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Parathyroid hormone, calcium and phosphate balance in hemofiltration.

The acute changes in calcium, phosphate and parathyroid hormone have been examined in chronic renal failure patients under-going hemofiltration therapy and the results compared to a similar group treated by hemodialysis. In both groups there was a significant increase in Catot (0.32 mEq/1 for hemodialysis; 0.56 m Eq/1 for hemofiltration) with Ca++ remaining constant. Plasma phosphate and parathyroid hormone decreased during hemofiltration. Calcium balances were slightly positive and phosphate balances distinctly negative in all cases. To date there is no indication of induced osteodystrophy during hemofiltration therapy, although long-term studies are needed. However, the present results indicate, that hemofiltration more closely approaches the physiological situation than conventional hemodialysis.

Calcium↗

[Serum levels of calcitonin, parathyroid hormone and 25-hydroxycholecalciferol in patients with diabetes mellitus].

Blood serum levels of calcitonin, parathyroid hormone, calcium, magnesium and inorganic phosphate have been measured in basal condition and following intravenous administration of calcium in 31 patients with diabetes of type I, in 31 patients with diabetes of type II and in 29 healthy subjects. The level of 25-hydroxy cholecalciferol was measured in all these patients in basal condition only. It was found that the basal calcitonin level was significantly higher in patients with both types of diabetes than in healthy subjects. The administration of calcium caused a significantly higher increase in the blood calcitonin level in patients with type I diabetes than in those with type II diabetes. It was found in addition that in women with type II diabetes blood serum level of parathyroid hormone was significantly higher than that in men suffering from diabetes of the same type, suggesting the participation of some sex-related factor in the pathogenesis of the abnormal parathyroid level in these patients.

Calcifediol↗

Histological studies of bone from normocalcemic post-menopausal osteoporotic patients with increased circulating parathyroid hormone.

Quantitative histological evaluations were made of nondecalcified iliac crest needle biopsies were obtained from 16 untreated, normocalcemic, normophosphatemic postmenopausal osteopenic females. Six of the patients had elevated circulating immunoreactive parathyroid hormone. Morphometric parameters, which were significantly increased in the hyperparathyroid group compared with the euparathyroid patients were the cortical osteoclast count and the percentage of trabecular surface covered by active or inactive osteoid. In addition, in all patients, the cortical osteoclast count, and the per cent of trabecular surface covered by osteoid and inactive osteoid were directly related to levels of immunoreactive parathyroid hormone. These data suggest that progressive osteopenia in some patients with crush fracture, or postmenopausal or senile osteoporosis, may be conditioned by an osteoclastosis, elevations in circulating parathyroid hormone, and a relative increase in poorly mineralized osteoid tissue. As such they emphasize the heterogeneity of a so-called "osteoporotic population" and stress the need for specific histological morphometric evaluation of bone before initiating long-term therapeutic modalities.

Aged↗

Prospective study of parathyroid graft function in patients with renal hyperparathyroidism after total parathyroidectomy and heterotopic autotransplantation by measurement of the intact parathyroid hormone concentrations in both antecubital veins.

OBJECTIVE: Evaluation of the value of gradients for intact parathyroid hormone after total parathyroidectomy and heterotopic autotransplantation for renal hyperparathyroidism. DESIGN: Prospective long-term follow-up study. SETTING: Teaching hospital, Germany. SUBJECTS: A total of 115 patients operated on for renal hyperparathyroidism between 1 August 1987 to 15 August 1997. INTERVENTIONS: 100/115 had total parathyroidectomy with autotransplantation. MAIN OUTCOME MEASURES: Analyses of serum calcium, alkaline phosphatase, and intact parathormone in serum 1, 4, 8, 12, 18 and 24 months postoperatively and annually thereafter. Parathormone gradients were calculated as the ratio of the parathormone concentrations in the antecubital venous blood of the grafted and the non-grafted arm. RESULTS: During follow-up (mean 32 months, range 1 month to 9 years), 111 of the 115 patients had one to 10 re-examinations (mean: 4) and in the patients who had had total parathyroidectomy with autotransplantation a total of 437 gradients could be calculated, 91% of which were < or =20. Postoperative hypocalcaemia caused by calcium deficiency of the skeleton led to an increase in parathormone secretion and gradients. Increasing parathormone gradients during follow-up as a result of excessive parathormone secretion in the grafted-arm indicated graft-dependent recurrence. In 6 of the 9 patients with graft-dependent recurrences the gradients exceeded 20. CONCLUSION: The combined sequential assessment of gradients for intact parathyroid hormone and of serum calcium concentrations permits objective evaluation of parathyroid graft function.

