Trastornos metabólicos urinarios en pacientes urolitiásicos con enfermedad renal poliquística y sin ella / Urinary metabolic disorders in urolithiasis patients with and without polycystic kidney disease

Introducción: La urolitiasis se ha incrementado en las últimas décadas. La enfermedad renal poliquística autosómica dominante (ERPAD), enfermedad renal hereditaria más frecuente, ocupa un lugar preponderante. Objetivos: Identificar la frecuencia de presentación de los trastornos metabólicos urinarios en pacientes litiásicos cubanos con ERPAD y sin ella Métodos: Estudio descriptivo, transversal. Fueron estudiados 579 pacientes adultos sin ERPAD, seleccionados por muestreo simple aleatorio y los 21 pacientes con ERPAD, del total de pacientes con litiasis urinaria que se realizó estudio metabólico renal en el Laboratorio de Fisiopatología Renal del Instituto de Nefrología, en el periodo 2010-2015. Los datos fueron tomados de la historia clínica y del informe de estudio metabólico renal. La información se procesó de forma automatizada (SPSS 22.0). Se utilizó el promedio, desviación estándar, análisis de distribución de frecuencias y el test de homogeneidad. Resultados: En los pacientes con ERPAD predominó el sexo femenino (57,1 por ciento), mientras que en los pacientes sin ERPAD, el masculino (63,4 por ciento). Los trastornos más frecuentes en la población no poliquística fueron hipercalciuria (45,3 por ciento) e hipofosfatemia (17,1 por ciento). En los poliquísticos, aclaramiento aumentado de ácido úrico (38,1 por ciento) e hipercalciuria (23,8 por ciento). Se encontraron diferencias estadísticamente significativas para aumento del aclaramiento de ácido úrico (p = 0,01) e hiperfosfatemia (p = 0,04). Conclusiones: Los principales trastornos metabólicos de los pacientes litiásicos, tanto poliquísticos como no poliquísticos, son el aclaramiento de ácido úrico aumentado, hipercalciuria, hiperuricosuria e hipofosfatemia, aunque el orden de presentación es diferente. El aclaramiento de ácido úrico aumentado y la hiperfosfatemia se presentan con mayor frecuencia en los pacientes litiásicos poliquísticos(AU)

Introduction: Urolithiasis has increased in recent decades. Autosomal dominant polycystic kidney disease (ADPKD), the most common of all hereditary kidney diseases, occupies a predominant position in terms of incidence. Objectives: Identify the frequency of occurrence of urinary metabolic disorders in Cuban urolithiasis patients with and without ADPKD. Methods: A descriptive cross-sectional study was conducted of 579 adult patients without ADPKD selected by simple random sampling, and 21 patients with ADPKD, from the total urolithiasis patients undergoing renal metabolic evaluation at the Renal Physiopathology Laboratory of the Institute of Nephrology in the period 2010-2015. Data were obtained from medical records and reports of renal metabolic studies. Information was processed with the statistical software SPSS version 22.0. Average and standard deviation were estimated and use was made of frequency distribution analysis and homogeneity testing. Results: A predominance was found of female sex among patients with ADPKD (57.1 percent) and male sex among patients without ADPKD (63.4 percent). The most common disorders were hypercalciuria (45.3 percent) and hypophosphatemia (17.1 percent) in the non-polycystic population, and increased uric acid clearance (38.1 percent) and hypercalciuria (23.8 percent) in polycystic patients. Statistically significant differences were found in uric acid clearance increase (p = 0.01) and hyperphosphatemia (p = 0.04). Conclusions: The main metabolic disorders of lithiasis patients, polycystic as well as non-polycystic, are increased uric acid clearance, hypercalciuria, hyperuricosuria and hypophosphatemia, with a varying order of presentation. Increased uric acid clearance and hyperphosphatemia are more common in polycystic lithiasis patients(AU)

Metabolic assessment in pure struvite stones formers: is it necessary? / Avaliação metabólica em formadores de cálculo de estruvita pura: é necessário?

Abstract Background and objective: Magnesium ammonium phosphate stones (MAP), also known as struvite stones, are associated with urinary infection and impairment of renal unit. The aim of this study is to evaluate the urinary metabolic risk factors for recurrence of renal calculi in patients submitted to nephrectomy due to MAP stones. Methods: We retrospectively reviewed the charts of patients > 18 years old submitted to total nephrectomy due to pure MAP stones and pure calcium oxalate (CaOx) stones from July 2006 to July 2016. Urinary metabolic parameters were assessed through 24-hour urine exams ≥ 3 months after nephrectomy. Urinary metabolic parameters and new event related to lithiasis were compared. Results: Twenty-eight and 39 patients were included in MAP and CaOx group, respectively. Abnormalities in 24-hour urine samples were similar between groups. Hypercalciuria occurred in 7.1 and 10.3% of patients in MAP and CaOx group, respectively (p = 0.66), whereas hypocitraturia was present in 65.2 and 59.0% of patients with MAP and CaOx group, respectively (p = 0.41). No significant difference in new events was found between MAP and CaOx groups (17.9 vs. 23.1%, respectively; p = 0.60). Conclusion: A 24-hour urine evaluation should be offered to patients submitted to nephrectomy due to pure MAP stones in order to detect metabolic risk, improve treatment, and prevent stone recurrence.

