Incidencia de Hipocalcemia Post Tiroidectomía. Factores predictores (PTH, Fósforo, Magnesio) y protocolo de manejo con alta precoz / Post-Thyroidectomy Hypocalcemia: Incidence, Prediction, and Outpatient Management Strategies Based on PTH and Calcium Levels

Se ha propuesto la medición de PTH como predictor de hipocalcemia postoperatoria transitoria y permanente. No hay un estándar de punto de corte o tiempo de toma de muestra. El OBJETIVO es reportar la incidencia de hipocalcemia post tiroidectomía en un grupo quirúrgico de alto volumen y proponer un protocolo de manejo ambulatorio (esquemas de I a V) según niveles postoperatorios (PO) de calcemia, PTHi (normal, baja o indetectable) y síntomas. Y determinar valores de PTH postoperatoria como predictores de hipocalcemia. En 106 pacientes con tiroidectomía total entre 2019 y 2021 se realiza medición de niveles pre y postoperatorios de calcio, magnesio, fosforo y PTHi. Se observó 29% y 1% de hipocalcemia transitoria ( 12 meses). Los puntos de corte para predecir hipocalcemia fueron PTH < 8,8 pg/ml y < 80% de descenso de % de PTH (d % PTH) al día siguiente. Con el manejo propuesto se indica el alta precoz (promedio 1.05 días) y el costo de la prescripción es acotado. No hay asociación significativa de hipomagnesemia e hiperfosfemia PO con la hipocalcemia PO. El tratamiento más utilizado es de carbonato de calcio exclusivo (esquemas I y II). Los pacientes se mantienen con síntomas leves a las 2 semanas PO en 5% y logran suspender el tratamiento vía oral en 93% en este mismo período. Los protocolos de medición de PTH como predictor de hipocalcemia son muy variados. Cada centro debe conocer y establecer sus propios protocolos de manejo. Con esta experiencia demostramos la utilidad y seguridad de un esquema de manejo basado en calcemia, PTH (normal, baja o indetectable) y síntomas, con indicación de tratamiento profiláctico para todos los pacientes y ajuste ambulatorio seguro y de menor costo que una hospitalización prolongada.

INTRODUCTION: PTH measurement has been proposed to predict transient and permanent postoperative hypocalcemia. There is no standard cut-off point or time for sampling. Aim: To report the incidence of post-thyroidectomy hypocalcemia in a high-volume surgical group and propose an outpatient management protocol according to postoperative (PO) calcium levels, iPTH (normal, low, or undetectable), and symptoms. Furthermore, determine postoperative PTH values as predictors of hypocalcemia. Methods: In 106 patients with total thyroidectomy between 2019 and 2021, pre-and postoperative levels of calcium, magnesium, phosphorus, and iPTH were measured. Results: Transient ( 12 months) hypocalcemia was observed in 29% and 1%. Cut-off points to predict hypocalcemia were PTH < 8.8 pg/mL and < 80% decrease in % PTH (d% PTH) the day after surgery. With the proposed management, early discharge is indicated (an average of 1.05 days), and the prescription cost is limited. There is no significant association between PO hypomagnesemia and hyperphosphatemia with PO hypocalcemia. The most widely used treatment is exclusive calcium carbonate (schemes I and II). Patients remain with mild symptoms at two weeks PO in 5% and discontinue oral treatment in 93% in this period. Conclusions: Protocols for measuring PTH as a hypocalcemia predictor vary. Each center must know and establish its management protocols. With this experience, we demonstrate the usefulness and safety of a management scheme based on calcium, PTH (normal, low, or undetectable), and symptoms with an indication of prophylactic treatment for all patients and a safe outpatient setting at a lower cost than prolonged hospitalization.

