RESUMO
Hypophosphatemia (serum phosphate < 2.5 mg/dL) is a major concern when initiating nutritional support. We evaluated which factors contribute to hypophosphatemia development in critically ill patients, as well as the association between hypophosphatemia and mortality. A retrospective cohort study of patients who were ventilated for at least 2 days in a 16-bed mixed ICU. Data collected includes demographics, Acute Physiology & Chronic Health Evaluation 2 (APACHE2) admission score, Sequential Organ Failure Assessment score at 24 h (SOFA24), hourly energy delivery, plasma phosphate levels during the first 2 weeks of admission, ICU length of stay (LOS), length of ventilation (LOV), and mortality (ICU and 90 days). For the hypophosphatemia development model, we considered mortality as a competing risk. For mortality analysis, we used the Cox proportional hazards model considering hypophosphatemia development as a time-varying covariate. 462 patients were used in the analysis. 59.52% of the patients developed hypophosphatemia. Several factors were associated with a decreased risk of hypophosphatemia: age, BMI, pre-admission diabetes diagnosis, APACHE2, SOFA24, first kidney SOFA score, hospital admission time before ICU admission, and admission after liver transplantation. Admission due to trauma was associated with an increased risk of hypophosphatemia. Survival analysis with hypophosphatemia as a time-varying covariate showed a protective effect of hypophosphatemia from mortality (HR 0.447, 95% CI 0.281, 0.712). Age, APACHE2, and SOFA24 score were found to be significantly associated with ICU mortality. Fasting duration in the ICU before nutritional support initiation was not found to be significantly associated with hypophosphatemia. We examined several fasting intervals (12 h, 24 h, 36 h, 48 h, 60 h, 72 h). In each fast interval, we compared the prevalence of hypophosphatemia among patients who fasted the specified length of time, with those who did not fast for the same length of time. In each fasting interval, hypophosphatemia prevalence was lower in the fasting group compared to the non-fasting group. However, this difference was insignificant. BMI, APACHE2, and hospital LOS before ICU admission were inversely associated with hypophosphatemia development. Fasting for up to 72 h in the ICU before starting nutritional support did not affect hypophosphatemia occurrence. Hypophosphatemia was associated with lower mortality.
Assuntos
Estado Terminal , Hipofosfatemia , Unidades de Terapia Intensiva , Respiração Artificial , Humanos , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Estado Terminal/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fatores de Risco , APACHE , Tempo de Internação , Modelos de Riscos Proporcionais , Mortalidade HospitalarRESUMO
BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.
Assuntos
Hipercalcemia , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias das Paratireoides , Paratireoidectomia , Humanos , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/patologia , Masculino , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/complicações , Pessoa de Meia-Idade , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hipercalcemia/sangue , Adenoma/cirurgia , Adenoma/diagnóstico , Adenoma/patologia , Adenoma/sangue , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Hipofosfatemia/etiologia , Hipofosfatemia/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/diagnóstico , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/patologia , Diarreia/etiologia , Diarreia/diagnóstico , Detecção Precoce de Câncer/métodos , Gastroscopia , Resultado do TratamentoRESUMO
The clinical presentation, treatment, and follow-up of two boys with type 1 Dent disease who exhibited a Bartter-like phenotype were retropectively analysed. The related literature of pediatric patients with type 1 Dent disease who had hypokalemia and metabolic alkalosis was screened through databases such as PubMed, CNKI, and Wanfang until February 1, 2024, and common features among these patients were summarized through literature review. A total of 7 literatures were included, and 9 children were included in the analysis. All patients were male, presenting with significant low molecular weight proteinuria and hypercalciuria. Other prominent characteristic phenotypes included short stature (7/8), hypophosphatemia (8/9), and rickets (6/8). Seven previously reported patients had missense or nonsense mutations, while 2 patients in this study carried possible pathogenic mutations in the CLCN5 gene, c.315+2T>A (p.?) and c.584dupT (p.I196Yfs*6), respectively. Five patients were able to maintain blood potassium levels around 3 mmol/L with oral potassium chloride solution combined with non-steroidal anti-inflammatory drugs (ibuprofen or indomethacin). The follow-up showed that 2 patients developed chronic kidney disease stage 4 and stage 3 at the age of 13 and 21 years, respectively. The phenotypic overlap between Dent disease and Batter syndrome is considerable,with the distinguishing feature being the presence of significant low molecular weight proteinuria. Patients with type 1 Dent disease presenting with the Bartter-like phenotype have a high prevalence of short stature, hypophosphatemia, and rickets. Non-steroidal anti-inflammatory drugs can be used to correct hypokalemia in patients under periodic renal function assessment.
