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.

Resumo Introdução: Alguns autores aconselham a favor de se fazer uma amostragem tardia de teste de paratormônio intraoperatório (PTHIO) durante paratireoidectomia em pacientes transplantados renais e em diálise. O objetivo do presente estudo foi avaliar a intensidade e o papel da amostragem tardia na interpretação do PTHIO durante paratireoidectomia em pacientes em diálise (2HPT) e pacientes com transplante renal bem sucedido (3HPT) em comparação com aqueles em pacientes com adenoma único de paratireoide (1HPT). Métodos: Este foi um estudo retrospectivo dos perfis de PTHIO em pacientes com 1HPT, 2HPT, e 3HPT operados em uma única instituição. Foram coletadas amostras de PTHIO basal (amostragem no início da operação), PTHIO-10 min (10 minutos após a excisão das glândulas paratireoides), e PTHIO-15 min (15 minutos após a excisão das glândulas paratireoides). Os valores foram comparados aos resultados basais. Resultados: Os valores percentuais medianos do PTHIO em comparação aos basais (100%) foram os seguintes: 1HPT, PTHIO-10 min = 20% e PTHIO-15 min = 16%; 2HPT, PTHIO-10 min = 14% e PTHIO-15 min = 12%; 3HPT, PTHIO-10 min = 18% e PTHIO-15 min = 15%. Discussão: A redução foi igualmente eficaz aos 10 minutos em todos os grupos. Em casos de sucesso, o PTHIO diminui satisfatoriamente 10 minutos após a excisão das glândulas paratireoides em pacientes em diálise e transplantados, apesar das diferenças significativas na função renal. A amostragem tardia de PTHIO parece ser desnecessária.

Abstract Introduction: Some authors advise in favor of delayed sampling of intraoperative parathormone testing (ioPTH) during parathyroidectomy in dialysis and kidney-transplanted patients. The aim of the present study was to evaluate the intensity and the role of delayed sampling in the interpretation of ioPTH during parathyroidectomy in dialysis patients (2HPT) and successful kidney-transplanted patients (3HPT) compared to those in single parathyroid adenoma patients (1HPT). Methods: This was a retrospective study of ioPTH profiles in patients with 1HPT, 2HPT, and 3HPT operated on in a single institution. Samples were taken at baseline ioPTH (sampling at the beginning of the operation), ioPTH-10 min (10 minutes after excision of the parathyroid glands), and ioPTH-15 min (15 minutes after excision of the parathyroid glands). The values were compared to baseline. Results: Median percentage values of ioPTH compared to baseline (100%) were as follows: 1HPT, ioPTH-10 min = 20% and ioPTH-15 min = 16%; 2HPT, ioPTH-10 min = 14% and ioPTH-15 min = 12%; 3HPT, ioPTH-10 min = 18% and ioPTH-15 min = 15%. Discussion: The reduction was equally effective at 10 minutes in all groups. In successful cases, ioPTH decreases satisfactorily 10 minutes after parathyroid glands excision in dialysis and transplanted patients, despite significant differences in kidney function. The postponed sampling of ioPTH appears to be unnecessary.

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.

RESUMO Objetivo: analisar as frequências de hipoparatireoidismo e de recidiva do hiperparatireoidismo após paratireoidectomia em pacientes dialíticos de acordo com diferentes classificações existentes. Métodos: estudo retrospectivo de 107 pacientes dialíticos consecutivamente submetidos à paratireoidectomia total com autoenxerto imediato em um hospital terciário no período de 2006 a 2010. A variação dos níveis de PTH no pós-operatório foi estudada ao longo do tempo. Os pacientes foram agrupados de acordo com diferentes metas de níveis de PTH recomendados de acordo com o método de dosagem e pelas sociedades de nefrologia americana, japonesa e de um consórcio internacional de especialistas. Resultados: após a paratireoidectomia, houve redução sustentada da calcemia e fosfatemia. O valor mediano do PTH reduziu-se de 1904pg/ml para 55pg/ml, em 12 meses. Dependendo do nível alvo considerado, a proporção de pacientes abaixo da meta variou entre 17% e 87%. Ao contrário, a proporção de pacientes com níveis acima da meta variou de 3% a 37%. Conclusão: O emprego de diferentes recomendações de níveis de PTH em pacientes dialíticos após paratireoidectomia pode levar a classificações incorretas de hipoparatireoidismo ou hiperparatireoidismo recidivado e implicar em condutas terapêuticas discordantes.