PTH como predictor de hipocalcemia postiroidectomía total / PTH as a predictor of hypocalcemia after total thyroidectomy

Resumen Objetivo: Evaluar la asociación entre el valor de PTH medido a las 6 h posoperatorias de los pacientes sometidos a una tiroidectomía total, y la presentación de hipocalcemia en las primeras 24 h posoperatorias. Materiales y Método: Estudio analítico retrospectivo que utiliza una base de datos de 173 pacientes operados de tiroidectomía total entre enero de 2016 a diciembre de 2018 en el Hospital Militar de Santiago (HMS). Se revisaron datos demográficos y perioperatorios. Se utilizó curva ROC para evaluar la asociación entre PTH e hipocalcemia en nuestros pacientes. Resultados: 106 pacientes que cumplen criterios de inclusión. Promedio de PTH 30,5 (1,4-169), 58% presentó hipocalcemia, solo 17 pacientes fueron sintomáticos. PTH promedio en pacientes sintomáticos fue de 7,8 pg/ml. Curva ROC con área bajo la curva de 0,83 (0,75-0,92). Considerando valores útiles para la práctica clínica, una PTH menor a 6,3 (valor más bajo en nuestro laboratorio), tiene sensibilidad de 97%. El valor 18 de PTH (límite inferior del rango de normalidad del laboratorio) se obtiene 88,89% de sensibilidad con 66,07% de especificidad. Y con un valor de 47 pg/ml, se obtiene con un 91% de especificidad para predecir pacientes que no tendrían hipocalcemia. Conclusión: Con un valor de PTH disminuido bajo su valor normal, se puede decir que el riesgo de tener hipocalcemia es sobre el 80%, por lo que se debería iniciar tratamiento profiláctico y desistir del alta. En cambio, para definir un valor superior sobre el cual dar de alta precoz con seguridad, faltan más estudios.

Aim: To evaluate the association between PTH (parathormone) value measured at 6 hours postoperatively of patients submitted to total thyroidectomy, and the presentation of hypocalcemia in the first 24 hours. Materials and Method: Retrospective study of 173 patients with total thyroidectomy between January 2016 to December 2018 in HMS. Demographic and perioperative data were reviewed. The ROC curve was used to evaluate the association between PTH and hypocalcemia in our patients. Results: 106 patients meet inclusion criteria. Average of PTH 30.5 (1.4-169), 58% presented hypocalcemia, 17 patients were symptomatic. ROC curve with area under the curve of 0.83 (0.75-0.92) was obtained considering useful values for clinical practice, a PTH less than 6.3 (lowest value in our laboratory), has 97% sensitivity to predict hypocalcemia. If we use the value 18 we obtain 88.89% sensitivity with 66.07% specificity. And with a value of 47, it is obtained with 91% specificity to predict patients who would not have hypocalcemia Conclusion: With a PTH value decreased below its normal value, it can be said that the risk of having hypocalcemia is over 80%, so that prophylactic treatment should be initiated. To define a value on which to register early with security, more study is needed.

Hiperparatiroidismo primario por carcinoma paratiroideo: caso problema y revisión / Primary hyperparathyroidism by parathyroid cancer: case report and review

El carcinoma paratiroideo (CP) es una neoplasia maligna con una incidencia de 0,015 cada 100.000 habitantes por año. Representa el 1% de los diagnósticos de hiperparatiroidismo primario y se manifiesta entre la 4.a y 5.a década de la vida, con una incidencia similar entre hombres y mujeres. La etiología del CP es incierta, ha sido asociada a formas esporádicas o familiares. Está caracterizado por altos niveles séricos de calcio y PTH y el desafío clínico-quirúrgico es el diagnóstico diferencial con otras entidades benignas como el adenoma o la hiperplasia de paratiroides. Aunque el diagnóstico de certeza es anatomopatológico, la sospecha clínica y el uso de métodos de baja complejidad (ecografía) con operadores avezados permite una correcta localización y abordaje pertinente del paciente para dirigir el tratamiento quirúrgico adecuado (resección en bloque) evitando persistencias y recurrencias de enfermedad. Se presenta el caso clínico de un paciente masculino que ingresa por síndrome de impregnación asociado a hipercalcemia, su abordaje diagnóstico, tratamiento y manejo interdisciplinario con discusión y revisión bibliográfica. (AU)

Parathyroid carcinoma (CP) is a malignant disease with an incidence of 0.015 per 100,000 inhabitants per year. It accounts for 1% of primary hyperparathyroidism diagnoses and occurs between the 4th and 5th decade of life, with a similar incidence between men and women. The etiology of CP is uncertain and has been associated with sporadic or family forms. CP is characterized by high serum calcium and PTH levels and the clinical-surgical challenge is the differential diagnosis with other benign entities such as parathyroid adenoma or hyperplasia. Although the diagnosis of certainty is achieved by pathological anatomy examination, the clinical suspicion and the use of low complexity methods (ultrasound) by experienced operators allows a correct localization and a patient-specific approach to direct the appropriate surgical treatment (block resection), avoiding persistence and recurrences of disease. The clinical case of a male patient admitted for severe hypercalcemia with multiple organ disfunction, the diagnostic approaches, treatment, and interdisciplinary management, together with review and discussion of the current literature are presented. (AU)

