de variação aguda da eGFR. De acordo com os critérios de IRA, 41,1% dos pacientes tiveram IRA estágio 1, 5,9% estágio 2 e 1,8% estágio 3. Outros 223 pacientes (45,1%) tiveram elevação da creatinina porém não preencheram critérios de IRA. Na análise univariada foram observadas correlações fracas, porém significativas, entre o percentual de variação aguda de eGFR e os seguintes fatores pré-operatórios: idade, PTH, cálcio e creatinina. Uma redução definitiva da eGFR foi observada em 60,7% dos pacientes, após 12 meses de seguimento. CONCLUSÃO: Houve significativa redução aguda da função renal após paratireoidectomia por HPTP, sendo que quase metade dos pacientes preencheram critérios de IRA. Observou-se importante recuperação da eGFR no primeiro mês de pós-operatório, podendo ocorrer algum grau de perda definitva de função renal
INTRODUCTION: In kidney transplant patients, parathyroidectomy is associated with acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been as extensively studied in primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Retrospective cohort study of 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post parathyroidectomy, and stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, PTH, and 25-hydroxyvitamin D (25OHD). EGFR were calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up. RESULTS: 391 (79.1%) patients were female and 422 (85.4%) were non-African American. Median age was 58 years old. Median (interquartile range) preoperative serum creatinine, PTH and total calcium were 0.81 mg/dL (0.68- 1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5) respectively. Median (interquartile range) preoperative eGFR was 86 mL/min/1.73m2 (65-101.3). After surgery the median acute decrease in eGFR was 26 mL/min/1.73m2 (p < 0.0001). Acutely, 41.1% patients developed AKI stage 1, 5.9% AKI stage 2 and 1.8% AKI stage 3. Acute eGFR decrease (%) correlated with age, PTH, calcium and preoperative creatinine, in univariate analysis. Permanent reduction in eGFR occurred in 60.7 % of the patients, after acute episode. CONCLUSION: There is a significant acute impairment in renal function after parathyroidectomy for PHPT and almost half of patients meet the criteria for AKI. Significant eGFR recovery was observed during first month after surgery, but a small permanent reduction may occur

Nos casos de hiperparatireoidismo secundário onde não é possível o tratamento clínico, é indicada a paratireoidectomia. No Serviço de Cirurgia de Cabeça e Pescoço do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, o tipo de cirurgia utilizada é a paratireoidectomia total com auto-implante de paratireóide em membro superior. Nesses casos, ao contrário da paratireoidectomia total, pode haver recidiva do hiperparatireoidismo no sítio do implante, com sintomas sistêmicos e com necessidade de intervenção para retirada do tecido hiperplásico. Já na paratireoidectomia total, há hipoparatireoidismo definitivo e risco de doença óssea adinâmica. O presente estudo tem como escopo avaliar os pacientes submetidos a paratireoidectomia com implante e esclarecer se há fatores clínicos e de imunohistoquímica que possam indicar antes da cirurgia algum risco de recidiva no implante
When clinical treatment of secondary hyperparathyroidism fails, parathyroidectomy is mandatory. Total parathyroidectomy and immediate parathyroid autotransplantation in the forearm is the treatment of choice at Head and Neck Surgery of Hospital das Clínicas of University of São Paulo Medical School. In this cases, recurrent hyperparathyroidism may be caused by hyperplastic graft tissue. Without autotransplantation, adinamic bone disease may occur. The present study seek to evaluate patients submitted to total parathyroidectomy and autotransplantation and try to clarify clinical or immunohistochemical

