Circadian rhythm in serum parathyroid hormone concentration in human subjects: correlation with serum calcium, phosphate, albumin, and growth hormone levels

A circadian variation in serum calcium, albumin and PTH concentration in normal subjects has been demonstrated. The levels of the three blood constituents were remarkably constant during the day, but striking night and early morning changes occurred. Serum calcium levels were highest at 8:00 p.m. and reached a nadir between 2:00 and 4:00 a.m. Serum albumin levels were parallel to those of serum calcium. PTH levels began to rise after 8:00 p.m., reached the highest levels between 2:00 and 4:00 a.m., and fell to baseline values by 8:00 a.m. The nocturnal fall in serum calcium levels appears to be secondary to dilution of serum proteins by increasing blood volume. The nocturnal rise in PTH levels appears to be independent of serum calcium levels within the normal range but it can be abolished by induced hypercalcemia.     

调整透析液钙浓度对血液透析患者血钙和甲状旁腺激素的影响

目的了解调整透析液钙浓度对血液透析患者血钙和甲状旁腺激素(PTH)的影响.方法选择北京大学第三医院肾脏内科23例血液透析患者,血PTH＞300pg/ml,调整其透析液钙浓度,以观察其血钙和PTH变化.结果按入选时的血钙水平将这些患者分成低血钙组和正常血钙组.将透析液钙浓度从1.25 mmol/L提高到1.5mmol/L后一个月,低血钙组患者的血钙水平显著升高[从(1.92±0.15)到(2.06±0.12)mmol/L,P＜0.001)],同时血PTH水平明显下降[从(615±305)到(306±180)pg/ml,P＜0.001),而正常血钙组患者的血钙和PTH水平变化不大.结论如果同时有低血钙和高PTH血症,提高透析液钙浓度可以使这些血液透析患者的血钙正常并使其血PTH水平下降.     

The pathogenesis of renal osteodystrophy: role of vitamin D, aluminium, parathyroid hormone, calcium and phosphorus

Biochemical data and bone histology from 44 haemodialysis patients was compared using an histologic technique capable of evaluating separately the individual components of osteodystrophy. Hyperparathyroid bone disease was diagnosed by an elevated osteoclast count, and in advanced disease there was also fibrosis and woven bone. Osteomalacia, defined as an impairment in the rate of bone mineralisation, was present in two distinct forms: osteomalacia type I, characterised by wide osteoid seams, and osteomalacia type II, characterised by extensive thin, inactive osteoid. The histologic diagnoses were hyperparathyroid bone disease (15), osteomalacia type I (3), osteomalacia type II (6), hyperparathyroid bone disease and osteomalacia type I (12), hyperparathyroid bone disease and osteomalacia type II (6), normal (2). Aluminium was evident histochemically in 17 biopsies. Vitamin D metabolite levels were low in most patients and did not correlate with any biochemical or histological parameter. Parathyroid hormone levels were highly correlated with histological features of hyperparathyroid bone disease, and also correlated with plasma calcium, suggesting a degree of autonomy of parathyroid hormone secretion. Urea and creatinine were higher in the hyperparathyroid bone disease than the osteomalacia groups suggesting that poor dialysis contributes to the former. Statistical analysis showed that osteomalacia type I was associated with relatively low plasma calcium and phosphorus levels; osteomalacia type II was associated with increased bone aluminium and with the uraemic process itself, as reflected in the plasma creatinine level. This study shows relationships between renal osteodystrophy and plasma calcium and phosphorus levels, but no relationship with vitamin D metabolites. Aluminium appears to impair mineralisation even at relatively low levels of accumulation. However there are other unidentified factors associated with the uraemic process, contributing to all three components of renal osteodystrophy.     

Effects of pravastatin and cholestyramine on circulating levels of parathyroid hormone and vitamin D metabolites

The subjects were 40 hypercholesterolemic patients (mean age, 58 years) receiving a low-fat diet and randomly assigned to treatment with placebo for eight weeks or 40 or 80 mg of pravastatin, 24 gm of cholestyramine, or 40 mg of pravastatin plus 24 gm of cholestyramine daily for 24 weeks. After eight weeks of active treatment, levels of total and low-density lipoprotein cholesterol were significantly reduced and the decline was maintained for the remaining 16 weeks. Parathyroid hormone levels and levels of the vitamin D metabolites 1,25(OH)2D3 and 25(OH)D3 did not change during treatment. The results indicate that 24 weeks of treatment with pravastatin and cholestyramine does not affect calcium metabolism.     

Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy, in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1,25(OH)₂D₃. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1,25(OH)₂D₃ with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were normocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols), and 1,25(OH)₂D₃ by radioreceptor assay (Nichols), in plasma in both groups of cancer patients. Using a logistic regression analysis, we found that the higher PTHrP in plasma, the higher association with hypercalcemia occurred in these patients. In addition, the decreased plasma levels of PTH and 1,25(OH)₂D₃ in the majority of cancer patients were found to be significantly associated with hypercalcemia. Our results indicate that the combined determination of PTH, PTHrP and 1,25(OH)₂D₃ in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor responsible for hypercalcemia in these patients.     

