Plasma Parathyroid Hormone Levels Research Articles

Uremic cardiomyopathy: potential role of vitamin D and parathyroid hormone.

44 patients receiving regular hemodialysis therapy were investigated using M-mode echocardiography and systolic time intervals to examine the effects of parathyroid hormone (PTH) and vitamin D on left ventricular function. 12 patients were treated with 1 microgram daily of 1, alpha-hydroxycholecalciferol for 6 weeks, which produced a decrease in plasma PTH concentration from 1,883 +/- 226 to 1,123 +/- 289 ng/l. Fractional fibre shortening (FS) increased from 34.6 to 37.6% (p less than 0.025) and mean velocity of fibre shortening (Vcf) increased from 1.21 to 1.32 circ/s (p less than 0.01). A second group of 20 patients was studied before and after the plasma magnesium concentration was increased from 1.25 to 1.70 mmol/l, resulting in a fall in plasma PTH concentration from 546 to 418 ng/l (p less than 0.001). This was associated with an increase in both FS from 32.4 to 34.3%, and Vcf from 1.19 to 1.21 circ/s. A third group of 6 patients with severe hyperparathyroidism underwent total parathyroidectomy, FS increased from 34.9 to 36.3% and Vcf increased from 1.22 to 1.38 circ/s. In conclusion, our results indicate that vitamin D and PTH do influence left ventricular function in uremic patients on chronic hemodialysis, and that a reduction in plasma PTH levels is beneficial to the uremic heart.

Basal parathyroid activity and renal calcium handling during an intravenous calcium load.

Urinary excretion of calcium and urinary cyclic AMP (cAMP), plasma parathyroid hormone (PTH) and ionized serum calcium concentration, and creatinine clearance were measured in 15 healthy humans. In the same subjects, renal tubular reabsorption of calcium was evaluated by analyzing the regression line of urinary calcium excretion rate on rising the level of serum calcium during an intravenous calcium infusion. The regression line intercept on the y-axis, which has been proposed to depend on the calcium reabsorption in the renal distal tubule, was found to be significantly related to both urinary cAMP and PTH levels. The theoretical renal threshold for calcium excretion was directly related to the y-axis intercept and thus also to the index of parathyroid activity. No relationship was found between urinary cAMP or plasma PTH levels and the regression line slope of urinary calcium to serum calcium. In healthy subjects, parathyroid activity significantly affects the extrapolated regression line of urinary calcium to serum calcium by changing the intercept, but not the slope.

A rat model for hormone and mineral changes in chronic renal failure.

Plasma parathyroid hormone (PTH) and calcitonin (CT) in rats with surgically induced chronic renal failure were measured by radioimmunoassay. Plasma PTH levels in uremic rats (2897 +/- 693 pg/ml) were significantly (P less than 0.001) higher than those in nonuremic rats (286 +/- 18 pg/ml). A low-phosphorus diet for 4 and 8 days increased serum calcium and decreased the elevated PTH level to the level of sham-operated rats. Plasma CT levels in uremic rats (60.1 +/- 7.8 pg/ml) were significantly (P less than 0.05) higher than those in nonuremic rats (37.6 +/- 2.4 pg/ml). The low-phosphorus diet for 4 days, but not 8 days, increased the CT levels in uremic rats. Our results demonstrate the importance of phosphate and calcium in influencing the secretion of PTH and CT in uremia. The rat, along with appropriate radioimmunoassays, appears to be a useful model for studying bone mineral metabolism in chronic renal failure.

A Case of Advanced Breast Cancer Associated with Hypocalcemia

Although hypercalcemia is a well-known complication of malignant diseases, hypocalcemia seems to be a rather rare one. A 34-yr-old woman with advanced breast cancer who presented hypocalcemia is described. She had generalized multiple osteolytic bone metastases which were progressive in spite of chemo-endocrine and radiation therapy. She was admitted because of severe bone pain and dyspnea caused by bilateral pleural effusion. Laboratory examination on admission showed that the serum calcium was 9.6 mg/dl, serum total protein 5.9 g/dl, serum inorganic phosphorus 4.6 mg/dl, and serum alkaline phosphatase 29.6 King-Armstrong units. The serum calcium gradually fell to 7.0 mg/dl on the 45th hospital day when the serum total protein was 6.8 g/dl and she complained of paresthesia in the extremities. On the 58th day, severe tachycardia and hypotension developed and she died of congestive heart failure on the 67th hospital day. At that time the serum calcium was 5.4 mg/dl. During her hospital course, the plasma parathyroid hormone levels were examined repeatedly and were 0.4, 0.6, 0.6 and 0.7 ng/ml (normal; less than 0.5 ng/ml). Autopsy revealed that cancer invaded the space between the thyroid and the trachea and no parathyroid glands could be found even in the mediastinum. Microscopically the parathyroid glands were replaced completely by the cancer cells. These observations indicate that metastasis of breast cancer to the parathyroid glands caused relative hypoparathyroidism, resulting in hypocalcemia. In addition, congestive heart failure which was refractory to digitalis and diuretics might have been caused by impaired contractility of the myocardium associated with hypocalcemia.

