El hiperparatiroidismo secundario es un factor de riesgo asociado con la sobrevida del injerto en pacientes pediátricos con trasplante renal: Un estudio de centro único / Secondary hyperparathyroidism is a risk factor associated with graft survival in pediatric patients with renal transplantation: A single-center study

Introducción: El trasplante renal en pediatría constituye el tratamiento de elección para la enfermedad renal crónica terminal (ERCT) con ventajas ampliamente comprobadas sobre los tratamientos dialíticos. El objetivo del presente estudio fue determinar los factores de riesgo relacionados con la sobrevida global y del injerto en un grupo de pacientes pediátricos con trasplante renal atendidos en un hospital de referencia nacional con observación de factores asociados al hiperparatiroidismo secundario. Métodos: En el presente estudio observacional, retrospectivo, se realizó en el Hospital Metropolitano de Quito - Ecuador desde el primero de enero del 2010 al treinta de junio del 2013. Se registró la mortalidad y la supervivencia del injerto, presencia de hiperparatiroidismo pre trasplante, variables demográficas, clínicas (compatibilidad). Se usa el método de Kaplan Meier para el análisis y se presentan riesgos relativos. Resultados: Ingresaron al estudio 33 pacientes, de edad 12±3.8 años. Donante cadavérico 21 casos (63.6%), donante vivo 12 pacientes 36.4%. 18 hombres (54.5%). La etiología de la ERCT fue indeterminada en 63.6%; nefropatías en 24.2% y uropatías en 12.1%. Rechazo agudo 1 paciente, rechazo tardío 10 pacientes. Las variables con significancia en la sobrevida del injerto fueron: hiperparatiroidismo RR= 6.0 (IC95%= 1.078-45.902) P=0.032. No recibir inmunosupresión completa RR=14.5 (IC95%= 3.807-55.225) P<0.001. La necesidad de diálisis pos trasplante la primera semana y biopsia temprana tuvieron RR=15 (IC95%= 3.9-57.2). Conclusiones: Este estudio demostró que el hiperparatiroidismo secundario es un factor de riesgo negativo para la sobrevida del injerto renal en pacientes pediátricos trasplantados

Introduction: Kidney transplantation in pediatrics is the treatment of choice for end-stage renal disease (ESRD) with widely proven advantages over dialysis treatments. The aim of the present study was to determine the risk factors related to global and graft survival in a group of pediatric kidney transplant patients treated at a national referral hospital with observation of factors associated with secondary hyperparathyroidism. Methods: In the present observational, retrospective study, it was carried out in the Hospital Metropolitano de Quito - Ecuador from January 1, 2010 to June 30, 2013. Mortality and graft survival, presence of hyperparathyroidism pre transplantation, demographic and clinical variables (compatibility). The Kaplan Meier method is used for analysis and relative risks are presented. Results: 33 patients, aged 12 ± 3.8 years, entered the study. Cadaveric donor 21 cases (63.6%), living donor 12 patients 36.4%. 18 men (54.5%). The etiology of ESRD was indeterminate in 63.6%; nephropathies in 24.2% and uropathies in 12.1%. Acute rejection 1 patient, late rejection 10 patients. Variables with significance in graft survival were: hyperparathyroidism RR = 6.0 (95% CI = 1.078-45.902) P = 0.032. Not receiving complete immunosuppression RR = 14.5 (95% CI = 3.807-55.225) P <0.001. The need for post-transplant dialysis the first week and early biopsy had RR = 15 (95% CI = 3.9-57.2). Conclusions: This study demonstrated that secondary hyperparathyroidism is a negative risk factor for kidney graft survival in pediatric transplant patients.

Parathyroid hemangioma

Background Hemangiomas are benign neoplasms of capillary proliferation that arise from a developmental anomaly where angioblastic mesenchyme fails to form canals. Most hemangiomas arise in the head and neck region, either superficially in the skin or deeper within endocrine organs such as the parotid gland. Parathyroid hemangiomas, however, are extremely rare, with only five cases previously reported in the literature. Case presentation Herein, we present a case of a 68-year-old man with a hemangioma almost completely replacing the right upper parathyroid gland, grossly measuring 1.3 × 1.3 × 1.2 cm and weighing 700 mg, associated with primary hyperparathyroidism. Conclusions Parathyroid gland enlargement due to vascular neoplasms such as hemangiomas can mimic, both clinically and radiographically, hyperplasias and/or adenomas. Surgeons need to be aware of the presence of this entity and should consider it in the differential diagnosis of hyperparathyroidism or parathyroid gland enlargement.