INTRODUÇÃO: O hiperparatireoidismo secundário (HPTS) é uma complicação da doença renal crônica que compromete a integridade do esqueleto. Pacientes com HPS submetidos à paratireoidectomia (PTX) passam de uma condição de níveis séricos de paratormônio (PTH) muito elevados para outra, onde esses níveis hormonais caem drasticamente. Os efeitos da PTX no tecido ósseo são mal compreendidos, especialmente no que se refere às proteínas expressas por osteócitos, como o fator de crescimento de fibroblastos 23 (FGF23), dentin matrix protein 1 (DMP-1), fosfoglicoproteína de matriz extracelular (MEPE), esclerostina, Fator nuclear Kappa beta ligante (RANKL) e osteoprotegerina (OPG), que regulam a remodelação e a mineralização óssea. OBJETIVOS: Caracterizar a expressão óssea dessas proteínas por imuno-histoquímica e estabelecer relações com os dados da histomorfometria do tecido ósseo em pacientes com HPS, antes e após a PTX. MÉTODOS: Estudamos biópsias ósseas obtidas de um banco de biópsias de 23 pacientes com DRC e HPTS, que foram realizadas antes e 12 meses após a PTX. RESULTADOS: A avaliação dos parâmetros histomorfométricos demonstrou uma melhora da microarquitetura óssea, porém com um maior retardo em sua mineralização após a PTX. A análise da expressão das proteínas osteocíticas revelou um aumento significativo na expressão da esclerostina e da OPG e uma diminuição da relação RANKL/OPG após a PTX, sugerindo a participação dessas proteínas na melhora das lesões ósseas decorrentes do HPTS. Observamos um aumento significativo na expressão da OPG no grupo de pacientes que evoluiu com defeito de mineralização somente após a cirurgia, sugerindo a participação dessa proteína no retardo de mineralização óssea desses pacientes. A expressão das proteínas osteocíticas que participam da formação e mineralização óssea apresentou correlação com parâmetros envolvidos na remodelação óssea. CONCLUSÕES: Mudanças significativas na expressão óssea de proteínas osteocíticas que podem potencialmente regular a remodelação e a mineralização óssea foram observadas após a PTX
INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease that compromises skeletal integrity. Patients with SHPT undergoing parathyroidectomy (PTX) go from a very high serum parathyroid hormone (PTH) condition to another, where these hormonal levels dramatically fall. The effects of PTX on bone tissue are poorly understood, especially as regards proteins expressed by osteocytes, such as fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP-1), extracellular matrix phosphoglycoprotein (MEPE), sclerostin, Kappa beta ligand nuclear factor (RANKL) and osteoprotegerin (OPG), which regulate bone remodeling and mineralization. OBJECTIVES: Characterize bone expression of these proteins by immunohistochemistry and establish relations with bone tissue histomorphometry data in SHPT patients, before and after PTX. METHODS: We studied bone biopsies obtained from a biopsy database of 23 patients with CKD and SHPT, which were performed before PTX and 12 months after PTX. RESULTS: Evaluation of histomorphometric parameters showed improvement of bone microarchitecture, but with longer delay in mineralization after PTX. Analysis of osteocyte protein expression revealed significant increase in sclerostin and OPG expression and decrease in RANKL/OPG ratio after PTX, suggesting participation of these proteins in improvement of bone lesions due to SHPT. We observed significant increase in OPG expression in the group of patients who evolved with mineralization defect only after surgery, suggesting participation of this protein in bone mineralization delay of these patients. Expression of osteocyte proteins that participate in bone formation and mineralization correlated with parameters involved in bone remodeling. CONCLUSIONS: Significant changes in bone expression of osteocyte proteins that can potentially regulate bone remodeling and mineralization were observed after PTX

BACKGROUND: Postoperative hypoparathyroidism due to damage to the parathyroid glands during a thyroidectomy is a well-known surgical complication. The current gold standard intraoperative method for identifying parathyroid glands is surgical judgment; other methods are limited in both their sensitivity and convenience. There is a clear need for an objective diagnostic tool that is effective in its identification of the parathyroid glands and of their viability. We hypothesized that an intraoperative tool using Elastic Scattering Spectroscopy (ESS) has the potential to differentiate optical signatures of the parathyroid gland from surrounding tissues in real-time. METHODS: ESS optical signatures were collected intraoperatively from perfused parathyroid, thyroid, fat, muscle, and nerve tissue during thyroidectomy. The ESS data was collected using a portable, handheld, noninvasive, "cold" fiber optic probe able to detect spectra in a non-ionizing, broadband spectrum of light (320 to 920 nm). Five measurements were collected at each tissue site over a total of 1.2 seconds. Visual analysis of tissue was analyzed and compared to pathology, and spectral measurements attained with ESS. RESULTS: No complications resulted from the use of the ESS probe. Of the 10 parathyroid glands evaluated to be at risk in the study, the optical probe utilizing ESS was able to detect unique spectral features associated with the parathyroid gland. All 10 parathyroid glands are optically differentiable from surrounding tissues with ESS. CONCLUSIONS: Utilizing spectroscopy in the form of a hand-held probe is feasible for intraoperative differentiation between tissue types. Preliminary results of this spectral technique warrant further investigation. If successful, implementation of a portable ESS probe to identify the parathyroid tissue during endocrine surgical procedures could reduce surgical complications and improve patient safety.

碩士
國立陽明大學
護理學系暨研究所
97
The purpose of this study was to explore the relationship between the symptoms distress and the quality of life in patients with End-Stage Renal Disease before and after parathyroidectomy. A descriptive and correlation study design was undertaken. Thirty-seven participants were recruited from a medical center over two years of period. Data was analyzed by using descriptive statistics, pair t-test and pearson，s correlation. The result reveals that joint pain, muscle weakness and itchy skin were the most annoying symptoms and the total scores of PCS was 31.7± 13.8,MCS 37.6±14.4 respectively. There were 86.5% of patients indicated experiencing adverse symptoms and as the result affecting their quality of life. However, the symptoms improved after parathyroidectomy. Among these cases, there was a noticeable negative correlation between the level of serum calcium and PCS and MCS; in contrast, a positive correlation between the calcium-phosphorus product and skin itching was observed. Preoperative serum albumin was related to PCS (r=0.354, p=0.047). In addition, after three months of operation there was a significant correlation between the serum albumin level and PCS (r= 0.374, p=0.035) and MCS (r=0.416,p=0.018). Joint pain, muscle weakness, and skin itching have alleviated greatly both at one month and three months of time after parathyroidectomy. The result of this research can facilitate nursing staff to understand the pre-operative symptoms distress and the necessity in patients with ESRD and parathyroidism; and provide them with individually appropriate care to better their quality of life.