Assuntos
Fenótipo , Humanos , Masculino , Criança , Hipopotassemia , Mutação , Doença de Dent/genética , Doença de Dent/diagnóstico , Canais de Cloreto/genética , Hipofosfatemia , Síndrome de Bartter/genética , Síndrome de Bartter/diagnóstico , Hipercalciúria , Raquitismo/diagnóstico , Proteinúria , Doenças Genéticas Ligadas ao Cromossomo X , NefrolitíaseRESUMO
AIMS: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass. METHODS: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering. RESULTS: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020). CONCLUSION: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.
Assuntos
Compostos Férricos , Derivação Gástrica , Hipofosfatemia , Maltose , Fosfatos , Humanos , Feminino , Masculino , Derivação Gástrica/efeitos adversos , Maltose/análogos & derivados , Maltose/administração & dosagem , Maltose/uso terapêutico , Compostos Férricos/administração & dosagem , Compostos Férricos/uso terapêutico , Estudos Retrospectivos , Adulto , Fosfatos/sangue , Pessoa de Meia-Idade , Infusões Intravenosas , SuíçaRESUMO
Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a-/- mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a-/- mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a-/- mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a-/- mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a-/- only, the latter might facilitate the increase in plasma Pi in Npt2a-/- mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3.
Assuntos
Cálcio , Colecalciferol , Homeostase , Camundongos Knockout , Fosfatos , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa , Animais , Fosfatos/metabolismo , Cálcio/metabolismo , Homeostase/efeitos dos fármacos , Camundongos , Colecalciferol/farmacologia , Colecalciferol/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética , Rim/metabolismo , Rim/efeitos dos fármacos , Fator de Crescimento de Fibroblastos 23 , Hormônio Paratireóideo/metabolismo , Masculino , Hipofosfatemia/metabolismo , Hipofosfatemia/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIbRESUMO
BACKGROUND: Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients. METHODS: This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64-0.8 mmol/L; G3, iP 0.8-1.16 mmol/L; G4, iP 1.16-1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records. RESULTS: A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An "L-shaped" non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4. CONCLUSIONS: Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention.
Assuntos
Mortalidade Hospitalar , Hipofosfatemia , Tempo de Internação , Fosfatos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fosfatos/sangue , Estudos Transversais , Tempo de Internação/estatística & dados numéricos , Hipofosfatemia/mortalidade , Hipofosfatemia/sangue , Hipofosfatemia/epidemiologia , Idoso , Adulto , PrevalênciaRESUMO
AIM: Late-onset sepsis (LOS) is common in extreme prematurity. These infants are at risk of refeeding syndrome-associated hypophosphataemia. Our objective was to investigate whether hypophosphataemia predisposes to LOS in extremely premature neonates. METHODS: A retrospective case-control study of neonates born before 29 weeks' gestation in an Australian NICU from 2016 to 2020. Cases developed LOS or localised infection. Two controls, matched within 2 gestational weeks and 90 calendar days, were selected per case. RESULTS: Amongst 48 cases and 93 controls, cases were smaller at birth (767 g vs. 901 g, P = 0.01), but were otherwise comparable. Hypophosphataemia was more common in cases (26% vs. 15%, P = 0.18). Increased intravenous protein intake in the first week was protective against LOS (OR = 0.9, 95% CI 0.76-1.00, P = 0.04); median 2.1 g/kg/day in cases, 2.3 g/kg/day in controls. CONCLUSIONS: Hypophosphataemia as part of refeeding syndrome is prevalent and under-recognised in extremely premature neonates. We did not find an association between hypophosphataemia and LOS. Low intravenous protein may be an independent risk factor for infection.