Variación estacional de 25-hidroxi-vitamina D3, hormona paratiroidea y fosfatasa alcalina en niños escolares / Seasonal variations in 25-hydroxy vitamin D3, parathormone and alkaline phosphatase in school-aged children

INTRODUCCIÓN: El principal rol de la vitamina D es la regulación del metabolismo del calcio, cuya principal fuen te es la vitamina D3 que se obtiene principalmente por la acción de la luz ultravioleta (UV) en la piel. OBJETIVO: Evaluar las diferencias estacionales en las concentraciones de 25-hidroxi-vitamina D3 (25OHVitD3), hormona paratiroidea (PTH), fosfatasa alcalina (FA) y calcio en niños en edad esco lar. SUJETOS Y MÉTODO: Se midieron las concentraciones de 25OHVitD3, PTH, FA y calcio en niños de 5 a 8 años, sin suplementación de Vitamina D, reclutados en Santiago de Chile (latitud -33.4372) en distintas estaciones del año. El estatus de VitD fue definido como suficiente con concentraciones de 25OHVitD3 > 20 ng/mL (50 nmol/L), insuficiente 12-20 ng/mL (30-50 nmol/L) y deficiente 20 ng/mL) en verano, lo que disminuyó significativamente en invierno (54,3%, p < 0,0001). CONCLUSIONES: Las concentraciones de 25OHVitD3 disminuyeron en aproximadamente la mitad de los niños durante el invierno, lo que se vio acompañado de un aumento de la PTH y FA, asociado a concentraciones normales de calcio. De acuerdo a nuestros resultados, la suplementación con VitD en niños podría ser necesaria durante otoño e invierno.

INTRODUCTION: The main role of Vitamin D is to regulate calcium metabolism, whose main source is vitamin D3 ob tained mostly from the action of ultraviolet (UV) light on the skin. OBJECTIVE: To evaluate the seaso nal differences in the concentrations of 25-hydroxy-vitamin D3 (25OHVitD3), parathyroid hormone (PTH), alkaline phosphatase (ALP), and calcium in school-age children. SUBJECTS AND METHOD: The concentrations of 25OHVitD3, PTH, ALP, and calcium were measured in children from Santiago, Chile (latitude -33.4372), aged 5 to 8 years, without Vitamin D supplementation, in different seasons of the year. VitD status was defined as sufficient with concentrations of 25OHVitD3 >20 ng/mL (50 nmol/L), insufficient 12-20 ng/mL (30-50 nmol/L) and deficient 20 ng/mL), which decreased significantly in winter to 54.3% (p <0.0001). CONCLUSIONS: In winter, 25OHVitD3 concentrations decreased in approximately half of the children, which was associated with an increase in PTH and ALP, and normal calcium concentrations. According to our results, children may need VitD supple mentation during fall and winter.

Characteristics of hypoparathyroidism in Colombia: data from a single center in the city of Medellín

ABSTRACT Objective Hypoparathyroidism is a rare condition, whose most common etiology is complications of neck surgery. The aim of the study was to identify the clinical and biochemical profile of the patients with diagnosis of hypoparathyroidism, including the frequency of symptoms, clinical signs, long-term complications and disease control. Additionally, the study sought to know what the medication profile was, and the doses required by the patients. Subjects and method A retrospective cohort study was conducted wherein all patients with ICD-10 codes associated with hypoparathyroidism between 2011 and 2018 at the Hospital Universitario San Vicente Fundación were included. We investigated the etiology of the disease; biochemical profile including lowest serum calcium, highest serum phosphorus, 25OHD levels, calciuria and calcium/phosphorus product; medication doses, disease control, and presence of complications, especially renal and neurologic complications were also evaluated. Results The cohort included 108 patients (99 women/9 men) with a mean age of 51.6 ± 15.6 years. The main etiology was postoperative (93.5%), the dose of elemental calcium received was relatively low (mean 1,164 mg/day), and in only 9.2% of cases more than 2,500 mg/day of elemental calcium was necessary. We were able to evaluate the follow-up in 89 patients, and found that only 57.3% met the criteria for controlled disease. Conclusion The clinical profile of patients with hypoparathyroidism in our cohort is similar to that described in other international studies, with predominantly postoperative etiology. With standard therapy, only adequate control is achieved in a little more than half of patients. Arch Endocrinol Metab. 2020;64(3):282-9