Resumo Contexto e objetivo: Cálculos de fosfato de amônio e magnésio (FAM), também conhecidos como cálculos de estruvita, estão associados à infecção urinária e ao comprometimento da unidade renal. O objetivo deste estudo é avaliar os fatores de risco metabólico-urinários para recorrência de cálculos renais em pacientes submetidos à nefrectomia devido a cálculo de FAM. Métodos: Revisamos retrospectivamente os prontuários de pacientes > 18 anos submetidos à nefrectomia total devido a cálculos de FAM puro e cálculos de oxalato de cálcio puro (OxCa) de julho de 2006 a julho de 2016. Os parâmetros metabólicos urinários foram avaliados através de exames de urina de 24 horas ≥ 3 meses após a nefrectomia. Os parâmetros metabólicos urinários e um novo evento relacionado à litíase foram comparados. Resultados: Vinte e oito e 39 pacientes foram incluídos nos grupos FAM e OxCa, respectivamente. As anormalidades em amostras de urina de 24 horas foram similares entre os grupos. A hipercalciúria ocorreu em 7,1 e 10,3% dos pacientes nos grupos FAM e OxCa, respectivamente (p = 0,66), enquanto a hipocitratúria esteve presente em 65,2 e 59,0% dos pacientes nos grupos FAM e OxCa, respectivamente (p = 0,41). Nenhuma diferença significativa em novos eventos foi encontrada entre os grupos FAM e OxCa (17,9 vs. 23,1%, respectivamente; p = 0,60). Conclusão: Uma avaliação de urina de 24 horas deve ser oferecida aos pacientes submetidos à nefrectomia devido a cálculos de FAM puro, a fim de detectar risco metabólico, melhorar o tratamento e prevenir a recorrência de cálculos.

X-linked hypophosphatemic rickets: a new mutation / Raquitismo hipofosfatêmico ligado ao X: uma nova mutação

Abstract Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur. Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient's outcome. Genetic analysis can help to establish a genotype-phenotype correlation.

Resumo O raquitismo fosfopênico pode ser causado por mutações no gene PHEX (ligado ao X do homólogo da endopeptidase que regula o fosfato). Atualmente, mais de 500 mutações no gene PHEX causam raquitismo hipofosfatêmico. Os autores relatam um caso clínico de uma menina de 4 anos com histórico familiar sem relevância, que apresentou falha no crescimento e arqueamento das pernas. Os exames laboratoriais mostraram hipofosfatemia, fosfatase alcalina elevada, cálcio normal, PTH levemente elevado e níveis normais de 25(OH)D e 1,25(OH)D. O estudo radiológico mostrou deformidades ósseas no rádio e no fêmur. O diagnóstico clínico do raquitismo fosfopênico foi realizado e o estudo genético detectou uma provável variante patogênica heterozigótica do gene PHEX: c.767_768del (p.Thr256Serfs*7). Esta variante não foi descrita anteriormente na literatura ou nas bases de dados. O conhecimento sobre novas mutações pode melhorar o desfecho de pacientes. A análise genética pode ajudar a estabelecer uma correlação genótipo-fenótipo.

Alterações hidroeletrolíticas em pessoas com cirrose / Hydroelectrolytic alterations in cirrhotic patients

O objetivo deste estudo foi evidenciar e discutir as principais alterações hidroeletrolíticas em pessoas com cirrose. Trata-se de uma revisão integrativa, de natureza qualitativa. Os artigos foram selecionados por meio da plataforma Medical Literature Analysis and Retrievel System Online. Os principais achados identificados a partir dos artigos selecionados foram a ocorrência de hiponatremia, o mau prognóstico diante da presença de distúrbios hidroeletrolíticos em relação à sobrevida em pessoas com cirrose e a importância da albumina. Indivíduos com cirrose são suscetíveis ao desenvolvimento de distúrbios hidroeletrolíticos devido às mudanças fisiopatológicas da doença e às condições clínicas apresentadas. A hiponatremia e a hipocalemia são os mais recorrentes, destacando, porém, a necessidade de atenção aos demais distúrbios. (AU)

The objective of this study was to show and discuss the main hydroelectrolytic alterations in cirrhotic patients. This is an integrative review, a qualitative study, in which articles were selected at the Medical literature Analysis and Retrieval System Online. The main findings identified in the articles selected were the occurrence of hyponatremia, the poor prognostic, due to the presence of hydroelectrolytic disorders, regarding cirrhotic individuals survival and the importance of albumin. Individuals with cirrhosis are susceptible to the development of hydroelectrolytic disorders due to the pathophysiological alterations of the disease and because of the clinical status presented. Hyponatremia and hypokalemia are the most recurrent, but attention shall be given to the other disorders too. (AU)