Assuntos
Hipofosfatemia , Lactente Extremamente Prematuro , Humanos , Recém-Nascido , Estudos de Casos e Controles , Estudos Retrospectivos , Feminino , Masculino , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Sepse/epidemiologia , Austrália/epidemiologia , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/etiologia , Unidades de Terapia Intensiva Neonatal , Fatores de Risco , Sepse Neonatal/epidemiologiaRESUMO
PURPOSE: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes. METHODS: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models. RESULTS: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p = < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p = < 0.05 for all comparisons) and overall (p = 0.0006). CONCLUSIONS: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.
Assuntos
Anemia Ferropriva , Compostos Férricos , Hipofosfatemia , Doenças Inflamatórias Intestinais , Qualidade de Vida , Humanos , Masculino , Feminino , Método Duplo-Cego , Adulto , Pessoa de Meia-Idade , Compostos Férricos/administração & dosagem , Compostos Férricos/uso terapêutico , Anemia Ferropriva/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/psicologia , Hipofosfatemia/tratamento farmacológico , Maltose/análogos & derivados , Maltose/administração & dosagem , Maltose/uso terapêutico , Administração Intravenosa , Europa (Continente)RESUMO
OBJECTIVES: Acute pancreatitis (AP) is a complex disease representing a significant portion of gastrointestinal-related hospitalizations in the U.S. Understanding risk factors of AP might provide attractive therapeutic targets. We evaluated hypophosphatemia a prognostic marker in AP. METHODS: We performed a retrospective review of electronic health records of patients with AP from 01/ 01/2012-12/31/2021 at Cedars-Sinai Medical Center with serum phosphate measured within 48 hours of admission. Multivariable logistic regression modeling was used to evaluate associations with ICU admission and AP severity. Multivariable log-linear modeling was employed to examine associations with length of stay (LOS). RESULTS: Of 1526 patients admitted for AP, 33% (499) had a serum phosphate level measured within 48 hours. Patients with hypophosphatemia were more likely to have ICU admission (adjusted odds ratio (AOR) = 4.57; 95% confidence interval (CI): 2.75-7.62; P < 0.001), have a longer hospital stay (log-LOS = 0.34; SE; 0.09; 95% CI: 0.17-0.52; P < 0.001), and have moderate or severe AP (AOR = 1.80; 95% CI: 1.16-2.80; P < 0.001) compared with those without hypophosphatemia. CONCLUSION: Serum phosphate is infrequently measured in patients with AP and shows promise as an early prognostic marker for outcomes of AP.
Assuntos
Biomarcadores , Hipofosfatemia , Tempo de Internação , Pancreatite , Humanos , Hipofosfatemia/sangue , Hipofosfatemia/diagnóstico , Feminino , Masculino , Estudos Retrospectivos , Pancreatite/sangue , Pancreatite/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Tempo de Internação/estatística & dados numéricos , Biomarcadores/sangue , Adulto , Idoso , Doença Aguda , Índice de Gravidade de Doença , Fosfatos/sangue , Fatores de Risco , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos LogísticosRESUMO
Diabetic ketoacidosis (DKA) is one of the most serious complications of type 1 diabetes mellitus. Its treatment requires fluid and electrolyte replacement and insulin. Hypophosphatemia as a complication of treatment has been scarcely evaluated. OBJECTIVES: To estimate the incidence of hypophosphatemia in children with DKA, treated with subcutaneous regular insulin (IRS), and to explore factors associated with this complication. PATIENTS AND METHOD: Prospective, observational study. Patients diagnosed with DKA hospitalized in the general care ward were included. Data on phosphatemia, glycemia, acid-base status, and IRS amount (U/kg) received were recorded at baseline and after 24 h of treatment. Hypophosphatemia was defined as values below 2.5 mg/dl. The correlation between initial phosphate and at 24 h of treatment was evaluated; the incidence of hypophosphatemia at 24 h was expressed as a percentage of the total number of patients. RESULTS: 30 patients were included, 15 were female, mean age 11.4 ± 3.2 years. At 24 h of treatment with IRS, 36.7% (95%CI 22-55%) presented hypophosphatemia, mean value 1.9 ± 1.5 mg/dl. Initial bicarbonate < 10 mmol/L acted as a predictor of hypophosphatemia (OR 7.5; 95%CI 1.4-39.8%; p = 0.01). No patient required intravenous phosphate correction, and no associated clinical complications were observed. CONCLUSION: In the group studied, the incidence of hypophosphatemia reached 36.7% at 24 hours of treatment. Initial bicarbonate lower than 10 mmol/L was significantly associated with hypophosphatemia. No complications associated with hypophosphatemia were observed.
