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Influence of extracorporeal dialysis on parathyroid hormone secretion in patients with acute renal failure.

Serum immunoreactive parathyroid hormone (iPTH) was estimated in 30 patients with renal failure before and after haemodialysis. All patients were anuric or oliguric at the time of the investigation. Pre-dialysis iPTH values were significantly elevated (3.4 ng/ml) as compared with normal subjects (less than 0.5 ng/ml). Simultaneously, a significant hypocalcaemia (4.15 mEq/litre) was confirmed which was negatively correlated with iPTH levels. After 7-8 h of haemodialysis using a calcium concentration of 4.0 mEq/litre in the dialysate, a significant drop of iPTH level to 1.8 ng/ml was noted.

Acute Kidney Injury↗

[Factors regulating parathyroid hormone and the mechanism of signal transduction].

The secretion of parathyroid hormone (PTH) is influenced by various factors, but extracellular calcium concentration ([Ca2+]e) is the sole factor established to be the physiological regulator. [Ca2+]e acts on Ca2+ sensing receptor recently cloned, and elevates intracellular calcium ([Ca2+]i) and inositol trisphosphate. Although the changes in cAMP level and C-kinase activity also have been demonstrated, the mediator directly operating secretory mechanism of PTH has not been defined. Recently, the activity of chromogranin A-related peptides to modulate PTH secretion was found and their role as the autocrine-paracrine regulator of PTH secretion has been proposed.

Calcium↗

A radioimmunoassay for rat serum parathyroid hormone using N-terminal of PTH.

Partially purified bovine parathyroid hormone (PTH) produced two kinds of antisera, GP-100 reacting with 125I-labeled bovine PTH (b-PTH 1-84) alone and GP-M reacting with 125I-labeled synthetic N-terminal portion of bovine PTH (b-PTH 1-34) as well as b-PTH 1-84. Rat serum PTH reacted with the latter but not in the former, suggesting a similarity to b-PTH 1-34. Rat serum PTH became undetectable after parathyroidectomy, and increased after Na2-EDTA injection and following renal injury with sodium sulfacetylthiazole.

Animals↗

Does bone resorption inhibition affect the anabolic response to parathyroid hormone?

One of the questions arising from the use of parathyroid hormone (PTH) as an anabolic agent is whether preventing bone loss with inhibitors of bone resorption might result in a greater amount of bone in response to PTH. Two recent independent reports indicate that the anabolic effect of PTH in osteoporotic women appears to be significantly reduced when alendronate is administered in combination with PTH in studies using biochemical markers, quantitative computed tomography and bone mineral density (BMD) measurements. The very different mechanisms of the two treatments reduces the impact of the BMD data, but if the overall conclusion is correct, an effect of PTH on resorption might be necessary for the anabolic effect to follow.

Alendronate↗

Parathyroid hormone: radioimmunoassay and clinical interpretation.

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue.

Adult↗

Regulation of parathyroid hormone secretion by plasma calcium in aging rats.

Plasma immunoreactive parathyroid hormone (irPTH) levels increase with aging. This study determined 1) whether NH2-terminal irPTH secretory responses to induced hypocalcemia differ between adult (6-mo-old) and aged (24- to 26-mo-old) male rats and 2) whether a higher set point for irPTH release by Ca is responsible for the elevated irPTH levels with aging. Basal irPTH levels were 68% higher and 1,25-dihydroxyvitamin D3 levels were 44% lower in aged rats. An acutely induced, constant hypocalcemic stimulus [0.32 mM decrement in ionized Ca (Ca2+) for 2 h] was developed in catheterized conscious adult and aged rats by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) infusion using the Ca clamp technique. The initial irPTH secretory response to acute hypocalcemia (5-10 min) was reduced in aged rats (1.9- vs. 3.1-fold increase), suggesting reduced hormone stores. However, higher sustained irPTH levels (30 min to 2 h) were maintained in aged rats, indicating increased irPTH synthesis and release. The EGTA infusion rate necessary to maintain constant hypocalcemia was less in aged rats, suggesting skeletal resistance to PTH. Slow EGTA and Ca infusions were used to determine irPTH secretion at plasma Ca2+ levels from 0.7 to 1.5 mM. In aged rats, irPTH levels were higher at all Ca2+ concentrations, but the set point for irPTH release by Ca2+ was the same as in adult rats. Thus the elevated irPTH secretion in aged rats is not caused by a change in the set point for irPTH release but does result in decreased irPTH stores.

Aging↗

Altered diurnal regulation of blood ionized calcium and serum parathyroid hormone concentrations during parenteral nutrition.