Diagnosis and surgical treatment of sinonasal phosphaturic mesenchymal tumor / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the diagnosis and surgical treatment of sinonasal phosphaturic mesenchymal tumor (PMT). Methods: The medical records of nine patients who had been diagnosed as sinonasal PMT in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai JiaoTong University Affiliated Sixth People's Hospital between January 2015 and May 2020 were collected, including 4 males and 5 females, ranging from 36 to 59 years. The patient's previous history, clinical manifestations, imaging findings, laboratory results, surgical procedure, pathological results and postoperative follow-up data were analyzed by descriptive statistical analysis. Results: All patients presented hypophosphatemia and tumor-induced osteomalacia (TIO) with a disease course of 1 to 19 years. The imaging examination and intraoperative findings identified two cases with peripheral tissue infiltration, two cases with contralateral nasal cavity invasion, and one case with intracranial invasion. Five patients underwent unilateral endoscopic resection while two patients underwent bilateral endoscopic resection, and the remaining two patients underwent unilateral transorbital ethmoid artery ligation plus endoscopic tumor resection and endoscopic combined with transfrontal tumor resection (n=1 each). Expect for one case developed recurrence and intracranial involvement, the other patients achieved clinical remission and no recurrence was observed during the six-month follow-up. Conclusions: The diagnosis of sinonasal PMT needs combination of clinical manifestation, imaging, and pathological findings. Complete surgical excision and long-term postoperative follow-up are imperative.

Prevalência de hipofosfatemia e risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva / Prevalence of hypophosphatemia and risk of refeeding syndrome in elderly patients admitted to an intensive care unit

Introdução: A presença de hipofosfatemia é fortemente relacionada à ocorrência de síndrome de realimentação em pacientes críticos, na qual um dos principais grupos de risco é a população idosa. Objetivos: Avaliar a prevalência de hipofosfatemia e o risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva. Métodos: Estudo observacional prospectivo, realizado numa unidade de terapia intensiva com pacientes idosos de ambos os sexos e em uso de terapia nutricional enteral. Foram coletados dados demográficos, clínicos e exames bioquímicos, e realizadas triagem e avaliação nutricional. As necessidades nutricionais foram calculadas e adotou-se o ponto de corte de 90% para estabelecer a adequação da oferta calórica. Para avaliar o risco e a ocorrência de síndrome de realimentação, foram utilizados os critérios propostos pelo grupo NICE. A análise estatística foi realizada com o auxílio do programa SPSS 13.0, com um intervalo de confiança (IC) de 95%. Resultados: Foram estudados 44 pacientes, dos quais 34,1% estavam em magreza; 86,4% dos pacientes iniciaram a terapia nutricional enteral em até 48 horas, com 43,2% de adequação calórica em até 72 horas. A hipofosfatemia foi encontrada em 9,1% dos pacientes na admissão e em 29,5% após o início da dieta. Com isso, 88,6% dos pacientes apresentaram algum risco para desenvolver síndrome de realimentação e 40,9% deles manifestaram a síndrome. Conclusão: Foi identificada elevada prevalência de hipofosfatemia após o início da terapia nutricional. Além disso, o risco de desenvolver síndrome de realimentação foi elevado e sua manifestação se assemelha aos dados encontrados na literatura. (AU)

Introduction: The presence of hypophosphatemia is strongly related to the occurrence of refeeding syndrome in critically ill patients, in which one of the main risk groups is the elderly population. Objectives: To assess the prevalence of hypophosphatemia and the risk of refeeding syndrome in elderly patients admitted to an intensive care unit. Methods: Prospective observational study carried out in an intensive care unit with elderly patients of both genders using enteral nutritional therapy. Demographic, clinical and biochemical data were collected, and nutritional screening and assessment were performed. The energy and nutrient requirements were calculated and a cutoff point of 90% was adopted to establish the adequacy of the caloric supply. To assess the risk and occurrence of refeeding syndrome, the criteria proposed by the NICE group were used. Statistical analyses were performed using the SPSS 13.0 program, with a 95% confidence interval (CI). Results: 44 patients were studied, of which 34.1% were malnourished; 86.4% of patients started enteral nutritional therapy within 48 hours, with 43.2% of caloric adequacy within 72 hours. Hypophosphatemia was found in 9.1% of patients on admission and in 29.5% after starting the diet. Thus, 88.6% of patients had some risk of developing the refeeding syndrome and 40.9% of them manifested the syndrome. Conclusion: A high prevalence of hypophosphatemia was identified after starting nutritional therapy. In addition, the risk of developing refeeding syndrome was high and its manifestation is similar to data found in the literature. (AU)

Hypophosphatemia and risk of refeeding syndrome in critically ill patients before and after nutritional therapy