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

Digital radiography as an alternative method in the evaluation of bone density in uremic rats / Radiografia digital como método alternativo na avaliação da densidade óssea em ratos urêmicos

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.

Chronic kidney disease is a main confounding factor for 25-vitamin D measurement / A doença renal crônica é um importante fator de confusão para a dosagem de 25-hidroxivitamina D

Abstract Background: Current guidelines recommend assessment of 25-vitamin D status in patients with chronic kidney disease (CKD). Although significant differences among assays have been described, the impact of CKD on this variability has never been tested. Methods: We tested the variability between two 25-vitamin D assays in patients with CKD (eGFR < 60 mL/min/1.73m2) who had consecutive 25-vitamin D measurements in 2015 (Assay 1 - Diasorin LIASON 25 TOTAL - D assay®) and 2016 (Assay 2 - Beckman Coulter Unicel Xl 800®). The cohort consisted of 791 adult patients (122 with normal renal function and 669 with CKD - 33, 30, and 37% in stages 3, 4, and 5 on dialysis, respectively). Results: Levels of 25-vitamin D were lower and the prevalence of hypovitaminosis D using assay 1 was higher than using assay 2 in patients with CKD, regardless of similar levels of calcium, phosphate, and parathyroid hormone. As kidney function decreased, the percentage of disagreement between the assays increased. Conclusion: There is a noteworthy variability between assays in patients with CKD such that the diagnosis of hypovitaminosis D is modified. The mechanism behind this result is still unclear and might be due to a possible interference in the analytical process. However, the clinical significance is unquestionable, as the supplementation of vitamin D can be erroneously prescribed to these patients.

Resumo Antecedentes: As diretrizes atuais recomendam a avaliação do estado da 25-hidroxivitamina D em pacientes com doença renal crônica (DRC). Embora significativas diferenças entre os ensaios tenham sido descritas, o impacto da nesta variabilidade DRC nunca foi testado. Métodos: Testamos a variabilidade entre dois ensaios de 25-hidroxivitamina D em pacientes com DRC (TFGe < 60 mL/min/1,73 m2) que realizaram medidas consecutivas de 25-hidroxivitamina D em 2015 (Ensaio 1 - Diasorin LIASON 25 TOTAL - D assay® ) e 2016 (Ensaio 2 - Beckman Coulter Unicel Xl 800®). A coorte consistiu de 791 pacientes adultos (122 com função renal normal e 669 com DRC - 33, 30 e 37% nos estágios 3, 4 e 5 em diálise, respectivamente). Resultados: Os níveis de 25-hidroxivitamina D foram menores e a prevalência de hipovitaminose D foi maior utilizando o ensaio 1 do que com o ensaio 2 em pacientes com DRC, independentemente dos níveis similares de cálcio, fosfato e paratormônio. Quando a função renal diminuiu, a porcentagem de discordância entre os ensaios aumentou. Conclusão: Existe uma notável variabilidade entre os ensaios em pacientes com DRC, de modo a modificar o diagnóstico de hipovitaminose D. O mecanismo por trás desse resultado ainda não está claro e pode ser devido a uma possível interferência no processo analítico. Entretanto, o significado clínico é inquestionável, pois a suplementação de vitamina D pode ser erroneamente prescrita a esses pacientes.

