Evidence for Skeletal Resistance to Parathyroid Hormone in Magnesium Deficiency: STUDIES IN ISOLATED PERFUSED BONE

Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83+/-0.1 mg/100 ml) and experimental dogs (serum Mg 1.34+/-0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5+/-3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1+/-1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8+/-0.2 to 17.5+/-0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5+/-0.1 pmol/min, and increased to only 7.1+/-0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency.     

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.     

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.     

Inhibitory effects of hypermagnesemia on the renal action of parathyroid hormone.

Available evidence indicates that serum magnesium (Mg++) levels influence the secretion rate of parathyroid hormone (PTH). Whether serum Mg++ concentrations also modify the action of PTH on its target organs has not been definitively established. The present experiments were designed to study this possibility. The effect of infusing PTH on the urinary excretion of cyclic AMP (cAMP) and PO4= was examined in five normal dogs at two different levels of serum Mg++. At normal serum Mg++ concentrations (1.89 +/- 0.14 mg/100 ml), PTH infusion increased cAMP excretion from 1.76 +/- 0.27 to 4.87 +/- 1.00 nmol/min and fractional PO4= excretion (FEPO4) from 1.58 +/- 0.36% to 23.1 +/- 2.17%. When an identical amount of PTH was given to the same dogs at a serum Mg++ of 4.36 +/- 0.20 mg/100 ml, FEPO4 increased to only 6.02+/-1.89% and cAMP from 1.31 +/- 0.23 to 1.89 +/- 0.39 nmol/min. Identical results were obtained in thyroparathyroidectomized hypermagnesemic dogs. Increased serum Mg++ levels had no effect on the phosphaturia produced by the infusion of dibutyryl cAMP to thyroparathyroidectomized dogs. In vitro studies using rat renal cortical slices revealed a progressive decrease in cAMP production in response to PTH as the Mg++ concentrations were increased in the incubation medium. The overall results indicate that hypermagnesemia inhibits the phosphaturic response to PTH by decreasing the renal production of cAMP. Plasma magnesium, therefore, may participate in a double feedback mechanism, not only controlling the release of PTH, but also altering the biological activity of the hormone at the level of the target organ.     

Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure.

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PTH] secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79 +/- 0.09 mg/dl and gradually increased up to 5.30 +/- 0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64 +/- 7.7 to 118 +/- 21 pg/ml. Serum 1,25(OH)2D3 decreased from 25.4 +/- 3.8 to 12.2 +/- 3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8 +/- 3.5 to a maximum of 69.6 +/- 4.4 pg/ml. In the second group the levels of serum 1,25(OH)2D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3. In summary, the dogs at no time developed hypocalcemia; however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.     

Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism

The immunoreactive forms of parathyroid hormone (iPTH) in the plasma of six patients with primary, adenomatous hyperparathyroidism and six patients with ectopic hyperparathyroidism due to non-parathyroid cancer were compared by using gel filtration on columns of Bio-Gel P-150 and radioimmunoassay of iPTH in eluted fractions after concentration. We found much less (p<0.001) small (mol wt<9,500) COOH-terminal fragments of iPTH in plasma samples from ectopic hyperparathyroid patients (0.52+/-0.13 ng eq/ml) than in samples from primary hyperparathyroid patients (3.70+/-1.15 ng eq/ml). The quantity of iPTH eluting with or before native bovine PTH [1-84] was the same in both syndromes (ectopic hyperparathyroidism, 0.82+/-0.22 ng eq/ml; primary hyperparathyroidism, 0.73+/-0.09 ng eq/ml), and these values correlated positively with plasma calcium concentration (ectopic hyperparathyroidism, r=0.908; primary hyperparathyroidism, r=0.919). In both syndromes, plasma samples had an iPTH component that eluted well before PTH [1-84] (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al. 1971. J. Clin. Invest. 50: 2079); (b) there appears to be sufficient iPTH with presumed biologic activity to account for the hypercalcemia in both syndromes; (c) a large PTH component, not previously recognized in plasma, is present in both ectopic and primary hyperparathyroidism and may exist as the predominant immunoreactive form of the hormone in some patients with ectopic hyperparathyroidism.     