Summary OBJECTIVE: To investigate the prevalence of hypophosphatemia as a marker of refeeding syndrome (RFS) before and after the start of nutritional therapy (NT) in critically ill patients. METHODS: Retrospective cohort study including 917 adult patients admitted at the intensive care unit (ICU) of a tertiary hospital in Cuiabá-MT/Brasil. We assessed the frequency of hypophosphatemia (phosphorus <2.5mg/dl) as a risk marker for RFS. Serum phosphorus levels were measured and compared at admission (P1) and after the start of NT (P2). RESULTS: We observed a significant increase (36.3%) of hypophosphatemia and, consequently, a greater risk of RFS from P1 to P2 (25.6 vs 34.9%; p<0.001). After the start of NT, malnourished patients had a greater fall of serum phosphorus. Patients receiving NT had an approximately 1.5 times greater risk of developing RFS (OR= 1.44 95%CI 1.10-1,89; p= 0.01) when compared to those who received an oral diet. Parenteral nutrition was more associated with hypophosphatemia than either enteral nutrition (p=0,001) or parenteral nutrition supplemented with enteral nutrition (p=0,002). CONCLUSION: The frequency of critically ill patients with hypophosphatemia and at risk for RFS on admission is high and this risk increases after the start of NT, especially in malnourished patients and those receiving parenteral nutrition.

RESUMO OBJETIVO: Determinar a frequência de hipofosfatemia como marcador da síndrome de realimentação (SR) antes e após o início da TN em pacientes críticos. MÉTODOS: Coorte retrospectiva realizada com 917 pacientes adultos de um hospital terciário em Cuiabá-MT. Foi determinada a frequência de hipofosfatemia (fósforo <2,5 mg/dl) como marcador de risco de SR, para valores de fósforo sérico da admissão (P1) e após o início da TN (P2). RESULTADOS: Foi observado um aumento significativo (36,3%) da hipofosfatemia entre P1 e P2 e, consequentemente, do risco de SR (25,6% vs 34,9%; p<0,001) com o início da TN. Após o início da TN, pacientes desnutridos apresentaram maior queda do fósforo sérico. Os pacientes com TN apresentaram aproximadamente 1,5 vez mais chance de desenvolver hipofosfatemia e risco de SR (OR=1,44 IC95% 1,10-1,89; p=0,01) quando comparado aos com dieta oral. Nutrição parenteral foi mais associada à hipofosfatemia versus nutrição enteral (p=0,001) e nutrição enteral suplementada com parenteral (p=0,002). CONCLUSÃO: A frequência de pacientes críticos com hipofosfatemia e em risco de SR é alta e esse risco aumenta após o início da TN, especialmente nos desnutridos e naqueles recebendo nutrição parenteral.

Osteomalacia oncogénica secundaria a tumor mesenquimal fosfatúrico del pie / Oncogenic osteomalacia secondary to phosphaturic mesenchymal tumour of the foot

RESUMEN La osteomalacia oncogénica es un síndrome metabólico paraneoplásico caracterizado por hipofosfatemia debida a la pérdida renal de fosfato, con nivel bajo de vitamina D. Este trastorno está asociado con la liberación de factores fosfatúricos por células tumorales, especialmente el factor de crecimiento fibrolástico 23 (FGF23). Las neoplasias relacionadas con la osteomalacia oncogénica suelen ser tumores pequeños de linaje mesenquimatoso y pueden ser difíciles de localizar en algunos casos debido a su tamaño y ubicación poco accesible al examen físico. Presentamos a un paciente que desarrolló fracturas vertebrales y de cadera debido a osteomalacia oncogénica asociada con un tumor mesenquimatoso fosfatúrico del tejido graso profundo de la planta del pie, que finalmente se diagnosticó después de 3 años del inicio de los síntomas, cuando el tumor pudo ser localizado por el rastreo gammagráfico óseo con pentatreótido marcado con indio-111 y por las imágenes de resonancia magnética nuclear.

ABSTRACT Oncogenic osteomalacia is a paraneoplastic metabolic syndrome characterised by a low phosphates in the blood due to renal phosphate losses with inadequately normal or low vitamin D levels. This disorder is associated with the release of tumour cell-secreted phosphaturic factor, most notably fibroblast growth factor 23 (FGF-23). The neoplasms related to oncogenic osteomalacia are usually small tumours of mesenchymal lineage, and they may be difficult to locate in the physical examination in some cases, due to their size and inaccessible location. The case is presented of a patient who developed vertebral and hip fractures due to oncogenic osteomalacia associated with a phosphaturic mesenchymal tumour of the deep fat tissue in the sole of the foot. This was finally diagnosed after 3 years of the onset of symptoms after being located by bone scintigraphy with Indium-111 labelled pentetreotide and magnetic resonance imaging.