Effects of physical exercise on serum calcium and parathyroid hormone

The effects of physical exercise on plasma ionized calcium, total serum calcium and parathyroid hormone (PTH) concentrations were evaluated in healthy subjects submitted to work on an ergometer bicycle. When the workload was increased stepwise there was a significant increase (P less than 0.001) in the calcium concentrations (ionized calcium from 1.13 +/- 0.03 (SD) to 1.24 +/- 0.03 mmol 1(-1) and total calcium from 2.35 +/- 0.07 to 2.48 +/- 0.07 mmol 1(-1] when the workload exceeded approximately 65% of the estimated maximum--i.e. a load that caused accumulation in blood of lactic acid. The rise in plasma ionized calcium was, therefore, presumably largely attributed to the acidosis but reduction of plasma volume and influx from extracellular sources might also have contributed. Beta blockade (with oral intake of propranolol) reduced physical capacity, shortened the duration of work and caused less acidosis. These factors were probably responsible for a smaller rise in ionized calcium during beta blockade (7 +/- 4%) than in control studies (21 +/- 5%) without medication in subjects examined during short-term maximal exercise. Long-term (1 h) steady-state work which caused fatigue without producing lactic acidosis did not affect the calcium concentrations. Despite the effects of work on calcium levels there was no discernible suppression of the PTH concentrations. This might have been due to a concomitant stimulation of PTH secretion by work.     

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.     

高通量血液透析对血清钙、磷和甲状旁腺素的影响

目的:探讨高通量血液透析对血清钙、磷和甲状旁腺素(PTH)的影响。方法:采用双盲随机对照,A组应用高通量透析,B组应用普通透析,分时点检测病人空腹透析前血清总钙、磷和全段PTH的水平。结果:A组病人血清钙各时点均数在正常范围,相互比较无显著变化(P>0.05);血清磷和血清全段PTH在3个月时显著降低并维持犤血磷(1.98±0.08)mmol/L,血清全段PTH(256.16±101.22)pg/L犦,P<0.05。B组病人血清钙在正常范围,血清磷和血清全段PTH水平较高,各时点均数比较,P>0.05。A组血清磷和PTH在3个月时明显低于B组(P<0.05),之后维持;血清钙两组无差异。结论:高通量透析可增加血磷的清除量,有效降低维持性血液透析患者的血磷和PTH。     

Data mining: Biological and temporal factors associated with blood parathyroid hormone,vitamin D,and calcium concentrations in the Southwestern Chinese population

BackgroundParathyroid hormone (PTH) and vitamin D plays a major role in calcium (Ca) homeostasis and bone turnover. The purpose of this study was to assess which factors (sex, age, time of blood sampling, season of the year, temperature and sunshine hours (SHH)) had the greatest impact on plasma PTH, 25-OH-VitD, and Ca levels, and then whether these effects were clinically acceptable in a large number of Southwestern Chinese subjects.MethodThe data was from West China Hospital Health Examination Center, Sichuan University from April 1, 2018 to June 30, 2019. A total of 18,664 physical examination subjects were included. PTH and 25-OH-VitD were measured by a Roche Cobas e 601, and Ca was measured by a Roche Cobas 8000. Linear regression models were used to assess correlations between PTH, 25-OH-VitD, Ca and the above factors.ResultsThe concentrations of serum PTH in females were significantly higher than those in males, while the 25-OH-VitD and Ca were opposite. The concentration of PTH in data collection decreased in summer and increased in spring. The concentration of 25-OH-VitD decreases in spring and increases in autumn. PTH concentrations were negatively correlated with last month temperature and SHH, while 25-OH-VitD were opposite. Linear regression showed that season may be the main factor affecting serum PTH and 25-OH-VitD levels, and these effects were not clinically acceptable.ConclusionIn order to avoid influencing clinicians' investigation of suspected hyperparathyroidism and hypovitaminosis, reference intervals for PTH, 25-OH-VitD, and Ca should be established, taking into account sex, age and the season.     

甲状旁腺素、25-羟维生素D及血清钙磷与原发性骨质疏松症的相关性分析

目的分析原发性骨质疏松症患者血清钙、磷、甲状旁腺激素(PTH)和25-羟维生素D水平,分析原发性骨质疏松症发生的主要危险因素,并探讨PTH水平与性别和年龄的关系。方法将2017年1月至2018年12月就诊于该院并确诊为原发性骨质疏松症的患者254例纳入研究作为病例组。另外,将同期于该院体检中心体检合格的健康体检者254例纳入研究作为对照组。比较两组生化指标,并进行Logistic回归分析。将2018年6-7月于该院体检中心体检合格的健康体检者2551例纳入研究作为健康人群,分析PTH水平与性别、年龄的关系。结果健康人群PTH水平与性别、年龄均无关(P>0.05)。病例组PTH水平高于对照组(P<0.001),病例组血清钙、磷及25-羟维生素D水平均低于对照组(P<0.001)。Logistic回归分析显示,PTH升高是导致原发性骨质疏松症的主要危险因素,OR值为1.495(95%CI:1.310~1.707,P<0.001)。结论健康人群PTH水平与性别和年龄无关。PTH升高是导致原发性骨质疏松症发生的主要危险因素。     

