Hypercalcitoninemia and hypocalcemia in acutely ill children: studies in serum calcium, blood ionized calcium, and calcium-regulating hormones

We studied the hypotheses that serum calcium and blood ionized calcium would be low in acutely ill children and would rise with clinical improvement. In 15 children admitted to the pediatric intensive care unit, the blood ionized calcium level was 4.45 +/- 0.06 mg/dl (1.11 +/- 0.015 mmol/L) on entry versus 5.17 +/- 0.03 mg/dl (1.29 +/- 0.01 mmol/L) in control subjects (p less than 0.005), rose significantly on days 2 and 3, and was 5.12 +/- 0.04 mg/dl (1.28 +/- 0.01 mmol/L) at discharge (p less than 0.005). Changes in serum calcium level were similar, whereas serum magnesium and phosphorus levels were normal and did not change. Basal serum parathyroid hormone concentrations were elevated, rose further during the study, and were normal at discharge. Serum parathyroid hormone levels correlated inversely with blood ionized calcium levels, indicating that compensatory hyperparathyroidism occurs with low blood ionized calcium concentrations. Basal serum calcitonin values were evaluated on entry and decreased with clinical improvement. Serum calcitonin levels correlated significantly with low blood ionized calcium levels, indicating that hypercalcitoninemia may play a role in the pathogenesis of hypocalcemia in these children. Urine calcium excretion was not increased in the four children studied. We speculate that with clinical improvement, a rise in serum parathyroid hormone levels and a decline in serum calcitonin levels may help restore normocalcemia in these acutely ill children.     

Calcium-regulating hormones and minerals from birth to 18 months of age: a cross-sectional study. II. Effects of sex, race, age, season, and diet on serum minerals, parathyroid hormone, and calcitonin

The influence of sex, race, age, season, and diet (cow's milk formula v human milk) on serum minerals and calcium-regulating hormones in infants less than 18 months of age is described in this study of 198 infants. No sex differences were observed in calcium, magnesium, phosphorus, parathyroid hormone, or calcitonin concentrations. Black infants had decreased serum phosphorus concentrations compared with white infants. There was a decrease in serum ionized calcium and phosphorus levels with age. During winter, there were significant increases in serum calcium and magnesium and decreases in serum phosphorus, parathyroid hormone, and calcitonin levels. Formula-fed infants had increased serum phosphorus and decreased ionized calcium concentrations compared with infants fed human milk. Thus, race, age, season, and diet appear to exert significant effects on serum minerals and calcium-regulating hormones in infancy. Interpretation of these mineral and hormone concentrations in normal or diseased states should be based on normative data specific to race, age, season, and diet.     

Interleukin-6 in cerebrospinal fluid of patients with central nervous system infections

Interleukin(IL)-6 levels were measured in cerebrospinal fluid (CSF) and serum samples from pediatric patients with central nervous system (CNS) infections by means of an enzyme-linked immunosorbent assay. Mean IL-6 concentrations in CSF samples from patients with bacterial meningitis (49017 44 730 pg/ml) were significantly higher than those in patients with aseptic meningitis (10761572 pg/ml) or encephalitis (409835 pg/ml). In aseptic meningitis and encephalitis, IL-6 levels in serum were within the lower ranges (< 100 pg/ml), in contrast with the highly elevated levels found in bacterial meningitis (14 33218 385 pg/ml). In 5 of the 15 patients with encephalitis, elevated levels of IL-6 were observed in the initial CSF samples despite normal findings of routine CSF examinations. Also, sequential CSF samples revealed that there was an increase in the CSF cell count in two of the five patients. These results validated the potential of measuring IL-6 in CSF samples for the purpose of providing additional information on routine laboratory test results. D Central nervous system infection, cerebrospinal fluid, children, enzyme-linked immunosorbent assay, interleukin-6.
M Narita, Department of Pediatrics, Hokkaido University School of Medicine, N 15 W 7, Kita-ku, Sapporo 060, Japan     

