Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism / Paratireoidectomia: ainda a melhor escolha para o tratamento do hiperparatireoidismo secundário grave

Abstract Introduction: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. Methods: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). Results: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. Conclusion: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Resumo Introdução: O manejo do hiperparat-ireoidismo secundário (HPTS) é uma tarefa desafiadora com diversos fatores que contribuem para o fracasso do tratamento. A terapia calcimimética revolucionou o manejo do HPTS, levando a alterações nas indicações e no momento apropriado da paratireoidectomia (PTX) em todo o mundo. Métodos: Comparamos taxas de resposta às abordagens clínica vs. cirúrgica do HPTS em pacientes em diálise de manutenção (DRC 5D) e pacientes transplantados renais (TxR). Foi realizada uma análise retrospectiva dos achados de um ano de acompanhamento. Pacientes com DRC 5D foram divididos em 3 grupos de acordo com a estratégia de tratamento: paratireoidectomia, manejo clínico sem cinacalcete (denominado padrão - P) e com cinacalcete (P + CIN). Os pacientes com TxR foram divididos em 3 grupos: PTX, CIN (uso de cinacalcete) e observação (OBS). Resultados: Na DRC 5D, encontramos uma redução significativa do paratormônio (PTH) em todos os grupos. Apesar de todos os grupos apresentarem um PTH mais elevado no início do estudo, identificamos uma redução mais acentuada no grupo PTX. Com relação ao HPTS grave, a diferença entre os grupos foi evidentemente maior: 31%, 14% e 80% dos grupos P, P + CIN e PTX atingiram níveis adequados de PTH, respectivamente (p< 0,0001). Com relação à população TxR, embora a diferença não tenha sido tão impressionante, também foi observada uma taxa maior de sucesso no grupo PTX. Conclusão: A PTX ainda parece ser a melhor escolha de tratamento para o HPTS, especialmente em pacientes com doenças prolongadas em cenários sem recursos.

Cost-effectiveness analysis of cinacalcet vs. paricalcitol in the treatment of hyperparathyroidism secondary to chronic kidney disease / Análise de custo-efetividade do cinacalcete vs. paricalcitol no tratamento do hiperparatireoidismo secundário à doença renal crônica

ABSTRACT Introduction For the reduction of PTH levels, two classes of drugs are available in the Brazilian market: non-selective and selective vitamin D receptor activators and calcimimetics. Among the mentioned drugs, the SUS provides oral calcitriol, paricalcitol and cinacalcet. Objectives: Develop cost-effectiveness (CE) and budgetary impact (BI) analysis of cinacalcet versus paricalcitol for patients on dialysis with SHPT, from the perspective of SUS. Methodology: A decision tree model was constructed for CE analysis, which considered the outcome of avoided parathyroidectomy and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of which was measured demand and other epidemiological, based on data from the Brazilian Society of Nephrology (BSN). Results: The CE analysis showed that the use of cinacalcet results in one-off savings of R$1,394.64 per year and an incremental effectiveness of 0.08, in relation to avoided parathyroidectomy. The incremental CE ratio (ICER) was - R$ 17,653.67 per avoided parathyroidectomy for cinacalcet, as it was more effective and cheaper compared to paricalcitol. As for the BI analysis, it was estimated that the incremental BI with the expansion of the use of cinacalcet in the SUS will be between - R$ 1,640,864.62 and R$ 166,368.50 in the first year, considering the main and the epidemiological scenarios. At the end of 5 years after the expansion of use, an BI was estimated between - R$ 10,740,743.86 and - R$ 1,191,339.37; considering the same scenarios. Conclusion: Cinacalcet was dominant to avoid parathyroidectomies, being cost-effective.

RESUMO Introdução: Para a redução dos níveis do paratormônio (PTH) estão disponíveis no mercado brasileiro duas classes de medicamentos: ativadores do receptor da vitamina D (não seletivos e seletivos) e calcimiméticos. Dentre os medicamentos supracitados, o SUS disponibiliza calcitriol oral, paricalcitol e cinacalcete. Objetivos: Desenvolver análise de custo-efetividade (CE) e de impacto orçamentário (IO) do cinacalcete versus paricalcitol para pacientes em diálise com HPTS, na perspectiva do SUS. Metodologia: Foi construído um modelo de árvore de decisão para a análise de CE, que considerou o desfecho paratireoidectomia evitada e um horizonte temporal de 1 ano. Quanto à análise de IO, foram considerados dois cenários, um de demanda aferida e outro de abordagem epidemiológica, baseado nos dados da Sociedade Brasileira de Nefrologia (SBN). Resultados: A análise de CE mostrou que o uso de cinacalcete resulta em economia de R$ 1.394,64 ao ano e efetividade incremental de 0,08, em relação a paratireoidectomia evitada. A razão de CE incremental (RCEI) foi de - R$ 17.653,67 por paratireoidectomia evitada para o cinacalcete, já que se mostrou mais efetivo e mais barato comparado ao paricalcitol. Estimou-se que o IO incremental com a ampliação do uso do cinacalcete no SUS estará entre - R$ 1.640.864,62 e R$ 166.368,50 no primeiro ano, considerando os cenários principal e epidemiológico baseado nos dados da SBN. Já ao final de 5 anos após a ampliação do uso, estimou-se um impacto incremental entre - R$ 10.740.743,86 e - R$ 1.191.339,37; considerando os mesmos cenários. Conclusão: Cinacalcete foi dominante para evitar paratireoidectomias, sendo custo-efetivo.