低钙透析液对CAPD患者钙磷代谢的影响

目的观察低钙腹膜透析液（1．25mmol／L）（LCD）与标准钙离子浓度（1．75mmol／L）的腹膜透析液（SCD）对CAPD患者钙磷代谢的影响。方法选择血钙高于正常或高钙磷乘积的CAPD患者57例，随机分成两组：SCD组24例；LCD组33例。观察两组患者血钙、磷、镁、全段甲状旁腺激素（iPTH）和皮肤瘙痒情况的变化，及不良反应。观察时间为6个月。结果共53例完成6个月的观察，其中SCD22例，LCD31例。6个月后两组的血钙水平均有所下降，但LCD组血钙水平较前明显下降（P〈0．05），SCD组无统计学意义（P〉0．05）；SCD组患者的血清磷、镁及钙磷乘积无明显变化，而LCD组上述指标明显下降，与SCD组比较具有统计学意义（P〈0．05）；与SCD相比，LCD组的iPTH水平明显升高（P〈0．05）；LCD患者皮肤瘙痒情况有所改善，但无统计学意义（P〉0．05）。观察期间LCD组患者无低血压、低钙抽搐等情况发生。结论低钙腹膜透析液能够较好控制血钙水平，降低血磷，减轻对甲状旁腺的抑制，可能在预防和改善动力缺失性骨病的发生和发展过程中发挥重要的作用。     

持续不卧床腹膜透析患者血清铁调素水平与钙磷代谢的相关性

目的研究持续不卧床腹膜透析（CAPD）患者血清铁调素（hepcidin）水平变化以及钙磷代谢状况与铁调素水平的相关性。 方法选取2014年6月至12月在江苏省苏北人民医院血液净化中心进行CAPD治疗的患者45例,将同期该院健康体检中心体检健康者40例作为健康对照组。采用ELISA法检测血清铁调素水平;采用成组t检验比较CAPD组和对照组的年龄、体质量指数（BMI）、血尿素氮（BUN）、肌酐（cr）、白蛋白、磷、钙、25（OH）-维生素D₃、血清铁、总铁结合力（TIBC）、可溶性转铁蛋白受体（sTfR）、血红蛋白、红细胞比容等指标;采用秩和检验（Mann-Whitney rank）比较两组全段甲状旁腺激素（iPTH）、铁蛋白、铁调素等指标;采用χ²检验比较两组性别分布;采用Pearson相关及多元逐步线性回归方法分析铁调素与钙磷代谢指标之间的相关性。 结果CAPD组患者与对照组比较,血清中血红蛋白、红细胞比容、白蛋白、血清铁、TIBC、转铁蛋白饱和度、25（OH）-维生素D₃水平明显降低,差异具有统计学意义［（89.62±20.04）g/L vs（121.53±4.06）g/L,t=-8.72,P<0.001;（26.81±5.68）% vs（40.82±2.04）%,t=-9.64,P<0.001;（43.25±1.23）g/L vs（45.26±1.29）g/L,t=-1.27,P=0.046;（10.27±2.36）μmol/L vs（18.52±4.41）μmol/L,t=-5.71,P<0.001;（65.40±2.89）μmol/L vs（75.84±5.03）μmol/L,t=-2.34,P=0.037;（15.34±5.44）% vs（29.65±4.77）%,t=-9.31,P<0.001;（39.57±7.23）nmol/L vs（79.12±10.38）nmol/L,t=-10.34,P<0.001］;CAPD组患者与对照组比较,BUN、cr、铁蛋白、sTfR、铁调素、iPTH和磷的水平明显升高,差异具有统计学意义［（18.87±7.64）mmol/L vs（4.26±1.18）mmol/L,t=8.27,P<0.001;（647.43±56.78）μmol/L vs（54.81±6.74）μmol/L,t=8.26,P<0.001;260.41（109.31,423.33）μg/L vs 109.33（60.54,159.62）μg/L,Z=-4.24,P=0.001;（4.27±1.45）mg/L vs（2.89±1.22）mg/L,t=1.79,P=0.048;234.24（134.22,437.19）μg/L vs 87.51（40.54,132.57）μg/L,Z=-5.27,P<0.001;26.10（15.04,50.35）ng/L vs 3.30（1.78,6.25）ng/L,Z=-5.61,P<0.001;（2.73±0.47）mmol/L vs （1.24±0.65）mmol/L,t=12.09,P<0.001］;pearson相关分析结果显示CAPD患者血清铁调素与血磷（r=0.300,P=0.003）和iPTH（r=0.313,P=0.02）水平呈正相关,但血清铁调素水平与血钙（r=0.064,P=0.531）及25（OH）-维生素D₃（r=0.007,P=0.943）水平无相关性。 结论血清铁调素水平在CAPD患者体内明显升高,与血清磷和iPTH水平呈正相关,血磷及iPTH可能参与铁调素的调节。     

Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia

OBJECTIVE: Based on preclinical investigations, magnesium sulfate (MgSO4) has gained interest as a neuroprotective agent. However, the ability of peripherally administered MgSO4 to penetrate the blood-brain barrier is limited in normal brain. The current study measured the passage of intravenously administered Mg into cerebrospinal fluid in patients with brain injury requiring ventricular drainage. DESIGN: A prospective evaluation of the cerebrospinal fluid total and ionized magnesium concentration, [Mg], during sustained hypermagnesemia was performed. SETTING: Neurosciences intensive care unit at a major teaching institution. PATIENTS: Thirty patients with acute brain injury secondary to subarachnoid hemorrhage, traumatic brain injury, primary intracerebral hemorrhage, subdural hematoma, brain tumor, central nervous system infection, or ischemic stroke were studied. INTERVENTIONS: Patients underwent 24 hrs of induced hypermagnesemia during which total and ionized cerebrospinal fluid [Mg] was measured. Serum [Mg] was adjusted to 2.1-2.5 mmol/L. Cerebrospinal fluid [Mg] was measured at baseline, at 12 and 24 hrs after onset of infusion, and at 12 hrs following infusion termination. MEASUREMENTS AND MAIN RESULTS: At baseline, total (1.25 +/- 0.14 mmol/L) and ionized (0.80 +/- 0.10 mmol/L) cerebrospinal fluid [Mg] was greater than serum total (0.92 +/- 0.18 mmol/L) and ionized (0.63 +/- 0.07 mmol/L) [Mg] (p < .05). Total (1.43 +/- 0.13 mmol/L) and ionized (0.89 +/- 0.12 mmol/L) cerebrospinal fluid [Mg] was maximally increased by 15% and 11% relative to baseline, respectively, during induced hypermagnesemia (p < .05). CONCLUSIONS: Hypermagnesemia produced only marginal increases in total and ionized cerebrospinal fluid [Mg]. Regulation of cerebrospinal fluid [Mg] is largely maintained following acute brain injury and limits the brain bioavailability of MgSO4.     

低钙透析液对血液透析患者钙磷代谢的长期影响

目的 观察长期应用钙离子浓度为1.25 mmol/L的低钙透析液(LCaD)对血液透析患者钙磷代谢的影响.方法 本研究共纳入38例稳定透析患者,以1.25 mmol/L钙浓度透析液替换原使用的1.75mmol/L钙浓度透析液(HCaD),回顾性观察使用低钙透析液2年后患者血清钙、磷、钙磷乘积、全段甲状旁腺素(iPTH)等指标的变化.结果 与高钙透析液相比,整体观察,采用低钙透析液后患者血钙水平降低[HCaD(2.32±0.23)mmol/L,LCaD(2.21±0.24)mmoI/L;t=2.286,P=0.028],iPTH水平明显升高[HCaD(20.92±16.04)pmoL/L,LCaD(40.02±30.55)pmoL/L;t=-4.029,P=0.000],血磷及钙磷乘积变化不明显.按照基点处iPTH水平分组观察,低iPTH组(iPTH＜11.0 pmol/L)患者的血钙水平较前下降[HCaD(2.46±0.19)mmoL/L,LCaD(2.11±0.23)mmol/L;t=4.047,P=0.002],钙磷乘积下降[HCaD(4.75±1.66)mmol2/L2,LCaD(3.54±0.77)mmol2/L2;t=3.784,P=0.004],血磷保持稳定,iPTH水平中度升高[HCaD(5.67±2.84)pmol/L;LCaD(27.72±27.79)pmol/L;t=-2.490,P:0.032].高iPTH组(iPTH≥11.0 pmol/L)患者的血钙、血磷及钙磷乘积未见显著差异,iPTH水平显著升高[HCaD(27.15±15.43)pmol/L,LCaD(45.03±30.68)pmol/L;t=-3.138,P=0.004].按照基点处血钙水平分组观察,低血钙组(Ca＜2.10 mmol/L)和正常血钙组(ca 2.10-2.37 mmol/L)患者的钙、磷、钙磷乘积基本保持相对稳定.高血钙组(ca＞2.37 mmol/L)患者的血钙水平下降[HCaD(2.52±0.12)mmol/L,LCaD(2.25±0.20)mmol/L;t=4.153,P=0.001],血磷水平保持稳定,钙磷乘积下降[HCaD(4.94±1.19)mmol2/L2,LCaD(4.10±0.80)mmol2/L2;t=2.587,P=0.012].iPTH水平于低血钙组保持相对稳定,于正常血钙组[HCaD(20.18±11.00)pmol/L;LCaD(37.45±32.61)pmol/L;t=-2.351,P=0.032]和高血钙组[HCaD(14.68±12.98)pmol/L,LCaD(40.19±33.20)pmol/L;t=-3.432,P=0.004]均有升高.结论 1.25 mmoL/L钙浓度透析液可应用于多数不同血钙浓度的患者,长期应用低钙透析液可以降低血钙,促进PTH分泌,有利于减少转移性钙化和动力缺失性骨病的发生,但同时增加了继发性甲状旁腺功能亢进的风险.     

