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PubMed2006

Does rapid intraoperative parathyroid hormone analysis predict cure in patients undergoing surgery for primary hyperparathyroidism? A prospective study.

BACKGROUND AND AIMS: Preoperative 99mTc-sestamibi scintigraphy is used by many surgeons to identify the anatomical location of pathological parathyroid glands in patients undergoing surgical treatment for hyperparathyroidism. However, false negative results do occur. It has been suggested that intraoperative parathyroid hormone (PTH) analysis may enhance the possibility of performing successful focused, unilateral neck surgery in these patients. This study aimed to evaluate whether an adequate fall in intraoperative parathyroid hormone values predicts the removal of all hyperfunctioning parathyroid tissue and postoperative normocalcemia. MATERIAL AND METHODS: One hundred consecutive patients undergoing surgery for hyperparathyroidism had preoperative 99mTc-sestamibi scintigraphy and intraoperative parathyroid hormone (PTH) analysis. A fall in intraoperative PTH value by more than 50% of baseline value ended the procedure. This prospective study presents the clinical and biochemical results. RESULTS: The overall sensitivity of the 99mTc-sestamib scintigraphy was 88% and for single adenomas 95%. The scintigraphy failed to detect the correct pathology in all cases with multiglandular disease (7 patients). A fall in intraoperative PTH value by more than 50% of baseline value was achieved in all patients. The combination of intraoperative PTH analysis and 99mTc-sestamibi scintigraphy enabled us to limit the operation to a focused, unilateral operation in 87 of the 100 patients. All patients were normocalcemic postoperatively. CONCLUSIONS: A fall in intraoperative PTH value more than 50 % of baseline value seems to predict postoperative normocalcemia and the removal of all hyperfunctioning parathyroid tissue. Bilateral neck exploration is avoided in the majority of patients.

Adult↗
PubMed1981

Effects of hepatectomy, nephrectomy, and nephrectomy/uremia on the metabolism of parathyroid hormone in the rat.

Reports from several laboratories, showing extensive hepatic extraction of circulating parathyroid hormone, led us to examine the effect of near-total hepatectomy on the metabolism of the hormone to circulating fragments, and on its clearance from plasma. The rate of disappearance of (125)I-labeled and unlabeled bovine parathyroid hormone from plasma, and the appearance, disappearance, and chemical and immunochemical characteristics of circulating fragments were examined by gel filtration and either sequence-specific radioimmunoassays or sequence analysis using the Edman reaction. Results from awake rats subjected to near-total hepatectomy were compared with those found in sham-treated, nephrectomized, and short-term uremic rats (studied 2 d after nephrectomy). When compared with the sham-treated group, all other groups clear (125)I-labeled hormone more slowly; after hepatectomy, however, the clearance rate is most strikingly decreased. After injection of intact hormone, the concentration of carboxy-terminal fragments in the circulation of hepatectomized rats is greatly reduced at all time intervals when compared with that in sham-treated rats. Sequence analysis of plasma samples, collected from rats into which (125)I-labeled hormone had been injected, shows that carboxy-terminal fragments having positions 34 and 37 of the intact hormone sequence as their amino-terminal amino acids are abundant in sham-treated, nephrectomized, and nephrectomized/uremic rats, but are undetectable in hepatectomized rats. The data suggest that inasmuch as the liver in vivo generates most of the carboxy-terminal fragments resulting from the metabolism of injected hormone, specific cell types within the liver must be the principal locus of the responsible enzyme(s); thus, studies of the enzymic properties of isolated hepatic cells in vitro most likely will yield information of physiologic relevance to the metabolism of the hormone in the intact animal.

Animals↗
PubMed1983

Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent).