Primary hyperparathyroidism with normal serum intact parathyroid hormone levels

To evaluate the features of primary hyperparathyroidism (HPT) with normal serum intact parathyroid hormone (iPTH) levels, we studied 271 consecutive patients undergoing surgery for primary HPT. In 20 patients, serum iPTH levels were within the normal range (10-65 ng/l). In their records, the most common clinical features were fatigue (n=13), polyuria (n=6), renal stone (n=5), and hypertension (n=5). Mean serum calcium and phosphorus were 2.78 and 0.85 mmol/l, respectively: 14 had serum phosphorus within the normal range. Mean serum iPTH was 48.5 ng/l, and was <45 ng/l in nine patients. Cervical ultrasound demonstrated a parathyroid adenoma in nine, and was normal in four. Tc sestamibi parathyroid scintigraphy always demonstrated an adenoma (9/9). In eight patients, normal iPTH values delayed diagnosis. Physicians should be aware of the possibility of HPT in patients with hypercalcaemia, even when serum phosphorus and iPTH levels are within the normal limits. Particularly, HPT cannot be excluded when serum iPTH levels are below the upper part of the normal range. In such cases, cervical imaging, which has the same sensitivity as in other HPT, should be undertaken. These explorations are useful, because many patients are symptomatic and can take advantage of surgery.     

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.     

Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.

In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium.     

骨科老年患者不同季节血清维生素D状态与骨代谢水平的研究

目的 探究骨科老年患者血清维生素D水平与季节变化的关系及其引起的骨代谢变化特点。方法 调取2014年11月至2020年1月北京医院骨科1 831例老年患者血清25羟基维生素D(25-OH-D)、人血清和血浆中总Ⅰ型前胶原氨基端延长肽(t P1NP)、N端中段骨钙素(OCN)以及Ⅰ型胶原羧基端肽β特殊序列(β-CTX)检验结果,采用Mann-Whitney U检验分析不同季节患者血清25-OH-D及骨代谢指标水平特点,以及不同性别、不同就诊类型患者之间指标的差异。结果 血清25-OH-D水平无论季节变化,均处于维生素D缺乏状态,夏、秋两季血清25-OH-D水平明显高于冬、春两季(P <0.05),且夏、秋两季男性水平明显高于女性(P <0.05);门诊患者一年四季血清25-OH-D水平均高于住院患者(P <0.001),t P1NP及β-CTX水平均低于住院患者(P <0.05)。结论 骨科老年患者维生素D水平夏秋季节最高;性别及就诊类型对维生素D和骨代谢指标的影响存在相关季节特点。     

钙剂和维生素D在老年骨质疏松症中的应用

随着人口老龄化日趋严重,骨质疏松症已经成为我国面临的重要公共健康问题。骨质疏松症是一种多见于绝经后女性和老年男性,以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性代谢性骨病。钙剂和维生素D作为骨健康基本补充剂,在骨质疏松症的防治中具有重要作用。该文就老年骨质疏松症患者钙剂和维生素D应用中的相关问题进行阐述。     

Circulating ionized calcium and parathyroid hormone levels following coronary artery by-pass surgery

In critically ill patients, hypocalcaemia is a common finding. Also variable derangements in the normally tight Ca2+-mediated control of the parathyroid hormone (PTH) secretion have been found. Utilizing coronary artery by-pass grafting (CABG) as a standardized model of severe trauma, 18 patients underwent determinations of blood levels of calcium, magnesium (Mg), ionized calcium (Ca2+), serum levels of intact PTH, procalcitonin (PCT) and the proinflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Samples were collected before, directly after, the morning after and 5 days after surgery. A significant, but minor, decrease in blood Ca2+ levels (mean 0.04 mmol/L, p<0.05) was seen shortly after CABG, not accompanied by any significant change of serum PTH levels. This alteration of the Ca2+ control of the steady-state PTH levels contrasted with the maintenance of the PTH secretory response to a sequential citrate and calcium infusion (CiCa clamp), which was normal in two patients evaluated in the morning following surgery. Serum Mg levels were transiently increased after operation (+0.25 mmol/L, p<0.001) and correlated to the TNF-alpha (r=0.62, p <0.01) and PCT (r=0.67, p < 0.006) levels in the morning after surgery. Serum levels of IL-6 and TNF-alpha were significantly (p < 0.0001) increased immediately after surgery, while the peak in serum PCT levels (p < 0.001) occurred in the morning after CABG. Serum PTH levels correlated positively with IL-6 (r=0.68, p<0.008) 5 days after surgery. In conclusion, CABG caused a decrease in ionized calcium levels without a rise in steady-state PTH levels, but rapid changes in Ca2+ during CiCa clamping revealed a normal PTH secretory response. These findings might relate to elevated serum Mg levels, while a direct action of TNF-alpha or IL-6 on the PTH release seem less possible.