Determinação de valores próprios de referência para vitamina D, hormônio paratireoideo e cálcio em um laboratório de análises clínicas / Determination of proper reference intervals for vitamin D, parathyroid hormone and calcium in a clinical laboratory

OBJETIVOS: Determinar os valores próprios de referência para vitamina D, hormônio paratireoideo (PTH) e cálcio em um laboratório de análises clínicas. MÉTODOS: Foi realizado um estudo transversal retrospectivo nas unidades do Laboratório Alfa Ltda., localizado em Caxias do Sul, na região serrana do Rio Grande do Sul. A amostra incluiu clientes e funcionários do laboratório, que se autodeclaravam saudáveis. O estudo foi baseado em dois métodos de pesquisa (direto e indireto) propostos pelo Clinical & Laboratory Standards Institute para a determinação de VR próprios de um laboratório. O método direto (MD) envolveu aplicação de questionário, coleta e análise de amostras de sangue e o método indireto (MI) consistiu em análise de banco de dados. RESULTADOS: No MD foram avaliados resultados de 241 indivíduos, sendo 120 do gênero feminino. A média de idade dos participantes foi de 33,8±10,6 anos. O MI resultou em 5.485 valores para as dosagens de vitamina D, 191 para o PTH e 856 para o cálcio. A média de idade dos indivíduos foi de 45,0±15,6 anos, 49,0±15,3 anos e 48,87±15,41 anos, respectivamente. Os valores de referência próprios obtidos pelo MD foram estatisticamente iguais aos do MI para as três dosagens. Quando comparados os valores de referência obtidos com os disponibilizados pelo fabricante, a vitamina D resultou em uma faixa mais baixa de normalidade (fabricante: >30 ng/mL; MD: 10-47 ng/mL; MI: 11-46 ng/mL), o PTH em uma faixa maior (fabricante: 15-68,3 ng/mL; MD: 19,2-81,6 ng/mL; MI: 26,1-94,3 ng/mL) e o cálcio apresentou valores muito próximos (fabricante: 8,3-10,6 ng/mL; MD: 8,3-10,2 ng/mL; MI: 8,2-10,1 ng/mL). Houve diferença estatística entre os valores de referência estabelecidos para vitamina D e cálcio entre os gêneros. CONCLUSÕES: Tanto o MD quanto o MI foram eficientes para a determinação de valores de referência. Os valores de referência estabelecidos no estudo, especificamente para a vitamina D e o PTH, foram diferentes dos sugeridos nas instruções do fabricante, o que reforça a recomendação de estabelecimento de valores de referência próprios para cada laboratório.

AIMS: To determine the proper reference intervals for vitamin D, parathyroid hormone (PTH) and calcium in a clinical laboratory. METHODS: A retrospective cross-sectional study was carried out at the units of Alfa Ltda. Laboratory, located in Caxias do Sul, in the mountain region of Rio Grande do Sul. The sample included self-declared healthy clients and laboratory workers. The study was based on two research methods (direct and indirect) proposed by the Clinical & Laboratory Standards Institute for the establishment of proper reference intervals for a specific laboratory. The direct method (DM) involved questionnaire application, collection and analysis of blood samples and the indirect method (IM) consisted of database analysis. RESULTS: Results of 241 individuals were evaluated in the DM, of which 120 were female. The mean age of participants was 33.8±10.6 years. IM resulted in 5,485 values for vitamin D, 191 for PTH, and 856 for calcium. The mean age of the individuals was 45.0±15.6 years, 49.0±15.3 years and 48.87±15.41 years, respectively. The proper reference intervals obtained by the DM were statistically equal to those of the IM for the three dosages. When comparing the reference intervals obtained with those available in the manufacturer report, vitamin D resulted in a lower range of normality (report: >30 ng/mL; MD: 10-47 ng/mL; MI: 11-46 ng/mL), PTH in a higher range (report: 15-68.3 ng/mL; MD: 19.2-81.6 ng/mL; MI: 26.1-94.3 ng/mL), and calcium presented very close values (report: 8.3-10.6 ng/mL; MD: 8.3-10.2 ng/mL; MI: 8.2-10.1 ng/mL). There was a statistical difference between the reference intervals established for vitamin D and calcium between genders. CONCLUSIONS: Both MD and MI were efficient for the determination of proper reference intervals. The reference intervals established in the study, specifically for vitamin D and PTH, were different from those suggested in the manufacturer's package insert, which reinforces the recommendation of establishing proper reference intervals for each laboratory.