碩士
高雄醫學大學
醫務管理學研究所碩士在職專班
94
Abstract The major purpose of this study was to investigate patient demographics, trend of parathyroidectomy rate, high risk groups and clinical factors of dialysis patients who underwent parathyroidectomy in Taiwan. The study design was a retrospective secondary data analysis. The study used hospitalization data covering the periods from 2000 to 2004, taken from Taiwan’s National Health Insurance Research Database (NHIRD), published by the National Health Research Institute, including files of registry for contracted medical facilities (HOSB), registry for catastrophic illness patients(HV), registry for board-certified specialists(DOC) and inpatient expenditures by admissions (DD).The study papulation consisted of a total number of 1,326 dialysis patients of secondary hyperparathyroidism (ICD-9-CM code 588.8) who underwent parathyroidectomy (ICD-9-CM code 068.1 and 068.9). In-patient service utilizations included length of stay (LOS) and cost per discharge. Moreover, the service utilization differences in parathyroidectomy was compared by type of dialysis, parathyroidectomy, number of co-morbidities, hospital characteristics and provider volumes. The computer software SPSS® 12.0 for Windows was used to conduct descriptive and theoretical comparison and analysis. According to planned statistical analyses, the results indicated that: (1)By trend analysis, the incidence of parathyroidectomy rate in 2000 was 5.11 per 1000 person-years. By 2004, the incidence rose to 9.42 per 1000 person-years. Male, younger age group, peritoneal dialysis and non-diabetic dialysis patients had higher incidence of parathyroidectomy. (2)The mean LOS was longer in the dialysis patients with toal parathyroidectomy, hemodialysis, more co-morbidities, and hospitals of medical center, north location (Taipei) , high volume hospitals and low volume surgeons. (3) The patient costs was higher in the dialysis patients of hemodialysis, longer duration, more co-morbidities, and hospitals of public, south location and low volume surgeons. In conclusion, male, younger, peritoneal dialysis and non-diabetic dialysis patients was particularly high risk groups for parathyroidectomy. Phosphate binder and Vit.D were administered especially. Public hospitals had longer and more stastistically significant costs. Medical center and high volume hospitals had longer LOS. Low voume surgeons had higher patient’s cost. It was then suggested that hospitals practiced “clinical pathway ” to decrease LOS and patient costs. However, the research databases was from NHRID secondary data. The major limitation of the research was lack of : (1)clinical data, (2)clinical symptoms and (3)complications. For further research, the clinical registry database may conduct by Taiwan Nephrology Society and integrate NHIRD and increase values of clinical research. Keywords: Secondary hyperparathyroidism、Parathyroidecotmy、Length of stay、Cost

For the past 40 years, most patients with Primary Hyperparathyroidism (PHPT) have presented with the asymptomatic form of PHPT. Despite the dominance of the asymptomatic PHPT phenotype, current National Institutes of Health (NIH) indications for parathyroidectomy fail to identify as many as 80% of patients afflicted with asymptomatic PHPT. To date, studies of the therapeutic benefits of parathyroidectomy among asymptomatic PHPT patients have relied on general health questionnaires and patient reports of their satisfaction with the surgery. The purpose of the present study was to implement objective, quantifiable metrics in assessing whether or not asymptomatic PHPT patients experience improvements in domains salient to them such as mobility and cognitive function following parathyroidectomy. This information may help set the foundation for more accurately identifying patients who would benefit from parathyroidectomy. We hypothesized that asymptomatic patients would exhibit improvement in motor-cognitive outcomes following successful parathyroidectomy. We performed a single-center prospective assessment of gait, frailty, and motor-cognitive function among patients diagnosed with PHPT. Demographics, medical history, and perioperative labs were recorded. Pre- and post-surgical measures included the Fried frailty criteria, the PROMIS 10 Global Health Scale, and gait analysis under habitual (ST), walking while performing working memory test (dual-task: DT), and fast-walking conditions, an upper extremity frailty (UEF) test, and an interactive trail-making task (iTMT) . Descriptive statistics, Chi-squared, 2-sample t tests, and repeated measures analysis of variance were applied where appropriate. 22 parathyroidectomy patients (male 7; 31.8%); median age of 54.9 (standard deviation=15.5) years participated. The prevalence of frailty/pre-frailty was 60% at baseline and reduced to 33% at 3 weeks post-op. PROMIS 10 physical health improved significantly by 3 months post-op (d=0.93, p=0.010). DT and fast walk velocities were significantly increased by 3 weeks post-op (p<0.050) with highest effect size observed during DT conditions (24%, Cohen's effect size d=1.30 , p=0.017). ST velocity increased but not significantly (17.5%, d=0.46, p=0.422). Results from UEF tests and iTMT did not achieve statistical significance at any visit date. Asymptomatic PHPT patients experience significant resolution of motor-cognitive symptoms as measured by DT gait and PROMIS 10 Global Health Scale following parathyroidectomy performed by a skilled surgeon.