We investigated the causes of the hypocalcemia associated with WR-2721, an investigational drug that protects normal tissues against the toxic effects of radiation and chemotherapy. Sixteen patients with advanced cancers had serial measurements of serum calcium and other studies of blood chemistry before and after taking the compound. In all 16 patients (18 courses) the mean serum calcium level fell from 2.33 to 1.90 mmol per liter (9.33 to 7.62 mg per deciliter, P less than 0.001) after WR-2721, and in all 8 patients from whom data were obtained, serum calcium levels remained depressed at 24 hours. In 12 patients, ionized calcium levels dropped from 0.98 to 0.80 mmol per liter (P less than 0.01). Serum magnesium values fell from 0.96 to 0.74 mmol per liter (1.91 to 1.48 mg per deciliter, P less than 0.001). There were no changes in arterial pH or serum phosphate concentrations. In nine patients urinary calcium excretion rose from 3.96 to 10.68 mumol per minute (P less than 0.01) after WR-2721. Despite hypocalcemia, parathyroid hormone levels fell in all subjects. WR-2721 also inhibited the release of parathyroid hormone from bovine parathyroid cells incubated in vitro in low (0.5 mM) concentrations of calcium. We conclude that WR-2721 inhibits the secretion of parathyroid hormone and enhances calciuria, thereby leading to hypocalcemia.

Amifostine↗
PubMed2001

[Role of parathyroid hormone in regulating the functional activity of platelets].

We studied the influence of parathyroid hormone (PTH) on the functional activity of white rat and human platelets, and examined in particular possible mechanisms of PTH influence on the platelet aggregation activity. It has been stated that PTH renders a marked dose-dependent proaggregative effect on platelets. Possible mechanisms of proaggregative effect of parathyroid hormone were examined on platelets using substances with defined mechanisms of the effect. Examination of PTH effect on lectin-intermediated aggregation in a suspension of washed platelets shows that metabolic activation of platelets by PTH causes an increased expression on their plasmic membrane mainly of glycoprotein complex IIb-IIIa and in a lesser degree of glycoprotein complexes Ia-IIa and IV which take part in the formation of interplatelet contact.

Animals↗
PubMed1981

Failure of cimetidine to suppress immunoreactive parathyroid hormone and hypercalcaemia in primary hyperparathyroidism.

Cimetidine has been reported as suppressing the excess parathyroid hormone secretion and hypercalcaemia seen in hyperparathyroidism. A case of primary hyperparathyroidism is described, in which the level of circulating parathyroid hormone and hypercalcaemia remain entirely unaffected by cimetidine. The drug is implicated in the management of primary hyperparathyroidism unsuitable for surgery, but present evidence, as reviewed, is insufficient to recommend the use of cimetidine in this way.

Aged↗
PubMed1978

Parathyroid hormone and triglyceride transport: effects on triglyceride secretion rates and adipose tissue lipoprotein lipase in the rat.

In order to determine the effects of parathyroid hormone on triglyceride transport, male Sprague-Dawley rats were injected with parathyroid extract for eight days and triglyceride secretion rates (TGSR) and adipose tissue lipoprotein lipase (LPL) activity were determined. Parathyroid hormone-treated rats demonstrated significantly lower (p less than .005) TGSR in the basal overnight fasted state 15 hours after the previous injection, but this effect on TGSR was not apparent 3 hours after PTE injection when the rats were allowed to eat. In contrast, LPL activity was significantly reduced in the PTH-treated animals at 3 hours and no effect was apparent on this index of triglyceride removal at 15 hours. These findings suggest that parathyroid hormone may exert independent influences on triglyceride production and removal and thus may alter triglyceride homeostasis in conditions in which parathyroid hormone levels are abnormally increased.

Adipose Tissue↗
PubMed2003

Prevention of osteoporosis in ovariectomized mice by electroporational gene transfer of parathyroid hormone.

Non-viral vector, pCMV-Pth, with full-length human parathyroid hormone (prepro-hPTH) cDNA was constructed and delivered into the ovariectomized mouse quadriceps to explore the effects of electroporational gene transfer of PTH on the bone. The expression of hPTH in the transfected mice was detected by RT-PCR and radioimmunoassay. Mechanical testing and the analysis of bone mineral content demonstrated the improvement of bone properties. These results suggest that the electroporational gene taransfer of parathyroid hormone might be a promising method to prevent the bone loss in the postmenopausal women.

Animals↗
PubMed1987

Effect of parathyroid hormone on gentamicin plasma membrane binding and tissue accumulation.