Estudio para determinar los niveles de calcio y paratohormona en pacientes con y sin vaciamiento central profiláctico, con diagnóstico de cáncer papilar de tiroides / Study to determine calcium and parathyroid hormone levels in patients with and without prophylactic central emptying, with diagnosis of papillary thyroid cancer

Contexto: El cáncer papilar de tiroides representa una patología que va en aumento, y el manejo quirúrgico es complejo. Una disección profiláctica cervical central para los pacientes con cáncer papilar de tiroides es controvertida. Dado que los riesgos de complicaciones transitorias probablemente son altas, y los beneficios parecen ser pequeños, de tal forma, que para realizarlo se utiliza un enfoque selectivo, en función de factores de riesgo del paciente y el nivel de experiencia del cirujano. Objetivo: determinar en el postquirúrgico los niveles de calcio y paratohormona en pacientes adultos, de ambos sexos con sospecha alta de cáncer papilar de tiroides, a los cuales se les realizó o no, vaciamiento central en los hospital Eugenio Espejo de la ciudad de Quito, durante un año. Sujetos y métodos: observacional, analítico, epidemiológico transversal, de cohortes. Se estudiaron todos los pacientes con sospecha citológica de cáncer papilar de tiroides, sometidos a tiroidectomía total, con o sin vaciamiento central profiláctico; se midió a las 24 horas los niveles de calcio y paratohormona. Las variables cuantitativas se reportaron como promedios y las cualitativas con sus valores absolutos y relativos. Las comparaciones de variables cuantitativas se realizaron con la prueba t-Student, mientras que para las cualitativas se usaron pruebas de independencia para proporciones x2 y prueba exacta de Fisher. Se hizo un análisis multivariados con regresión logística reportada como Odds Ratios ajustados (ORadj). Resultados: con respecto al calcio el grupo con vaciamiento central presentó valores significativamente menores que el grupo sin vaciamiento, esta diferencia fue de -0.07 mmol/L (IC 95 %: -0.036, -0.097 mmol/L;p < 0.0001). Los pacientes sometidos a vaciamiento central tuvieron tasas significativamente menores de paratohormona (para valores inferiores a los 10pg/ml) hasta el 53.9%, mientras que en el grupo sin vaciamiento solo el 11.1%(IC 95%: 29.5, 56.2%; p < 0.0001). Conclusión: se observó que en el grupo de tiroidectomía con vaciamiento central profiláctico, hubo una tasa importante de hipocalcemia e hipoparatiroidismo, todos estos pacientes presentaron signos de hipocalcemia durante su periodo postquirúrgico, lo que prolongo su estadía hospitalaria, (AU)

Introduction: Papillary thyroid cancer is on the rise and surgical treatment is complex. Prophylactic central neck dissection for papillary thyroid cancer patients is controversial because of the possibility of higher risk of transient complications and the benefits of the surgery are low. As a result, the surgery is performed based of the risk factors of the patient and the experience of the surgeon. Objective: to determine the levels of calcium and parathyroid hormone post-surgery in adult male and female patients with suspected risk of papillary thyroid cancer, to who prophylactic central drainage, was and was not performed. Subjects and methods: this is an epidemiological, observational, analytic, cross-sectional, of cohorts. The research will be done on all patients suspected of cytological papillary thyroid cancer in Hospital Eugenio Espejo, and who underwent total thyroidectomy with and without prophylactic central drainage. Calcium and parathyroid hormone levels will be checked 24 hours post-surgery. The quantitative variables will be reported as averages and the qualitative variables as absolute and relative data. t-Student test was used to compare qualitative data. Qualitative data was compared using independent test with scales of x2 and the Fisher exact test. A logistic regression analysis was done and reported as Adjusted Odds ratios (AOR). Results: calcium level on the group with central drainage had significant lower levels compare to the group without central drainage, the difference was of -0.07 mmol/L (IC 95 %: -0.036, -0.097 mmol/L; p<0.0001). The patients with central drainage had significantly lower levels of parathyroid hormone (levels lower than 10pg/ml) up to 53.9%; while the group without central drainage only had 11.1% %(IC 95%: 29.5, 56.2%; p < 0.0001). Conclusion: though the study the thyroidectomy with prophylactic central drainage group had a significant rate of hypocalcemia and hypoparathyroidism. These patients had symptoms of hypocalcemia post-surgery, which prolong their hospital stay. (AU)

Incidentalomas paratiroideos: un nuevo diagnóstico, un nuevo problema. Prevalencia en Argentina / Parathyroid incidentaloma: a new diagnosis, a new problem. Prevalence in Argentina