ABSTRACT Objective: to analyze the frequency of hypoparathyroidism and of its recurrence after parathyroidectomy in dialysis patients according to different existing classifications. Methods: we conducted a retrospective study of 107 consecutive dialysis patients undergoing total parathyroidectomy with immediate autograft in a tertiary hospital from 2006 to 2010. We studied the changes in PTH levels in the postoperative period over time. Were grouped patients according to different PTH levels targets recommended according to the dosage method and by the American and Japanese Nephrology Societies, and by an International Experts Consortium. Results: after parathyroidectomy, there was sustained reduction in serum calcium and phosphatemia. The median value of PTH decreased from 1904pg/ml to 55pg/ml in 12 months. Depending on the considered target level, the proportion of patients below the target ranged between 17% and 87%. On the other hand, the proportion of patients with levels above the target ranged from 3% to 37%. Conclusion: the application of different recommendations for PTH levels after parathyroidectomy in dialysis patients may lead to incorrect classifications of hypoparathyroidism or recurrent hyperparathyroidism and resultin discordant therapeutic conducts.

Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.

INTRODUCTION: Kidney transplantation corrects endocrine imbalances. Nevertheless, these early favorable events are not always followed by rapid normalization of parathyroid hormone secretion. A possible deleterious effect of parathyroidectomy on kidney transplant function has been reported. This study aimed to compare acute and longterm renal changes after total parathyroidectomy with those occurring after general surgery. MATERIALS AND METHODS: This was a retrospective case-controlled study. Nineteen patients with persistent hyperparathyroidism underwent parathyroidectomy due to hypercalcemia. The control group included 19 patients undergoing various general and urological operations. RESULTS: In the parathyroidectomy group, a significant increase in serum creatinine from 1.58 to 2.29 mg/dl (P < 0.05) was noted within the first 5 days after parathyroidectomy. In the control group, a statistically insignificant increase in serum creatinine from 1.49 to 1.65 mg/dl occurred over the same time period. The long-term mean serum creatinine level was not statistically different from baseline either in the parathyroidectomy group (final follow-up creatinine = 1.91 mg/dL) or in the non-parathyroidectomy group (final follow-up creatinine = 1.72 mg/dL). CONCLUSION: Although renal function deteriorates in the acute period following parathyroidectomy, long-term stabilization occurs, with renal function similar to both preoperative function and to a control group of kidney-transplanted patients who underwent other general surgical operations by the final follow up.

OBJETIVOS: Realizar rastreamentos clínico e gênico para Neoplasia Endócrina Múltipla tipo 1 (NEM1) e analisar seu impacto no seguimento clínico desses pacientes no Hospital das Clínicas, SP. MÉTODOS: O diagnóstico clínico de NEM1 foi realizado de acordo com o Consenso sobre neoplasias endócrinas múltiplas. A análise genética para identificação de mutações foi realizada por sequenciamento automático de todas as regiões codificadoras e fronteiras exon/intron do gene MEN1. Os casos afetados foram sub-divididos em 3 grupos e analisados separadamente: casos-índices (grupo I), familiares diagnosticados clinicamente (grupo II) e genicamente (grupo III). RESULTADOS: Um total de 154 casos participou desse estudo, sendo 52 diagnosticados com NEM1: 13 do grupo I, 28 do grupo II e 11 do grupo III. A idade média ao diagnóstico no grupo III (27 anos) foi significativamente menor que a dos grupos I (39,5 anos; p = 0,03) e II (42,4 anos; p = 0,01). A maioria dos pacientes dos grupos I e II apresentou 2 ou 3 tumores, enquanto que 81,8% dos casos do grupo III apresentavam 1 ou nenhum tumor relacionado à NEM1. Além disto, 45,4% dos casos do grupo III eram assintomáticos, não sendo observados nenhuma metástase ou óbito. Os demais 102 familiares sob-risco estudados não herdaram mutação MEN1 e foram excluídos do rastreamento clínico. Um caso de fenocópia NEM1 foi também localizado. DISCUSSÃO: Nossos dados demonstraram importantes benefícios no seguimento dos pacientes NEM1, obtidos pela implementação dos rastreamentos clínico e gênico para essa doença.

