RESUMO
OBJECTIVES: To characterize the stone risk and the impact of parathyroidectomy on the metabolic profile of patients with primary hyperparathyroidism (PHPT) and urolithiasis. PATIENTS AND METHODS: We analysed the prospectively collected charts of patients treated at our stone clinic between January 2001 and January 2016 searching for patients with PHPT and urolithiasis. Imaging evaluation of the kidneys, bones and parathyroid glands was assessed. We analysed the demographic data, serum and urinary variables before and after parathyroidectomy. We used a paired t-test, Fisher's test, Spearman's test and anova in the statistical analysis. RESULTS: A total of 51 patients were included. The mean patient age was 57.1 ± 12.1 years and 82.4% were women. Before parathyroidectomy, mean calcium and parathyroid hormone (PTH) levels were 11.2 ± 1.0 mg/dL and 331 ± 584 pg/dL, respectively. Hypercalcaemia was present in 84.3% of patients. All eight patients with normal calcium levels had elevated PTH levels. Only two patients did not have PTH above the normal range, although both had elevated calcium levels. The most common urinary disorders were low urinary volume (64.7%), hypercalciuria (60.8%), high urinary pH (41.2%) and hypocitraturia (31.4%). After parathyroidectomy, the number of patients with hypercalcaemia (n = 4; 7.8%), elevated PTH (n = 17; 33.3%) and hypophosphataemia (n = 3; 5.9%) significantly decreased (P < 0.001). The number of urinary abnormalities decreased and there was a reduction in urinary calcium (P < 0.001), pH (P = 0.001) and citrate levels (P = 0.003). CONCLUSION: Individuals with PHPT and nephrolithiasis frequently have elevated baseline PTH and calcium levels. Low volume, hypercalciuria, high urinary pH, and hypocitraturia are the most frequent urinary disorders. Parathyroidectomy is effective in normalizing serum calcium and PTH levels, although other urinary metabolic may persist. Patients should be monitored for the need for citrate supplementation.
Assuntos
Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Urolitíase/complicações , Idoso , Cálcio/sangue , Cálcio/urina , Ácido Cítrico/urina , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipercalcemia/sangue , Hipercalcemia/etiologia , Hipercalciúria/etiologia , Hipercalciúria/urina , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/urina , Hipofosfatemia/sangue , Hipofosfatemia/etiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Índice de Gravidade de Doença , Urina/química , Urolitíase/sangue , Urolitíase/urinaRESUMO
La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son caracteriÌsticos, aunque variables y de caraÌcter evolutivo. La gammagrafiÌa ósea es la teÌcnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnoÌstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)
Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Displasia Fibrosa Óssea/etiologia , Displasia Fibrosa Óssea/tratamento farmacológico , Osteogênese/genética , Osteomalacia/complicações , Anormalidades Congênitas , Vitamina D/uso terapêutico , Osteossarcoma/etiologia , Cálcio/uso terapêutico , Hipofosfatemia/sangue , Cistos Ósseos Aneurismáticos/etiologia , Diagnóstico Diferencial , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Fraturas Ósseas/patologia , Células-Tronco Mesenquimais/patologia , Manejo da Dor , Displasia Fibrosa Monostótica/etiologia , Displasia Fibrosa Óssea/genética , Displasia Fibrosa Óssea/sangue , Displasia Fibrosa Óssea/diagnóstico por imagem , Displasia Fibrosa Poliostótica/etiologia , Displasia Fibrosa Poliostótica/diagnóstico por imagem , Displasia Fibrosa Craniofacial/etiologia , Mutação/genéticaRESUMO
El hiperparatiroidismo familiar y la hipercalcemia hipocalciúrica familiar (HHF) constituyen un subgrupo heterogéneo de trastornos con herencia mendeliana, que representan en conjunto el 5% de las causas de hipercalcemia PTH dependiente. La HHF se asocia con mutaciones del gen del receptor sensor de calcio (CaSR). Esta entidad se manifiesta, en la mayoría de los casos, con la presentación asintomática y familiar de hipercalcemia e hipocalciuria y valores elevados o normales de hormona paratiroidea (PTH). Los avances en la biología molecular han contribuido al diagnóstico, evaluación del fenotipo de cada entidad y elección del tratamiento. Se describe el caso de una paciente con hipercalcemia estudiada a partir de una tumoración de cuello asociada con una glándula paratiroides quística. Luego de un exhaustivo proceso diagnóstico se halló en el estudio genético