Cost-effect analysis of surgical and medical treatment for patients of secondary hyperparathybridism / 中华普通外科杂志

Objective:To explore the cost-effectiveness of alfacalcidol and cinacalcet for the treatment of secondary hyperparathyroidism in dialysis patients compared with parathyroidectomy.Methods:A total of 60 patients with secondary hyperparathyroidism treated at the Third People's Hospital of Chengdu from 2011 to 2020 were studied, patients were randomly divided into three groups: cinacalcet group, alfacalcidol group and parathyroidectomy group, with 20 cases in each group.Result:The improvement rate of bone pain and skin pruritis in parathyroidectomy group were higher than that in cinacalcet group and alfacalcidol group ( χ2=16.282, P<0.001; χ2=12.823, P=0.002). After 12 months of treatment, iPTH in the parathyroidectomy group and the cinacalcet group was significantly lower than that in the alfacalcidol group ( HR=1.36, 95% CI: 1.00-1.72, P<0.001; HR=1.27, 95% CI: 0.91-1.63, P<0.001); Serum calcium in the parathyroidectomy group was significantly lower than that of the other two groups ( HR=0.18, 95% CI: 0.12-0.24, P<0.001; HR=0.14, 95% CI: 0.08-0.20, P<0.001). The cost of complications management in the parathyroidectomy group was the lowest ( H=40.534, P<0.001), with bone pain being the most cost concern ( H=38.494, P<0.001). Patients with iPTH>2 800 pg/ml had the highest costs than with 800~1 800/ml and 1 800~2 800/ml ( H=43.798, 37.260, P<0.001). Conclusion:Surgical treatment should be the first choice for patients with secondary hyperparathyroidism, especially for patients with iPTH>2 800 pg/ml and bone pain.

Sestamibi scan in renal parathyroidectomy: a worthwhile preoperative exam? / Cintilografia com sestamibi na paratireoidectomia renal: um exame pré‐operatório que vale a pena?

Abstract Introduction Surgical treatment of hyperparathyroidism related to chronic kidney disease is a real challenge for Brazilian public health care. High cost medications and long waiting lines to perform preoperative exams, especially technetium Tc 99m Sestamibi (MIBI) are some of the reasons. Despite the reality that the aid of localization exams are questionable in this scenario, doctors are too apprehensive in performing surgery without it. Objective The study aimed at evaluating the efficacy of surgery for renal hyperparathyroidism without preoperative MIBI. Methods A total of 114 patients were surgically treated. Total parathyroidectomy with autotransplantation and subtotal parathyroidectomy were carried out without preoperative MIBI. Results and conclusion Among the 114 patients undergoing surgery, 37 had secondary hyperparathyroidism in dialysis replacement, and 77 patients had post-renal transplant persistent disease. We were successful in 107 cases with only 7 failures (93.8% of success rate). Among these failures, only one parathyroid gland was not found in 4 cases, 2 parathyroid glands were not found in 2 cases and in 1 patient the 4 glands were found but this patient remained hypercalcemic and a postoperative diagnosis of supernumerary parathyroid gland was made. Surgery for treatment of renal hyperparathyroidism proved to be an effective (93.8%) and reproductible procedure, even without MIBI.

Resumo Introdução O tratamento cirúrgico do hiperparatireoidismo relacionado à doença renal crônica é um verdadeiro desafio para a saúde pública brasileira. Medicamentos de alto custo e longas filas de espera para exames pré‐operatórios, principalmente a cintilografia com tecnécio Tc‐99m Sestamibi, MIBI, são alguns dos motivos. Apesar da contribuição de exames de localização ser questionável nesse cenário, os médicos ficam muito apreensivos por fazer uma cirurgia sem ele. Objetivo Avaliar a eficácia da cirurgia para hiperparatireoidismo renal sem o MIBI pré‐operatório. Método Foram tratados cirurgicamente 114 pacientes. A paratireoidectomia total com autotransplante e a paratireoidectomia subtotal foram feitas sem MIBI pré‐operatório. Resultados e conclusão Entre os 114 pacientes submetidos à cirurgia, 37 apresentavam hiperparatireoidismo secundário em reposição dialítica e 77 doença persistente pós‐transplante renal. Tivemos sucesso em 107 casos, com apenas 7 falhas (93,8% de taxa de sucesso). Entre essas falhas, uma glândula paratireoide não foi encontrada em 4 casos, 2 glândulas paratireoides não foram encontradas em 2 casos e em um paciente as 4 glândulas foram encontradas, mas ele permaneceu hipercalcêmico com diagnóstico pós‐operatório de glândula paratireoide supranumerária. A cirurgia para tratamento do hiperparatireoidismo renal mostrou‐se um procedimento eficaz (93,8%) e reprodutível mesmo sem MIBI.