Lack of rapid effects of cortisol on parathyroid hormone levels in cattle.

Experiments were performed to study plasma concentrations of parathyroid hormone in association with short-term changes of cortisol and dexamethasone. Parathyroid hormone was not significantly modified during 3-hour intravenous infusions of cortisol, leading to marked elevations (p less than 0.001) of plasma cortisol levels, and during intravenous administration of dexamethasone. Thus glucocorticoids, at least in cattle, apparently cause no short-term changes of plasma parathyroid hormone levels.

Parathyroid suppressibility in hyperparathyroidism due to chronic renal failure: studies with autotransplanted parathyroid tissue.

SUMMARYSuppressibility of parathyroid hormone (PTH) secretion by calcium was evaluated in six patients with chronic renal failure and parathyroid tissue autotransplanted into the forearm. One patient was reinvestigated after renal transplantation. Plasma PTH levels were measured in the venous effluent of transplanted parathyroid tissue (VE) and in peripheral blood (PB) with two radioimmunoassays (RIA). One of these detected predominantly the intact human parathyroid hormone‐(1–84) [PTH‐(1–84)] (N‐assay) and another in addition carboxyl (COOH)‐terminal fragments (C‐assay). At 5 min after the start of 12‐min calcium infusions, resulting in a mean increase of plasma calcium levels of 0±6 mmol/l (P < 0±01), PTH was lowered to 44±10% (mean ± SE) (P < 0±01) of preinfusion levels in the VE and to 88±4% (P < 0±05) in PB, when measured in the N‐assay; subsequently the plasma calcium level remained raised and PTH level lowered. When estimated in the C‐assay, PTH was significantly lowered to 82± 6% (P < 0–05) in the VE at 120 min, and to between 91 ± 2% and 96 ± 2% (P < 0±01‐ < 0±05) in the PB at 20 to 120 min after the start of the calcium infusions. The results were extended with gel permeation chromatography of representative plasma samples. After renal transplantation and restoration of renal function gel filtration analysis indicated that the levels of intact PTH‐(1–84) were 49±6 and of its COOH‐terminal fragments 3±5 higher in the VE than in PB. In response to i.v. calcium administration intact PTH and its COOH‐terminal fragments were lowered to 25% and 62% in the VE, and to 29% and 86% in PB, respectively. These findings demonstrate that the secretion of intact PTH‐(1–84) is suppressed within minutes in response to i.v. calcium administration; a slower fall of the secretion of COOH‐terminal PTH fragments was demonstrated only after restoration of near‐normal renal function.

Role of prolactin in vitamin D metabolism and calcium absorption during lactation in the rat.

Intestinal calcium absorption and plasma levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in lactating and non-lacting rats and the effects of bromocriptine and exogenous prolactin treatment were evaluated. In lacting rats calcium absorption and plasma levels of parathyroid hormone, 1,25(OH)2D3 and alkaline phosphatase activity were significantly increased. Bromocriptine treatment significantly reduced the enhanced calcium absorption and levels of plasma 1,25(OH)2D3 and alkaline phosphatase but had no significant effect on plasma levels of parathyroid hormone. Prolactin administered with bromocriptine to lactating animals prevented all the changes observed with bromocriptine treatment alone. It was concluded that the increased plasma levels of prolacting during lactation lead to high plasma levels of 1,25(OH)2D3 which are responsible for the enhanced intestinal calcium absorption.

Effects of L-dopa on plasma levels of parathyroid hormone in calves.

After oral administration of l-dihydroxyphenylalanine (L-dopa) to calves, plasma concentrations of L-dopa, dopamine, norepinephrine and parathyroid hormone increased whereas prolactin and calcium decreased while epinephrine remained unchanged. The decrease of prolactin presumably occurred as a consequence of the conversion of L-dopa to dopamine (in the hypothalamus), whereas the increase in parathyroid hormone was caused by hypocalcemia, by elevated dopamine and possibly by norepinephrine.

Effects of somatostatin on parathyroid hormone levels and on responses of parathyroid hormone to beta-adrenergic agonists and hypocalcaemia.