Hipofosfatasemia crónica persistente de causa no determinada y su repercusión músculo-esquelética / Persistent hypophosphatasemia and its musculoskeletal repercussion

La fosfatasa alcalina baja o hipofosfatasemia, ya sea debida a causas genéticas (hipofosfatasia) o secundarias, presenta correlato clínico. Nuestro objetivo es estimar la prevalencia de hipofosfatasemia crónica persistente y describir sus hallazgos osteometabólicos. Se realizó una búsqueda electrónica de afiliados adultos al Hospital Italiano de Buenos Aires, entre 2013 y 2017, con al menos 2 determinaciones de fosfatasa alcalina igual a 30 UI/l o menor y ninguna mayor de 30 UI/l (rango de referencia 30-100 UI/l). Se excluyeron aquellos con causas secundarias diagnosticadas y se analizaron los correlatos clínico y bioquímico. Se detectó hipofosfatasemia crónica persistente en 78 de 105.925, 0,07% (0,06-0,09) de los afiliados. Solo uno fue excluido por tener causa secundaria. Eran 61,1% mujeres de 44 (34-56) años, fosfatasa alcalina 24 (20-27) UI/L, fosfatemia 4,1 (3,8-4,6) mg/dl. Se observaron osteoartritis, calcificaciones vasculares y fracturas, menos frecuentemente litiasis renal, calcificación del ligamento longitudinal común anterior, pérdida dental y convulsiones. El 63,6% tenían al menos una de las características clínico-radiológicas evaluadas, pero en solo 5,2% fue mencionado el diagnóstico de hipofosfatasemia en la historia clínica. La densitometría evidenció algún grado de afección (osteopenia u osteoporosis) en 76,2%. Se constataron 19 fracturas, con predominio en radio. La prevalencia de hipofosfatasemia fue similar a lo previamente reportado. El reconocimiento fue bajo; sin embargo, se observaron variadas manifestaciones músculo-esqueléticas, similares a las descriptas en la hipofosfatasia del adulto, por lo cual ­ante una hipofosfatasemia sin causa secundaria­ se sugiere considerar este diagnóstico. (AU)

Low alkaline phosphatase (ALP) or hypophosphatasemia either due to genetic (hypophosphatasia) or secondary causes, presents a clinical correlate. Our objectives are to estimate the prevalence of persistent hypophosphatasemia and to describe the clinical findings. We performed a search using the electronic medical records of the members of the Hospital Italiano de Buenos Aires health care system, between 2013 and 2017. Adult members with ≥ 2 ALP ≤ 30 IU/l, no ALP >30 IU/l (normal range 30-100 UI/l) and without diagnosed secondary causes were analyzed. Persistent hypophosphatasemia was detected in 78 of 105.925, 0.07% (0.06-0.09) of members. Only one was excluded due to a secondary cause, 61.1% were women, 44 (34-56) year-old, ALP 24 (20-27) IU/l and phosphatemia 4.1 (3.8-4.6) mg/dl. Osteoarthritis, vascular calcifications and fractures were detected, and nephrolithiasis, DISH (Diffuse idiopathic skeletal hyperostosis), tooth loss, and seizures were less frequently observed. At least one of the mentioned characteristics were present in 63.6 %, but only 5.2% had hypophosphatasemia registered in their clinical record. Densitometry showed osteopenia or osteoporosis in 76.2%. There were 19 fractures, most of them in radius. The prevalence of hypophosphatasemia was similar to what has been previously reported. Hypophosphatasemia finding in medical records was low, but far from being asymptomatic, clinical manifestations were observed. In the presence of hypophosphatasemia without a secondary cause, adult hypophosphatasia should be uspected. (AU)

Hipofosfatemia inducida por drogas: fierro carboximaltosa e imatinib. Casos clínicos / Hypophosphatemia induced by carboxymaltose iron and imatinib. Report of two cases

Hypophosphatemia is a relatively frequent and a potentially serious adverse drug effect. Clinically it is characterized by bone pain and muscle weakness. There are several mechanisms by which a drug can induce hypophosphatemia and they can be classified according to whether or not they are mediated by an excess of Fibroblast Growth Factor 23 (FGF23). We report two patients with the condition: (i) A 49-year-old woman with Chronic Myeloid Leukemia (CML) and gastric sleeve surgery at 46 years of age. After receiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary phosphate losses associated with high FGF23 levels were confirmed. Plasma phosphate returned to normal values 90 days after the iron administration. (ii) A 40-year-old man with a history of CML in whom imatinib was started. He developed symptomatic hypophosphatemia due to non FGF23-mediated hyperphosphaturia. As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases illustrate the importance of recognizing and treating drug-induced hypophosphatemia in a timely manner, and thus avoid the morbidity associated with this entity.

Debilitating pain and fractures: A rare case of Hypophosphatemic Osteomalacia with Concomitant vitamin D Deficiency in Neurofibromatosis Type 1 / Journal of the ASEAN Federation of Endocrine Societies

@#Hypophosphatemic osteomalacia is a rare form of metabolic bone disorder in neurofibromatosis type 1 (NF1). The exact disease mechanism of this disorder in NF1 is yet to be established. We present a 44-year-old female known to have NF1, who presents with debilitating bone pain, weakness and multiple fractures. Laboratory investigations showed persistent hypophosphatemia with renal phosphate wasting suggestive of hypophosphatemic osteomalacia. She also had concomitant vitamin D deficiency which contributed to the disease severity. Medical therapy with oral phosphate and vitamin D improved her symptoms without significant changes in fracture healing or phosphate levels.