Reportedly, the initiating event in the renal uptake of gentamicin is its binding to anionic, plasma membrane phospholipids. Because parathyroid hormone is known to affect phospholipid metabolism, the plasma membrane binding and tissue accumulation of gentamicin were examined as a function of the parathyroid hormone status of the animal. The experiments were conducted by evaluating the parameters in isolated brush border and basolateral membranes from control, hyper- and hypoparathyroid rats. Scatchard analysis revealed that [125I]gentamicin bound with equal affinity to either membrane to a single class of noninteracting sites. The basolateral membrane had more binding sites than did the brush border, 28 +/- 0.5 vs. 1.8 +/- 0.3 nmol/mg of protein, respectively. Neither the affinity constants nor the number of binding sites were affected by the parathyroid hormone status of the donor animal. On the other hand, in the hypoparathyroid state the amount and the rate of gentamicin accumulation were less than in the hyperparathyroid state. The difference in accumulation cannot be explained on the basis of a change in the number or affinity of the putative receptor. Therefore, the alteration must reflect some difference subsequent to the binding site.

Animals↗
PubMed1992

Age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of bone metabolism in Chinese women.

OBJECTIVE: To study the age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of calcium metabolism in Chinese women who habitually have a low calcium intake. DESIGN: Cross-sectional study. SUBJECTS: One hundred and fifty-six healthy Chinese women aged 20-83 years. None were on any medication or vitamin supplements. Subjects over the age of 60 years were all living in a hostel; younger subjects were nurses or subjects attending a family clinic for minor illnesses. MEASUREMENTS: Fasting blood and urine samples were collected for biochemical measurements and calcium absorption was measured using 45Ca by the method of Marshall and Nordin. Bone density was measured by dual energy X-ray densitometry (Norland X R20 X-ray bone densitometer) at the left hip and lumbar spine. Serum parathyroid hormone was measured by a chemiluminometric assay. RESULTS: Plasma ionized calcium concentration, alkaline phosphatase, bicarbonate, plasma creatinine and serum B2 microglobulin were significantly higher in the elderly than in the young, whereas plasma phosphate and the anion gap were higher in the young. Urinary excretion of calcium, phosphate and hydroxyproline were all higher in older women. Plasma parathyroid hormone concentration was positively correlated with age even after taking into account the decline in renal function (as indicated by the rise in B2 microglobulin (r = 0.506, P less than 0.001). Serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were not lower in the older women. Fractional calcium absorption from an oral load of radiolabelled calcium was significantly lower in the older women and 37% of the older women were below the 2.5 percentile found in the younger women. Bone density measured by dual energy X-ray densitometry was also significantly lower in the elderly. CONCLUSION: In Chinese women there is an increase in PTH and a decrease in calcium absorption with age in spite of the presence of normal vitamin D metabolites.

Absorption↗
PubMed1996

Parathyroid-hormone-related peptide in hematologic malignancies.

PURPOSE: To determine whether parathyroid-hormone-related peptide (PTHRP) is an important pathogenetic mediator of hypercalcemia in patients with hematologic malignancies. PATIENTS AND METHODS: We conducted a cohort analytic study in 76 consecutive patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease, multiple myeloma, and Waldenstrom's macroglobulinemia, 14 of which were hypercalcemic. Thirty normal subjects served as a control group. RESULTS: Using the NH2 -terminal radioimmunoassay, PTHRP concentrations in heavy controls were undetectable (<7.5 pmol equivalents of PTHRP [fragment 1-34] per liter). The majority of hypercalcemic patients (8/14) had non-Hodgkin's lymphoma, and 62.5% of these (5/8) had significant elevations of circulating PTHRP concentrations (mean 70.5 +/- 38.5 pmol equivalents of PTHRP per liter) (P <0.01). In non-Hodgkin's lymphoma, 11 of 30 patients with advanced disease (stage IV) had elevated PTHRP concentrations, and of these, 8 of 11 had high-grade pathology. In contrast, only 3 or 21 patients with less advanced disease (stage I to III) had elevated PTHRP concentrations. In 4 NHL patients with less advance PTHRP concentrations sampled prior to cytotoxic chemotherapy, tumor response was associated with a decrease in PTHRP. Concomitant suppression of 1,25(OH)2D3 concentrations was observed in 66% of hypercalcemic patients with non-Hodgkin's lymphoma. CONCLUSIONS: These results suggest that PTHRP may be an important pathogenetic factor in the development of hypercalcemia in hematologic malignancies, notably in non-Hodgkin's lymphoma.