基质金属蛋白酶检测对鉴别化脓性脑膜炎与病毒性脑炎的价值

目的通过对血清和脑脊液(CSF)基质金属蛋白酶(MMPs)水平检测,探讨其对小儿化脓性脑膜炎(化脑)与病毒性脑炎(病脑)的鉴别诊断价值。方法采用ELISA法检测18例化脑及22例病脑患儿急性期血清和CSF中MMP-2、MMP-9水平,并与正常对照组比较。结果化脑、病脑患儿血清和CSF中MMP-2、MMP-9水平显著高于正常对照组(P<0.001),且化脑组显著高于病脑组(P<0.001)。结论血清和CSF中MMP-2、MMP-9检测,对小儿化脑与病脑有早期诊断和鉴别诊断价值,为临床尽早用药提供实验室依据。     

The value of CSF adenosine deaminase levels in the differential diagnosis of childhood meningitis.

In this study, adenosine deaminase (ADA) levels of serum and cerebrospinal fluid (CSF) in a total 28 children (13 with bacterial meningitis, 5 with mumps meningoencephalitis and 10 with febrile convulsions) were determined. The comparisons between the serum values were insignificant (p greater than 0.05) but the CSF levels of the children with bacterial meningitis were higher than in the others (p less than 0.05). These findings suggest that serum ADA levels are not important in the diagnosis and differential diagnosis of these diseases. However, ADA levels of CSF may be useful in differentiating between bacterial and viral meningitis.     

中枢神经系统感染患儿脑脊液和血清补体C3、C4变化

目的：观察中枢神经系统感染患儿脑脊液（CSF）和血清补体C3、C4水平变化。方法：采用免疫透射比浊法检测14例细菌性脑膜炎（化脑组）及18例病毒性脑炎（病脑组）患儿急性期CSF和血清中补体C3、C4水平，并选取上呼吸道感染患儿16例为对照组，同时检测对照组CSF及血清补体C3、C4水平。对3组进行对照分析。结果：1．化脑组CSF和血清补体C3、C4水平明显高于病脑和对照组（F=46．878，93．104，22．603，80．647 Pa〈0．01），病脑与对照组比较差异无统计学意义（Pa〉0．05）。2．化脑组CSF中补体C3、C4水平与其血清水平均无相关性（r=0．036，0．129 Pa〉0．05）。结论：测定CSF和血清补体C3、C4水平有助于早期诊断及鉴别诊断中枢神经系统感染。     

Countercurrent immunoelectrophoresis in the evaluation of childhood infections

Samples of CSF, serum, and urine from 162 children with a clinical diagnosis of possible bacterial infection were examined by CIE within 1 hr of admission to the hospital. Results obtained were compared to information derived from gram stain and bacterial cultures of these specimens. Thirty-eight of 59 patients with culturally proved bacterial infections had positive CIE determinations at the time of admission. Highest correlation between culture and CIE results was in patients with meningitis due to Hemophilus influenzae type b while poorest correlation was obtained in children with pneumococcal septicemia. PRP within serum or CSF was quantitated on 21 occasions in patients with H. influenzae meningitis. Patients who experienced sequelae of their meningitis had significantly (p less than 0.005-0.025) higher levels of PRP within CSF and serum than those whose recovery was uneventful.     

