Hypophosphatemia

Ethical aspects of this study were reviewed and approved by the Human Research Ethics Committee at the Ashikaga Red Cross Hospital. This study was performed after obtaining informed consent from all participants upon admission. For a patient below the age of 18 years, informed parental consent was also obtained. Diagnosis was based on criteria in the ICD-10, and each patient was diagnosed by two of the three psychiatrists (MF, AK, and TT), each of whom had > 10 years of experience in psychiatry at the time of the study. Participants were recruited from the neuropsychiatric unit in Ashikaga Red Cross Hospital during the period from April 1999 to March 2018. Among 96 admissions with eating disorders that were managed in our unit (F50.0, anorexia nervosa; F50.2, bulimia nervosa), only those with a body mass index of < 16 (68 admissions) were included to investigate refeeding hypophosphatemia, which are considered severe malnutrition among patients with anorexia nervosa [6 (link)]. The five patients who discharged themselves from the hospital against medical advice or declined repeated blood tests were excluded. Thus, 63 admissions met the abovementioned criteria and were included in this study. Consecutive admissions with recurrences of anorexia nervosa were included as separate admissions [2 (link), 4 (link)] because weight and nutritional status, and thus risk of refeeding syndrome, changed with each admission [2 (link)]. In this study, among a total of 37 patients, all of whom were Japanese, 12 had two or more consecutive admissions, which adds up to a total of 63 admissions. However, considering a potential bias toward a correlation, analyses were repeated using only 37 independent patients.

Electronic medical records of eligible participants were retrospectively reviewed. As outcome indicators, the following two measures were used: the extent of the decrease in serum phosphorus levels from admission to the nadir phosphorus level during the first 2 weeks after admission and the development of refeeding hypophosphatemia (< 2.5 mg/dl serum phosphorus). Explanatory variables included data at admission, i.e., age, sex, body mass index, anorexia nervosa subtype (restrictive or binge-purge), data obtained from laboratory tests (BUN/Cr ratio, serum phosphorus and potassium levels, hemoglobin, and albumin), and indicators involving treatment, i.e., the rate of weight gain during the first 7 days, caloric intake, and amount of intravenous phosphate administered. Classification of anorexia nervosa subtype, restrictive or binge-purge (bulimic-type), was carried out because binge-purge behavior often influences serum electrolytes levels through repeated vomiting, in particular, serum potassium level [7 (link)]. Body mass index was calculated as the weight of the individual (in kilograms) divided by the square of the height of the individual (in meters). To calculate the rate of weight gain during the first 7 days, we divided the kilograms gained during the first 7 days by the initial weight. Total caloric intake (kilocalories) refers to the average total caloric intake from day 1 through day 7 [4 (link)], including both oral intake and intravenous infusion therapy. If the patient ate only half the provided 1200-kcal meal, the actual amount of total caloric intake was reduced to 600 kcal. To accurately investigate the effect of energy intake on an individual patient depending on his or her weight, an indicator of total caloric intake per body weight was used for this analysis (total caloric intake divided by body weight), which is widely used for diet therapy for diabetes mellitus [8 (link)]. Intravenous phosphorus administration, which was not measured in previous studies of predictors for refeeding hypophosphatemia, was included in this study and was defined as the average total intravenous phosphorus administration (millimoles) from day 1 through day 7. In our unit, phosphorus administration is done intravenously, not orally, during the first 7 days. To better calculate the effect of intravenous phosphorus supplementation on refeeding syndrome, the amount of intravenous phosphorus administered was divided by total caloric intake, and this value was used in the statistical analysis. This is because intracellular movement of serum phosphorus is dependent on reintroduction of nutrients, which is mediated by surges in insulin [9 (link)].
A laboratory panel, including serum phosphorus, was carried out on admission. From the second examination onwards, each blood test was conducted at 7:30 in the morning before breakfast. To precisely identify the nadir serum phosphorus level, the patients underwent serial laboratory tests; 47 admissions (74.6%) had the test again on the second hospital day, 45 (71.4%) on the third hospital day, 45 (71.4%) on the fourth hospital day, 29 (46.0%) on the fifth hospital day, and 34 (53.6%) on the sixth day, and they continued to have blood tests until the serum phosphorus level went up again. We note that 59 of 63 admissions (93.7%) had the second laboratory test within 48 h of the first.

We conducted a multicenter, prospective, non-interventional study to determine reference ranges for intact PTH in apparently healthy, normocalcemic, normophosphatemic individuals according to vitamin D status, using the Elecsys^® PTH and Elecsys^® Vitamin D total II electrochemiluminescence immunoassays. Volunteers were enrolled at three geographic sites across the USA (Century Clinical Research Inc., Daytona Beach, Florida, USA; NB Research, Indianapolis, Indiana, USA; Prism Research, LLC., St Paul, Minnesota, USA). Prior to study initiation, ethical approval was obtained from relevant institutional review boards. The study was conducted in accordance with the principles of the Declaration of Helsinki and International Conference on Harmonisation guidelines for Good Clinical Practice; all participants provided written informed consent.
Apparently, healthy individuals aged ≥ 21 years with body mass index (BMI) 18–30 kg/m² were enrolled. Key inclusion criteria were: calcium (≤ 60 years, 8.6–10.0 mg/dL; > 60 years, 8.8–10.2 mg/dL), phosphate (2.5–4.5 mg/dL), and creatinine (female 0.51–0.95 mg/dL; male 0.67–1.17 mg/dL), based on medical history and confirmatory testing; geographic location within ± 2° latitude or 138 miles north/south of collection site for ≥ 4 weeks. Key exclusion criteria were pregnancy (self-declared/≤ 12 months); breastfeeding or lactation (≤ 3 months); endocrine/metabolic disease known to affect vitamin D metabolism or interfering with bone metabolism; abnormal calcium, including hypocalcemia, hypocalciuria, hypophosphatemia, or hypercalcemia caused by primary hyperparathyroidism, vitamin D overdose/intoxication, or cancer; bariatric surgery; vigorous exercise (> 2 h/day); hospitalization/immobilization > 7 days (≤ 3 months); bone fracture (≤ 3 months). Individuals taking the following supplements or drugs influencing bone and calcium/phosphorus metabolism were excluded: PTH analogs and/or modified PTH compound; other anabolic medication; anticonvulsants; antiresorptive drugs, e.g., bisphosphonates, calcitonin; hormone replacement therapy; calcium carbonate; diuretics; fluoride; glucocorticoids; high-dose vitamin D supplements (> 1000 IU/day).