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PubMed2001

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

Adenoma↗
PubMed1977

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man.

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.

Adult↗
PubMed1984

Phosphorylation of parathyroid hormone by human and bovine parathyroid glands.

Human and bovine parathyroid gland slices were incubated in vitro for varying time periods with inorganic 32P and [35S]methionine or [3H]serine. Tissue was then extracted with aqueous medium, and parathyroid hormone (PTH) purified. Incorporated 32P was found to coelute with immunoreactive PTH in multiple chromatographic systems, and a peak of phosphorylated material could be resolved from the nonphosphorylated hormone by reversed phase high pressure liquid chromatography. The amino acid composition of both the phosphorylated and the nonphosphorylated entities conformed to that of the major glandular species of PTH, and phosphorylated hormone accounted for 10-20% of the total. A time course revealed slow incorporation of 32P into hormone, and after a 4-h preincubation with inorganic 32P, co-elution of 32P with both PTH and its precursor was observed. Phosphoserine was identified in purified PTH labeled with [3H]serine. Additionally dilute acid hydrolysis of PTH, labeled with [35S]methionine and containing 32P, generated an 35S-labeled fragment with which 32P co-chromatographed. The results are consistent with in vitro phosphorylation of PTH on serine residues within the NH2-terminal region of the hormone by both human and bovine glands and suggest that phosphorylation of the prohormone occurs as well.

Amino Acids↗
PubMed1975

Avian parathyroid glands in organ culture: secretion of parathyroid hormone and calcitonin.

Parathyroid (PT) glands from 20-day-old embryonic chicks cultured in a chemically defined medium secreted a stimulator of in vitro bone resorption. This stimulator was presumed to be parathyroid hormone (PTH) because: 1) the in vitro dose response curve was parallel to that obtained with bovine PTH; 2) the activity was eluted on Sephadex G-1-- chromatography at a position similar to that for PTH; and 3) the material produced hypercalcemia in vivo in chicks. The amount of PTH-activity secreted was inversely proportional to the calcium concentration of the medium over the range of 0.75-2.25 mM. The chick PT glands also secreted an inhibitor of PTH-stimulated bone resorption in vitro. This inhibitor was presumed to be calcitonin (CT) because: 1) the in vitro dose-response curve was parallel to that obtained with synthetic salmon CT; 2) the activity was eluted on Sephadex G-50 chromatography at a position similar to that for salmon CT; and 3) the material produced hypocalcemia in vivo in rats. In contrast to what would be expected for CT secretion, the CT-activity was secreted by the PT glands in response to a low, not high calcium concentration. The data suggest that the secretion of avian PTH is similar to that of the mammalian hormone, and that the ultimobranchialectomized chick with an intact parathyroid gland may not be deficient in CT.

Animals↗
PubMed1978

The cleavage and adsorption of parathyroid hormone at high dilution: implications for receptor binding studies.

Like other polypeptide hormones, purified intact parathyroid hormone (1-84)parathyroid hormone is notoriously unstable and is subject to large adsorptive losses in routine laboratory manipulation. The present studies were undertaken with 125I-labeled hormone to quantitate the problem and to develop preventative measures, particularly with concentrations of physiological interest, 1 . 10(-10) M. It was found that spontaneous cleavage of the hormone takes place upon its incubation in air or oxygen. This can be prevented by the presence of mercaptoethanol or by plasma levels of cysteine and ascorbate. Under non-cleavage conditions, adsorption was found to be extensive on all materials tested. This adsorption increased with time up to 2 h, was independent of ionic strength, increased with increasing temperature and was presumed to involve hydrophobic interactions. Under given conditions, adsorption was proportional to concentration (constant percentage). However, at very high concentrations, 1 . 10(-6) M, adsorption was markedly reduced. Adsorption was minimized at low pH (2). Bovine serum albumin reduced adsorption under all conditions when present at concentrations of 2 mg/ml or more. Coating laboratory ware with cetyl alcohol also was helpful. Using optimal conditions, cleavage is prevented and losses are less than 5% at neutral pH, and under 2% at pH 2.

Adsorption↗
PubMedDate not supplied

[The dynamics of parathyroid hormone and calcitonin in surgery with artificial circulation].

The use of considerable amounts of gelatinol in hypothermal perfusion determined the occurrence of marked hypercalcemia. The hormonal mechanism (parathyroid hormone and calcitonin) responsible for hypercalcemia compensation proved to be inefficient under hypothermal perfusion. A forced diuresis failed to result in rapid normalization of blood calcium concentrations. The volume of gelatinol used during extracorporeal circulation is not to exceed 500 ml.

Adult↗
PubMed1988

Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2.

The purpose of this study was to determine whether plasma levels of the vitamin D hormone and parathyroid hormone (PTH), two potent activators of bone remodeling sites, were altered in four astronauts during the 8-day (d) Spacelab 2 mission (SL2). Increased circulating levels of either hormone could change calcium homeostasis and bone cell activity and, thus, contribute to bone loss in crewmembers in space. The vitamin D hormone was elevated in all astronauts at the end of the first inflight day but returned to normal by the seventh day. Biologically active PTH tended to be normal throughout the mission. Both hormones were within the normal range by the end of the 8-d flight of this SL2 crew. Plasma levels of 25OHD, 24,25(OH)2D, calcium, phosphorus, and albumin were essentially normal during the mission.