化脓性脑膜炎患儿血清及脑脊液中C反应蛋白变化及临床意义

目的　探讨化脓性脑膜炎患儿血清和脑脊液(CSF)中C反应蛋白(CRP)变化及其与病原菌的关系。方法　将2 0 0 1年3月至2 0 0 4年3月在广西右江民族医学院附属医院住院的6 2例化脓性脑膜炎患儿分为革兰阳性(G+ )组与革兰阴性(G-)组,选取同期非感染患儿2 6例作为对照组,采用快速免疫透射比浊法分别检测血清和CSF中CRP质量浓度;同时分别计算G+ 组与G-组CSF中CRP与血清CRP的比值。结果　G+ 组、G-组血清CRP质量浓度明显高于对照组(均P <0 .0 1) ,G+ 组与G-组血清CRP质量浓度差异无显著性(P >0. 0 5 ) ,G-组CSF中CRP质量浓度明显高于G+ 组和对照组(均P <0 . 0 1) ,G+ 组与对照组CSF中CRP质量浓度差异无显著性(P>0 . 0 5 ) ;CSF中CRP与血清CRP比值G-组高于G+ 组(P <0 .0 1)。结论　G+ 脑膜炎CSF中CRP变化不明显,而G-脑膜炎CSF中CRP明显升高,CSF与血清CRP比值升高,其变化对化脓性脑膜炎病原菌的鉴别有一定的临床意义。     

Biological effects and activity threshold of a long-acting purified porcine calcitonin in the child

The biologic effects of a purified long-acting porcine calcitonin (pTCT) were investigated in 45 children without any known renal, skeletal, endocrine, or metabolic disorder. pTCT was given as a single im injection at dose levels varying from 1 to 150 MRC u/1.73 m2. Administration of the highest dose was followed by a decrease in serum calcium and phosphorus concentrations and in tubular reabsorption of phosphorus, serum calcium and phosphorus concentrations and in tubular reabsorption of phosphorus. Mean maximal variation of serum calcium was -- 13.8 +/- 2.1 mg/l in children less than 3 years old, versus -- 8.2 +/- 0.9 mg/l (p less than 0.01) in older ones. Such an age-related differences was not observed for the hypophosphatemic action of pTCT. In 40 subjects aged 3 to 14 years the threshold for pTCT hypocalcemic activity was between 1 and 5 MRC u/1.73 m2. No significant differences in the effects on serum calcium of either 10, 25, 75 or 150 MRC u/1.73(2) m could be found. The threshold for pTCT hypophosphatemic activity was between 10 and 25 MRC u/1.73 m2 with, similary, no dose-response relationship for doses varying from 25 to 150 MRC u/1.73 m2. The present data demonstrate the high sensitivity of children, especially those younger than 3 years, to pTCT; furthermore, the lack of a dose-response relationship indicates that the pharmacological use of pTCT in pediatrics at doses higher than 10 to 25 MRC u/1.73 m2 is unnecessary.     

LATE EVOLUTION OF SERUM IMMUNOREACTIVE PARATHYROID HORMONE, CALCITONIN AND PLASMA 25-HYDROXY CHOLECALCIFEROL CONCENTRATIONS IN VERY LOW BIRTHWEIGHT INFANTS

ABSTRACT. Sunn, L., Rigal, D., Krederich, A. and Lahet, C. (Department of Neonatology, Hopital Debrousse and Laboratory of polypeptide hormones, Hopital E. Herriot, Lyon, France). Late evolution of serum immunoreactive parathyroid hormone, calcitonin and plasma-hydroxycholecalciferol concentrations in very low birthweight infants. Acta Paediatr Scand, 70:479,.–The plasma concentrations of 25-hydroxycholecalciferol (25-OH-CC), immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) were measured at the age of 30 and 66 days in thirteen preterm neonates (birthweight: 970 to 1300 g). At the age of 30 days when all infants were fed only with breast milk (BM) serum iCT and iPTH levels were normal. During the second month 7 infants were fed with BM only (control group) and 6 infants were supplemented with formula (supplemented group). At the age of 66 days, mean ± S.D. serum iPTH concentration was higher in the supplemented group than in the control group: 169±79 vs. 60±33 μlEq/ml (p≤0.01). Serum iCT levels remained undetectable (<150 pg/ml) in both groups. Plasma 25-OH-CC concentrations were normal and similar in both groups. Serum iPTH concentrations were positively correlated with phosphorus intake and negatively correlated with calcium intake from BM only. The results suggest that secondary hyperparathyroidism can be detected in very low birthweight infants supplemented with a formula, probably because of a phosphorus load or decreased intestinal absorption of calcium.     