基线甲状旁腺激素水平对腹膜透析患者预后影响的探讨

目的本研究旨在探讨新进入腹膜透析人群中甲状旁腺激素水平分布,影响因素,及其对腹膜透析患者长期生存的影响。方法新进入腹膜透析治疗的成人终末期肾病患者按患者全段甲状旁腺激素(intact parathyroid hormone,iPTH)水平分为A组iPTH<150pg/ml;B组iPTH 150~300pg/ml;C组iPTH 300~600pg/ml;D组iPTH≥600pg/ml。比较各组患者的临床及化验资料;使用多元线性回归筛选与基线iPTH相关的危险因素。应用COX回归模型分析影响生存率的因素。应用Kaplan-Meier生存分析、COX回归模型分析比较4组患者的生存情况。结果共222例腹膜透析患者入选。其中,基线iPTH<150pg/ml的患者占43.7%。这组患者的特点包括:年龄大(F=6.235,P<0.001),合并糖尿病比例高(F=16.277,P=0.001),合并症多(F=4.348,P=0.005),eGFR较高(F=5.699,P=0.001)。但经过元线性回归分析,仅年龄(β=-8.700,P<0.001)、是/否合并糖尿病(β=145.400,P=0.012)对基线iPTH有独立的影响。生存曲线显示不同基线iPTH组间总体生存率存在差异(P=0.002)。多因素COX回归分析发现,仅年龄(B=0.066,P<0.001)是预测死亡的独立危险因素,基线iPTH(B<0.001,P=0.507)不能独立预测死亡。结论初进入腹膜透析治疗的患者中,年龄大、合并糖尿病的患者,更容易出现低iPTH的情况。但是,基线iPTH并不能独立预测死亡。     

Increased levels of osteoprotegerin in hemodialysis patients.

Recently identified soluble circulating osteoprotegerin (OPG), a member of tumor necrosis factor receptor family, is the osteoclastogenesis inhibitory factor (OCIF). It acts as a "decoy" receptor for receptor activator of NF-kappaB ligand (RANKL) and antagonises RANKL/RANK activity. This way OPG exerts the protective effect on bone, which is also important in hyperparathyroidism. The studies measuring OPG levels in secondary hyperparathyroidism have shown contradictory results and inconsistent conclusions. The aim of our work was to evaluate OPG levels in hemodialysis patients and their correlation with the intensity of bone turnover, bone formation and bone resorption. Serum OPG levels, bone alkaline phosphatase activity (bALP) and beta-CrossLaps (CTx) were measured in a control group (n = 20, age 30+/-6.7 years) and in two groups of dialysis patients: the first group with serum intact parathyroid hormone (iPTH) concentration below 200 pg/ml (n = 28, age 62.6+/-14.8 years) and the second group with iPTH concentration above 200 pg/ml (n = 16, age 63.7+/-14.8 years). Compared to controls, serum OPG levels were 6.4-fold higher in dialysis patients. OPG levels in patients with high PTH were approximately 1.2-fold higher than in the low-PTH group. OPG correlated weakly with bALP (r = 0.277, p = 0.153), as well as with CTx (r = 0.018, p = 0.929) in the low-PTH group, and there was an insignificant negative correlation in the high-PTH group (r = -0.145, p = 0.593 and r = -0.219, p = 0.416, respectively). In conclusion, 6.4-fold increase in OPG might protect bone against intensive bone loss in hemodialysis patients, but this increase is probably not mediated by the increased bone formation; rather, it seems to be the consequence of the imbalance of bone kinetics in renal disease. The precise role of OPG in the pathogenesis of renal osteodystrophy remains unknown and establishing it requires further studies.     

