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PubMed1984

Rapid radioimmunoassay for parathyroid hormone: its use in hypercalcemic crisis.

Patients with severe hypercalcemia often require intensive medical therapy to avoid a fatal outcome. When therapy with saline and loop diuretics cannot control the hypercalcemia, use of the toxic drug mithramycin is most appropriate for malignancy-associated hypercalcemia, but parathyroidectomy is indicated for parathyroid crisis. Although differentiation of these two syndromes is possible in many cases on clinical grounds, the determination of immunoreactive parathyroid hormone values provides a direct assessment of parathyroid function. Radioimmunoassay for parathyroid hormone has traditionally required four to seven days, but more rapid results would be desirable in this medical emergency. We report a modification of a previously published midregion-specific PTH assay that provides accurate results within 24 hours and describe its use in six patients with life-threatening hypercalcemia.

Adenoma↗

PubMedDate not supplied

[Changes in parathyroid hormone levels during the treatment of fractures of long tubular bones using the Ilizarov method].

Content of parathyroid hormone in blood plasma was studied in the course os treatment of 62 patients with fractures of crus bones. Alterations in the hormone content, depending on the type of trauma, were observed: the most severe injures caused the most distinct alterations. Maximal increase in the hormone content were observed during the initial period of the treatment, contributing to lysis of bone fragments and to formation of bone organic matrix. Decrease in the parathyroid hormone content coincided with complete consolidation of bone fragments. Content of the hormone was normalized within 35-42 days.

Adolescent↗

PubMed1980

Parathyroid hormone and extrarenal acid buffering.

The role of parathyroid hormone (PTH) on the extrarenal buffering of an acid load was examined during HCl infusion (5 meq x kg-1 x h-1) to bilaterally nephrectomized rats. Thyroparathyroidectomized (TPTX) rats replaced with PTH had significantly higher blood pH and HCO3 values than TPTX rats not infused with PTH. Administration of EDTA, in a dose shown to release PTH, was associated with a significant increase in buffering capacity in intact but not in TPTX rats. Colchicine, given in a dose capable of stimulating PTH release, was also associated with enhanced buffering capacity in intact but not in TPTX rats. In TPTX rats infused with acetazolamide and PTH, the hormone failed to enhance extrarenal buffering of an acid load. Animals with chronic renal failure, induced by infarction of the kidney, also had an enhanced capacity to buffer an acid load. This enhanced buffering capacity in chronic renal failure was abolished by TPTX. Acute renal failure induced by bilateral ureteral ligation was also associated with increased buffering only in the presence of parathyroid glands. These data demonstrated that PTH, from either an exogenous or endogenous source, enhances extrarenal buffering capacity of an acid load. Chronic and acute renal failure are associated with increased buffering capacity, which is dependent on the presence of parathyroid glands. The data suggest that this effect is mediated through carbonic anhydrase.

Acid-Base Equilibrium↗

PubMed2004

The use of intermittent human parathyroid hormone as a treatment for osteoporosis.

Parathyroid hormone (PTH), given intermittently, is an anabolic agent. PTH has been demonstrated to increase bone mass and reduce vertebral and nonvertebral fractures, and has been approved for use in the US and Europe. PTH is a genetically engineered 34 amino acid protein with the designation teriparatide (recombinant DNA origin) or recombinant human PTH 1-34. A recombinant DNA preparation with all 84 amino acids of the native PTH molecule is in clinical trials. These PTH preparations are self-administered daily injections, and it is approved for women and men at high risk for fractures, including patients with prevalent fractures, low bone mass, and multiple risk factors. PTH is likely to be used most frequently in patients who fracture on therapy, but can be used in high-risk treatment-naïve patients. Previous treatment with alendronate appears to impair the anabolic response of PTH preparations. Patients who have Paget's disease, prior radiation therapy to the skeleton, as well as children and young adults with open epiphyses, are at higher risk for osteosarcoma and should not be given PTH. Patients with hypercalcemia and hyperparathyroidism also should not receive the drug.

Alendronate↗

PubMed1977

Interaction between parathyroid hormone and catecholamines on renal cortical cyclic AMP.