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目的观察中枢神经系统感染患儿血清和脑脊液(CSF)中基质金属蛋白酶(MMP-2、MMP-9)水平,并结合CSF白蛋白指数(AQ),探讨MMP-2、MMP-9在中枢神经系统感染血脑屏障(blood-brainbarrier,BBB)破坏中的作用。方法2004-09—2005-10河北医大附属二院采用ELISA法检测18例化脓性脑膜炎患儿急性期、恢复期及22例病毒性脑炎患儿急性期血清和CSF中MMP-2、MMP-9水平,并与非中枢神经系统感染对照组比较。结果化脓性脑膜炎(化脑)、病毒性脑炎(病脑)患儿急性期血清和CSF中MMP-2、MMP-9水平显著高于正常对照组(P<0·001),且化脑组显著高于病脑组(P<0·001)。化脑组恢复期患儿血清和CSF中MMP-2、MMP-9水平与对照组无明显差异(P>0·05)。结论中枢神经系统感染患儿血清和CSF中MMP-2、MMP-9水平显著增高,提示MMP-2、MMP-9可能参与了中枢神经系统感染的病理过程。     

Calcium, magnesium, and glucose levels in blood and CSF of children with febrile convulsions.

Levels of calcium, magnesium, and glucose were measured in the blood and cerebrospinal fluid (CSF) of children with febrile convulsions. Calcium and magnesium levels were within the normal range and the blood: CSF ratios were similar to those of normal subjects. Hyperglycaemia was a frequent finding and was reflected in raised CSF glucose levels. Blood glucose levels were only transiently raised and none of the children had diabetes mellitus.     

新生儿缺氧缺血性脑病血浆与脑脊液降钙素基因相关肽的研究

目的　 探讨降钙素基因相关肽 (CGRP)在新生儿缺氧缺血性脑病 (HIE)中的变化及其意义。 方法 　应用放射免疫分析法测定 3 1例新生儿HIE患儿和 12例正常新生儿血浆CGRP水平及 2 4例HIE患儿脑脊液CGRP水平。 结果 　HIE患儿急性期血浆CGRP水平显著高于对照组 (P <0 0 5 ) ,且随HIE程度加重而增高。中、重度HIE急性期与恢复期比较均具有显著性差异 (P均 <0 0 1)。CT异常组血浆和脑脊液CGRP水平均高于CT正常组。血浆与脑脊液CGRP之间呈正相关关系。 结论 　CGRP参与了HIE的病理过程 ,在HIE病程中对脑损伤可能具有一定保护作用。     

HYPOCALCEMIA IN INFANTS OF DIABETIC MOTHERS

ABSTRACT. Twenty-two infants of diabetic mothers (IDM) were studied and were divided into two groups: a first group of 14 IDM did not receive vitamin D3 and was studied at birth and at 2, 24, 48 and 120 hours; a second group was given daily dosage of 60 μg of vitamin D3 from 3 hours to 120 hours and was studied at 2 hours and 120 hours.
In the first group, serum calcium levels decreased markedly during the first 24 hours of life (mean ± SD: 1.77±0.3 mmol/1, p <0.01) and remained low at 5 days. Serum phosphorus levels remained normal but serum magnesium levels decreased significantly at 24 hours (mean ± SD: 0.64±0.108 mmol/1, p <0.01) and returned to normal at 5 days. Serum immunoreactive parathormone levels increased consistently to high levels at 24 hours and remained elevated at 120 hours ( p <0.001). Serum immunoreactive calcitonin levels increased at 24 hours ( p <0.001) and decreased at 120 hours to low or undetectable values in all infants.
In group II, serum 25O-HD levels and 1.25 OH₂ D levels increased significantly ( p <0.001) respectively to 27.2±2.7 ng/ml and 114±20 pg/ml at 5 days. The results of this study show hypocalcemia to be a common event in IDM during the first days of life and furthermore hypophosphatemia, hypoparathyroidism, hypomagnesemia or defect of vitamine D metabolism would not seem to be the main etiological factors.     