BACKGROUND: Little is known about parathyroid gland function in patients receiving total parenteral nutrition (TPN). OBJECTIVE: Our objective was to determine whether parathyroid gland function is abnormal in TPN recipients. DESIGN: Six patients with a mean (+/-1 SD) age of 45.5 +/- 8.0 y who had been receiving TPN for 18.7 +/- 2. 8 y underwent bone biopsy, bone mass measurements with dual-energy X-ray absorptiometry, and dynamic tests of parathyroid gland function. Diurnal variations in blood ionized calcium (iCa(2+)) and serum parathyroid hormone (PTH) concentrations were also assessed. Results were compared with those of healthy volunteers. RESULTS: Bone mass and bone formation were subnormal in all patients. Basal serum PTH concentrations were moderately higher in the TPN recipients than in healthy volunteers, and values obtained every 30 min over 24 h were significantly higher (P < 0.001) in TPN recipients (5.0 +/- 0.9 pmol/L) than in healthy volunteers (2.6 +/- 0.6 pmol/L). The percentage increase in serum PTH during citrate-induced hypocalcemia was lower in the TPN recipients, consistent with secondary hyperparathyroidism. Evening infusions of calcium-containing TPN eliminated the nocturnal rise in serum PTH, increased the amplitude of change for iCa(2+) and PTH over 24 h, increased the orderliness of change for iCa(2+) and PTH as measured by approximate entropy (ApEn), and enhanced the synchrony of change between iCa(2+) and PTH. Treatment for 10 d with calcium-free TPN restored the nocturnal rise in serum PTH and increased ApEn for PTH. ApEn for iCa(2+) remained low, suggesting that a component of nutrient solutions, but not calcium per se, enhances the regularity of PTH release in TPN recipients. CONCLUSION: Parathyroid gland function is abnormal in long-term TPN recipients, which may contribute to disturbances in bone metabolism.

Adult↗

The parathyroid hormone level in Thai women.

Study of the correlation of parathyroid hormone (PTH) with age, radial bone mass and Nitrogenous mid fragment osteocalcin (NMID osteocalcin) in 226 menopausal women and 123 menstrual women. In menopausal women, aged between 50 and 69, the level of PTH did not increase with age (r=0.001, p=NS). Elderly women (n=123, age>70) showed a slight increase of PTH, 7.8 per cent compared to menstruating women. In elderly women (n=100, age>60) there was no weak correlation (r=0.11, p=0.0001) with bone mass of the distal end of the radius measured by Dual X-ray Absorptiometry (DXA) (Panasonic BDM-3) and no correlation between PTH and the resorptive bone marker, (betacrosslap) (r=0.11, n=122).

Adult↗

Effects of age, estrogen depletion, and parathyroid hormone treatment on vertebral cancellous wall width in female rats.

The main goal of this study was to determine whether vertebral cancellous wall width changes with age and parathyroid hormone (PTH) treatment in rats. Female Sprague-Dawley rats were subjected to sham surgery or ovariectomy at 3 months of age. One month after surgery, ovariectomized (ovx) rats were injected subcutaneously (s.c.) 5 days/week for 6 weeks with vehicle or human parathyroid hormone [hPTH (1-34)] at a dose of 80 microg/kg body weight. Sham-operated control rats were injected s.c. with vehicle alone. All rats from this first study were 5.5 months of age at the time of killing. In the second study, control and ovx rats were subjected to the same treatments for a 10-week period beginning at one year after surgery. These animals were 17.5 months of age at the end of the study. The first lumbar vertebra was collected from each rat and processed undecalcified for measurements of cancellous wall width. At 5.5 months of age, control and ovx rats had nearly identical mean values for vertebral cancellous wall width, but this remodeling variable was significantly increased in PTH-treated ovx rats. At 17.5 months of age, wall width in control and ovx rats decreased significantly compared with wall width in the younger rats. PTH treatment of aged ovx rats induced a significant increase in vertebral cancellous wall width when compared with vehicle treatment of aged ovx rats. These results, which are consistent with findings in humans, indicate that vertebral cancellous wall width decreases with age in intact female rats and in ovx rats, but increases in ovx rats in response to PTH treatment. Furthermore, the results add to the growing body of evidence that substantial cancellous bone remodeling occurs in the vertebral bodies of rats.

Aging↗

Pseudohypoparathyroidism showing positive phosphaturic and negative cyclic AMP excretion response to parathyroid hormone.