Niveles de vitamina D en médicos: ¿son los anestesiólogos el único grupo de riesgo? / Vitamin D levels among anesthesiologists and other physicians

Background Sun exposure is the main source of 25-hydroxy-vitamin D. Since anesthesiologists work inside operating rooms, they are identified as a deficiency risk group. As medical activity in general occurs indoors, added to the work excess and sedentary lifestyle, physicians in general have low sun exposure. Aim To investigate the determinants of vitamin D levels in physicians. Material and Methods Anesthesiologists and physicians not working in operating rooms were included. A survey that comprised working hours, diet, skin color, sunscreen use and outdoor activities was also applied. Measurements of vitamin D and parathormone levels in blood were performed. Results We analyzed samples from 81 volunteers. Median vitamin D values of the whole sample were in the range of insufficiency (25.3 [interquartile range 12.4] ng/ml). Multiple linear regression analysis detected no differences between anesthesiologists and non-anesthesiologists. A higher body mass index was a risk factor for vitamin D deficiency, (p = 0.025). The only protective factor was the intake of a vitamin D supplement (p < 0.01). Conclusions Anesthesiologists and other specialists were both at risk for vitamin D deficiency. Obesity was a risk factor and the use of a vitamin D supplement was the only protective factor.

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.

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

ABSTRACT Objective To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. Subjects and methods 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. Results One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. Conclusion PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

On the genetic determinants of hypovitaminosis D

Hypovitaminosis D, defined by low serum levels of 25(OH)D, is a recognized worldwide public health problem. The most accepted definition considers that deficiency occurs with serum levels fall below 12 ng/ml of 25(OH)D. Long term vitamin D deficiency results in decreased bone mineralization, secondary hyperparathyroidism, increased cortical bone loss (pathogenesis of osteoporosis and hip fractures), differentiation and division of various cell types, muscle strength, diabetes type 2, blood pressure, etc. Twin- and family-based studies indicate that genetic factors influence serum 25(OH)D levels. Genetic studies have shown single-nucleotide polymorphisms (SNPs) are linked to low serum 25(OH)D concentrations through changes in the activity of the enzymes of the 1α,25(OH)2D metabolic pathway. Carriers of high genetic risk scores would need a h igher amount of vitamin D supplementation to achieve adequate serum 25(OH)D concentrations. Clinicians would not need to indicate studies to identify patients with vitamin D insufficiency of genetic origin. They should instruct their patients on their own care, to control the intake of vitamin D and the serum 25(OH)D levels until the latter are adequate. Overall, the literature reveals that the consequences of hypovitaminosis D on bone health are observed in old and infrequently in young subjects. A probable explanation for the latter is: if the rate of bone remodeling allows it, bone tissue has endogenous (genetics, hormones) and exogenous determinants (diet, physical activity) that may compensate the variables of bone health. The consequences of vitamin D deficit on bone health, has not been completely uncovered.

La hipovitaminosis D, definida por bajos niveles séricos de 25(OH)D (<12 ng/ml), es un reconocido problema de salud pública mundial. La deficiencia de vitamina D a largo plazo resulta en una disminución de la mi neralización ósea, hiperparatiroidismo secundario, pérdida de hueso cortical (patogénesis de la osteoporosis y fracturas de cadera), diferenciación y división de varios tipos de células, fuerza muscular, diabetes tipo 2, pres ión arterial, etc. Estudios genéticos han demostrado que algunos "polimorfismos de un solo nucleótido" (SNP) están relacionados con bajas concentraciones séricas de 25(OH)D a través de reducción en la actividad de las enzimas implicadas en la síntesis de 1α,25(OH)2D. Los médicos no necesitan indicar un estudio genético para identificar a la insuficiencia de vitamina D de causa genética. Bastará con instruir a los pacientes sobre su propio cuidado y controlar la ingesta de vitamina D y los niveles séricos de 25(OH)D hasta que estos últimos sean adecuados. En general, la literatura revela que las consecuencias de la hipovitaminosis D sobre la salud ósea se observan en las personas añosas y con poca frecuencia en sujetos jóvenes. Una explicación probable para esta situación es: si la tasa de remodelación ósea lo permite, el tejido óseo tiene factores endógenos (genéticos, hormonales) y exógenos (dieta, actividad física) que pueden compensar las variables de la salud ósea. Las consecuencias del déficit de vitamina D sobre la salud ósea aún no se conocen completamente.