Effects of Early Phosphorus Intake on Respiratory Distress in Extremely Low-Birth-Weight Infants

PURPOSE: This study was aimed to investigate the effect of early phosphorus intake on respiratory distress in extremely low-birth-weight infants (ELBWIs) with a high incidence of hypophosphatemia. METHODS: We performed a retrospective study to target 164 ELBWIs admitted to the neonatal intensive care unit in Seoul National University Children's Hospital. Birth characteristics, nutritional intake, and electrolyte levels during the first week were investigated as predictors that would affect the clinical outcomes. The correlations among invasive ventilation at postnatal age of 2 weeks, moderate-to-severe bronchopulmonary dysplasia (BPD), and phosphorous intake were analyzed. RESULTS: Hypophosphatemia (phosphorus level <4 mg/dL) was observed in 72.0% of the subjects. The rates of invasive ventilation (P=0.001) and moderate-to-severe BPD (P=0.005) were significantly lower in the high phosphorus intake group (≥0.7 mM/kg/day) than in the low phosphorus intake group (<0.7 mM/kg/day). Phosphorus intake during the first week was a significant factor affecting invasive ventilation at 2 weeks of age (adjusted odds ratio [OR], 8.212; 95% confidence interval [CI], 2.256 to 28.896; P=0.001) and moderate-to-severe BPD (adjusted OR, 3.402; 95% CI, 1.274 to 9.084; P=0.015). CONCLUSION: Early insufficient phosphorus intake confers a significantly higher risk with invasive ventilation at 2 weeks of age and moderate-to-severe BPD. Therefore, early sufficient phosphorus supply may improve respiratory outcomes in ELBWIs.

Skeletal mineralization: mechanisms and diseases

Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments.

Refeeding Syndrome as a Possible Cause of Very Early Mortality in Acute Pancreatitis

BACKGROUND/AIMS: Refeeding syndrome (RFS) is a fatal clinical complication that can occur as a result of fluid and electrolyte shifts during early nutritional rehabilitation for malnourished patients. This study was conducted to determine the clinical implications of RFS in patients with acute pancreatitis (AP). METHODS: Between 2006 and 2016, AP patients with very early mortality were retrospectively enrolled from three university hospitals. RESULTS: Among 3,206 patients with AP, 44 patients died within 3 days after diagnosis. The median age was 52.5 years (range, 27 to 92 years), male-to-female ratio was 3:1, and median duration from admission to death was 33 hours (range, 5 to 72 hours). The etiology of AP was alcohol abuse in 32 patients, gallstones in five patients, and hypertriglyceridemia in two patients. Ranson score, bedside index for severity of AP, and acute physiology and chronic health evaluation-II were valuable for predicting very early mortality (median, [range]; 5 [1 to 8], 3 [0 to 5], and 19 [4 to 45]). RFS was diagnosed in nine patients who died of septic shock (n=5), cardiogenic shock (n=2), or cardiac arrhythmia (n=2). In addition, patients with RFS had significant hypophosphatemia compared to non-RFS patients (2.6 mg/dL [1.3 to 5.1] vs 5.8 mg/dL [0.8 to 15.5]; p=0.001). The early AP-related mortality rate within 3 days was approximately 1.4%, and RFS occurred in 20.5% of these patients following sudden nutritional support. CONCLUSIONS: The findings of current study emphasize that clinicians should be aware of the possibility of RFS in malnourished AP patients with electrolyte imbalances.

Infantile hypercalcemia with novel compound heterozygous mutation in SLC34A1 encoding renal sodium-phosphate cotransporter 2a: a case report

Idiopathic infantile hypercalcemia is characterized by hypercalcemia, dehydration, vomiting, and failure to thrive, and it is due to mutations in 24-hydroxylase (CYP24A1). Recently, mutations in sodium-phosphate cotransporter (SLC34A1) expressed in the kidney were discovered as an additional cause of idiopathic infantile hypercalcemia. This report describes a female infant admitted for evaluation of nephrocalcinosis. She presented with hypercalcemia, hypercalciuria, low intact parathyroid hormone level, and high 1,25-dihydroxyvitamin D3 level. Exome sequencing identified novel compound heterozygous mutations in SLC34A1 (c.1337G>A, c.1483C>T). The patient was treated with fluids for hydration, furosemide, a corticosteroid, and restriction of calcium/vitamin D intake. At the age of 7 months, the patient's calcium level was within the normal range, and hypercalciuria waxed and waned. Renal echogenicity improved on the follow-up ultrasonogram, and developmental delay was not noted. In cases of hypercalcemia with subsequent hypercalciuria, DNA analysis for SLC34A1 gene mutations and CYP24A1 gene mutations should be performed. Further studies are required to obtain long-term data on hypercalciuria and nephrocalcinosis.