Distúrbio mineral e ósseo: prevalência subestimada nos estágios iniciais da doença renal crônica / Mineral and bone disorder: underestimated prevalence in the early stages of chronic kidney disease / Trastorno mineral y óseo: prevalencia subestimada en las primeras fases de la enfermedad renal crónica

Introdução: o objetivo foi avaliar a prevalência do distúrbio mineral e ósseo em pacientes com doença renal crônica e a associação entre Taxa de Filtração Glomerular estimada (TFGe) e os indicadores do distúrbio mineral e ósseo (DMO) (cálcio, fósforo e PTH) em pacientes renais crônicos não dialíticos. Materiais e Métodos: estudo seccional da linha de base de uma coorte de dois anos, com adultos e idosos renais crônicos em tratamento conservador. Para identificação do DMO utilizamos os seguintes valores séricos: PTH (> 150 pg/mL) e/ou hipocalcemia (Ca < 8,8mg/dl) e/ou hiperfosfatemia (P > 4,6 mg/dl). Na análise estatística utilizou-se: regressão de Poisson; T de Student, Mann Whitney e correlações de Pearson e Spearman. Nível de significância foi de 5%. Resultados: prevalência de DMO de 54,6% (n=41) (IC 95%: 43,45 - 65,43). A maior prevalência de DMO foi em pessoas do sexo feminino, alfabetizadas, idosas, não etilistas, não tabagistas, sedentárias e de cor de pele branca, porém, sem diferença estatística entre os grupos com e sem DMO. As correlações entre P e PTH com TFGe foram significativas, inversas, de força moderada (p= <0,005 e p = 0,003; coeficientes de correlação = - 0,312 e - 0,379 respectivamente). Discussão:os achados desse estudo mostraram que existe uma lacuna no acompanhamento do DMO-DRC pela atenção primária e a prática clínica deve ser revista. Conclusão:identificou-se prevalência robusta de DMO nos estágios precoces da DRC, além de correlações significativas entre o aumento dos níveis de fósforo e PTH e piora das funções renais.

Introduction: mineral and bone disorder (BMD) is a serious complication of chronic kidney disease (CKD) that increases risks for death from cardiovascular causes and impairs quality of life of affected patients. Objetive: to evaluate the prevalence of BMD in patients with CKD and the association between estimated Glomerular Filtration Rate (eGFR) and BMD indicators (calcium, phosphorus and PTH) in non-dialysis patients. Materials and Methods:sectional study of a two-year cohort of chronic renal adults and elderly patients on conservative treatment. BMD was identified by serum values of: PTH (> 150 pg/mL) and/or hypocalcemia (Ca < 8.8mg/dl) and/or hyperphosphatemia (P > 4.6 mg/dl). The statistical analysis used: Poisson regression; Student's T, Mann Whitney and Pearson and Spearman correlations with 5% significance level. Results:BMD prevalence was 54.6% (n=41) (95% CI: 43.45 - 65.43), more frequent in women, literate, elderly, non-drinkers, non-smokers, sedentary and white skin color. Correlations between P and PTH with GFRe were significant, inverse, moderate strength (p= <0.005 and p = 0.003; correlation coefficients = - 0.312 and - 0.379 respectively). Discussion: the findings of this study highlighted gaps in the monitoring of BMD-DRC by primary care, requiring a review of clinical practices. Conclusion: robust prevalence of BMD in the early stages of CKD was identified, in addition to correlations between increased phosphorus and PTH levels and worsening kidney function.

Introducciòn: el trastorno mineral y óseo (TMO) es una complicación grave de la enfermedad renal crónica (ERC) que aumenta el riesgo de muerte por causas cardiovasculares y deteriora la calidad de vida de los pacientes afectados. Objetivo: evaluar la prevalencia de la DMO en pacientes con RDC y la asociación entre la tasa de filtración glomerular estimada (TFGe) y los indicadores de DMO (calcio, fósforo y PTH) en pacientes no dialíticos. Materiales y Métodos: estudio seccional de una cohorte de dos años de pacientes renales crónicos adultos y ancianos en tratamiento conservador. La DMO se identificó por los valores séricos de: PTH (> 150 pg/mL) y/o hipocalcemia (Ca < 8,8mg/dl) y/o hiperfosfatemia (P > 4,6 mg/dl). El análisis estadístico utilizado: regresión de Poisson; T de Student, Mann Whitney y correlaciones de Pearson y Spearman con un nivel de significación del 5%. Resultados: la prevalencia de DMO fue del 54,6% (n=41) (IC 95%: 43,45 - 65,43), más frecuente en mujeres, alfabetizadas, de edad avanzada, no bebedoras, no fumadoras, sedentarias y de color de piel blanca. Las correlaciones entre el P y la PTH con el GFRe fueron significativas, inversas, de fuerza moderada (p= <0,005 y p = 0,003; coeficientes de correlación = - 0,312 y - 0,379 respectivamente). Discusión: los resultados de este estudio evidencian lagunas en el seguimiento de la DMO-DRC por parte de la atención primaria, lo que requiere una revisión de las prácticas clínicas. Conclusión: se identificó una fuerte prevalencia de la DMO en las primeras fases de la ERC, además de correlaciones entre el aumento de los niveles de fósforo y PTH y el empeoramiento de la función renal.