Hypocalcemia and hyperphosphatemia in severely dehydrated children with and without convulsions

Tetanic convulsions are not uncommon among severely dehydrated children in the developing countries. This raises the question whether these children have disturbances in the homeostasis of divalent ions. Serum values are reported of calcium, magnesium, phosphorus, sodium and potassium, as well as blood pH in children below 3 years of age with acute watery diarrhoea and with an estimated weight loss of about 10%. The study was performed on dehydrated children with (DC) or without (D) convulsions. Values were obtained on admission and following rehydration therapy (RT). On admission serum calcium was low in both D and DC children. Serum phosphorus was likewise elevated in both D and DC children. Serum magnesium was slightly elevated in the DC but not in the D group. No patient had hypernatremia. During RT, serum calcium increased significantly and serum phosphorus decreased significantly in D and DC children. Serum calcium showed a significant inverse correlation with serum phosphorus and a significant direct correlation with blood pH. Treatment of DC children with i.v. calcium and i.m. magnesium had no immediate effect on the convulsions. Our conclusion is that severely dehydrated children will develop hypocalcemia. The cause may be a redistribution of calcium into the cells, parallelled by a redistribution of phosphorus from the intra- to the extracellular space.     

Calcium homeostasis in the first days of life in relation to feeding

Determinations of serum calcium (Ca), phosphorus (P), magnesium (Mg), calcitonin (CT) and parathyroid hormone (PTH) were carried out in full term newborn infants during the first 168h of life. The infants were randomly assigned to two different diets: glucose and breast feeding (BF) only or early formula feeding (F). The Ca serum levels decreased from birth to the 24th h; after that time they increased until the 72nd h. The values of serum Ca at the 48th and 72nd h were significantly lower in the F than in the BF group. In contrast, the P serum levels increased from birth to the 48th h and then they decreased; the values of serum P at the 48th h were significantly higher in F than in the BF group. The CT serum levels increased from birth to the 24th h and then they decreased. No difference between the F and BF groups was found during the first 48 h, while at the 72nd h the F group demonstrated significantly higher values of serum CT. PTH serum levels also increased from birth to the 24th h with significantly higher values at the 72nd h in the F group. The results of this investigation demonstrate that the difference in feeding in the first hours of life affects the calcium homeostasis and the secretion of hormones involved in the regulation of serum Ca levels.Abbreviations CT calcitonin - PTH parathyroid hormone - BF breast feeding - F early formula feeding - RIA radio-immunoassay     

Polycythemia, hypomagnesemia, and hypocalcemia in infants of diabetic mothers

Hypomagnesemia (serum magnesium concentration, less than 1.5 mg/dL [0.62 mmol/L]) and hypocalcemia (serum calcium concentration, less than 8 mg/dL [2.00 mmol/L]) have been reported in polycythemic infants, as well as in infants of diabetic mothers (IDMs). These latter infants are at risk for neonatal polycythemia (venous hematocrit, greater than or equal to 65% [0.65]). We tested the hypothesis that neonatal polycythemia in IDMs is associated with increased serum calcitonin concentration, hypomagnesemia, and hypocalcemia. Serum magnesium and calcium concentrations were measured at 24 and 72 hours of age in 76 IDMs; serum calcitonin concentration was measured at 24 hours of age. Peripheral venous spun hematocrit was measured between 2 and 4 hours of age. The rates of hypomagnesemia and hypocalcemia were similar in polycythemic and nonpolycythemic IDMs (0% vs 9% and 56% vs 49%, respectively). The serum calcitonin concentration was similar in both groups. There was no correlation between hematocrit and the serum magnesium or calcium concentration; a significant association existed between hypocalcemia and hypomagnesemia.     