Hypophosphatemic osteomalacia caused by urinary mesenchymal tumor: A case report / 北京大学学报(医学版)

This case report concerns a 34-year-old woman who had been diagnosed with ankylosing spondylitis (AS), fibromyalgia syndrome (FMS), osteoarthritis (OA), lumbar disc herniation and the like in different hospitals during the past 18 months. She had progressive osteoarthrosis, significant muscle weakness, gait abnormalities in weightbearing areas, however without typical inflammatory low back pain, while the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was invalid, with normal inflammation index, negative results for rheumatic factor (RF) and human leukocyte antigen (HLA)-B27, and normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She had hyphosphatemia, normal serum calcium, 1,25-(OH)2-D3 reduction, elevated alkaline phosphatase (ALP) and normal parathyroid hormone (PTH), however with elevated urinary phosphorus. Finally, the medial thigh nodule was found in the subcutaneous of her inner leg by careful examination and imaging scans including B-ultrasound and PET/CT. The final pathology confirmed that the nodule was phosphate urinary mesenchymal tumors. After the tumor was removed, the patient was treated with anti-osteoporosis and phosphorus supplementation. The symptoms of bone pain and muscle weakness were alleviated, and hypophosphatemia was corrected. It was confirmed that the patient had low-phosphorus osteomalacia due to tumor. Tumor-induced hypophosphatemia osteomalacia (TIO) was a rare paraneoplastic syndrome which was caused by excessive phosphorus excretion induced by the tumor, and was thus categorized as an acquired hypophosphatemic osteomalacia. TIO had an occult onset and was associated with a high rate of misdiagnosis, although TIO has some typical clinical features. Early diagnosis, correctly positioning of the tumor, and surgical resection can achieve good outcomes.

Hipercalcemia e hipofosfatemia en prematuros que reciben nutrición parenteral agresiva / Hypercalcemia and hypophosphatemia among preterm infants receiving aggressive parenteral nutrition

Introducción. La nutrición parenteral agresiva constituye un estándar de cuidado en prematuros de muy bajo peso. Sin embargo, investigaciones recientes evaluaron su impacto en los resultados a corto plazo, como la homeostasis mineral y electrolítica. El objetivo fue comparar la prevalencia de hipercalcemia e hipofosfatemia en prematuros que recibían nutrición parenteral agresiva o estándar. Métodos. Estudio observacional retrospectivo que comparó a un grupo de prematuros menores de 1250 gramos que recibían nutrición parenteral agresiva con un grupo control histórico. Se calculó la prevalencia de hipercalcemia y se buscó la asociación con nutrición parenteral agresiva ajustando por confundidores. Se estimó la media de fosfatemia del grupo control mediante regresión lineal y se la comparó con el otro grupo. Resultados. Se incluyeron 40 pacientes por grupo. La prevalencia de hipercalcemia fue mayor en el grupo de nutrición parenteral agresiva (87,5% vs. 35%, p= 0,001). La nutrición parenteral agresiva se asoció con hipercalcemia al ajustar por peso al nacer, restricción del crecimiento intrauterino, aporte de aminoácidos y calorías (ORa 21,8; IC 95%: 3,7-128). La media de calcemia fue diferente entre ambos grupos (p= 0,002). El grupo de nutrición parenteral agresiva presentó más sepsis sin alcanzar significancia estadística y su fosfatemia media resultó menor que la estimada para el grupo control (p= 0,04). La prevalencia de hipofosfatemia en este grupo fue de 90% (IC 95%: 76-97%). Conclusiones. Nuestros datos muestran una asociación entre hipercalcemia/hipofosfatemia y nutrición parenteral agresiva. Se recomienda monitorizar la calcemia y la fosfatemia frecuentemente, ya que pueden estar asociadas con resultados clínicos adversos.

Introduction. Aggressive parenteral nutrition is the standard of care among very-low-birth weight preterm infants. However, in recent studies, its impact on short-term outcomes, has been evaluated. The objective was to compare the prevalence of hypercalcemia and hypophosphatemia among preterm infants receiving aggressive or standard parenteral nutrition. Methods. Observational, retrospective study comparing a group of preterm infants weighing less than 1250 grams who received aggressive parenteral nutrition with a historical control group. The prevalence of hypercalcemia was estimated and its association with aggressive parenteral nutrition was searched adjusting by confounders. The mean phosphate level was estimated for the control group by linear regression and was compared to the value in the other group. Results. Forty patients per group were included. The prevalence of hypercalcemia was higher in the group who received aggressive parenteral nutrition (87.5% versus 35%, p= 0.001). Aggressive parenteral nutrition was associated with hypercalcemia when adjusting by birth weight, intrauterine growth restriction, amino acid, and calorie intake (adjusted odds ratio: 21.8, 95% confidence interval -amp;#91;CI-amp;#93;: 3.7-128). The mean calcium level was different between both groups (p= 0.002). Infants who received aggressive parenteral nutrition had more sepsis without reaching statistical significance and the mean phosphate level was lower than that estimated for the control group (p= 0.04). The prevalence of hypophosphatemia in this group was 90% (95% CI: 76-97%). Conclusions. Our data show an association between hypercalcemia/hypophosphatemia and aggressive parenteral nutrition. It is recommended to frequently monitor calcium and phosphate levels since they might be associated with adverse clinical outcomes.