Effects of different dialysis modalities on long-term prognosis after parathyroidectomy in patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis.Methods:Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First People′s Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death.Results:A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group ( n=45), HD group ( n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age ( HR=1.066, 95% CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg ( HR=2.601, 95% CI 1.002-6.752, P=0.049) and increasing IVST ( HR=1.269, 95% CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old ( AUC=0.673, 95% CI 0.545-0.802, P=0.013) and 75.0 months ( AUC=0.654, 95% CI 0.528-0.780, P=0.027) and 13.5 mm ( AUC=0.680, 95% CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95% CI 0.677-0.875, P<0.001). Conclusions:There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Risk factors for hypocalcemia after parathyroidectomy in maintenance hemodialysis patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To explore the risk factors of hypocalcemia and the correlation between calcium supplementation and clinical parameters after parathyroidectomy (PTX) in maintenance hemodialysis patients with secondary hyperparathyroidism (SHPT), and to analyze the effect of calcium supplementation after PTX on the long-term prognosis of patients.Methods:This study was a single-center retrospective study. The patients who underwent PTX in maintenance hemodialysis patients with SHPT in the Huashan Hospital affiliated to Fudan University from October 2014 to March 2021 were retrospectively enrolled. Total PTX with auto transplantation or total PTX alone were the surgical procedures. According to the postoperative requirement of calcium in the first week, the patients were divided into two groups: high calcium supplement (>16.05 g/week) group and low calcium supplement group (≤16.05 g/week). According to the average serum calcium level in the first week after operation, the patients were divided into hypocalcemia group (≤2.1 mmol/L) and non-hypocalcemia group (>2.1 mmol/L) and the differences of clinical parameters between the two groups were compared. The correlation between clinical parameters and the postoperative calcium requirement was examined through Pearson or Spearman correlation analysis. The influencing factors for hypocalcemia after PTX were examined through logistic regression analysis. The survival curve was made by Kaplan-Meier method, and the difference of cumulative survival rate between the two groups was compared by log-rank test.Results:A total of 98 maintenance hemodialysis patients with SHPT were enrolled. The levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) after the operation decreased significantly than those of preoperation (all P<0.05). Multiple linear regression analysis showed age ( β=-0.160, P=0.030), iPTH ( β=0.004, P=0.025) and C-reactive protein ( β=0.186, P=0.011) were correlated with postoperative calcium requirement. Preoperative alkaline phosphatase ( OR=1.002, 95% CI 1.000-1.004, P=0.018) and hemoglobin ( OR=0.977, 95% CI 0.954-1.000, P=0.048) independently predicted the occurrence risk of postoperative hypocalcemia through multivariate logistic regression analysis. The recurrence rate of high calcium supplement group was higher than that of low calcium supplement group (10.26% vs 0, P=0.023) and there was no significant difference in all-cause mortality between the two groups (17.95% vs 5.08%, P=0.086). The recurrence rate between the hypocalcemia group and non-hypocalcemia group was no significantly different (8.3% vs 1.8%, P=0.451) and there was no significant difference in all cause mortality between the two groups (12.5% vs 12.7%, P=1.000). Kaplan-Meier survival curve showed that the cumulative survival rate between the two groups was no significantly different (log-rank test χ2=0.147, P=0.702). Conclusions:PTX is a safe and effective therapeutic method to reduce the level of iPTH and improve the metabolism of calcium and phosphorus in SHPT patients. Age, iPTH and C-reactive protein are correlated with the postoperative requirement of calcium in the first week. Preoperative alkaline phosphatase and hemoglobin are independent risk factors for postoperative hypocalcemia. Correcting preoperative electrolyte disorder, improving infection and anemia can reduce the incidence of hypocalcemia after PTX.

Current status of surgical treatment of secondary hyperparathyroidism / 国际外科学杂志

Secondary hyperparathyroidism (SHPT) is the most common complication of chronic kidney disease. It is usually manifested as a series of symptoms such as bone and joint pain, bone deformity, limb numbness and fatigue, which seriously affect the quality of patients’life. Effective therapeutic interventions are very important to reduce the mortality and morbidity of SHPT patients. For most early stage patients, durg therapy combined with adequate dialysis is very effective for disease control, but as the disease progresses, SHPT will enter the irrevesible stage and patients will become resistant to durg therapy. Surgery is the only effective treatment for advanced SHPT. However, there are still some problems such as different surgical methods, unclear surgical indications, higher perioperative risk and recurrence rate, surgery has not been widely used in clinical treatment. Now the present status of surgery treatment of SHPT is introduced in order to provide reference for the further research and development of surgery treatment.

High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism / Índice tornozelo-braquial elevado prediz eventos e mortalidade cardiovasculares nos pacientes em hemodiálise com hiperparatireoidismo secundário grave

Abstract Introduction: Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population. Methods: We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting. Results: The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019). Conclusion: The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.