We report a patient with pseudohypoparathyroidism (PHP) in whom parathyroid hormone (PTH) infusion failed to produce an increase in urinary adenosine 3', 5' monophosphate (cAMP) excretion in spite of the positive urinary phosphate excretion. The dbcAMP infusion test showed almost the same increase in phosphate as in the E-H test, although high urinary cAMP excretion was detected. Furthermore, a PTH infusion test in combination with calcium antagonist (diltiazem) administration markedly increased phosphate excretion, whereas the response of urinary cAMP excretion also remained negative. After treatment with 1 alpha(OH)D3, phosphaturic response increased by at least 14.3 mg/2 h compared with that in the pretreatment period. Therefore, intra and extra cellular calcium seem to affect the phosphaturic response induced by PTH.

Adult↗

Dissociation of parathyroid hormone bioactivity and immunoreactivity in pseudohypoparathyroidism type I.

Circulating levels of parathyroid hormone (PTH) in six patients with pseudohypoparathyroidism type I (PSPI) have been measured by two immunoassays and by cytochemical bioassay and compared with measurements in normal subjects and patients with clinically defined hyper- and hypoparathyroidism. In all PSPI patients, the levels of immunoreactive PTH were in the hyperparathyroid range, whereas the bioactive levels were either in the normal or close to the normal range. In one patient from whom the dihydrotachysterol therapy was withdrawn, both immunoreactive and bioactive PTH concentrations increased. The finding that the PTH measured by RIA in these PSPI patients may have reduced biological activity may explain some of the clinical findings of hypoparathyroidism in this syndrome.

Adult↗

Stability of parathyroid hormone ex vivo in haemodialysis patients.

BACKGROUND: The stability of parathyroid hormone (PTH) in blood ex vivo is a significant practical problem for laboratories and clinicians. Several studies have suggested that PTH is more stable in blood collected into a potassium edetate (EDTA) preservative. METHODS: To confirm that this was applicable to renal dialysis patients using our assay (Nichols chemiluminescence), we examined PTH stability in 13 patients with end-stage renal failure using three different blood collection tubes. RESULTS: PTH remained stable in EDTA plasma for up to 48 h at room temperature. PTH was significantly reduced in serum collected into plain tubes after 2 h, and after 4 h in serum collected into serum separator tubes, at room temperature. CONCLUSION: In the assessment of renal osteodystrophy, the use of EDTA plasma can confer significant benefit, especially in busy laboratories where rapid frozen separation of blood may be hard to achieve.

Edetic Acid↗

Development and application of a mid-region specific assay for human parathyroid hormone.

A new peptide spanning residues 28-54 of human parathyroid hormone (PTH) was synthesized and used to develop a homologous immunoradiometric assay specific for the mid-region of human PTH. The peptide was coupled to cellulose and used to absorb mid-region antibodies from a goat antiserum against intact human PTH. This assay has been applied to the measurement of circulating PTH in man: in normal subjects the concentration in serum ranged from undetectable (less than 40 pg/ml) to 70 pg/ml, the reference standard being the human PTH 28-54 peptide. In patients with primary hyperparathyroidism concentrations ranged from 120 to 1800 pg/ml. Hormone was not detected in patients with hypoparathyroidism. In normal subjects and in patients with primary hyperparathyroidism the mid-region PTH concentrations were similar to those obtained in an amino-terminal specific assay. By contrast, carboxy-terminal PTH concentrations were markedly higher being 10-fold greater in both groups studied. In patients with primary hyperparathyroidism undergoing parathyroidectomy and in chronic renal failure patients who were infused with calcium, mid-region and amino-terminal PTH disappeared much more rapidly than carboxy-terminal PTH. However, although mid-region PTH was initially cleared as quickly as amino-terminal PTH, it then reached a plateau and remained at a higher level. Thus the mid-region specific assay described here is proving to be of value in the study of the secretion and metabolism of PTH.

Calcium↗

Sensitive homologous radioimmunoassay for human parathyroid hormone to diagnose hypoparathyroid conditions.

A sensitive radioimmunoassay for human parathyroid hormone (hPTH) to diagnose hypoparathyroid conditions is described. The antiserum was raised in goats against extracted hPTH. Synthetic human PTH fragment (53-84) is used as a standard and 125I-Tyr52hPTH (53-84) as a tracer. After a two-step incubation (24 h + 24 h) at 4 degrees C, the bound and free fractions are separated by a mixture of second antibody and polyethylene glycol solution. The detection limit for hPTH (53-84) is 2 pmol/L hPTH (53-84) (2 mol/tube). The PTH level in 36 healthy subjects was 5-12 pmol/L. Of 14 patients with hypoparathyroidism 11 patients had PTH concentrations below normal, two patients had levels on the lower limit of the normal range (5 pmol/L). The concentration of one patient with pseudohypoparathyroidism was markedly elevated. This assay is suitable for detecting low PTH levels and for studying changes of PTH concentration within the normal range.