血液透析患者成纤维细胞生长因子23水平及相关性分析

目的观察维持性血液透析（maintenance hemodialysis,MHD）患者成纤维细胞生长因子23（fibroblast growth factor 23,FGF-23）的水平,分析其与全段甲状旁腺激素（intact parathyroid hormone,iPTH）等生化指标的关系,探讨FGF-23对MHD患者的临床意义。方法选取行MHD治疗的患者41例,健康志愿者12例为对照组,收集一般情况及化验指标,采集血清检测FGF-23,并进行相关性分析。结果①MHD各组与对照组年龄、性别无显著差异,但MHD患者FGF-23显著高于对照组[（1077.4±967.46）pg/ml比（73.99±19.58）pg/ml,P〈0.001];②依据甲状旁腺激素（iPTH）不同将MHD分为A组（低iPTH组）、B组（iPTH达标组）、C组（高iPTH组）;FGF-23在3组间有显著性差异,[分别为（477.44±2293.53）pg/ml、（176.57±402.39）pg/ml、（1433.1±1984.76）pg/ml,P=0.016];③将MHD患者依据血磷不同水平分组比较,观察到高血磷组与非高血磷组相比,iPTH显著升高[（1319.66±1015.96）pg/ml比（583.36±980.81）pg/ml（P=0.012）]、FGF-23也显著升高[（1506.83±957.97）pg/ml比（452.31±696.12）pg/ml（P〈0.001）];④相关性分析显示：血钙（r=0.381,P=0.005）、磷（r=0.593,P〈0.001）、钙磷乘积（r=0.656,P〈0.001）、碱性磷酸酶（ALP）（r=0.276,P=0.045）均与FGF-23呈正相关。而iPTH在B组及C组与FGF-23呈正相关（r=0.384,P=0.005）,在A组与FGF-23无相关性。结论 MHD患者中FGF-23与血清钙、磷、钙磷乘积、ALP、iPTH密切相关,在继发性甲状旁腺功能亢进症（secondary hyperparathyroidism,SHPT）的发生中起着重要作用。     

Effects of active vitamin D3 and parathyroid hormone on the serum osteocalcin in idiopathic hypoparathyroidism and pseudohypoparathyroidism.

Serum osteocalcin was measured in patients with idiopathic hypoparathyroidism or pseudohypoparathyroidism, before or during the treatment with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3). Serum osteocalcin and plasma 1,25(OH)2D were decreased in 11 patients with idiopathic hypoparathyroidism before treatment (2.8 +/- 1.27 ng/ml, P less than 0.001 and 14.3 +/- 4.27 pg/ml, P less than 0.001, respectively). In 24 patients with idiopathic hypoparathyroidism during the treatment, serum osteocalcin and plasma 1,25(OH)2D were within the normal range (4.5 +/- 0.74 ng/ml and 25.7 +/- 5.69 pg/ml, respectively). In five patients with pseudohypoparathyroidism before treatment, plasma 1,25(OH)2D was decreased (15.6 +/- 10.6 pg/ml, P less than 0.001) but serum osteocalcin was normal (7.8 +/- 1.66 ng/ml). In nine patients with pseudohypoparathyroidism during the treatment with active vitamin D3, serum osteocalcin and plasma 1,25(OH)2D were normal (6.8 +/- 1.47 ng/ml and 27.2 +/- 6.0 pg/ml, respectively). Serum PTH in pseudohypoparathyroidism was increased before treatment (0.70 +/- 0.34 ng/ml, P less than 0.05) and was normal during the treatment (0.50 +/- 0.13 ng/ml). In idiopathic hypoparathyroidism, the active vitamin D3 increased serum osteocalcin without PTH. In pseudohypoparathyroidism, PTH may increase serum osteocalcin or modulate the effect of active vitamin D3 on serum osteocalcin.     

Hypocalcemia and parathyroid hormone secretion in critically ill patients

OBJECTIVE: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN: Combined cross-sectional and prospective study. SETTING: ICU in a university hospital. PATIENTS: Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.     

Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients.

Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered.     