Resumo Introdução: A calcificação vascular relacionada ao hiperparatireoidismo secundário (HPTS) grave é uma causa importante de complicações cardiovasculares e ósseas, levando a alta morbidade e mortalidade em pacientes com doença renal crônica (DRC) em hemodiálise (HD). O presente estudo objetivou analisar se o índice tornozelo-braquial (ITB), uma ferramenta diagnóstica não invasiva, pode predizer desfechos cardiovasculares nesta população. Métodos: Selecionamos 88 adultos em HD há pelo menos 6 meses, com PTHi sérico>1.000pg/mL. Coletamos dados clínicos, parâmetros bioquímicos e hormonais, e ITB (sonar-Doppler). A calcificação foi avaliada por radiografia lateral do abdome e por escore de calcificação vascular simples (ECVS). Esta coorte foi monitorada prospectivamente entre 2012 e 2019 para desfechos cardiovasculares (óbito, infarto do miocárdio (IM), acidente vascular cerebral e calcifilaxia) para estimar a precisão do ITB neste cenário. Resultados: Os valores basais foram: PTHi: 1770±689pg/mL, P: 5,8±1,2 mg/dL, Ca corrigido: 9,7±0,8mg/dL, 25(OH)vit D: 25,1±10,9ng/Ml; 65% dos pacientes apresentaram ITB>1,3 (variando de 0,6 a 3,2); 66% tiveram ECVS≥3, e 45% calcificação da aorta (Kauppila≥8). A avaliação prospectiva (51,6±24,0 meses) forneceu os seguintes desfechos cardiovasculares: 11% de óbitos, 17% de IM não fatal, um AVC, 3% de calcifilaxia. Após ajustes, pacientes com ITB≥1,6 tiveram risco 8,9 vezes maior de eventos cardiovasculares (p=0,035), e ITB≥1,8 apresentaram risco 12,2 vezes maior de mortalidade cardiovascular (p=0,019). Conclusão: A presença de calcificações vasculares e rigidez arterial foi altamente prevalente em nossa população. Sugerimos o ITB, uma ferramenta diagnóstica simples e econômica, para ser usada em ambulatório para prever eventos cardiovasculares em pacientes com HPTS grave em HD.

Parathyroid hormone levels after parathyroidectomy for secondary hyperparathyroidism

SUMMARY OBJECTIVE: The parathormone level after parathyroidectomy in dialysis patients are of interest. Low levels may require cryopreserved tissue implantation; however, the resection is necessary in case of recurrence. We analyzed post parathyroidectomy parathormone levels in renal hyperparathyroidism. METHODS: Prospective observation of postoperative parathormone levels over defined periods in a cohort of dialysis patients that underwent total parathyroidectomy and immediate forearm autograft from 2008 to 2010, at a single tertiary care hospital. RESULTS: Of 33 patients, parathormone levels until 36 months could be divided into four patterns. Patients with stable function (Pattern 1) show relatively constant levels after two months (67% of the cases). Early function and later failure (Pattern 2) were an initial function with marked parathormone reduction before one year (18%). Graft recurrence (Pattern 3) showed a progressive increase of parathormone in four cases (12%). Complete graft failure (Pattern 4) was a nonfunctioning implant at any period, which was observed in one patient (3%). Parathormone levels of Pattern 3 became statistically different of Pattern 1 at 36 months. CONCLUSIONS: Patients that underwent the total parathyroidectomy and autograft present four different graft function patterns with a possible varied therapeutic management.

Long-term clinical evaluation on total parathyroidectomy in patients with secondary hyperparathyroidism / 中华普通外科杂志

Objective:To evaluate the safety and long-term effect of total parathyroidectomy in patients with secondary hyperparathyroidism.Methods:One hundred fifty-four patients with secondary hyperparathyroidism who underwent total parathyroidectomy in Zhongshan Hospital,Dalian University from Mar 2012 to Mar 2018 were followed up for 3-9 years,including the level of iPTH, serum calcium and phosphorus and dosing of calcium supplement.Results:Among the 154 patients, the iPTH level in 149 patients fluctuated within 15-60 pg/ml. After oral calcium carbonate, the blood calcium fluctuated in 1.8-2.4 mg/ml, and serum phosphorus was 0.8-1.6 mg/ml. The level of iPTH in 5 patients was between 80-150 pg/ml, which was higher than the normal value 10-70 pg/ml. The clinical symptoms of all patients were significantly relieved.Conclusion:Total parathyroidectomy is safe and reliable in the treatment of secondary hyperparathyroidism with low recurrence rate and stable long-term effect.