PURPOSE: To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. METHODS: The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS: In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION: Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.

CONTEXTO E OBJETIVO: A abordagem adequada do carcinoma de paratireóide parece relacionada à capacidade de identificação pelo cirurgião na primeira operação. O objetivo do estudo foi avaliar o papel da suspeita clínica pré-operatória na abordagem do carcinoma de paratireóide. TIPO DE ESTUDO E LOCAL: Análise retrospectiva realizada no Departamento de Cirurgia de Cabeça e Pescoço, da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil. MÉTODOS: De 1995 a 2000, 143 pacientes foram operados por hiperparatireoidismo. Esses casos foram revistos para verificar se a suspeita clínica pré e intra-operatória de carcinoma de paratireóide foi útil para a realização de operação mais extensa e quais fatores melhor se relacionaram com a suspeita de carcinoma. RESULTADOS: Entre 66 casos de hiperparatireoidismo primário, houve quatro casos de carcinoma de paratireóide (6,1%), e um caso foi encontrado em hiperparatireoidismo secundário (1,3%). Nódulos palpáveis foram observados em cinco pacientes com hiperparatireoidismo primário, quatro deles com carcinoma de paratireóide. Os níveis pré-operatórios da calcemia nos casos de carcinoma de paratireóide de hiperparatireoidismo primário variaram entre 12,0 mg/dl e 18,2 mg/dl. Em dois pacientes, o tumor tinha invasão macroscópica de estruturas adjacentes. Com exceção de um caso, com doença extensa, houve ressecção completa em monobloco dos tumores. No hiperparatireoidismo secundário, o carcinoma de paratireóide foi identificado numa quinta glândula mediastinal. Houve um caso de adenoma atípico. CONCLUSÕES: O nível de calcemia muito elevado, o tumor palpável e a aderência a estruturas próximas são comuns no carcinoma de paratireóide. Esses sinais clínicos podem ser úteis na tomada de decisão nas operações sobre a glândula paratireóide.

CONTEXT AND OBJECTIVE: Adequate management of parathyroid carcinoma apparently relates to the surgeon’s ability to identify it at the first operation. The objective of this paper was to evaluate the role of clinical suspicion in the management of parathyroid carcinoma. DESIGN AND SETTING: Retrospective analysis of parathyroid carcinoma patients treated in Department of Head and Neck Surgery, Faculdade de Medicina da Universidade de São Paulo. METHODS: Cross-sectional study of 143 patients who underwent surgery from 1995 to 2000, due to hyperparathyroidism. These cases were reviewed to ascertain whether preoperative and intraoperative suspicion of parathyroid carcinoma were helpful during the operation, and which factors demonstrated the suspicion of cancer best. RESULTS: Among 66 patients with primary hyperparathyroidism there were four cases of parathyroid carcinoma (6.1%), and one case was found in secondary hyperparathyroidism (1.3%). Palpable nodules were found in five patients with primary hyperparathyroidism, four of them with parathyroid carcinoma. Preoperative levels of calcium in primary hyperparathyroidism with cancer patients varied from 12.0 mg/dl to 18.2 mg/dl. Two patients had gross macroscopic spread of the tumor to adjacent structures. Except for one patient, with extensive disease, tumors were resected en bloc. In secondary hyperparathyroidism, parathyroid carcinoma was found in a fifth mediastinal gland. One atypical adenoma was observed. CONCLUSIONS: High levels of calcium, palpable tumors and adherence to close structures are more common in parathyroid carcinoma. These clinical signs may be helpful for decision-making during parathyroid surgery.