una mutación inactivante en el gen CaSR. Teniendo en cuenta la presencia de la relación clearance calcio/clearance creatinina <0,01 y la falta de respuesta al tratamiento quirúrgico, se consideró la entidad de HHF con forma de presentación atípica. La paciente, sin tratamiento, presentaba un progresivo incremento de la calcemia luego de la cirugía de las glándulas paratiroides, que no se controló con el uso de bifosfonatos y evolucionó con episodios de mareos y desmayos frecuentes sin causa neurológica o cardiovascular detectada. Por lo tanto, se inició el tratamiento con cinacalcet, con el cual se obtuvo una buena respuesta terapéutica: descenso de la calcemia y mejoría de la sintomatología luego de un año de su comienzo. El cinacalcet es una herramienta terapéutica de importancia en estos raros casos de HHF. (AU)
Familial hyperparathyroidism including familial hypocalciuric hypercalcemia (FHH) is an heterogeneous subgroup of disorders with Mendelian inheritance, that account for 5% of PTH dependent hypercalcemia. FHH is associated with mutations of the calcium receptor (CaSR) gene. This entity is manifested by hypercalcemia with hypocalciuria and high or normal levels of parathyroid hormone (PTH) generally asymptomatic and with familial presentation. Advances in molecular biology have contributed to the diagnosis, evaluation of the phenotype of each entity and the choice of treatment. We describe a patient with hypercalcemia diagnosed following the finding of a neck tumor associated with cystic parathyroids. After an exhaustive diagnostic process, an inactivating mutation in the CaSR gene was found. Considering the presence of a ratio clearance calcium / clearance creatinine <0.01 and the lack of response to surgical treatment, HHF entity with atypical presentation was considered. The patient exhibited progressive increase in serum calcium following parathyroid surgery, which was not controlled with the use of bisphosphonates and evolved into episodes of frequent dizziness and fainting, without neurological or cardiovascular causes. Treatment with cinacalcet was initiated, with a good therapeutic response. The use of cinacalcet is a useful therapeutic tool in these rare cases of FHH. (AU)
Assuntos
Humanos , Feminino , Adolescente , Receptores de Detecção de Cálcio/genética , Cinacalcete/farmacologia , Hipercalcemia/genética , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/cirurgia , Vitamina D/sangue , Cálcio/urina , Cálcio/sangue , Reação em Cadeia da Polimerase , Hipofosfatemia/sangue , Creatinina/sangue , Receptores de Detecção de Cálcio/fisiologia , Diagnóstico Diferencial , Difosfonatos/uso terapêutico , Cinacalcete/administração & dosagem , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hipercalcemia/metabolismo , Hipercalcemia/tratamento farmacológicoRESUMO
BACKGROUND: Hypophosphatemia, hypomagnesemia, and hypokalemia occur in patients receiving parenteral nutrition (PN), mainly when the body's stores are depleted due to fasting or inflammation. Although these disorders are potentially fatal, few studies have reported the incidence in the pediatric population. METHODS: This study evaluated, in a historical cohort of pediatric patients, the prevalence of hypophosphatemia, hypokalemia, and hypomagnesaemia until 48 hours before initiation of PN infusion (P1) and from days 1-4 (P2) and days 5-7 (P3) of PN infusion and investigated if malnutrition, calories, and protein infusion were correlated to these disorders. RESULTS: Malnutrition was present in 32.8% (n = 119) of the subjects; 66.4% of the patients were in the pediatric intensive care unit. Survival rate was 86.6%. P1 had the highest prevalence of mineral disorders, with 54 events (58.1%; P2, n = 35, 37.6%; P3, n = 4, 4.3%). Hypokalemia events were related to malnutrition (odds ratio, 2.79; 95% confidence interval, 1.09-7.14; P = .045). In the first 7 days, infused calories were below the amount recommended by current guidelines in up to 84.9% of patients, and protein infused was adequate in up to 75.7%. Protein infused above the recommendation in the first 4 days was related to hypomagnesaemia (odds ratio, 5.66; 95% confidence interval, 1.24-25.79; P = .033). CONCLUSION: Hypophosphatemia, hypokalemia, and hypomagnesemia were frequent in hospitalized pediatric patients before and during the first 4 days of PN infusion. Patients with malnutrition had more chances of having hypokalemia, and those who received high protein infusion had an increased chance of developing hypomagnesemia.