Humans↗

Basal cell nevus syndrome: normal responsiveness to parathyroid hormone.

The basal cell nevus syndrome is an autosomal dominant trait which includes among its features jaw cysts, basal cell carcinomas, ectopic calcification and skeletal anomalies. It had been previously reported that such persons have had "resistance" to parathyroid hormone. In the current study, six persons with this syndrome from two families had a normal response to parathyroid hormone as measured by changes in serum calcium and phosphate and urinary excretion of calcium, phosphate and cyclic 3',5'-adenosine monophosphate. These results do not support the previous reports of "resistance" to parathyroid hormone in this syndrome.

Adolescent↗

Inhibition of the calcium pump by human parathyroid hormone-(1-34) and human calcitonin in liver plasma membranes.

The effect of human parathyroid hormone-(1-34) (hPTH) and human calcitonin (hCT) on the activity of the Ca2(+)-extrusion pump in liver plasma membranes was studied. Both hormones were found to be potent inhibitors of Ca2+ transport and the related high-affinity (Ca2(+)-Mg2+)-ATPase activity, causing maximal inhibition of 25-30% at concentrations of 100 nM. Half-maximal inhibition was observed with 20 nM-hPTH and with 0.5 nM-hCT. By comparison, salmon calcitonin and intact bovine parathyroid hormone-(1-84) were inhibitory only at 10 microM. The effects of hCT and hPTH on the Ca2+ pump activity were not mimicked by cyclic AMP. Also, 10 microM of either hPTH-(1-34) or hCT did not alter the 45Ca2+ influx rate into isolated hepatocytes. We conclude that inhibition of Ca2+ efflux, rather than the stimulation of Ca2+ influx, may play a functional role in the control of hepatic calcium homeostasis by hPTH-(1-34) and hCT.

Biological Transport, Active↗

Circulating levels of biologically active parathyroid hormone in rheumatic diseases.

There has been doubt as to whether elevated levels of parathyroid hormone, reported previously by radioimmunoassay, reflect increased concentrations of the biologically active hormone. The application of a recently developed, highly sensitive bioassay has shown considerable disparity between bioactivity and immunoreactivity in 5 rheumatic conditions and in normal subjects. Six patients with chondrocalcinosis had elevated levels; 3 of these did not have hypercalcaemia or any obvious cause other than possible subclinical hyperparathyroidism. One patient, assayed during an acute episode, had an elevated concentration of the hormone which reverted to normal when she was asymptomatic. Most patients with osteoarthrosis (13 our of 15) had low normal levels; 2 showed unexplained slightly elevated concentrations. Of 6 patients with haemochromatosis 3 had elevated levels, though this may have been related to the associated presence of diabetes mellitus. A third of patients with ankylosing spondylitis (10 out of 30) showed elevated parathyroid hormone levels but without hypercalcaemia. A number of spondylitic patients also showed anomalous results in this assay, possibly due to the presence of an antagonist. This would be consistent with the absence of clinical or biochemical evidence of hyperparathyroidism.

Adult↗

Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs.

The effects of parathyroid hormone and related polypeptides on the heart were examined using the canine heart-lung preparation supported by a donor. Synthetic bovine parathyroid hormone (PTH) containing 34 amino acids [PTH-(1--34)] and natural bovine PTH containing 84 amino acids [PTH-(1--84)] showed slight positive chronotropic and inotropic action and prominent coronary vasodilator action. The effects of the two compounds were very similar. The cardiac stimulatory action was not blocked by pindolol. The coronary vasodilation occurred without increase in the myocardial oxygen consumption, suggesting that it is due to a direct action on the coronary vasculature. All effects occurred soon after intra-arterial injection, lasted only about 20 min, and were not accompanied by changes in plasma Ca and Pi levels. Fragments of PTH, PTH-(24--34) containing 11 amino acids. PTH-(24--28) containing 5 amino acids, and PTH-(25--27) containing 3 amino acids showed very weak transient coronary dilatory action without cardiac stimulatory effects.

Animals↗

Distal site of action of parathyroid hormone on phosphate reabsorption.