Effect of vitamin D supplementation on 24-hour urine calcium in patients with calcium Urolithiasis and vitamin D deficiency

ABSTRACT Purpose: Hypercalciuria is one of the risk factors for calcium kidney stone formation (the most common type of urinary stones). Although vitamin D deficiency is prevalent among urolithiasis patients, the effect of vitamin D supplementation on urine calcium in these patients is still unclear. Materials and Methods: In this retrospective study, medical and laboratory tests records of 26 patients with recurrent calcium kidney stones and vitamin D deficiency treated with 50000IU vitamin D per week for 8-12 weeks were analyzed. The changes in 24-hour urine calcium (24-h Ca), serum 25-hydroxyvitamin D (25 (OH) D), serum parathormone (PTH), other 24-hour urine metabolites and calculated relative supersaturations of calcium oxalate (CaOxSS), calcium phosphate (CaPSS) and uric acid (UASS) were assessed. Moreover, correlations between changes in 24-h Ca and other aforementioned variables were assessed. Results: Serum 25 (OH) D and 24-h Ca increased after vitamin D supplementation, while serum PTH decreased (p < 0.001, for all analyses). The levels of 24-hour urine sodium and urea increased significantly (p = 0.005 and p = 0.031, respectively). The levels of CaOxSS and CaPSS increased, but the changes were not significant (p = 0.177, and p = 0.218, respectively). There were no correlations between the changes in 24-h Ca and serum 25 (OH) D or PTH. Conclusions: The result of current study suggests that although urine Ca increased in vitamin D supplemented patients, this increase was not associated with the increase in serum vitamin D and may be due to other factors such as dietary factors. Further randomized clinical trials considering other factors associated with urine Ca are warranted.

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

ABSTRACT Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

Evaluation of bone disease in patients with cystic fibrosis and end-stage lung disease / Avaliação de doença óssea em pacientes com fibrose cística e doença pulmonar terminal

ABSTRACT Objective: Bone disease is a common comorbidity in patients with cystic fibrosis (CF). We sought to determine risk factors and identify potential biochemical markers for CF-related bone disease (CFBD) in a unique cohort of CF patients with end-stage lung disease undergoing lung transplantation (LTx) evaluation. Methods: All of the CF patients who were evaluated for LTx at our center between November of 1992 and December of 2010 were included in the study. Clinical data and biochemical markers of bone turnover, as well as bone mineral density (BMD) at the lumbar spine and femoral neck, were evaluated. Spearman's rho and multivariate logistic regression analysis were used. Results: A total of 102 adult CF patients were evaluated. The mean age was 28.1 years (95% CI: 26.7-29.5), and the mean body mass index was 17.5 kg/m2 (95% CI: 17.2-18.2). Mean T-scores were −2.3 and −1.9 at the lumbar spine and femoral neck, respectively, being lower in males than in females (−2.7 vs. −2.0 at the lumbar spine and −2.2 vs. −1.7 at the femoral neck). Overall, 52% had a T-score of < −2.5 at either skeletal site. The homozygous Phe508del genotype was found in 57% of patients without osteoporosis and in 60% of those with low BMD. Mean T-scores were not particularly low in patients with severe CFTR mutations. Although the BMI correlated with T-scores at the femoral neck and lumbar spine, serum 25-hydroxyvitamin D and parathyroid hormone levels did not. Conclusions: CFBD is common in CF patients with end-stage lung disease, particularly in males and patients with a low BMI. It appears that CF mutation status does not correlate with CFBD. In addition, it appears that low BMD does not correlate with other risk factors or biochemical parameters. The prevalence of CFBD appears to have recently decreased, most likely reflecting increased efforts at earlier diagnosis and treatment.