Antineoplastic Agents↗
PubMed1981

Plasma parathyroid hormone and insulin concentrations in cows administered potassium chloride and sodium citrate.

Two age group 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 phosphorous 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.

Animals↗
PubMed1987

Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males.

The serum and urinary calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and parathyroid hormone (PTH) were studied in healthy black and white males living in Belgium, and the results were compared to data in blacks of similar age living in Zaïre. Dietary calcium and vitamin D were estimated in a sub-sample of blacks and whites examined in Belgium. Compared to whites (9.51 +/- 0.28 mg%) serum calcium was somewhat lower in blacks (9.26 +/- 0.27 mg% in Belgium; 9.19 +/- 0.48 mg% in Zaïre). The 24 hour urinary calcium excretion averaged 215.0 +/- 16.7 mg% in whites and was higher (P less than 0.05 or less) than in blacks (115 +/- 71 mg% in Belgium; 36 +/- 33 mg% in Zaïre). The serum 25OHD levels were similar in whites and blacks evaluated in Zaïre, both being higher (P less than 0.05 or less) than in blacks living in Belgium. In the latter blacks, an inverse correlation was observed between the 25OHD level and the duration of the stay in a temperate climate. Parathyroid hormone levels were slightly higher in blacks living in Belgium than in the other two groups of subjects. The serum levels of 1,25(OH)2D3 and human vitamin D-binding protein were similar in the three groups of subjects. Dietary calcium averaged 541 +/- 152 mg/day in blacks and was significantly (P less than 0.001) less than in whites (1,203 +/- 508 mg/day), whereas no significant difference was observed in dietary vitamin D intake between blacks and whites. It is concluded that calcium intake is low in blacks but stimulation of parathyroid hormone and 1,25(OH)2D3 required to achieve normocalcemia does not occur.

25-Hydroxyvitamin D 2↗
PubMed1975

Differential hydrolysis of bovine parathyroid hormone and its N-terminal peptide by rat kidney.

Highly purified bovine parathyroid hormone (b-PTH 1-84) and its synthetic N-terminal peptide (b-PTH 1-34) were labelled with 125-I and incubated with rat kidney homogenate at 37 degrees C for 1 hour to assess the degree of hydrolysis of the iodinated peptides through measurement of the increase of trichloroacetic acid soluble 125-I fraction. Rat kidney homogenate rapidly hydrolyzed b-PTH 1-84 but was scarcely effective in hydrolyzing b-PTH 1-34. When 125-I labelled b-PTH 1-84 and b-PTH 1-34 were injected intravenously in rats, hydrolysis in vivo of the former appeared to be much more rapid than that of the latter, as shown by the faster disappearance from plasma of trichloroacetic acid precipitable fraction. Incubation of b-PTH (1-84) with rat kidney homogenate caused a shift of 125-I PTH peak almost to the position of salt peak, while the position of 125-I b-PTH (1-34) was almost unchanged by incubation with rat kidney homogenate. N-terminal peptide of bovine parathyroid hormone thus appears to be less susceptible to hydrolytic degradation by rat tissue than the intact hormone, with resultant longer retention in the blood stream.

Animals↗
PubMed1983

Epinephrine is a hypophosphatemic hormone in man. Physiological effects of circulating epinephrine on plasma calcium, magnesium, phosphorus, parathyroid hormone, and calcitonin.