Parathyroid hormone (PTH) and catecholamines (CA) increased cAMP levels in isolated tubules of rat renal cortex. A rise in cAMP could be detected 10 sec after the addition of agonists, and it reached the peak in 30-60 sec and then decreased despite the presence of active agonists. Direct relationships exist between theophylline concentrations and cAMP levels in response to agonists. Three- to fivefold rises in cAMP levels were observed with a maximal dose of PTH compared with that of CA, and there was no additive effect. Both PTH and CA stimulated renal gluconeogenesis; when added together with each maximal dose, no additive effect was observed. These results suggest the important role of phosphodiesterase to control tubular cAMP in response to hormonal stimuli, and there is a tubule cell group responding to both PTH and CA.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1977

Plasma kinetics of exogenous bovine parathyroid hormone in calves.

The metabolism of purified bovine parathyroid hormone-(1-84) [bPTH-(1-84)] administered i.v. by constant infusions or rapid injections was investigated in 11 normocalcemic calves. Plasma kinetics of bPTH-(1-84) were derived with a radioimmunoassay system which recognised the intact hormone but no fragments. The metabolic clearance rates ranged from 9.1-22.9 ml/min/kg. The disappearance of the intact hormone and the reversible appearance of its NH2- and COOH-terminal fragments was investigated with additional and specific radioimmunoassay systems. At 2 min after the i.v. injection of bPTH-(1-84) a NH2-terminal fragment (M approximately 3500) was recognised and at 4 and 20 min COOH-terminal fragments (M approximately 7000 and 3500, respectively) were detected. The survival time in the circulation of the intact hormone and of its fragments was comparable. In conclusion, bovine bPTH-(1-84) and its NH2- and COOH-terminal fragments are metabolised in normocalcemic calves within minutes.

Animals↗

PubMed1987

Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone.

A variety of solid tumors secrete proteins that are immunochemically distinct from parathyroid hormone (PTH) but activate PTH-responsive adenylate cyclase. Such PTH-like proteins have been proposed as mediators of the hypercalcemia and hypophosphatemia frequently associated with malignancies. We purified to apparent homogeneity a PTH-like protein with a molecular weight of 6,000, that is produced by human renal carcinoma cells. The amino-terminal sequence of the PTH-like protein and that of human PTH were found to display at least five identities in the first 13 positions. The purified protein bound to PTH receptors, activated adenylate cyclase in renal plasma membranes, and stimulated cAMP formation in rat osteosarcoma cells. The PTH-like protein reproduced two additional effects of PTH, stimulation of bone resorption in fetal rat limb bone cultures and inhibition of phosphate uptake in cultured opossum kidney cells. These properties are consistent with a role for PTH-like proteins as mediators of the syndrome of malignancy-associated hypercalcemia.

Carcinoma, Renal Cell↗

PubMed1996

Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone.

It is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.

Animals↗

PubMed1997

Parathyroid-hormone-related protein in human milk and its relation to milk calcium.

Parathyroid-hormone-related protein (PTHrP) is found in high concentrations in human milk. One of the possible physiological roles of PTHrP may be the regulation of calcium transport through the mammary gland. The relationship between milk PTHrP and Ca concentrations was evaluated in lactating women in the present study. Milk PTHrP has been quantified by immunoradiometric assay (IRMA) and radioimmunoassay (RIA). The IRMA detects PTHrP 1-72, and the RIA carboxyterminal region of PTHrP (C-PTHrP). Milk PTHrP 1-72 and C-PTHrP concentrations did not significantly change by breast-feeding. Milk PTHrP 1-72 changed significantly by the time of day, in contrast to C-PTHrP. Thus, PTHrP 1-72 rather than C-PTHrP may reflect an acute change in mammary PTHrP secretion. In lactating women in whom milk PTHrP and calcium concentrations were serially measured at 5-day intervals up to 26-30 days after delivery, milk PTHrP 1-72 progressively increased with duration of lactation. In contrast to PTHrP 1-72, milk C-PTHrP decreased during this period. And milk PTHrP 1-72 levels inversely correlated with C-PTHrP levels. Milk C-PTHrP but not PTHrP 1-72 levels correlated significantly with milk Ca concentrations. Although it is not certain whether the correlation between milk C-PTHrP and Ca levels is causally related, it may be that fragments of PTHrP detected as C-PTHrP are involved in the regulation of Ca transport through the mammary gland in women.

Calcium↗

PubMed1994

Effect of parathyroid hormone on myocardial bloodflow and infarct size following coronary artery occlusion in the dog.