RESUMO Objetivo: A doença óssea é uma comorbidade comum em pacientes com fibrose cística (FC). Nosso objetivo foi determinar os fatores de risco e identificar possíveis marcadores bioquímicos de doença óssea relacionada à FC (DOFC) em uma coorte única de pacientes com FC e doença pulmonar terminal submetidos a avaliação para transplante de pulmão (TxP). Métodos: Todos os pacientes com FC avaliados para TxP em nosso centro entre novembro de 1992 e dezembro de 2010 foram incluídos no estudo. Foram avaliados dados clínicos e marcadores bioquímicos de remodelação óssea, bem como a densidade mineral óssea (DMO) na coluna lombar e colo do fêmur. Foram usados rô de Spearman e análise de regressão logística multivariada. Resultados: Foram avaliados 102 pacientes adultos com FC. A média de idade foi de 28,1 anos (IC95%: 26,7-29,5), e a média do índice de massa corporal foi de 17,5 kg/m2 (IC95%: 17,2-18,2). A média do escore T foi de −2,3 e −1,9 na coluna lombar e colo do fêmur, respectivamente, sendo menor nos homens que nas mulheres (−2,7 vs. −2,0 na coluna lombar e −2,2 vs. −1,7 no colo do fêmur). No geral, 52% apresentaram escore T < −2,5 em um dos dois sítios esqueléticos. O genótipo homozigoto para Phe508del foi encontrado em 57% dos pacientes sem osteoporose e em 60% daqueles com DMO baixa. A média do escore T não foi particularmente baixa em pacientes com mutações graves do gene CFTR. Embora o IMC tenha se correlacionado com o escore T no colo do fêmur e coluna lombar, os níveis séricos de 25-hidroxivitamina D e paratormônio não o fizeram. Conclusões: A DOFC é comum em pacientes com FC e doença pulmonar terminal, particularmente em homens e pacientes com IMC baixo. O estado de mutação da FC aparentemente não se correlaciona com a DOFC. Além disso, aparentemente não há correlação entre DMO baixa e outros fatores de risco ou parâmetros bioquímicos. A prevalência de DOFC parece ter diminuído recentemente, o que provavelmente é reflexo do aumento dos esforços para antecipar o diagnóstico e tratamento.

Disparity between Preoperative and Pre-Excisional Intraoperative Parathyroid Hormone in Parathyroid Surgery

Abstract Introduction Intraoperative parathyroid hormone (ioPTH) testing is a widely accepted standard for assessing the parathyroid gland function. A decline of preoperative parathyroid hormone (PTH) levels by more than 50% is one accepted measure of parathyroid surgery adequacy. However, there may be a variation between preoperative PTH levels obtained at a clinic visit and pre-excisional ioPTH. Objective Our study explores the differences between preoperative PTH and pre-excisional ioPTH levels, and the potential impact this difference has on determining the adequacy of parathyroid surgery. Methods A retrospective study that consisted of 33 patients that had undergone parathyroid resection between September 2009 and March 2016 at a tertiary academic center was performed. Each subject's preoperative PTH levels were obtained from clinic visits and pre-excisional ioPTH levels were recorded along with the time interval between the measurements. Results There was a significant difference between the mean preoperative PTH and the pre-excisional ioPTH levels of 147 pg/mL (95% confidence interval [CI] 11.43 to 284.47; p= 0.0396). The exclusion of four outliers revealed a further significant difference with a mean of 35.09 pg/mL (95% CI 20.27 to 49.92; p< 0.0001). The average time interval between blood draws was 48 days + 32 days. A weak correlation between the change in PTH values and the time interval between preoperative and pre-excision blood draws was noted (r2 = 0.15). Conclusion Our study reveals a significant difference between the preoperative PTH levels obtained at clinic visits and the pre-excisional intraoperative PTH levels. We recommend routine pre-excisional intraoperative PTH levels, despite evidence of elevated preoperative PTH levels, in order to more accurately assess the adequacy of surgical resection.

Evaluation of prevalence, biochemical profile, and drugs associated with chronic kidney disease-mineral and bone disorder in 11 dialysis centers / Avaliação da prevalência, perfil bioquímico e drogas associadas ao distúrbio mineral ósseo-doença renal crônica em 11 centros de diálise

ABSTRACT Introduction: The diagnosis and treatment of mineral and bone disorder of chronic kidney disease (CKD-MBD) is a challenge for nephrologists and health managers. The aim of this study was to evaluate the prevalence, biochemical profile, and drugs associated with CKD-MBD. Methods: Cross-sectional study between July and November 2013, with 1134 patients on dialysis. Sociodemographic, clinical, and laboratory data were compared between groups based on levels of intact parathyroid hormone (iPTH) (< 150, 150-300, 301-600, 601-1000, and > 1001 pg/mL). Results: The mean age was 57.3 ± 14.4 years. The prevalence of iPTH < 150 pg/mL was 23.4% and iPTH > 601 pg/mL was 27.1%. The comparison between the groups showed that the level of iPTH decreased with increasing age. Diabetic patients had a higher prevalence of iPTH < 150 pg/mL (27.6%). Hyperphosphatemia (> 5.5 mg/dL) was observed in 35.8%. Calcium carbonate was used by 50.5%, sevelamer by 14.7%, 40% of patients had used some form of vitamin D and 3.5% used cinacalcet. Linear regression analysis showed a significant negative association between iPTH, age, and diabetes mellitus and a significant positive association between iPTH and dialysis time. Conclusion: The prevalence of patients outside the target for iPTH was 50.5%. There was a high prevalence of hyperphosphatemia (35.8%), and the minority of patients were using active vitamin D, vitamin D analogs, selective vitamin D receptor activators, and cinacalcet. These data indicate the need for better compliance with clinical guidelines and public policies on the supply of drugs associated with CKD-MBD.