Los incidentalomas paratiroideos (IP) fueron descriptos como hallazgos intraquirúrgicos y luego en estudios ecográficos de tiroides. Escasos estudios se han realizado, por lo que su incidencia no es clara. Más aún, la presencia de una imagen hipoecogénica en topografía paratiroidea puede también ser tejido tiroideo o linfático. Se evaluaron retrospectivamente las historias clínicas de 7 años buscando los pacientes en los que se diagnosticó un IP durante una ecografía tiroidea. Se diagnosticó IP en 24 pacientes (4,0% del total). Tenían hipotiroidismo autoinmune 21 pacientes y nódulos tiroideos 3 pacientes. En 10 casos la lesión fue única y en 14 eran 2 o más. En la evolución se repitió la ecografía en 13 pacientes, hallando imágenes similares a la primera en todas. La calcemia y la PTH fueron normales en 23 pacientes, pero en una de ellas, con una imagen de 6 mm, hubo PTH levemente elevada con calcemia normal, que luego se elevó, y se diagnosticó adenoma paratiroideo. El hallazgo de IP parece cada vez más frecuente; nuestra incidencia del 4% como imágenes compatibles (sin confirmar la naturaleza paratiroidea) es más alta que las escasas publicaciones existentes sobre el tema. Es posible que muchas no presenten cambios ni ecográficos ni de laboratorio, pero otros casos, como el hallado en una de nuestras 24 pacientes, pueden ser un estadio inicial de hiperparatiroidismo primario, por lo que el seguimiento es aconsejable.

Parathyroid incidentalomas (PI) were first described as intraoperative findings and then in ultrasound thyroid scan studies. Few studies have been performed to investigate this, so their incidence is unclear. Moreover, the presence of a hypo-echogenic image in parathy- roid topography may also be thyroid or lymphatic tissue. A retrospective evaluation was performed on the seven-year clinical records of patients in whom a PI was diagnosed during a thyroid ultrasound scan. PI was diagnosed in 24 patients (4.0%). Twenty one patients had autoimmune hypothyroidism and 3 patients had thyroid nodules. In 10 cases the lesion was unique, and in 14 cases there were two or more lesions. During follow-up, ultrasound was repeated in 13 patients, and all showe findings. Serum calcium and PTH were normal in 23 patients, but in one of them, with an image of a lesion of 6 mm, PTH was slightly elevated, with normal serum calcium. Later, hypercalcaemia was detected and a parathyroid adenoma was diagnosed. The incidence of PI seems to be increasing, with our rate of 4% of compatible images (without confirming the parathyroid origin of the lesion) is higher than that reported in the few existing publications on the subject. Many patients with PI may not present with biochemical abnormalities, but as our experience shows, these lesions may represent the first stage of primary hyperparathyroidism; therefore careful follow-up is advisable.

A rare case of a parathyroid adenoma inside a parathyroid cyst / Um caso raro de adenoma de paratireoide em um cisto de paratireoide

Parathyroid cysts (PCs) are rare lesions, located in the neck and anterior mediastinal region. The vast majority are non-functioning, presented as nodular cervical lesions. Large, non-functioning PCs can manifest with compressive symptoms of the surrounding tissues. Rarely, PCs produce excessive amounts of parathyroid hormone (PTH), resulting in primary hyperparathyroidism. We report a case of functional PC, describing its diagnostic and therapeutic approach.

Os cistos de paratireoide (PCs) são lesões raras, localizadas no pescoço e na região do mediastino anterior. A grande maioria é não funcionante, apresentando-se como lesões cervicais nodulares. PCs não funcionantes de grandes dimensões podem se manifestar com sintomas compressivos. Raramente, PCs produzem quantidades excessivas de hormônio da paratireoide (PTH), o que resulta em hiperparatiroidismo primário. Relatamos um caso de PC funcional, descrevendo sua abordagem diagnóstica e terapêutica.