OBJECTIVE: To investigate the cardioprotective effect of both the amino terminal of bovine parathyroid hormone (bPTH-[1-34]) and human parathyroid hormone (hPTH-[1-84]) following coronary artery occlusion. DESIGN: Animals were randomly assigned to one of three treatment groups following circumflex coronary artery occlusion. ANIMALS: Experiments were performed using 19 mongrel dogs of either sex. As four animals died during experimentation, data are shown for 15 dogs (n = 5 for each treatment group). INTERVENTIONS: Animals received saline, bPTH-(1-34) or hPTH-(1-84) following occlusion of the circumflex coronary artery. Peptides were given at 0.008 nmol/kg/min. All treatments were infused directly into the coronary circulation. Infusion rate was 1 mL/min for 10 mins at 30 min intervals until the end of the experiment (480 mins after onset of occlusion). Hemodynamic variables were monitored throughout the experiment. Radioactive microspheres were injected 10 mins before, and 30, 240 and 480 mins following, occlusion of the coronary vessel to determine regional myocardial blood-flows. At the end of the experiment, area at risk and infarct size were measured by simultaneous infusion of Evans blue dye and triphenyl tetrazolium chloride stain. MAIN RESULTS: Neither bPTH-(1-34) nor hPTH-(1-84) significantly reduced area of risk or infarct size as a percentage of area at risk compared with controls. These results were corroborated by regional blood-flows measured using radioactive microspheres. There was no significant difference in hemodynamic variables among the groups except that left atrial pressure was consistently lower following treatment with hPTH-(1-84). CONCLUSIONS: No evidence was found that either bPTH-(1-34) or hPTH-(1-84) salvaged ischemic myocardium in a canine model of myocardial infarction. Treatment with hPTH-(1-84) was associated with a reduction in left atrial pressure. This latter phenomenon may constitute a beneficial effect of this peptide on diastolic myocardial function.

Animals↗

PubMed1971

Serum parathyroid hormone in X-linked hypophosphatemia.

Serum immunoreactive parathyroid hormone(IPTH) is normal in patients with X-linked hypophosphatemic rickets who are not treated with phosphate salts. Phosphate raises IPTH in these patients. Endogenous IPTH does not influence the existing defect in tubular reabsorption of phosphate in male patients.

Calcium↗

PubMed1992

Isolation and characterization of two biologically active O-glycosylated forms of human parathyroid hormone produced in Saccharomyces cerevisiae. Identification of a new motif for O-glycosylation.

Expression and secretion of human parathyroid hormone in Saccharomyces cerevisiae were achieved by fusing a cDNA encoding the mature human parathyroid hormone (hPTH) to the preproregion of the yeast mating factor alpha. Purified hPTH from yeast-culture medium was found to contain, in addition to the native unglycosylated form, two mannosylated variants with different molecular masses. The three hPTH forms were processed identically, resulting in the same 84 amino acid polypeptides with amino acid sequences identical to the native hormone. In both the O-glycosylated forms that were separated by isocratic reverse-phase HPLC, two mannose-linked residues were localized to Thr79. In addition, the most glycosylated form showed a heterogeneous modification of three, four or five mannosyl residues linked at Ser66. Lysine is N-terminally located to Ser66 and probably stimulates this glycosylation, which introduces a possible new motif for O-glycosylation in yeast. The two glycosylated forms of hPTH had similar biological activity which was identical to the native form of hPTH in a hormone-sensitive adenylate cyclase assay in bone sarcoma cells. Thus, a C-terminal O-glycosylation of hPTH with up to seven mannosyl residues/molecule did not affect the biological activity of the hormone, making possible production of hPTH with potential different pharmacokinetic properties.

Adenylyl Cyclases↗

PubMed1986

Degradation of parathyroid hormone by placental homogenate.

Degradation of the bovine parathyroid hormone (PTH) fragment (amino acids 35-84) up to 70% was observed during passage through human placenta in an in vitro perfusion model. Fractionation of the subcellular fractions of human placental homogenate revealed the degradation to take place only in the mitochondrial fraction. It is concluded that human placenta, like kidney and liver, has the ability to degrade PTH.

Female↗

PubMed1983

Parathyroid hormone in patients with diabetes mellitus and end-stage renal disease on chronic haemodialysis.

Serum immunoreactive parathyroid hormone in patients with juvenile-onset diabetes mellitus and end-stage renal failure on chronic haemodialysis treatment is significantly lower than the values obtained from patients with adult-onset diabetes mellitus and non-diabetic patients with end-stage renal disease being similarly dialysed. The major determinants of parathyroid hormone secretion, such as calcium and magnesium, do not seem to be the factors responsible for this difference. The histology of the parathyroid glands in juvenile-onset patients shows fibrosis and collagen infiltration which reduce the functional mass of the glands.