Families of children with idiopathic hypercalciuria. Evidence for the hormonal basis of familial hypercalciuria

Six children with idiopathic hypercalciuria and their families were examined with an oral calcium loading test. Family members were divided into two clinical categories: group 1 consisted of the six index children and their parents and siblings with urolithiasis or unexplained hematuria; group 2 comprised the remaining parents and siblings without signs or symptoms associated with hypercalciuria. The results revealed that fasting urinary excretion of calcium was similar in both groups, but group 1 displayed a greater calciuric response to an oral calcium load. Serum concentrations of calcitriol (1,25-dihydroxyvitamin D3) and calcium were higher in group 1 than in group 2, while parathyroid activity was lower in group 1 patients. Urinary excretion of sodium, phosphorus, and magnesium, urine pH, serum levels of calcifediol (25-hydroxyvitamin D3) and phosphorus, and the renal tubular threshold for phosphate were not significantly different in the two groups. These findings suggest that idiopathic hypercalciuria may arise from a disturbance in the regulation of vitamin D metabolism that mediates enhanced intestinal absorption of calcium.     

Control of vitamin D metabolism in preterm infants: feto-maternal relationships.

To assess the relationship between maternal and fetal mineral homeostasis, serum calcium, magnesium, inorganic phosphate, parathyroid hormone, and vitamin D metabolite concentrations in venous cord sera from 15 preterm singletons and 3 twin pairs were compared with the levels found in maternal sera. Cord calcium, magnesium, and phosphorus levels were significantly higher than the respective levels in maternal samples. There was a significant relationship between the two compartments for all three analyses. Cord serum 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D levels were significantly lower than those observed for the mothers. Association of the cord concentration with that of the mothers was observed only for the first two metabolites. There was no relationship between the maternal 1,25-dihydroxyvitamin D levels and gestational age, calcium, magnesium, inorganic phosphate, or 25-hydroxyvitamin D. Cord 1,25-dihydroxyvitamin D correlated significantly only with cord calcium levels. Immunoreactive parathyroid hormone levels were within normal limits both in cord and maternal samples. Our data suggest that after 31 weeks of gestation: (1) calcium, magnesium, and inorganic phosphate cross the placental barrier against a concentration gradient; (2) the fetus depends on the maternal supply for 25-hydroxyvitamin D and 24,25 dihydroxyvitamin D; (3) the feto-placental unit synthesizes 1,25-dihydroxyvitamin D according to fetal needs.     

Hypocalcemia and Hyperphosphatemia in Severely Dehydrated Children with and without Convulsions

ABSTRACT. Tetanic convulsions are not uncommon among severely dehydrated children in the developing countries. This raises the question whether these children have disturbances in the homeostasis of divalent ions. Serum values are reported of calcium, magnesium, phosphorus, sodium and potassium, as well as blood pH in children below 3 years of age with acute watery diarrhoea and with an estimated weight loss of about 10%. The study was performed on dehydrated children with (DC) or without (D) convulsions. Values were obtained on admission and following rehydration therapy (RT). On admission serum calcium was low in both D and DC children. Serum phosphorus was likewise elevated in both D and DC children. Serum magnesium was slightly elevated in the DC but not in the D group. No patient had Hypernatremia. During RT, serum calcium increased significantly and serum phosphorus decreased significantly in D and DC children. Serum calcium showed a significant inverse correlation with serum phosphorus and a significant direct correlation with blood pH. Treatment of DC children with i.v. calcium and i.m. magnesium had no immediate effect on the convulsions. Our conclusion is that severely dehydrated children will develop hypocalcemia. The cause may be a redistribution of calcium into the cells, parallelled by a redistribution of phosphorus from the intra- to the extracellular space.