Patología hiperparatiroidea atendida en tres hospitales costarricenses / Hyperparathyroid pathology treated in three Costa Rican hospitals

Objetivo: determinar la frecuencia y características de los pacientes que por patología hiperparatiroidea, se atendieron en los hospitales México, San Juan de Dios y "Dr. Rafael Angel Calderón Guardia", en un periodo de tres años. Métodos: análisis de registros de parathormona intacta sérica elevada, expedientes clínicos y revisión bibliográfica. Estudio descriptivo, cuya muestra fue pacientes hiperparatiroideos atendidos entre enero 2007 y diciembre 2009. La determinación de frecuencias y proporciones para las variables cualitativas se realizó por medio de la prueba chi cuadrado, y las cuantitativas, mediante la estimación de la prueba t de student. Resultados: de 199 pacientes estudiados, se excluyeron 9. El sexo femenino predominó (68.9 por ciento), el grupo etario más frecuente fue de 60 y más años de edad (33,1 por ciento). El hiperparatiroidismo primario fue la enfermedad más frecuente (n=46;24,2 por ciento;73,9 por ciento mujeres, 69,5 por ciento mayores de 50 años), luego hipovitaminosis D y falla renal crónica. La mayoría vivía en San José (59,4 por ciento) y se atendió en el Hospital México (65,8 por ciento). No se posee el concepto claro y se desdeña el hiperparatiroidismo normocalcémico, por parte de algunos médicos, y la mayoría no solicita determinaciones de vitamina D. Discusión: los pacientes con parathormona intacta elevada por diversas causas están expuestos a muchas patologías que pueden comprometer su sobrevivencia y calidad de vida. La hipovitaminosis D probablemente sería más frecuente, si su medición se solicitara más. Debe enfatizarse la solicitud de calcecifediol en cualquier patología paratiroidea...

Revisión histórica de la fisiología de las glándulas paratiroides / Historical review of the physiology of parathyroid glands

Las glándulas paratiroides fueron identificadas por primera vez en humanos, por Ivan Sãndstrom (1880). Von Recklinghausen en 1891 describe un "linfonódulo marrón rojizo" bajo la tiroides de un paciente con fibrosis quística ósea. Ese mismo año Gley asocio la pérdida en la función de las paratiroides con la tetania. Vassale y Generali publicaron un trabajo en 1897 realizado tras tiroidectomías en perros y concluyen que una de las funciones de las paratiroides era la remoción de toxinas, concordando con la "teoría de detoxificación". G. Moussu (1898) clamó haber tratado satisfactoriamente a un paciente con tetania administrándole extracto acuoso de paratiroides equinas. En 1903 Askanazy establece que los tumores de la glándula tiroides u otras glándulas endocrinas y afecciones descalcificantes esqueléticas podrían relacionarse al describir el primer caso de asociación entre un tumor paratiroideo y la enfermedad de Von Recklinghausen. MacCallum y Voegtlin (1924), tras numerosos estudios, dedujeron que la paratiroides actuaba como moduladora del metabolismo del calcio. Collip (1925) confirmó el rol protagónico de las paratiroides en la regulación del calcio mediante experimentos basados en que la "paratirina" podía aliviar la tetania post-paratiroidectomía Barnicot en 1948 concluye que la hormona paratiroidea estimula la resorción osteoclásica de forma directa; ese nismo año, Jahan y Pitts demostraron que esta hormona incrementa la reabsorción renal tubular de calcio y magnesio. En 1973, Aurbach purifica cierta cantidad de hormona paratiroidea, caracterizándose su estructura proteica y molecular. La clonación de su receptor por Jüppner y Abou-Samra (1991) permitió estudiar con mayor énfasis sus acciones celulares.

Parathyroid glands were identified by the first time in human beings by Ivan Sãndstrom (1880). Von Recklinghausen in 1891 describes "lymph node reddish brown" low thyroid of patients with fibrosis cystic in bones. The same year Gley associated the loss in the function of the parathyroids with tetania. Vassale and Generali published a review in 1897 realized after thyroidectomies in dogs and they concluded that one of the parathyroid functions was the renoval of toxins, agreeing with "theory of detoxification". G. Moussu (1898) cried out to have treated satisfactorily a patient with tetania administering watery extract of equine parathyroids. In 1903 Askanazy establishes that the tumors of the thyroid gland or other endocrines glands and decalcifying affections of the skeleton might be related on having described the first case of association between a parathyroid tumor and Von Recklinghausen's disease. Mac callum and Voegtlin (1924), alter numerous studies, deduced that parathyroid was actuating like modulating of the metabolism of the calcium. Collip (1925) confirmed the leading role of the parathyroid glands in the regulation of calcium by means of experiments based on which the "parathyrina" could relieve the postparathyroidectomy tetania. Barnicot in 1948 concludes that the parathyroid hormone stimulates the osteoclastic resorption directly, the same year, Jahan and Pitts demonstrated that this hormone increases the renal tubular reabsorption of calcium and magnesium. In 1973, Aurbach purifies certain quatity of parathyroid hormone, its multifaceted and molecular structure being characterized. The cloning of its receptor for Jüppner and Abou-Samra(1991) allowed to study with bigger emphasis its cellular actions.