Adult↗

PubMed1983

Parathyroid hormone concentration gradients across the human bone marrow.

Parathyroid hormone (PTH) concentrations were compared in blood drawn from the bone marrow and antecubital vein of patients undergoing marrow biopsy for suspected hematological neoplasia. Radioimmunological analysis revealed that the bone marrow blood had a higher PTH content than blood from the peripheral circulation. Thyroid hormone-binding globulin was not distributed asymmetrically, showing that the gradient is PTH specific. The intact PTH content of marrow blood was 65% greater than that in the venous system, whereas carboxyl regional PTH levels showed a 34% gradient in favor of the marrow. Although the majority of patients were found to have hematological malignancies, there was no discernible influence of tumor on the PTH gradients. The physiological implications and possible origins of the asymmetrical PTH distribution are discussed.

Bone Marrow↗

PubMed2005

Parathyroid hormone (1-84) and treatment of osteoporosis.

OBJECTIVE: To present the chemistry, pharmacology, and pharmacokinetics of parathyroid hormone (PTH) (1-84) and review the available clinical trials that evaluate its efficacy and safety; clinical applicability of this agent and its relationship to other Food and Drug Administration (FDA)-approved medications for treatment of osteoporosis are also discussed. DATA SOURCES: A MEDLINE search (1996-December 2004) was completed, along with a review of information obtained from the manufacturer, NPS Pharmaceuticals. Key search terms included parathyroid hormone, PTH (1-84), and ALX 111. STUDY SELECTION AND DATA EXTRACTION: Studies were selected based on their relevance and availability. Pertinent information, including objectives, design, demographics, outcomes, adverse events, dosing strategies, and therapeutic controversies, was extracted. DATA SYNTHESIS: PTH (1-84) is being developed for treatment of osteoporosis. Recent studies have shown that, when administered intermittently as a subcutaneous injection, PTH (1-84) produces an increase in bone mineral density and prevents vertebral fractures. The fact that this agent contains the C-terminal region of PTH may differentiate it from PTH (1-34), teriparatide, which is approved by the FDA for treatment of osteoporosis. Further trials are necessary to determine the role of PTH (1-84) in combination with other treatments for osteoporosis and/or the order in which PTH (1-84) is given with these other agents. There are currently no comparative trials with other osteoporosis treatment modalities. CONCLUSIONS: PTH (1-84), when given intermittently as a subcutaneous injection, appears to be a safe and efficacious treatment option for osteoporosis. Further trials are needed to determine its specific place in therapy compared with other treatment options.

Aged↗

PubMed1994

A new, practical intraoperative parathyroid hormone assay.

BACKGROUND: The clinical usefulness of intraoperative parathyroid hormone (PTH) monitoring has been shown using an immunoradiometric assay (IRMA) with several significant limitations. PTH measurement by immunochemiluminometric assay (ICMA) is a nonradioisotopic technique that is more practical for use during parathyroidectomy. METHODS: Plasma from a 15-second microcentrifugation was mixed with 2 antibodies, incubated at 45 degrees C, shaken at 400 rpm for 7 minutes, washed and counted for 2 seconds on a portable luminometer; PTH level was reported in 10 minutes. RESULTS: Sixteen patients had multiple samples taken during parathyroidectomy. PTH levels measured 5 minutes after excision of a suspected abnormal gland were compared with preoperative or preexicision samples and either confirmed complete excision or indicated the need for more exploration in each patient. Correlation of 88 ICMA samples with standard 24-hour IRMA controls was excellent (r = 0.9218, P < 0.0001). The sensitivity of the test in predicting postoperative calcium levels was 94%. CONCLUSION: This new assay can serve as a very practical adjunct for the parathyroid surgeon.

Calcium↗

PubMed1978

Preliminary studies with the sensitive cytochemical assay for parathyroid hormone.

A modification of the cytochemical assay for parathyroid hormone (PTH) is described which permits the measurement of as little as 0.1 fg ml-1. Using this assay circulating concentrations in normal humans range between 1 and 30 pg ml-1 using a bovine PTH standard. Elevated values are found in hyperparathyroidism with reduced concentrations in hypoparathyroidism. Where detectable, PTH concentrations measured by radioimmunoassay are on average fourteen-fold higher than by cytochemical assay. No cross reactivity was found with AVP, calcitonin and 1,25 dihydroxy vitamin D in concentrations normally found in health or disease.

Adult↗