Exploration on total parathyroidectomy for secondary hyperparathyroidism / 中华耳鼻咽喉头颈外科杂志

To evaluate the clinical significance of dissection parathyroidectomy for secondary hyperparathyroidism (SHPT) in patients with renal disease on maintenance dialysis. We retrospectively reviewed 195 patients with SHPT treated in the Department of Otolaryngology & Head and Neck Surgery of Beijing Civil Aviation General Hospital between September 2009 and September 2017, including 92 males and 103 females, aged from 23 to 77 years old. There were 167 patients by operated firstly and 28 patients by operated secondly for persistent or recurrent SHPT after operation. All patients received dissection parathyroidectomy with parathyroid autograft in the sternocleidomastoid. The easement of symptoms, the levels of serum intact parathyroid hormone (iPTH), serum-ionized calcium, phosphorus, and hemoglobin were compared before and after operation. Data were analyzed by SPSS 22.0 software. Confirmed by postoperative pathology, a total of 804 hyperplastic parathyroid glands were removed in 195 patients with SHPT. Among them, 765 parathyroid glands were clearly identified and located with naked eye. The anatomic distribution of the glands showed 577 (75.4%) in the tracheoesophageal groove. The incidence of ectopic parathyroid glands was 24.6% (188/765). Other 39 (4.9%) hyperplastic parathyroid glands from 22(11.3%) patients, which were not identified and located with naked eye during operation, were pathologically detected in the dissected tissue specimens. Among 195 patients, 28(14.4%) showed supernumerary parathyroid glands. No serious complications occurred after operation. Within 6 months after the operation, the bone pain and skin itch symptoms were completely relieved and, also, the symptoms of muscle weakness, restless leg, anemia and poor sleep quality were significantly alleviated. Following-up at 6 months after surgery showed the serum levels of iPTH [(70.31±60.12) pg/ml], calium [(2.13±0.22) mmol/L], and phosphorus [(1.17±0.27) mmol/L] decreased significantly respectively compared with the preoperative serum levels of iPTH [(1 501.02±167.26) pg/ml], calium [(2.40±0.32) mmol/L], and phosphorus[(2.27±0.50)mmol/L], all with statistically significant differences (0.01); the levels of hemoglobin [(120.32±10.63) g/L] and hematocrit [(39.20±3.21)%] were higher than the preoperative levels of hemoglobin[(104.11±15.17) g/L] and hematocrit [(31.25±5.12)%], both with statistically significant differences ( valve was 12.22,18,37,respectively, all 0.05). Dissection parathyroidectomy is a beneficial and safe surgical procedure for patients with medically refractory SHPT.

Exploration on total parathyroidectomy for secondary hyperparathyroidism / 中华耳鼻咽喉头颈外科杂志

Objective@#To evaluate the clinical significance of dissection parathyroidectomy for secondary hyperparathyroidism (SHPT) in patients with renal disease on maintenance dialysis.@*Methods@#We retrospectively reviewed 195 patients with SHPT treated in the Department of Otolaryngology & Head and Neck Surgery of Beijing Civil Aviation General Hospital between September 2009 and September 2017, including 92 males and 103 females, aged from 23 to 77 years old. There were 167 patients by operated firstly and 28 patients by operated secondly for persistent or recurrent SHPT after operation. All patients received dissection parathyroidectomy with parathyroid autograft in the sternocleidomastoid. The easement of symptoms, the levels of serum intact parathyroid hormone (iPTH), serum-ionized calcium, phosphorus, and hemoglobin were compared before and after operation. Data were analyzed by SPSS 22.0 software.@*Results@#Confirmed by postoperative pathology, a total of 804 hyperplastic parathyroid glands were removed in 195 patients with SHPT. Among them, 765 parathyroid glands were clearly identified and located with naked eye. The anatomic distribution of the glands showed 577 (75.4%) in the tracheoesophageal groove. The incidence of ectopic parathyroid glands was 24.6% (188/765). Other 39 (4.9%) hyperplastic parathyroid glands from 22(11.3%) patients, which were not identified and located with naked eye during operation, were pathologically detected in the dissected tissue specimens. Among 195 patients, 28(14.4%) showed supernumerary parathyroid glands. No serious complications occurred after operation. Within 6 months after the operation, the bone pain and skin itch symptoms were completely relieved and, also, the symptoms of muscle weakness, restless leg, anemia and poor sleep quality were significantly alleviated. Following-up at 6 months after surgery showed the serum levels of iPTH [(70.31±60.12) pg/ml], calium [(2.13±0.22) mmol/L], and phosphorus [(1.17±0.27) mmol/L] decreased significantly respectively compared with the preoperative serum levels of iPTH [(1 501.02±167.26) pg/ml], calium [(2.40±0.32) mmol/L], and phosphorus[(2.27±0.50)mmol/L], all with statistically significant differences (P<0.01); the levels of hemoglobin [(120.32±10.63) g/L] and hematocrit [(39.20±3.21)%] were higher than the preoperative levels of hemoglobin[(104.11±15.17) g/L] and hematocrit [(31.25±5.12)%], both with statistically significant differences (t valve was 12.22,18,37,respectively, all P<0.05).@*Conclusions@#Dissection parathyroidectomy is a beneficial and safe surgical procedure for patients with medically refractory SHPT.