Nonfunctional parathyroid cyst: case report / Cisto de paratireóide não funcionante: relato de caso

CONTEXT: Parathyroid cysts are rare clinical and pathological entities, with less than 300 cases reported. The inferior parathyroid glands are most commonly involved, with left-side predominance. Parathyroid cysts may be functional or nonfunctional, depending on their association with hypercalcemia. CASE REPORT: A 25-year-old man presented a palpable asymptomatic left-side neck mass. Ultrasound revealed a cystic structure contiguous with the left thyroid lobe. Serum ionic calcium was normal. The patient underwent left thyroid lobectomy plus isthmectomy with excision of the cyst. The histological findings revealed a parathyroid cyst. Parathyroid cysts typically present as asymptomatic neck masses, and surgical excision appears to be the treatment of choice.

CONTEXTO: Cistos de paratireóide são entidades clínicas e patológicas raras, com menos de 300 casos relatados. As glândulas paratireóides inferiores são mais comumente envolvidas, com predomínio do lado esquerdo. Cistos de paratireóide podem ser funcionais ou não, dependendo de sua associação com hipercalcemia. RELATO DE CASO: Um homem de 25 anos apresentou-se com massa cervical esquerda palpável assintomática. A ultrassonografia revelou uma estrutura cística contígua com o lobo tireoidiano esquerdo. O cálcio iônico sérico estava normal. O paciente foi submetido a lobectomia esquerda com istmectomia e excisão do cisto. Os achados histopatológicos revelaram cisto de paratireóide. Cistos de paratireóide tipicamente se apresentam como massas cervicais assintomáticas e a ressecção cirúrgica parece ser o tratamento de escolha.

Toxicidad sistémica asociada con la inyección intramuscular de mercurio metálico: reporte de un caso / Systemic poisoning associated with the intramuscular injection of metallic mercury: a case report

Los informes de toxicidad relacionada con el mercurio metálico aluden principalmente a la inhalación de vapores con efectos sobre los riñones. Hay pocos informes de casos de toxicidad relacionada con la inyección subcutánea, muscular o venosa de este metal. El espectro de manifestaciones es variado y depende de la afectación de los sistemas renal, endocrino y neurológico. Presentamos un caso de toxicidad sistémica secundaria a la inyección intramuscular intencional de mercurio metálico en una mujer de 16 años; en un comienzo la paciente no recibió quelantes y evolucionó con disfunción renal, hiperparatiroidismo y osteoporosis secundaria con fractura patológica de cadera.

Reports of toxicity by metallic mercury are mainly related with exposure by inhalation, leading to renal dysfunction. There are few reports of toxicity related with subcutaneous, muscular or intravenous injections of this metal. The clinical spectrum of manifestations is wide arising from the renal, endocrine and neurologic lesions. We report the case of a 16 year-old woman who suffered from systemic mercurial toxicity after an intentional muscular injection of this metal. She did not initially receive a chelating agent and developed renal dysfunction, hyperparathyroidism and secondary osteoporosis with a pathological hip fracture.

Update on clinical trials with cinacalcet in secondary hyperparathyroidism due to chronic kidney disease / Atualização sobre os Ensaios clínicos com cinacalcete no hiperparatireoidismo secundário associado à doença renal crônica

Data from several recent clinical trials reaffirm the efficacy of treatment with cinacalcet for controlling plasma PTH levels among dialysis patients with established secondary HPT. In contrast to results reported previously from studies where cinacalcet was used together with relatively large but constant doses of vitamin D sterols, plasma PTH levels can be reduced effectively during treatment with cinacalcet among patients receiving lower doses of vitamin Dsterols. Compared to conventional treatment with vitamin D sterols, serum calcium and phosphorus levels are better controlled with this therapeuticapproach, and a larger proportion of patients are able to achieve serum calcium and phosphorus concentrations and values for Ca x P with the ranges recommended in current practice guidelines. Additional prospective clinical trials are needed, however, to determine whether the use of cinacalcet among dialysis patients with secondary HPT affects other important and clinically relevant outcomes such bone morphology, bone mass and/or bone density, skeletal fracture rates, and the need for parathyroidectomy.