Experiments were designed to study the effect of exogenous somatostatin (S) on basal levels or parathyroid hormone (PTH) and on PTH responses to isoproterenol (ISO), adrenaline (A) or ethyleneglycol-bis (beta-aminoethylether) N,N'-tetraacetate (EGTA) in cattle. During S infusions (6.11 nmol injected iv as a bolus and 0.82 nmol/kg/min infused iv for 30 or 60 min) plasma levels of PTH and calcium (Ca) did not change, whereas concentrations of immunoreactive insulin (IRI) decreased significantly (P less than 0.01). In response to ISO (0.09 nmol/kg/min) or EGTA (5.6 mumol/kg/min, depressing plasma Ca by 0.27 nmol/l) PTH levels were similarly increased (P less than 0.05) both in the absence and presence of S. On the other hand, S suppressed IRI responses to ISO. During 60-min infusions of EGTA (3.15 mumol/kg/min) plasma Ca fell to significantly lower levels (P less than 0.01) during simultaneous infusions of S than in the absence of exogenous S, while the magnitude of PTH responses was similar. The results do not support a role of somatostatin on basal PTH levels and on PTH responses to beta-adrenergic agonists or hypocalcaemia under conditions, in which S markedly lowers IRI levels and IRI responses to ISO. However, S apparently reduces Ca mobilisation during abrupt hypocalcaemia.

Secondary hyperparathyroidism in X-linked hypophosphatemic mice.

Plasma parathyroid hormone (PTH) was measured in adult, age-matched, intact normal mice and Hyp male mice (n = 11/genotype). Hyp mice are an animal model for the human disease X-linked hypophosphatemia. A RIA was used which detects intact and carboxyl-terminal fragments of PTH. Hyp mice were found to have significantly higher plasma PTH levels (0.21 +/- 0.03 ng bovine PTH eq/ml) than normal mice (0.04 +/- 0.03 ng/ml; P less than 0.01). This hyperparathyroidism in the slightly hypocalcemic, osteomalacic Hyp mice may be the result of skeletal resistance to endogenous PTH and may contribute to their characteristically elevated renal excretion of phosphate and urinary cAMP

Increased plasma 1,25-dihydroxyvitamin D after low calcium challenge in X-linked hypophosphatemic mice.

Hyp mice are a model for human X-linked hypophosphatemic (vitamin D-resistant) rickets. We have reported reduced plasma 25-hydroxyvitamin D (25OHD) and normal plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels and (2) failure of low phosphate diets to increase plasma 1,25-(OH)2D in Hyp mice. In this study, we tested the other principal regulatory system of plasma 1,25-(OH)2D by challenging with a low calcium diet. Normal and Hy p mice were fed a control or a low calcium diet for 3 or 7 days. Both normal and Hyp mice showed unchanged plasma phosphate levels and slightly but significantly reduced plasma calcium levels on the low calcium diet. The Hyp mice had significantly elevated plasma parathyroid hormone levels while on the low calcium diet. Plasma 25OHD and 1,25-(OH)2D were measured in the same 4-ml plasma sample by modifications of the Eisman method for 1,25-(OH)2D and the competitive binding assay of Haddad for 25OHD. Each sample was the pooled plasma of 10-14 mice at 13 weeks of age. On the control diet, plasma 1,25-(OH)2D levels were not significantly different in Hyp and normal mice. Plasma 1,25-(OH)2D was elevated in both genotypes on the low calcium diet, but the level in Hyp animals was significantly (P less than 0.05) higher than the level in normal mice. Plasma 25OHD was lower in Hyp than normal and was unaffected by the low calcium diet in either genotype. In summary, whereas Hyp mice do not respond to low phosphate challenge with elevated plasma 1,25-(OH)2D levels, they do respond to low calcium challenge.

Lokalisation eines mediastinalen Nebenschilddrüsenadenoms

Hyperparathyroidism persisted in a 36-yr-old woman after surgical exploration of the neck and removal of 2-V2 normal parathyroid glands. Arteriography, selective venous sampling and radioimmunoassay allowed identification of the source of excess parathyroid hormone (PTH) as a mediastinal lesion at the level of the tracheal bifurcation. The artery feeding the lesion was deliberately compromised by embolic occlusion with a mixture of autologous clot and gelfoam. This procedure led to transient hypoparathyroidism. Se- rial monitoring of plasma parathyroid hormone levels, renal phosphate clearance, and urinary cyclic-adenosine monophosphate excretion indi- cated that parathyroid ischemia had not resulted in release of large amounts of biologically or immuno- logically active parathyroid hormone. Within five days after the procedure the concentration of parathyroid hormone in plasma increased indicating the presence of residual parathyroid tissue in the neck or mediastinum. Mild hyperparathyroidism reappeared within several months with less marked elevations of PTH and calcium levels suggesting that the tumor had not infarcted completely. (J Clin Endocrinol Metab 39: 1110, 1974)