The sites of inhibited phosphate transport following administration of bovine parathyroid hormone (bPTH) to thyroparathyroidectomized (TPTX) dogs were investigated. Phosphate reabsorption by the proximal and distal nephron was studied using recollection micropuncture, stop-flow methodology, and electron-probe microanalysis. Following bPTH, delivery of phosphate from the proximal tubule increased from 26 to 37% of the filtered load, P less than .01. Fractional phosphate excretion increased from 2.3 +/- 1.5 to 21.4 +/- 2.3%, P less than .001. The increased delivery of phosphate at the point of micropuncture in the proximal tubule accounted for approximately half of the phosphaturia. In six TPTX dogs, which were saline loaded, similiar increases in phosphate delivery from the proximal tubule from 27 +/- 1 to 36 +/- 2% of the filtered load resulted in a strikingly smaller phosphaturia, 5.1 +/- 1 to 9.8 +/- 2.4%, NS. In stop-flow experiments, phosphate concentratin ratios were slightly increased in the proximal nephron and markedly increased in the distal nephron following bPTH. It is concluded that parathyroid hormone markedly decreases phosphate transport in the distal nephron.

Aminohippuric Acids↗

Renal response to parathyroid hormone in the weanling rat.

The renal response to parathyroid hormone and the activity of alkaline phosphatase in kidney cortex were studied in weanling and adult rats. Clearance studies for the determination of glomerular filtration rate and phosphate excretion were started 2 h after sham operation or thyroparathyroidectomy in 24- or 40-day-old rats. Urine was collected under basal conditions and following infusions with 0.5 and 1.0 mumol phosphate per 100 g body wt min-1. For enzyme studies, rats aged 14-40 days were used, and the activity of alkaline phosphatase in renal cortical slices was determined. Glomerular filtration rate was not influenced by thyroparathyroidectomy or phosphate infusions. Plasma phosphate increased during phosphate infusions and was significantly higher in thyroparathyroidectomized rats in all clearance periods. Both the net and the fractional excretions of phosphate were higher in intact than in thyroparathyroidectomized rats and the phosphate-retaining effect of thyroparathyroidectomy was similar in weanling and adult rats. Alkaline phosphatase activity in renal cortical slices increased between days 14 and 24 (1400-3190 IU mg-1 protein, P less than 0.01). During later development, no significant change was seen. It is concluded that the immature kidney of the weanling rats shows a parathyroid hormone-dependent adaptation to acute phosphate loading, and that changes in alkaline phosphatase activity are consistent with a maturation of this system only during early development.

Alkaline Phosphatase↗

Incomplete suppression of parathyroid hormone activity in sarcoidosis presenting with hypercalcaemia.

An adult patient presenting in summertime with sarcoidosis and demonstrating raised levels of serum calcium and 1,25-dihydroxycholecalciferol was observed to have a serum immuno-reactive parathyroid hormone concentration in the mid-normal range. Renal function was normal. Corticosteroid administration quickly depressed serum calcium and 1,25-dihydroxycholecalciferol into the normal range; serum parathyroid hormone also fell to low levels. It was concluded that corticosteroid suppression, when incorporating measurements of serum calcium and 1,25-dihydroxycholecalciferol concentrations, can distinguish between sarcoidosis-related hypercalcaemia and primary hyperparathyroidism. The significance of the changes in parathyroid hormone concentration is obscure.

Adult↗

Parathyroid hormone-, 25-OH-vitamin D-, and digoxin levels in patients treated by chronic hemofiltration.

Immunoreactive parathyroid hormone (iPTH) was measured in the serum and filtrate before, during and after hemofiltration. iPTH regularly declines during hemofiltration; one patient, investigated for a longer period, showed a normalization of iPTH serum level with this treatment. The iPTH values found in the hemofiltrate were remarkably high, a finding that could be explained by non-specific effects, by the occurrence of hormone fragments or by an increased secretion rate. At any rate, the results suggest a filtration of parathyroid hormone and/or hormone fragments. On the other hand, it was impossible to detect any 25-OH-vitamin D in the hemofiltrate. Finally, digoxin could be found in the filtrate, but only in very low concentrations.

Digoxin↗

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.

Age Factors↗

[New intraoperative diagnostic methods in parathyroid surgery: intraoperative measurement of parathyroid hormone].

In thirty-seven patients undergoing parathyroidectomy from November 1999 to July 2000 with diagnosis of primary hyperparathyroidism the intraoperative intact parathyroid hormone level were studied. Preoperative samples of blood were taken from a peripheral vein before the beginning the operation. The second sample was taken 5 minutes after removal of parathyroid adenoma. The plasma intact parathyroid hormone concentration was measured by quick IRMA method. The preoperative high PTH levels reduced after excision of adenoma to the mean 18%. 33 patients had normal PTH levels after 5 minutes of removing. The total measuring time of quick PTH assay was about 30 minutes. The QPTH assay was a quantitative adjunct for the surgeon to ensure a successful parathyroidectomy. When the intraoperative QPTH level is not reduced to 50%, then the exploration should be continued and the probability of reoperation is decreased. They propose the application of the routine intraoperative measurement of QPTH level in all parathyroidectomy.