Assuntos
Cetoacidose Diabética , Hipoglicemiantes , Hipofosfatemia , Insulina , Humanos , Feminino , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Masculino , Cetoacidose Diabética/epidemiologia , Criança , Estudos Prospectivos , Insulina/uso terapêutico , Adolescente , Injeções Subcutâneas , Prevalência , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , IncidênciaRESUMO
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility fractures, muscle pain, and progressive weakness. TIO has been associated with increased production of the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) usually by mesenchymal tumors of soft tissue or bone (Phosphaturic Mesenchymal Tumors-PMTs). In rare cases TIO may be observed in association with other malignancies. We report the case of a 66-year-old woman with an occasional diagnosis of both a PMT and an ovarian cancer during the evaluation of TIO. We also systematically review the literature to discover possible correlations between osteomalacia, FGF23 production, and ovarian cancer. Four studies were eligible for the analysis. Two case reports described an association between TIO development and ovarian cancer, whereas the two case-control studies hypothesized a possible correlation between FGF/FGF receptor axis and cancer development. Although it does not provide conclusive evidence regarding the association between TIO and ovarian cancer, this case report highlights the possibility that in the diagnostic workup of suspected TIO, both FGF23-secreting tumors distinct from PMT and tumors unrelated to the clinical presentation of TIO could be identified. This information is important for guiding successful tumor staging and determining the necessity for surgical intervention and/or eventual adjuvant therapy.
Assuntos
Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Osteomalacia , Neoplasias Ovarianas , Síndromes Paraneoplásicas , Humanos , Feminino , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Idoso , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/diagnóstico , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Neoplasias de Tecido Conjuntivo/diagnóstico , Neoplasias de Tecido Conjuntivo/complicações , Neoplasias de Tecido Conjuntivo/etiologia , Hipofosfatemia/etiologia , Hipofosfatemia/complicaçõesRESUMO
Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and renal excretion, which are regulated by various hormones, such as PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23. In this review we provide an update of several genetic disorders that affect phosphate transporters through cell membranes or the phosphate-regulating hormones, and, consequently, result in hypophosphatemia.
Assuntos
Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Hipofosfatemia , Hormônio Paratireóideo , Humanos , Hipofosfatemia/genética , Hipofosfatemia/etiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Hormônio Paratireóideo/metabolismo , Fosfatos/metabolismo , Vitamina D/metabolismo , Vitamina D/análogos & derivados , Proteínas Klotho , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Absorção Intestinal/genética , Glucuronidase/genética , Glucuronidase/metabolismo , Fósforo/metabolismoRESUMO
Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated. 68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.