Clinical efficacy of microwave ablation in treatment of secondary hyperparathyroidism ineligible for surgical resection / 中国介入影像与治疗学

Objective: To observe the efficacy and safety of microwave ablation (MWA) in treatment of secondary hyperparathyroidism (SHPT) ineligible for surgical resection. Methods: Clinical data of 51 patients with SHPT ineligible for surgical resection who underwent MWA were retrospectively analyzed. The maximum diameter of single proliferative nodule, serum intact parathyroid hormone (iPTH), calcium and phosphorus were assessed and compared before and after ablation. The complications, local recurrence rate and new incidence rate were counted during follow-up. Results: Totally 83 parathyroid hyperplasia nodules in 51 SHPT patients were completely ablated at one time. Three, 6 months after MWA and at the end of the follow-up, the maximum diameter of single proliferative nodule was all smaller than that before MWA (all P<0.05), and serum iPTH, calcium, and phosphorus levels were all lower than that before MWA (all P<0.05). During follow-up, 9 patients (9/51, 17.65%) had minor complications related to MWA, while no serious complication occurred. At the end of follow-up, the local recurrence rate was 5.88% (3/51) and the new incidence rate was 7.84% (4/51). Conclusion: MWA is safe and effective in treatment of SHPT ineligible for surgical resection.

Safety and efficacy of modified liquid isolation method in microwave ablation in treatment of secondary hyperparathyroidism / 中国介入影像与治疗学

Objective: To observe the safety and efficacy of modified liquid isolation method during ultrasound-guided microwave ablation in treatment of secondary hyperparathyroidism (SHPT). Methods: Clinical data of 82 SHPT patients who underwent ultrasound-guided microwave ablation were retrospectively analyzed. Among them, 41 cases adopted improved liquid isolation method (observation group), while the other 41 cases received traditional liquid isolation method (control group). Unit volume ablation time, serum intact parathyroid hormone (iPTH), iPTH change rate and serum calcium before and 7 days after operation, the incidence and recovery rate of recurrent laryngeal nerve injury during and 6 months after operation were compared between the two groups. Results: There was no significant difference of unit volume ablation time, serum iPTH, iPTH change rate nor serum calcium level before and 7 days after operation between the two groups (all P>0.05). The incidence of recurrent laryngeal nerve injury in observation group during and 6 months after operation was 14.63% (6/41), lower than that of control group (43.90%[18/41], P=0.004). Six months after operation, all 6 patients (6/6, 100%) with recurrent laryngeal nerve injury in observation group and 13 patients (13/18, 72.22%) in control group recovered (P=0.003). Conclusion: Modified liquid isolation microwave ablation can effectively treat SHPT and reduce recurrent laryngeal nerve injury.

Ultrasound-guided microwave ablation of secondary hyperparathyroidism after renal transplantation / 中国介入影像与治疗学

Objective: To observe the safety and efficacy of ultrasound-guided microwave ablation (MWA) for treatment of patients with secondary hyperparathyroidism (SHPT) after renal transplantation (RT). Methods: Data of 20 SHPT patients after RT who underwent MWA were retrospectively analyzed. The level of intact parathyroid hormone (iPTH), serum calcium, serum phosphorus, creatinine and blood urea nitrogen concentrations before and after MWA were assessed and compared. Results: Complete ablation was achieved in a total of 34 parathyroid nodules among 20 SHPT patients. The mean maximum diameter of parathyroid nodule was (1.41±0.61)cm, and the median ablation time was 219 s. The mean iPTH, serum calcium and phosphorus concentrations after MWA were significantly lower than those before MWA (P0.05). No major operation-related complication occurred in 20 patients. Conclusion: Ultrasound-guided MWA is a safe and effective method for treating SHPT after RT.

Brain white matter changes and correlations with cognition in end-stage renal disease patients with secondary hyperparathyroidism based on local diffusion homogeneity values / 中国医学影像技术

Objective: To investigate the changes of white matter in patients of end-stage renal disease (ESRD) with secondary hyperparathyroidism (SHPT) by using local diffusion homogeneity (LDH). Methods: Fifty patients diagnosed as ESRD and underwent hemodialysis were selected. According to whether with SHPT or not, the patients were divided into SHPT group and non-SHPT group (each n=25). The cognitive function was evaluated with Montreal cognitive assessment (MoCA). Then MR plain scan was performed. The LDH value of white matter fiber in the whole brain were compared between 2 groups based on voxel. Results: Compared with non-SHPT group, SHPT group showed diffuse and symmetrical LDH decreased area in bilateral cerebral hemispheres, and in the focal right cerebellar hemispheres (all P0.05). Conclusion: LDH value can provide information of the white matter's LDH in ESRD patients with SHPT, and the changes are related to cognition and clinical indicators.