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal / Hypophosphatemia in preterm infants: a bimodal disorder

Las estrategias nutricionales para prematuros extremos con alto aporte de proteínas, han mostrado alteraciones metabólicas con hipofosfemia precoz, especialmente en el grupo de pacientes con restricción de crecimiento intrauterino (Rein). También se presenta hipofosfemia tardía, característica de la enfermedad metabólica ósea. En este artículo se revisan y actualizan conceptos en relación a la fisiopatología del metabolismo del fósforo en recién nacidos prematuros y uso de parenterales precoces en el contexto de enfermedad metabólica ósea. Los artículos fueron identificados en base de datos electrónicas como Pubmed y Rima. Fueron incluidos artículos en inglés y español. Fueron filtrados por título y resumen. La literatura actual propone diversas estrategias de nutrición precoz que permitan asegurar una adecuada cantidad de nutrientes para continuar con el crecimiento y desarrollo extrauterino. En pacientes con nutrición parenteral pero con diferentes aportes de fósforo, o relación calcio: fósforo inadecuada, a mayor contenido de aminoácidos, se presenta hipofosfemia, hipercalcemia, hipomagnesemia, hipokalemia e hiperglicemia, especialmente en casos de Rein. Estas alteraciones se asocian a prolongación de ventilación mecánica, mayor riesgo de displasia broncopulmonar y aumento de sepsis tardía. La hipofosfemia tardía, descrita ya hace muchos años, se presenta con normocalcemia y aumento de fosfatasas alcalinas, en la enfermedad metabólica ósea del prematuro, con alteración de la mineralización en distintos grados, secundaria a un inadecuado aporte de este mineral para los altos requerimientos de estos pacientes. Esta presentación de hipofosfemia precoz y tardía en el prematuro alerta sobre el control oportuno de fosfemia para ajustar el aporte nutricional. En el prematuro con nutrición parenteral precoz, el control en conjunto con la calcemia en la primera semana de vida, especialmente en Rein, permite tratar la hipofosfemia y prevenir sus complicaciones. En hipofosfemia tardía, el seguimiento semanal o quincenal desde las 4 semanas a los prematuros con riesgo, permite lograr un aporte óptimo de minerales.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Síndrome de realimentación: el diagnóstico pendiente / Refeeding syndrome: the pending diagnosis

Introducción: El síndrome de realimentación (SR) puede definirse como el conjunto de alteraciones metabólicas desencadenadas tras la rápida reintroducción del soporte nutricional en pacientes severamente desnutridos o con ayuno prolongado. Puede tener repercusiones clínicas, neurológicas y cardiológicas. La hipofosfatemia es el fenómeno predominantemente asociado con el SR. Paciente masculino de 68 años con antecedentes de tabaquismo, EPOC y depresión. Ingresa a UTI por sepsis a foco respiratorio severamente desnutrido (por Valoración Global Subjetiva), con IMC 14.6 kg/m². Inicia nutrición enteral (NE) al 30% de sus requerimientos por riesgo de SR con P sérico basal de 3,9 mg/dl. Al 2do día no se dosa P ni Mg séricos, pero sí se observa K dentro de parámetros normales. Se progresa NE al 50%, y se observa al 3ro°día una disminución significativa del P a 2,1 mg/dl, llegando a 1,9 mg/dl el 4to°día, sin haber progresado aportes (K y Mg en descenso pero dentro de parámetros normales). Se carga al 4to°día con una ampolla de fosfato de potasio, evolucionando favorablemente. Objetivo: Destacar la importancia de prevenir el SR. Discusión: Se observó la repercusión bioquímica característica del SR. El momento de detección de la hipofosfatemia significativa (3ro°día) coincide con el promedio general visto en otros estudios. No hubieron signos clínicos, probablemente porque el P no tuvo un valor crítico. Como terapéutica, se utilizó la lenta progresión de aportes y la corrección de P fue tardía. Podría haber sido adecuada la suplementación de tiamina previo inicio de NE

Introduction: The refeeding syndrome (SR) can be defined as the metabolic alterations developed after a rapid nutrition repletion (oral, enteral, as well as parenteral feeding) of severely malnourished patients. It can have clinical, neurological and cardiological effects. Hypophosphatemia is the predominantl phenomenon associated with SR. A 68-year-old male patient with a history of smoking, COPD, and depression, who is admitted in ICU severely malnourished (Subjetive Global Assesment) due to sepsis at a respiratory focus, with a BMI of 14.6 kg / m². The patient initiates enteral nutrition (NE) at 30% of its requirements due to risk of SR, with baseline serum P value of 3.9 mg/dl. At day 2, no serum P or Mg is given, but K is observed within normal parameters. NE is progressed up to 50%, and a significant decrease of P at 2.1 mg/dl is observed at day 3, reaching 1.9 mg/dl at day 4, with no progress (K and Mg in decline but within normal parameters). He is loaded at day 4 with a potassium phosphate ampoule, evolving favorably. Objective: Highlighting the importance of preventing SR. Discussion: The characteristic biochemical repercussion of SR was observed. The moment of detection of significant hypophosphatemia (day 3) coincides with the general average seen in other studies. There were no clinical signs, probably because P didn´t have a critical value. As therapy, the slow progression of caloric contributions was used, and the correction of P was late. Thiamine supplementation may have been adequate prior to initiation of NE.