The physiologic effects of epinephrine on mineral metabolism are not known. In six healthy men, insulin-induced hypoglycemia, a potent stimulus to endogenous epinephrine secretion, resulted in a decrement of 0.9+/-0.1 mg/dl (mean+/-SE, P < 0.001) in serum inorganic phosphorus and smaller increments in magnesium and total and ionized calcium. Plasma immunoreactive parathyroid hormone (iPTH) decreased and plasma immunoreactive calcitonin (iCT) increased appropriately with the increments in calcium and magnesium. We wished to determine to what extent these changes in mineral metabolism might be attributable to epinephrine. Therefore, in the same protocol, we infused the hormone over 60 min in these six men, in doses that resulted in steady-state plasma epinephrine concentrations ranging from 52 to 945 pg/ml (levels that span the physiologic range), for a total of 25 studies. Serum ionized calcium, iPTH, and iCT concentrations were unaltered by these physiologic elevations of plasma epinephrine. However, epinephrine resulted in dose-dependent decrements in serum inorganic phosphorus of 0.6+/-0.1 mg/dl (P < 0.005) for the highest epinephrine infusion rate. The plasma epinephrine concentration threshold for this hypophosphatemic effect was approximately 50-100 pg/ml. Thus, the sensitivity of the hypophosphatemic response to epinephrine is comparable to that of the cardiac chronotropic, systolic pressor, and lipolytic responses to epinephrine, and considerably greater than that of the diastolic depressor, glycogenolytic, glycolytic, and ketogenic responses to the hormone in human beings. In view of its rapidity, the hypophosphatemic effect of epinephrine is probably the result of a net shift of phosphate from the extracellular compartment to intracellular compartments. We suggest that it is a direct effect of epinephrine, in that it is not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated by changes in other hormones, such as insulin, cannot be excluded. The hypophosphatemic response is also not attributable to increments in plasma calcium. These data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man.

Adult↗
PubMed1986

Toxicity of parathyroid hormone in uremia.

The most significant complication of elevated parathyroid hormone (PTH) levels in uremia is the development of osteitis fibrosa cystica. The hormone also appears to play a role in soft-tissue and organ calcification, metabolic abnormalities (glucose, lipids), and electroencephalographic changes seen in uremic patients. Its role in the hematological abnormalities of uremia (anemia, bleeding) is controversial. A role for PTH in heart and skeletal muscle dysfunction in uremia has not been clearly established. Further studies are required to establish PTH as a "universal" toxin in uremia.

Anemia↗
PubMed1968

Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin.

Adenyl cyclase from plasma membrane fractions of rat renal cortex or medulla was assayed by measuring conversion of adenosine triphosphate labeled at the alpha-phosphate with (32)P to cyclic 3',5'-adenosine monophosphate labeled with 32P. Parathyroid hormone activated the enzyme primarily in cortex; vasopressin acted primarily in medulla. These experiments support the conclusion that cyclic adenosine monophosphate mediates the action of parathyroid hormone on the kidney and show that parathyroid hormone and vasopressin stimulate adenyl cyclase at anatomically separable areas within the kidney.

Adenine Nucleotides↗
PubMed1984

Cardiac actions of bovine parathyroid hormone fragment (1-34) in some lower vertebrates.

Only recently have the cardiac actions of parathyroid hormone and its N-terminal (1-34) fragment (bPTH(1-34] been examined. Parathyroid hormone was found to exert a positive chronotropic effect on the heart tissue of several mammals and one amphibian in vivo and/or in vitro. The purpose of the present study was to examine in vitro the heart tissue of several lower vertebrates, particularly aquatic vertebrates, for responsiveness to bPTH(1-34) and, for comparative purposes, isoproterenol. Heart tissue (atrium or the entire heart) from all the animals studied (trout, mudpuppy, bullfrog tadpole, and adult bullfrog) responded to isoproterenol in a dose-dependent fashion with increased heart rate and contractile force. Only the atria from the adult bullfrog, however, responded in a similar manner to the administration of bPTH(1-34). In all cases propranalol (10(-6) M) was able to block both chronotropic and inotropic effects of isoproterenol but had no effect on the cardiac stimulation induced by bPTH(1-34) in the adult bullfrog atrium. The data suggests that cardiac responsiveness to bPTH(1-34) is associated with a terrestrial as opposed to an aquatic existence.

Animals↗