Value of parathyroid hormone assay for preoperative sonographically guided parathyroid aspirates for minimally invasive parathyroidectomy

PURPOSE: The key to successful parathyroid surgery is accurate preoperative tumor localization. This study investigates the use of ultrasound (US)-guided parathyroid fine needle aspiration (FNA) as a confirmatory diagnostic method in patients with hyperparathyroidism undergoing minimally invasive parathyroidectomy. METHODS: Patients were selected for minimally invasive parathyroidectomy based on the finding of a single parathyroid adenoma identified with US and/or sestamibi scans and confirmation of the suspected parathyroid lesion via FNA and parathyroid hormone (PTH) assay. The value of aspirate obtained from the thyroid gland intraoperatively served as the negative control. RESULTS: A total of 56 tissue FNAs were performed in 27 patients. US detected masses suggestive of parathyroid lesion in all 27 patients, and 31 US-guided FNAs were performed. No complications related to the procedure were noted. Intraoperatively, FNA was performed in the thyroids of 25 patients undergoing minimally invasive parathyroidectomy. Aspirates from lesions subsequently confirmed as having developed from the parathyroid gland had a mean PTH level of 4,677 +/- 123 pg/ml (range, 3,600-5,000 pg/ml), which was significantly higher than thyroid aspirates, which yielded a mean PTH level of 48 +/- 7 pg/ml (range, 5-57 pg/ml). The sensitivity of US and sestamibi scans in the detection of abnormal parathyroid glands was 88% and 77%, respectively. The sensitivity of US-guided FNA in confirming the parathyroid origin of a lesion was 100%. CONCLUSION: US-guided FNA for PTH assay can be performed safely for the confirmation of lesions identified with preoperative US for the selection of patients eligible for minimally invasive parathyroidectomy.     

Normal or low initial PTH levels are not a predictor of morbidity/mortality in patients undergoing chronic peritoneal dialysis.

OBJECTIVE: During the past few decades, the pattern of bone disease in uremic patients has changed significantly. There has been an increase in the number of patients with normal or low initial parathyroid hormone (PTH) levels, particularly in patients on chronic peritoneal dialysis (CPD). Previous authors have described a higher prevalence of bone pain, microfractures, and fractures, and higher mortality among these patients. The aim of this study was to determine the incidence, morbidity, and mortality of patients who had a low or normal intact PTH (iPTH) level when they started CPD. DESIGN: We reviewed the records of 251 patients in our program that started CPD during the past 5 years (January 1996-December 2000). Clinical data, laboratory variables, medication, and dialysis parameters/dose were available at every clinic visit (approximately every 4 weeks). Intact PTH was used to express parathyroid function; values 3 times higher than the upper limit of normal (ULN) were assumed to be optimal. Variables predictive of the development of parathyroid dysfunction were calculated by univariate and multivariate logistic regression analysis. RESULTS: Of the patients who started CPD, 15.5% had iPTH values below the ULN (7.6 pmol/L), and an additional 29.5% had an iPTH of less than 3 times the ULN (i.e., between 7.6 and 22.8 pmol/L). We call these two groups of patients the normal/low initial iPTH group. During the follow-up period (3-63 months), we found a trend toward increasing iPTH levels. By the end of the study period, 61.2% of those with normal/low initial iPTH remained in the normal/low iPTH range, and 38.8% had converted to a group with an iPTH range higher than 22.8 pmol/L. The patients who converted their iPTH grouping were younger, fewer of them were diabetics (p = not significant), and they were more frequently on low calcium dialysate (p < 0.05). Hyperphosphatemia was an independent risk factor for subsequent iPTH changes during the course of continuous ambulatory PD treatment. All patients in the normal/low iPTH groups had a low prevalence of bone fractures (3.5%). Also, patients who remained in the normal/low iPTH group at the end of the follow-up period did not have more fractures than those who converted to the hyperparathyroid group (3.8% vs 3.1%). We found no differences in bone fractures between patients with iPTH levels below 22.8 and those with levels above 22.8 pmol/L (3.5% vs 5.4%), nor were there differences in patient and technique survival between these two groups. CONCLUSION: Normal/low initial iPTH is a frequent finding among patients starting CPD. Serum phosphorus was an independent risk factor for subsequent iPTH changes during the course of CPD treatment. Use of low calcium dialysate was significantly higher in patients who converted their iPTH into the high iPTH range. Very few patients with low/normal iPTH had bone-related symptoms (pain and fractures), and their morbidity and mortality did not differ from those patients with a high initial iPTH level.