Plasma Parathyroid Hormone and Insulin Concentrations in Cows Administered Potassium Chloride and Sodium Citrate

Two age groups of nonpregnant cows were used to study plasma changes in parathyroid hormone, insulin, and glucose, and renal clearance rates of magnesium, calcium, and inorganic phosphorus after intraruminal administration of 1.5 g potassium chloride (KCl)/kg body weight (BW) or 1.5 g sodium citrate/kg BW. Magnesium (2.4 mg/kg BW) was simultaneously infused intravenously for 120 minutes to facilitate the measurement of changes in magnesium clearance rate and kidney tubular resorption due to the treatments. Elevated plasma concentrations of potassium from intraruminal infusion of KCl increased plasma parathyroid hormone, insulin, glucose, and magnesium levels. Net tubular resorption of magnesium (TMg) was also increased after potassium dosing, and the old cows had lower TMg values compared with the young cows. Plasma magnesium and calcium clearance rates were increased only by citrate, while phosphorus was not influenced by either treatment. These results provide evidence for a relationship between potassium and the endocrine factors, parathyroid hormone, and insulin; citrate appears to antagonize tubular resorption of magnesium and calcium.parathyroid hormone insulin potassium glucose cows renal clearance

Primary hyperparathyroidism: four- to eight-year postoperative follow-up demonstrating persistent functional insignificance of microscopic parathyroid hyperplasia and decreased autonomy of parathyroid hormone release.

Thirty-nine patients with primary hyperparathyroidism were studied four to eight years after their initial operation. In six patients, both the pathologist and surgeon agreed on the diagnosis of solitary adenoma; in 16 patients, the surgeon diagnosed solitary adenoma and the pathologist parathyroid hyperplasia (microscopic hyperplasia). In 16 patients, primary chief cell hyperplasia was agreed upon by the pathologist and surgeon. In the 16 patients with microscopic hyperplasia, there have been no long-term recurrences of hypercalcemia, but, in two patients, plasma parathyroid hormone levels are high. Parathyroid hormone--total calcium regression curves demonstrate significant preoperative correlation in solitary adenoma, p less than 0.01, and primary chief cell hyperplasia, p less than 0.05. After operation, significant correlations were not found between parathyroid hormone and total calcium. T-testing slope differences of pre- and postoperative parathyroid hormone--total calcium regression curves demonstrates a significant (p less than 0.01) shift to the right of the microscopic hyperplasia patients after operation, moving them to a broader range of total calcium per picogram parathyroid hormone. We conclude that 1) in primary hyperparathyroidism, positive regulation of total calcium by autonomously released parathyroid hormone exists in patients with solitary adenoma and chief cell hyperplasia; 2) autonomously functioning parathyroid tissue has been removed by operation for solitary adenoma with coexistent microscopic parathyroid hyperplasia. In this four- to eight-year follow-up period, it is clear that microscopic parathyroid hyperplasia is not associated with recurrent hypercalcemia. Two functionally distinct forms of parathyroid suppression are suggested; positively regulated microscopic hyperplasia and negatively regulated pathologically suppressed glands.

Secondary hyperparathyroidism in idiopathic renal hypercalciuria: fact or theory?

Secondary hyperparathyroidism (HP) has been reported to be characteristic of idiopathic hypercalciuria (IHC) of the renal type. Out of the 155 patients with urinary stone disease and a normal plasma calcium level, only 1 had a distinctively increased plasma parathyroid hormone (PTH) level; however, he was found to be hypercalcemic in a second control study. In 33 patients with renal IHC, none had an elevated PTH level measured under normal, low, and high calcium intake. The mean basal PTH level of these patients was identical to that of 86 normal controls; it was significantly lower than that of the patients with primary or secondary HP who had normal PTH levels. During EDTA infusion, seven of eight patients with primary HP and a normal basal PTH level showed PTH responses greater than those observed in six patients with renal IHC, all of the latter responses being in the normal range. Chlorthalidone, given to seven patients with renal IHC during 4 weeks (100 mg/day), did not decrease the PTH levels. Measurement of nephrogenous cAMP performed in only a few patients revealed a slightly increased value in one of them who had an exceptionally severe hypercalciuria. Beside this latter result, no evidence for secondary HP could be found. Although secondary HP is tempting pathophysiological explanation for many characteristics of renal IHC, it seems to be quite rare.