RESUMO Introdução: O diagnóstico e tratamento do distúrbio mineral ósseo-doença renal crônica (DMO-DRC) é um desafio para os nefrologistas e gestores de saúde. O objetivo deste estudo foi avaliar a prevalência, perfil bioquímico, e drogas associadas a DMO-DRC. Métodos: Estudo transversal entre julho e novembro de 2013, em 11 centros com 1134 pacientes em diálise. Dados sociodemográficos, clínicos, e laboratoriais foram comparados entre os grupos, com base em níveis do paratormônio intacto (PTHi) (< 150,151-300, 301-600,601-1000, e > 1001 pg/mL). Resultados: A idade média foi de 57,3 ± 14,4 anos, 1071 pacientes estavam em hemodiálise, e 63 em diálise peritoneal. A prevalência de PTHi < 150 pg/mL foi 23,4% e PTHi > 601 pg/mL foi de 27,1%. A comparação dos grupos mostrou que o nível de PTHi diminuiu com o aumento da idade. Pacientes diabéticos apresentaram uma maior prevalência de PTHi < 150 pg/mL (27,6%). Carbonato de cálcio foi usado por 50,5%, Sevelamer por 14,7%, 40% dos pacientes utilizaram alguma forma de vitamina D, e 3,5% utilizaram cinacalcet. A hiperfosfatemia (> 5,5mg/dL) foi observada em 35,8%. A análise de regressão linear mostrou uma associação negativa significativa entre PTHi, idade, e diabetes mellitus e uma associação positiva significativa com o tempo em diálise. Conclusão: A prevalência de pacientes fora do alvo para PTHi foi de 50,5%. Houve uma alta prevalência de hiperfosfatemia e um baixo uso de vitamina D ativa, análogos da vitamina D, ativadores seletivos da vitamina D, e cinacalcet. Estes dados chamam a atenção para a necessidade de uma maior conformidade com as diretrizes e políticas públicas sobre o fornecimento de medicamentos associados à DMO-DRC.

Progranulin concentration in relation to bone mineral density among obese individuals

ABSTRACT Objective Adipose tissue, particularly visceral adipose tissue, secretes a variety of cytokines, among which progranulin is a glycoprotein related to the immune system. Along with other secreted proteins, progranulin may be associated with bone mineral density. The aim of this study was to find out whether there are associations between the progranulin and bone mineral density among obese people. Subjects and methods This cross-sectional study was conducted on 244 obese participants (aged 22-52). Serum progranulin, high sensitive C-reactive protein, oxidised-low dencity lipoprotein, tumor necrosis factor-α, parathormone, vitamin D, and interleukins of 1 β, 4, 6, 10, 13, and 17 concentrations were measured. Anthropometric measurements, body composition and bone mineral density were also assessed. Results Serum progranulin was directly associated with interleukin-6 and interleukin-1β, while it had a negative association with interleukin-17 and tumor necrosis factor-α. We also observed a statistically significant direct association between progranulin concentration and visceral fat, abdominal fat, waist, abdominal and hip circumferences, hip T-score, and Z-score and T-score for the lumbar region. A partial correlation test has also shown a significant positive correlation regarding serum progranulin and the hip Z-score. Moreover, progranulin level is inversely associated with ospteopenia (P = 0.04 and CI: 0.17,0.96). Conclusion Our study revealed that central obesity may be related to increased progranulin concentration. In addition, progranulin concentration was directly related to bone formation parameters, which indicates the protective effects of progranulin on bone density. Further studies are needed to clarify the exact mechanisms underlying these associations.

Humoral hypercalcemia of pregnancy treated with bisphosphonates

SUMMARY Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.