Dados de vários ensaios clínicos recentes reafirmam a eficácia do tratamento com cinacalcete para controlar o nível plasmático do PTH em pacientes em diálise com hiperparatireoidismo secundário estabelecido. Em contraste com resultados previamente relatados, derivados de estudos onde cinacalcete era usado junto com doses relativamente altas porém constantes de vitamina D ou derivados, os níveis plasmáticos de PTH podem ser efetivamente reduzidospor cinacalcet em pacientes recebendo doses mais baixas de esteróides da vitamina D. Em comparação ao tratamento convencional com esteróides da vitamina D, os níveis séricos de cálcio e fósforo são melhor controlados com esta abordagem terapêutica e uma maior proporção de pacientes podealcançar concentrações séricas de cálcio e fósforo e valores do produto Ca x P dentro das faixas recomendadas pelas diretrizes atuais. Entretanto, ensaiosclínicos prospectivos adicionais são necessários para determinar se o uso de cinacalcete em pacientes em diálise com hiperparatireoidismo secundárioafeta outras variáveis importantes e clinicamente relevantes como, por exemplo, a morfologia do osso, a massa e/ou a densidade óssea, a taxa de fraturas, e a necessidade de paratireoidectomia.

Diagnóstico clínico e laboratorial do hiperparatiroidismo secundário / Clinical and laboratory diagnoses of secondary hyperparathyroidism

O hiperparatiroidismo secundário (HPTS), observado nos doentes urémicos, apesar de se instalar desde estadios precoces da insuficiência renal,apresenta manifestações clínicas pouco específicas e frequentemente tardias. Para além da promissora técnica de avaliação da arquitectura trabecularóssea por tomografia quantitativa microcomputorizada os métodos imagiológicos são de escassa utilidade no diagnóstico das alterações ósseasassociadas ao HPTS. Ao longo dos últimos anos foram avaliados diversos marcadores bioquímicos da remodelação óssea e a respectiva utilidade nodiagnóstico não invasivo da osteodistrofia renal. Finalmente, é ainda discutido o eventual papel de factores locais (citoquinas e factores de crescimento) na modulação da remodelação óssea.

Secondary hyperparathyroidism represents one extreme of the spectrum of the bone and endocrine changes observed in uraemic patients, and may develop since early stages of renal failure. The clinical symptoms and signs are non-specific and the contribution of image evaluation in the diagnosis of secondary hyperparathyroidism is, frequently, misleading. In this review, in addition to the classic modulators of bone remodeling, like parathyroid hormone (and PTHfragments), calcitriol and calcitonin, the role of others local factors involved in osteoblast and osteoclast activation, like cytokines and growth factors, is alsodiscussed.

Relación entre hiperparatiroidismo y gamapatía monoclonal / Relationship between hyperthyroidism and monoclonal gammapathy

Se presenta el caso de un paciente de 66 años con la asociación de hiperparatiroidismo primario (HPTP) y gamapatía monoclonal de significado incierto (GMSI). Se plantea la posible relación patogénica entre el HPTP y la GMSI, a través de procesos moleculares donde la interleuquina-6 podría desempeñar un papel determinante.

A 66-year-old man with primary hyperparathyroidism (PHPT) and monoclonal gammapathy associatedto it of uncertain signifi cance (MGUS). A possible pathogenic relationship between HPTP and MGUS is analyzed. Interleukin 6 could play a pivotal role.

The calcium-sensing receptor and related diseases / O receptor sensor de cálcio e doenças associadas

The calcium-sensing receptor (CASR) adjusts the extracellular calcium set point regulating PTH secretion and renal calcium excretion. The receptor is expressed in several tissues and is also involved in other cellular functions such as proliferation, differentiation and other hormonal secretion. High extracellular calcium levels activate the receptor resulting in modulation of several signaling pathways depending on the target tissues. Mutations in the CASR gene can result in gain or loss of receptor function. Gain of function mutations are associated to Autossomal dominant hypocalcemia and Bartter syndrome type V, while loss of function mutations are associated to Familial hypocalciuric hypercalcemia and Neonatal severe hyperparathyroidism. More than one hundred mutations were described in this gene. In addition to calcium, the receptor also interacts with several ions and polyamines. The CASR is a potential therapeutic target to treatment of diseases including hyperparathyroidism and osteoporosis, since its interaction with pharmacological compounds results in modulation of PTH secretion.