Parathyroid hormone does not increase nephrogenous cyclic AMP excretion by the dog.

The renal excretion of nephrogenous cyclic AMP (NcAMP) increases in response to parathyroid hormone (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH interrelationships in dogs we observed no change in total urinary cAMP (UcAMP) excretion when endogenous plasma PTH levels were increased up to 10-fold. This study was designed to investigate the effects of physiologic and pharmacologic levels of PTH on NcAMP and UcAMP excretion in the dog. Maintaining plasma Ca 2 mg/dl below normal for 40 minutes caused an 8-fold increase in plasma PTH concentration, a 50% increase in the urinary fractional excretion of phosphate (FEP) but no changes in plasma cAMP levels or in UcAMP or NcAMP excretion. Infusion of a pharmacologic amount of parathyroid extract (15 U/min for 20 min) increased plasma cAMP 5-fold, UcAMP excretion 3-fold and FEP by 50% but was without effect on NcAMP excretion. We conclude that NcAMP excretion is not stimulated by PTH in the dog and thus cannot be used as an index of PTH action in vivo. The increase in UcAMP excretion by pharmacologic amounts of PTH results from glomerular filtration of increased plasma cAMP, which may be generated in bone.

Parathyroid hormone response to dopamine in cattle.

The effects of dopaminergic agonists on plasma levels of parathyroid hormone (PTH) have been studied in cattle. PTH increased within minutes in a dose-dependent manner during intravenous infusions of dopamine (DA) or epinine. Bromocriptine, in amounts that lowered plasma prolactin, inconsistently elevated PTH. Pimozide suppressed PTH responses to DA, whereas propranolol, phentolamine, phenylephrine, and atropine were ineffective. Plasma calcium and magnesium remained unaltered during DA and epinine infusions. Therefore DA appears to stimulate PTH secretion directly. After prolonged DA infusions, the secretion of PTH became resistant to both the administration of DA and isoproterenol, whereas the parathyroid glands remained responsive to a hypocalcemia. On the other hand, calcium suppressed PTH responses to DA. The results suggest that DA, beta-adrenergic agonists, and low calcium stimulate PTH secretion by separate but closely related mechanisms. Based on biochemical and histochemical observations on DA occurring in high amounts in bovine parathyroid glands, it is conceivable that this amine might stimulate PTH secretion at the level of the gland.

Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D.

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.

Osseous Changes and Abnormalities of Mineral Metabolism in Rats with Glycopeptide-Induced Nephritis

A laboratory model of renal osteodystrophy was developed in rats by a single injection of glycopeptide isolated from renal cortical tissues of rats according to the method used by Shibata et al. to induce glomerulonephritis. Approximately 60-70 days after injection, severe proteinuria appeared and continued for at least 170 days at a rate of more than 1 g/day. Morphological changes in the kidney were typical of chronic glomerulonephritis. The plasma calcium concentration was lowered transiently by the 96th day after injection, but was restored to the normal range thereafter. Plasma parathyroid hormone levels, however, continued to rise in parallel with the degree of proteinuria. Marked secondary hyperparathyroidism was induced which led to severe bone atrophy. Histological examinations showed a marked increase of resorbing cavities, with a quantitatively larger number of osteoclasts in cortical bone tissues compared with the control animals. No spontaneous remission was observed. It is emphasized that all of the biochemical and morphological changes reported here were induced by a single injection of homologous renal glycopeptide, and they were highly reproducible.

Metabolic bone disease in patients receiving long-term total parenteral nutrition.

We have prospectively investigated calcium and bone metabolism in 16 patients receiving total parenteral nutrition for periods ranging from 7 to 89 months. In 12 patients, bone biopsies at 6 to 73 months after the start of parenteral nutrition showed osteomalacia. Plasma 25-hydroxyvitamin D levels were normal in all patients. Seven persons developed hypercalcemia, and 10 had hypercalciuria with a negative calcium balance. Serum phosphorus was normal and plasma parathyroid hormone level, normal or decreased. Three patients with the severest form of the disease had vitamin D withdrawn from their solutions. Subsequently, urinary calcium decreased, and serum calcium became normal; two persons reverted to a positive calcium balance. Thus, patients receiving total parenteral nutrition may develop metabolic bone disease characterized by osteomalacia, hypercalcemia, hypercalciuria, and a negative calcium balance. This may be caused by both defective mineralization and increased bone resorption induced by vitamin D, its metabolites, or another unrecognized factor.