Assuntos
Hipopotassemia/epidemiologia , Hipofosfatemia/epidemiologia , Deficiência de Magnésio/epidemiologia , Desnutrição/epidemiologia , Nutrição Parenteral/efeitos adversos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Ingestão de Energia , Feminino , Hospitalização , Humanos , Hipopotassemia/sangue , Hipopotassemia/etiologia , Hipofosfatemia/sangue , Hipofosfatemia/etiologia , Incidência , Lactente , Unidades de Terapia Intensiva Pediátrica , Deficiência de Magnésio/sangue , Deficiência de Magnésio/etiologia , Masculino , Desnutrição/sangue , Desnutrição/etiologia , Micronutrientes/administração & dosagem , Micronutrientes/sangue , Estado Nutricional , Prevalência , Adulto JovemRESUMO
PURPOSE: Tumor-induced osteomalacia (TIO) is a paraneoplastic bone mineral disturbance related to fibroblast growth factor 23 (FGF23) overproduction by the tumor, usually from mesenchymal origin. Such condition leads to high phosphate renal wasting and, consequently, to cumbersome symptoms as weakness, bone pain, and fractures. METHOD: Case report. RESULT: We report a case of an advanced castration-refractory prostate cancer patient, which developed severe hypophosphatemia with elevated phosphate excretion fraction. TIO was suspected, and increased levels of FGF23 reinforced such diagnosis. The patient died 4 months after being diagnosed with TIO. CONCLUSION: This case suggests that TIO has a dismal prognosis in prostate cancer patients. The clinical oncology community must be aware about such disturbance that can be present in those patients with weakness, bone pain, and hypophosphatemia.
Assuntos
Neoplasias de Tecido Conjuntivo/etiologia , Neoplasias de Tecido Conjuntivo/secundário , Neoplasias da Próstata/complicações , Brasil , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Hipofosfatemia/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/diagnóstico , Osteomalacia , Síndromes Paraneoplásicas , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologiaRESUMO
The purpose of this paper is to review clinical studies on hypophosphatemia in pediatric intensive care unit patients with a view to verifying prevalence and risk factors associated with this disorder. We searched the computerized bibliographic databases Medline, Embase, Cochrane Library, and LILACS to identify eligible studies. Search terms included critically ill, pediatric intensive care, trauma, sepsis, infectious diseases, malnutrition, inflammatory response, surgery, starvation, respiratory failure, diuretic, steroid, antiacid therapy, mechanical ventilation. The search period covered those clinical trials published from January 1990 to January 2004. Studies concerning endocrinological disorders, genetic syndromes, rickets, renal diseases, anorexia nervosa, alcohol abuse, and prematurity were not included in this review. Out of 27 studies retrieved, only 8 involved pediatric patients, and most of these were case reports. One clinical trial and one retrospective study were identified. The prevalence of hypophosphatemia exceeded 50%. The commonly associated factors in most patients with hypophosphatemia were refeeding syndrome, malnutrition, sepsis, trauma, and diuretic and steroid therapy. Given the high prevalence, clinical manifestations, and multiple risk factors, the early identification of this disorder in critically ill children is crucial for adequate replacement therapy and also to avoid complications.
Assuntos
Cuidados Críticos , Estado Terminal , Hipofosfatemia/etiologia , Criança , Ensaios Clínicos como Assunto , Humanos , Hipofosfatemia/sangue , Unidades de Terapia Intensiva Pediátrica , Fatores de RiscoRESUMO
Este estudo objetivou realizar revisão da literatura para verificar prevalência, fatores de risco e condições clínicas associadas à hipofosfatemia em crianças gravemente doentes. Para a pesquisa foram utilizadas as bases de dados Medline, Embase, Cochrane Library, Lilacs abrangendo estudos clínicos publicados de janeiro de 1990 a janeiro de 2004. Os termos utilizados para pesquisa foram: critically ill, pediatric intensive care, trauma, sepsis, infectious diseases, malnutrition, inflammatory response, surgery, starvation, respiratory failure, diuretic, steroid, antiacid therapy, mechanical ventilation. Foram excluídos estudos referentes a distúrbios endócrinos, síndromes genéticas, raquitismo, nefropatias, anorexia nervosa, alcoolismo e prematuridade. Dos 27 artigos inicialmente identificados, 8 referiam-se à faixa etária pediátrica, sendo a maioria deles relatos de casos isolados. Nos estudos clínicos selecionados, a prevalência de hipofosfatemia foi superior a 50%. Os principais fatores associados à hipofosfatemia foram realimentação, desnutrição, sepse, trauma, uso de diuréticos e corticoesteróides. Considerando-se a elevada prevalência, as repercussões clínicas e os múltiplos fatores de risco para hipofosfatemia em crianças internadas em unidade de cuidados intensivos, a identificação precoce de pacientes suscetíveis a esse distúrbio é essencial para o tratamento oportuno e prevenção de complicações.