O receptor sensor de cálcio (CASR) ajusta o set point do cálcio extracelular através da regulação da secreção de PTH e da excreção renal de cálcio. O receptor é expresso em diversos tecidos e também está envolvido em outras funções celulares como proliferação, diferenciação e secreção de outros hormônios. Concentrações altas de cálcio extracelular ativam o receptor resultando em modulação de inúmeras vias de sinais intracelulares dependendo do tecido-alvo. Mutações no gene do CASR podem resultar em ganho ou perda de função do receptor. Mutações com ganho de função são associadas à Hipocalcemia autossômica dominante e à Síndrome de Bartter tipo V, enquanto que mutações com perda de função são associadas à Hipercalcemia hipocalciúrica familiar e ao Hiperparatireoidismo neonatal grave. Mais de cem mutações foram descritas neste gene. Além do cálcio, o receptor também interage com inúmeros íons e poliaminas. CASR é um alvo terapêutico potencial para tratamento de doenças incluindo hiperparatireoidismo e osteoporose, pois a sua interação com compostos farmacológicos resulta em modulação da secreção de PTH.

Paratireoidectomia subtotal no tratamento do hiperparatireoidismo secundário à doença renal crônica / Subtotal parathyroidectomy in the treatment of secondary hyperparathyroidism to chronic renal disease

Objetivos: apresentar os resultados obtidos com a paratireoidectomia (PTX) subtotal em pacientes com hiperparatireoidismo (HPT) secundário àinsuficiência renal crônica (IRC), enfocando a contribuição e as dificuldades técnicas da cirurgia. Pacientes e Métodos: no período de janeiro de 1998 ajunho de 2005 foram operados consecutivamente no Hospital Universitário Antonio Pedro, 33 pacientes renais crônicos portadores de HPT secundário. Ascirurgias foram realizadas pelo mesmo cirurgião e a mesma equipe de nefrologista se encarregou do controle pré e pós-operatório. Esse grupo foiconstituído por 19 homens e 14 mulheres com idade média de 40,5 (16/68) anos e todos se encontravam em tratamento dialítico regular, com tempo médiode diálise de 113 (20/189) meses. Além dos cuidados habituais, todos os pacientes receberam calcitriol após as três últimas sessões de diálise queantecederam a cirurgia. Resultados: os resultados mais expressivos se refletiram sobre o aparelho músculo-esquelético e foram muito significativas as remissões das queixas de dor ósteo-articular, fraqueza e prurido; as calcificações não vasculares foram reabsorvidas e sinais de remineralização ósseaforam identificados após a cirurgia. As complicações pós-operatórias mais freqüentes foram a rouquidão transitória (21%), a hiperpotassemia (12%) e osangramento pós-operatório (12%). Nesse grupo há uma recidiva comprovada e já reoperada e dois pacientes encontram-se em fase de investigação, por provável insucesso na cirurgia, já que o PTH continua elevado. Os resultados menos favoráveis foram mais freqüentes nos casos onde foram encontradas apenas três glândulas paratireóides. Não houve mortalidade operatória. Conclusões: a PTX subtotal pode ser realizada com segurança e é efetiva para a remissão de diversas manifestações do HPT secundário, desde que continuem sob rigoroso controle clínico para evitar possíveis recidivas por hiperplasia do resíduo glandular.

Objective: to report the results obtained with subtotal parathyroidectomy (PTX) in patients with hyperparathyroidism (HPT) secondary to chronic renaldisease (CRD), focusing on the contribution and technical difficulties of the surgery. Methods: From January of 1998 to June of 2005, thirty-three end-stagerenal disease (ESRD) patients consecutively underwent PTX in the university hospital. Their mean age was 40.5 years; Nineteen were male, and 14 female.Mean time on dialysis was 113 months. Surgeries were accomplished by the same surgeon and the same nephrologist was in charge of the pre- andpostoperative care of the whole patients. Among the clinical manifestations those related to the osteopathy were the most prevalent ones. All patientsunderwent preoperative care and received calcitriol after the last three dialysis sessions that preceded the surgery. Results: the most expressiveimprovements pertained to the muscle-skeletal system. The alleviation of bone pain, joint pain, muscle weakness and itch were marked. Extra-vascularcalcifications were reabsorbed and radiological signs of bone remineralization were identified after the surgery. The most frequent postoperativecomplications were temporary hoarseness (21%), hyperkalemia (12%), and postoperative bleeding (12%). So far, we have faced one proven recurrencethat was managed by a surgical reintervention. In addition, PTH continues to be high in two patients who are undergoing prepare for a new surgery. Bad results seemed to be more frequent on patients in which only three parathyroid glands were found during the operation. Surgery was not associated to fatalities. Conclusions: subtotal PTX can be accomplished with safety in ESRD patients being effective for the alleviation of several manifestations of the secondary HPT. Patients should be maintained under strict clinical control to monitor for recurrences due to hyperplasia of the residual glandular tissue.