Assuntos
Fator de Crescimento de Fibroblastos 23 , Neoplasias de Tecido Conjuntivo , Osteomalacia , Humanos , Osteomalacia/etiologia , Feminino , Neoplasias de Tecido Conjuntivo/diagnóstico , Neoplasias de Tecido Conjuntivo/cirurgia , Adulto , Síndromes Paraneoplásicas/diagnóstico , Hipofosfatemia/etiologia , Fatores de Crescimento de Fibroblastos/sangue , Fraturas do Fêmur/cirurgia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/cirurgia , Fraturas Espontâneas/diagnóstico por imagem , Fosfatos/sangueRESUMO
Phosphaturic mesenchymal tumors (PMT) are rare and distinctive tumors that typically result in paraneoplastic syndrome known as tumor-induced osteomalacia (TIO). We report a case of bilateral osteoporotic femoral neck fracture caused by PMT. PMT was surgically resected, followed by sequential treatment of bilateral femoral neck fractures with total hip arthroplasty (THA). A 49-year-old perimenopausal woman experienced consistent bone pain with limb weakness persisting for over 2 years. Initially, she was diagnosed with early osteonecrosis of the femoral head and received nonsurgical treatment. However, from 2020 to 2022, her pain extended to the bilateral shoulders and knees with increased intensity. She had no positive family history or any other genetic diseases, and her menstrual cycles were regular. Physical examination revealed tenderness at the midpoints of the bilateral groin and restricted bilateral hip range of motion, with grade 3/5 muscle strength in both lower extremities. Laboratory findings revealed moderate anemia (hemoglobin 66 g/L), leukopenia (2.70 × 109/L), neutropenia (1.28 × 109/L), hypophosphatemia (0.36 mmol/L), high alkaline phosphatase activity (308.00 U/L), and normal serum calcium (2.22 mmol/L). After surgery, additional examinations were performed to explore the cause of hypophosphatemic osteomalacia. After definitive diagnosis, the patient underwent tumor resection via T11 laminectomy on August 6, 2022. Six months after the second THA, the patient regained normal gait with satisfactory hip movement function without recurrence of PMT-associated osteomalacia or prosthesis loosening. By providing detailed clinical data and a diagnostic and treatment approach, we aimed to improve the clinical understanding of femoral neck fractures caused by TIO.
Assuntos
Fraturas do Colo Femoral , Neoplasias de Tecido Conjuntivo , Osteomalacia , Síndromes Paraneoplásicas , Humanos , Feminino , Osteomalacia/etiologia , Pessoa de Meia-Idade , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/etiologia , Fraturas do Colo Femoral/complicações , Síndromes Paraneoplásicas/etiologia , Neoplasias de Tecido Conjuntivo/etiologia , Neoplasias de Tecido Conjuntivo/diagnóstico , Neoplasias de Tecido Conjuntivo/cirurgia , Hipofosfatemia/etiologia , Artroplastia de QuadrilRESUMO
PURPOSE OF REVIEW: Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders. RECENT FINDINGS: The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region. SUMMARY: Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies.
Assuntos
Anticorpos Monoclonais Humanizados , Raquitismo Hipofosfatêmico Familiar , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Osteomalacia , Humanos , Fatores de Crescimento de Fibroblastos/sangue , Osteomalacia/etiologia , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hipofosfatemia/etiologia , Síndromes Paraneoplásicas , Neoplasias de Tecido Conjuntivo/etiologia , Anticorpos Monoclonais/uso terapêutico , Fosfatos/metabolismo , Fosfatos/sangueRESUMO
BACKGROUND: Physiological processes rely on phosphate, which is an essential component of adenosine triphosphate (ATP). Hypophosphatasia can affect nearly every organ system in the body. It is crucial to monitor newborns with risk factors for hypophosphatemia and provide them with the proper supplements. We aimed to evaluate the risk factors and develop a nomogram for early hypophosphatemia in term infants. METHODS: We conducted a retrospective study involving 416 term infants measured serum phosphorus within three days of birth. The study included 82 term infants with hypophosphatemia (HP group) and 334 term infants without hypophosphatemia (NHP group). We collected data on the characteristics of mothers, newborn babies, and childbirth. Furthermore, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for hypophosphatemia in term infants, and a nomogram was developed and validated based on the final independent risk factors. RESULTS: According to our analysis, the multivariate logistic regression analysis showed that male, maternal diabetes, cesarean delivery, lower serum magnesium, and lower birth weight were independent risk factors for early hypophosphatemia in term infants. In addition, the C-index of the developed nomogram was 0.732 (95% CI = 0.668-0.796). Moreover, the calibration curve indicated good consistency between the hypophosphatemia diagnosis and the predicted probability, and a decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSIONS: The analysis revealed that we successfully developed and validated a nomogram for predicting early hypophosphatemia in term infants.