Assuntos
Criança , Humanos , Cuidados Críticos , Estado Terminal , Hipofosfatemia/etiologia , Ensaios Clínicos como Assunto , Hipofosfatemia/sangue , Unidades de Terapia Intensiva Pediátrica , Fatores de RiscoRESUMO
AIM: To analyse the role of serum and urinary calcium and phosphorus levels in early detection of mineral deficiency in very low birthweight (VLBW) infants born appropriate (AGA) and small for gestational age (SGA). METHODS: 64 VLBW infants were included in a cohort study and divided into two groups: AGA (n = 30) and SGA infants (n = 34). Then, they were divided according to the presence of radiological signs of metabolic bone disease (MBD): with MBD (n = 21) and without MBD (n = 34). Blood samples and 6 h urine collections were obtained for calcium, phosphorus, alkaline phosphatase activity and creatinine determinations between 3 and 5 wk of life. RESULTS: There were no biochemical differences between AGA and SGA. Higher values of urinary calcium (MBD = 31.9 +/- 20.2, without MBD = 19.8 +/- 15.4; p = 0.017), calciuria (MBD = 2.3 +/- 0.3, without MBD = 1.4 +/- 0.8; p = 0.037) and alkaline phosphatase activity (MBD = 369 +/- 114, without MBD = 310 +/- 93; p = 0.04) were found in infants who developed MBD. Both groups showed high tubular phosphorus reabsorption indicating mineral deficiency. CONCLUSION: Serum calcium and phosphorus levels are not good markers in early detection of mineral deficiency. However, the monitoring of calcium urinary levels may be helpful in early detection of mineral deficiency.
Assuntos
Cálcio/sangue , Cálcio/urina , Hipofosfatemia/sangue , Hipofosfatemia/urina , Fósforo/sangue , Fósforo/urina , Fosfatase Alcalina/sangue , Fosfatase Alcalina/urina , Doenças Ósseas Metabólicas/etiologia , Estudos de Coortes , Creatina/sangue , Creatina/urina , Humanos , Hipofosfatemia/complicações , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Estudos ProspectivosRESUMO
BACKGROUND: Hypophosphatemia is common in acutely ill patients and possibly may occur in the acute-phase response syndrome (APR), secondary to hyperglycemia and shifts of extracellular phosphorus into cells. AIM: To compare the frequency of hypophosphatemia in patients with or without APR. METHODS: All plasma phosphorus results (n = 822) corresponding to a 6-month period were searched using an university hospital mainframe. Relevant laboratory and clinical details were also registered. All cases of alcohol withdrawal, diabetic ketoacidosis, parenteral nutrition, and chronic respiratory alkalosis and patients receiving antacids or intravenous dextrose (5%) in water at a rate higher than 50 g glucose/day were excluded. APR was defined on the basis of severe trauma or infection and at least two of the following: fever, leukopenia (WBC <5,000/mm3), or leukocytosis (WBC >9,000/mm3). Hypophosphatemia was defined as a serum phosphorus concentration <2.0 mg/dl. RESULTS: A total of 227 patients were studied. Thirty-five (15.4%) patients fulfilled the criteria for APR. Hypophosphatemia was observed in 11.4% of the APR-positive patients, in contrast to 0.5% in the APR-negative group. Hyperglycemia was more common in APR-positive patients (60.0 vs. 36. 8%). CONCLUSION: Our results suggest that hypophosphatemia may be attributed to increased serum glucose levels secondary to tissue injury and infection in APR-positive patients.