Adenoma↗

Acute responses of parathyroid hormone and 1,25 dihydroxyvitamin D3 to unilateral nephrectomy in healthy donors.

Plasma immunoreactive parathyroid hormone (iPTH), 1,25(OH)2D3, calcium and phosphate and urinary creatinine, calcium and phosphate were measured before and following unilateral nephrectomy in six kidney donors. Unexpectedly, plasma calcium rose, from 2.27 +/- 0.02 mmol/l (mean +/- SEM) to 2.41 +/- 0.03 mmol/l on day 7 and to 2.37 +/- 0.02 mmol/l on day 30 (P less than 0.02). A parallel rise in iPTH occurred, from 0.61 +/- 0.16 ng/ml initially, to 1.83 +/- 0.54 ng/ml on day 7 (P less than 0.05) and to 1.18 +/- 0.18 on day 30 (P less than 0.01). The ratio of maximal tubular reabsorption of phosphate to GFR (TmP/GFR) fell by day 2 (P less than 0.01), remaining reduced on day 30 (P less than 0.05). The significance of elevated iPTH in renal insufficiency was further assessed by determining the time course of the disappearance of iPTH after parathyroidectomy in three haemodialysis subjects. Fifty per cent baseline iPTH level occurred after an average of 104.7 min, suggesting that the assay did not predominantly recognize C-terminal PTH fragments. By day 2, plasma 1,25(OH)2D3 had fallen from 34.3 +/- 4.5 pg/ml to 22.8 +/- 3.8 pg/ml (P less than 0.001), but by day 4 had regained its pre-nephrectomy value. Our results suggest that hypocalcaemia may not be the sole stimulus to parathyroid hormone secretion. It is speculated that reduction in circulating 1,25(OH)2D3 may be involved.

Adult↗

Ca2+-induced increases in steady-state concentrations of intracellular calcium are not required for inhibition of parathyroid hormone secretion.

It has been well established that increases in extracellular calcium concentration ([Ca2+]) inhibit parathyroid hormone (PTH) secretion. The effects of [Ca2+] are mediated through a G-protein-coupled receptor that has been cloned and characterized. Additionally, it has been demonstrated in parathyroid cells that an increase in [Ca2+] results in an increase in steady-state levels of intracellular calcium ([Ca2+]i). At present, it has not been fully resolved whether changes in [Ca2+]i are related to changes in PTH secretion. In the current study, the effect of increased [Ca2+] on PTH secretion and the connection regarding changes in concentrations of intracellular calcium [Ca2+]i have been examined in primary cultures of bovine parathyroid cells. PTH secretion was measured by radioimmunoassay and intracellular calcium was determined by single cell calcium imaging. Bovine parathyroid cells pre-incubated with either 0.5 or 1 mM calcium responded to rapid increases in [Ca2+] (> or = 0.5 mM) with an immediate and sustained increase in steady-state levels of [Ca2+]i that persisted for time intervals greater than 15 minutes. Although the magnitude of the sustained increase in [Ca2+]i varied among individual cells (approximately 40% to > 300%), the overall pattern and course of time were similar in all cells examined (n = 142). In all trials, [Ca2+]i immediately returned to baseline levels following the addition of the calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Additional control studies, however, suggest that sustained increases in [Ca2+]i do not correlate with regulation of parathyroid hormone secretion. Sustained elevations of [Ca2+]i were not observed when [Ca2+] was gradually increased by the addition of 0.1 mM increments at 1 minute intervals. Furthermore, the effect on inhibition of PTH secretion was the same regardless of whether [Ca2+] was increased by gradual or rapid addition.

Animals↗

Parathyroid hormone: secretion and metabolism in vivo.

Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood (obtained by venous catheterization) from patients with hyperparathyroidism, as well as from calves and from cattle. Hormone secreted in vivo from normal bovine parathyroid glands and from human parathyroid adenomas is similar in size to the 84-amino-acid peptide (molecular weight of 9500) extracted from the parathyroids. However, much of the immunoreactive parathyroid hormone present in the peripheral circulation of man and cattle is smaller than the extracted or secreted hormone; it elutes from gel columns at a position corresponding to a molecular weight of about 7000. The immunological characteristics of extracted and secreted hormone are identical, while hormone in the general circulation is immunologically dissimilar to extracted and secreted hormone. The results indicate that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

Amino Acids↗