Calcium↗

Failure of parathyroid hormone to cross the nonhuman primate placenta.

Following infusion of parathyroid extract (PTE), parathyroid hormone (PTH) did not cross the placenta from the monkey mother to her fetus. Although maternal PTH levels increased four- to 12-fold, fetal PTH levels remained at the base line at all times tested. To determine if PTH crossed the placenta from fetus to mother, PTE was infused into the fetal aorta while the monkey baby remained in utero. PTH in the fetal serum increased ten-fold without a significant change in maternal serum PTH. Thus, PTH does not cross the placenta in either direction. Blood ionized calcium levels in nonpregnant female monkeys, following infusions of ethylenediaminetetra-acetate (EDTA) were shown to decrease, with a subsequent increase in blood PTH levels. Thus, the monkey arathyroid gland was shown to be physiologically responsive to lowered calcium levels. Biological half-life disappearance times of beef PTH in monkey fetuses and their mothers were similar to those found in human beings.

Animals↗

[The influence of parathyroid hormone on the process of fracture healing].

The influence of parathyroid hormone (PTH) on the process of fracture healing was examined using the fractured rats which were parathyroidectomized or given synthetic PTH. The biochemical and histological changes were studied. The results were as follows: I) Parathyroidectomized rats (PTX rats) showed decreased serum Ca, increased serum P and decreased serum PTH as observed in hypoparathyroidism. The fracture healing was impaired due to delay of both chondroclasis at the phase of endochondral ossification and secondary remodeling of primary cancellous bone. II) In rats treated with PTH (PTH rats) both serum Ca and P levels were increased at the early stage. Bone resorption as well as formation was also promoted at the early stage. At the late stage only bone formation remained good with poor bone resorption, indicating that secondary bone remodeling is decreased. The union of callus was impaired. Fracture healing was consequently delayed in both PTX and PTH rats. It is therefore suggested that PTH may be one of the important factors in fracture healing.

Alkaline Phosphatase↗

Interactions between parathyroid hormone and prostaglandins on renal cortical cyclic AMP.

Effects of parathyroid hormone (PTH) and several prostaglandins (PGs) on cyclic AMP (cAMP) metabolism were studied and compared in isolated renal cortical tubules from male hamsters. Both production and intracellular degradation of cAMP were increased by PTH and each of the PGs tested (PGE2, PGE1, PGI2). Production of cAMP was increased to similar levels by maximal concentrations of PTH and each PG, however, degradation of cAMP was significantly higher in response to PTH than with any of the PGs. This difference in intracellular degradation of cAMP was responsible for the much higher concentrations of cAMP in renal cortical tubules exposed to PGs (PGE1, PGE2, PGI2) than to PTH. Submaximal amounts of each PG produced additive increases in cAMP concentrations in the presence of maximal amounts of PTH. Additivity of the combined responses was lost, however, as the PGs concentrations reached their maxima. The results suggest that renal PGs (PGE2 and PGI2) may modulate the effects of PTH on cAMP concentrations in renal cortical tubules.

Alprostadil↗

Catch-up growth with normal parathyroid hormone levels in chronic renal failure.

The optimum range for parathyroid hormone (PTH) levels in children with chronic renal failure (CRF) remains undefined. We aimed to determine growth velocity in children with CRF managed with normal PTH levels. We performed a retrospective case note review of 99 children (77 boys), with a glomerular filtration rate (GFR) <41 ml/min per 1.73 m(2), who had at least 2 years of 3-monthly follow-up. The age range at entry was 0.5-6.0 years; data collection was continued until 10 years of age or the commencement of growth hormone or renal replacement therapy. The median GFR was 22 ml/min per 1.73 m(2); over the study period mean serum calcium and phosphate levels were approximately equal to the mid-point of the respective normal ranges. Median PTH levels were equal to the upper limit of the normal range. Height standard deviation score (Ht SDS) at entry was -1.73. During the study period the overall mean change in Ht SDS was +0.3, significantly greater than the no change expected of a normal population ( P=0.004). The median dose of calcium carbonate was 150 mg/kg per day and 1-alpha calcidol 0.015 microg/kg per day. The growth rate was independent of all parameters, including age, PTH levels, the use of enteral feeds, and 1-alpha calcidol prescription. Our results indicate that catch-up growth can occur in infants and children with CRF when medical therapy is aimed at normalizing PTH levels.

Biomarkers↗