Assuntos
Hipofosfatasia , Hipofosfatemia , Recém-Nascido , Lactente , Feminino , Gravidez , Masculino , Humanos , Nomogramas , Estudos Retrospectivos , Hipofosfatemia/diagnóstico , Hipofosfatemia/etiologia , Trifosfato de AdenosinaRESUMO
Refeeding syndrome (RFS) is a potentially life-threatening complication in malnourished (critically ill) patients. The presence of various accepted RFS definitions and the inclusion of heterogeneous patient populations in the literature has led to discrepancies in reported incidence rates in patients requiring treatment at an intensive care unit (ICU). We conducted a prospective observational study from 2010 to 2013 to assess the RFS incidence and clinical characteristics among medical ICU patients at a large tertiary center. RFS was defined as a decrease of more than 0.16 mmol/L serum phosphate to values below 0.65 mmol/L within seven days after the start of medical nutrition therapy or pre-existing serum phosphate levels below 0.65 mmol/L. Overall, 195 medical patients admitted to the ICU were included. RFS was recorded in 92 patients (47.18%). The presence of RFS indicated significantly altered phosphate and potassium levels and was accompanied by significantly more electrolyte substitutions (phosphate, potassium, and magnesium). No differences in fluid balance, energy delivery, and insulin requirements were detected. The presence of RFS had no impact on ICU length of stay and ICU mortality. Screening for RFS using simple diagnostic criteria based on serum phosphate levels identified critically ill patients with an increased demand for electrolyte substitutions. Therefore, stringent monitoring of electrolyte levels is indicated to prevent life-threatening complications.
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Hipofosfatemia , Terapia Nutricional , Síndrome da Realimentação , Humanos , Estado Terminal/terapia , Eletrólitos , Hipofosfatemia/etiologia , Fosfatos , Potássio , Síndrome da Realimentação/etiologia , Estudos ProspectivosRESUMO
OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.
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Estado Terminal , Hipofosfatemia , Fosfatos , Humanos , Hipofosfatemia/economia , Masculino , Feminino , Pessoa de Meia-Idade , Estado Terminal/terapia , Estado Terminal/economia , Fosfatos/sangue , Estudos Prospectivos , Idoso , Nutrição Enteral/economia , Nutrição Enteral/métodos , Hidratação/métodos , Hidratação/economia , Adulto , Custos de Cuidados de Saúde/estatística & dados numéricos , Unidades de Terapia IntensivaRESUMO
Fibroblast growth factor 23 (FGF23) production has recently been shown to increase downstream of Gαq/11-PKC signaling in osteocytes. Inactivating mutations in the gene encoding Gα11 (GNA11) cause familial hypocalciuric hypercalcemia (FHH) due to impaired calcium-sensing receptor signaling. We explored the effect of Gα11 deficiency on FGF23 production in mice with heterozygous (Gna11+/-) or homozygous (Gna11-/-) ablation of Gna11. Both Gna11+/- and Gna11-/- mice demonstrated hypercalcemia and mildly raised parathyroid hormone levels, consistent with FHH. Strikingly, these mice also displayed increased serum levels of total and intact FGF23 and hypophosphatemia. Gna11-/- mice showed augmented Fgf23 mRNA levels in the liver and heart, but not in bone or bone marrow, and also showed evidence of systemic inflammation with elevated serum IL-1ß levels. Furin gene expression was significantly increased in the Gna11-/- liver, suggesting enhanced FGF23 cleavage despite the observed rise in circulating intact FGF23 levels. Gna11-/- mice had normal renal function and reduced serum levels of glycerol-3-phosphate, excluding kidney injury as the primary cause of elevated intact FGF23 levels. Thus, Gα11 ablation caused systemic inflammation and excess serum FGF23 in mice, suggesting that patients with FHH - at least those with GNA11 mutations - may be at risk for these complications.