Granuloma Periférico de Células Gigantes e Hiperparatiroidismo. Presentación de un Caso / Peripheral Giant Cell Granuloma and Hyperparathyroidism. Case Report

RESUMEN: Se presenta el caso de un paciente sexo femenino 31 años, insuficienciente renal crónica en hemodiálisis, hipertensa secundaria, consulta por aumento de volumen oral en relación a encía marginal vestibular izquierda, 6 meses de evolución. Al examen se observa aumento de volumen de 15 mm en relación a piezas. 3.6 y 3.7. Radiografía muestra compromiso periodontal pieza 3.7. Se realiza biopsia excisional y exodoncia pieza 3.7. Histopatología informa granuloma periférico de células gigantes. Se solicitan exámenes de laboratorio para estudio de hiperparatiroidismo (PTH elevada, calcemia fosfatemia normales). Evoluciona favorablemente. Sin signos de recidiva a los 3 meses. El diagnóstico histopatológico de lesión de células gigantes debe ser complementado con la clínica, exámenes de laboratorio e imagenología, el objetivo final es definir si tal diagnóstico corresponde a un tumor pardo, a un granuloma central de células gigantes o a un granuloma periférico de células gigantes. En la literatura los reportes de asociación entre granuloma periférico de células gigantes e hiperparatiroidismo son escasos. Este caso corresponde a granuloma periférico células gigantes, asociado a hipersecreción de paratohormona.

ABSTRACT: A 31-year-old female patient with chronic renal insufficiency in hemodialysis and secondary hypertension consulted due to an enlarging intraoral lesion in relation to the left marginal vestibular gingival, with 6 months of evolution. A 15mm mass in relation to mandibular left molars was noted. Radiograph showed periodontal involvement of mandibular left second molar. Excisional biopsy and tooth 3.7 extraction were performed. Histopathology reported a peripheral giant cell granuloma. Laboratory tests were requested for suspected hyperparathyroidism (aiding in the diagnosis) (high PTH, normal phosphatemia and calcemia). Evolution was favorable, without signs of reappearance after 3 months. The histopathological diagnosis of giant cell lesions should be complemented with clinical, laboratory and imaging tests. The final objective is to make the differential diagnosis between brown tumor, central giant cell granuloma and peripheral giant cell granuloma because the treatment varies considerably. There are few reports in the literature about the association between peripheral giant cell granuloma and hyperparathyroidism. This case corresponds to peripheral giant cell granuloma, possibly associated with parathormone hypersecretion.

The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism / Impacto de cinacalcete em marcadores do metabolismo mineral de pacientes em diálise portadores de hiperparatireoidismo secundário grave

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

Resumo Introdução: O tratamento do hiperparatireoidismo secundário (HPTs), patologia comum e associada à mortalidade na doença renal crônica, é um desafio para o nefrologista. Advento dos calcimiméticos propiciou terapêutica medicamentosa diferente da usual, baseada em quelantes de fósforo e vitamina D ativa. O objetivo deste estudo foi avaliar segurança e efetividade de cinacalcete no controle do HPTs grave de pacientes em diálise crônica. Métodos: Estudo retrospectivo 26 pacientes [idade: 52 ± 12 anos; 55% mulheres; tempo em diálise: 54 (4-236) meses], em hemodiálise (N = 18) ou diálise peritoneal (N = 8), com HPTs grave (nível de paratormônio intacto (PTHi) > 600 pg/mL), com hiperfosfatemia e/ou hipercalcemia persistentes, em tratamento com cinacalcete. Período de seguimento de 12 meses. Avaliados níveis séricos de cálcio (Ca), fósforo (P), fosfatase alcalina (FA) e PTHi no início do seguimento, 30, 60, 90, 180 e 365 dias. Resultados: Indicações para início do cinacalcete: hiperfosfatemia (57,7%), hipercalcemia (23%), ou ambos (19,3%) com PTH > 600 pg/mL. Ao final do seguimento, observada redução dos níveis PTHi (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0,001), Ca (9,5 ± 1,0 vs. 9,1 ± 0,6 mg/dl; p = 0,004), P (6,0 ± 1,3 vs. 4,9 ± 1,1 mg/dl; p < 0,001) e FA (202 ± 135 vs. 155 ± 109 UI/L; p = 0,006). Eventos adversos: hipocalcemia (26%) e queixas digestivas (23%). No fim do estudo, 73% pacientes utilizavam vitamina D ativada associada ao cinacalcete. Três (11,5%) pacientes, todos em DP, não responderam ao cinacalcete, mantendo níveis PTHi > 800 pg/mL. Conclusão: Utilização de cinacalcete, associado à terapia tradicional, em pacientes com HPTs grave foi segura, eficiente e associada a melhor controle do metabolismo mineral.

Uremic lion face syndrome / Face Leonina na Síndrome Urêmica

Abstract Mineral bone disorder is a common feature of chronic kidney disease. Lion face syndrome is rare complication of severe hyperparathyroidism in end-stage renal disease patients, which has been less commonly reported due to dialysis and medical treatment advances in the last decade. The early recognition of the characteristic facial deformity is crucial to prompt management and prevent severe disfigurement. The authors present a rare case of severe hyperparathyroidism presenting with lion face syndrome and bone fractures.

Resumo O distúrbio mineral e ósseo é uma característica comum da doença renal crônica. A síndrome da face leonina é uma complicação rara do hiperparatireoidismo grave em pacientes com doença renal terminal, que tem sido menos relatada devido aos avanços na diálise e tratamento médico na última década. O reconhecimento precoce da deformidade facial característica é crucial para estimular o tratamento precoce e prevenir a desfiguração severa. Os autores apresentam um caso raro de hiperparatireoidismo grave, apresentando síndrome da face leonina e fraturas ósseas.