24,25-Dihydroxyvitamin D 3↗
PubMed1977

Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells.

The effects of dopaminergic agonists and antagonists have been studied in dispersed bovine parathyroid cells. Dopaminergic agonists caused a transient 20- to 40-fold increase in cellular cyclic AMP and a 2- to 3-fold increase in parathyroid hormone release. Dose-response relationships were similar for cyclic AMP accumulation and hormone release, whether studied by increasing agonist concentration or by increasing concentration of antagonist with constant agonist. The effects on the dopamine receptor could be differentiated from those of the previously characterized beta-adrenergic receptor by specific inhibitors. These results appear to represent proof with a homogeneous cell population that dopaminergic receptors linked to adenylate cyclase can regulate a secretory process mediated by cyclic AMP. This system should be useful in further studies on dopamine receptors and should provide a valid tool for determining interactions of radiolabeled ligands with such receptors.

Adrenergic beta-Agonists↗
PubMed1991

Lack of effect of human parathyroid hormone and calcitonin on cytokine and prostaglandin secretion by blood mononuclear cells.

The interactions between the endocrine and immune systems are complex and not well understood. Several data suggest the existence of a particular relation between bone and immune cells. Cells of the immune system express specific receptors for various calciotropic hormones, including parathyroid hormone (PTH) and calcitonin. In addition, several drugs used in the therapy of osteoporosis have been reported to modify the release of bone-active substances by immune cells. These facts prompted us to study in vitro the possible influence of PTH and calcitonin on the secretion of interleukin-1 (IL-1), tumor necrosis factor (TNF) and prostaglandin E2 (PGE) by peripheral blood mononuclear cells (PBMC). These three mediators show potent bone-resorbing activity. However, we did not find any significant effect of pharmacological concentrations of PTH or calcitonin on the secretion of IL-1, TNF or PGE by PBMC.

Adult↗
PubMed2000

Correlation of estradiol, parathyroid hormone, interleukin-6, and soluble interleukin-6 receptor during the normal menstrual cycle.

Rodent models suggest that estradiol deficiency promotes bone loss through increasing interleukin-6 (IL-6) activity. However, it is controversial as to whether these findings are applicable to humans. To evaluate estradiol-mediated modulation of IL-6 activity in relation to bone metabolism in humans, we measured serum IL-6, soluble interleukin-6 receptor (sIL-6R), estradiol (E2), progesterone, luteinizing hormone, follicle-stimulating hormone, intact parathyroid hormone (PTH), serum and urine Ca, and bone biochemical markers (serum bone-specific alkaline phosphatase, osteocalcin, and serum and urine deoxypyridinoline [Dpd]) across one menstrual cycle for 211 women. Neither IL-6 nor sIL-6R levels differed between the follicular phase (FP) and the luteal phases (LP). However, IL-6 was negatively correlated with E2 during the FP (p =0.003). Furthermore, IL-6 correlated positively with serum Ca over the entire cycle (p = 0.0091. Serum Ca correlated positively with serum (p = 0.040) and urine (p = 0.006) Dpd. PTH was significantly higher during the FP than in the LP (p = 0.004). PTH was negatively related to E2 (p = 0.002), serum Ca (p < 0.001), and urine Ca (p = 0.036), whereas it was positively correlated with IL-6 (p = 0.027). These data demonstrate that IL-6 and PTH fluctuate with E2, and serum II-6 is associated with PTH levels during the menstrual cycle. However, the role of 11-6 in bone remodeling during the normal menstrual cycle remains to be determined.

Adult↗
PubMed1976

Aging and parathyroid hormone secretion.

Influence of age on parathyroid hormone secretion and release was studied in vitro using rat parathyroid glands in culture and in vivo by EDTA injection. Parathyroid hormone was measured by radioimmunoassay using guinea pig antibody for bovine parathyroid hormone and 125I-labeled synthetic N-terminal peptide of bovine parathyroid hormone. Significantly less PTH was released from parathyroid glands of 18-mo-old rats than from those of 1 mo of age at various calcium concentrations of the medium in vitro. Secretion of parathyroid hormone in response to EDTA-induced hypocalcemia in vivo was also less in older rats than in younger ones, giving lower deltaPTH/deltaCa values in the older animal. Secretion of parathyroid hormone therefore appears to decrease along with aging in rats.

Aging↗
PubMed1996

Protamine and acute depletion of magnesium limit bone response to parathyroid hormone.

The effect of protamine on calcium homeostasis was studied in nine pediatric patients undergoing cardiopulmonary bypass. Total serum calcium decreased from 8.44 mg/dL to 7.49 mg/dL (P < 0.05) after protamine. Ionized calcium decreased from 1.39 to 1.31 mmol/L (P < 0.05). A bioassay determined the etiology of this response. Bone disks were placed in sera, protamine, parathyroid hormone, parathyroid hormone antibody, or magnesium-depleted solutions, then were incubated in solutions with known calcium content. The change in the media's calcium concentration reflects the bone's response to the initial stimulus. Calcium change is expressed as Experimental delta/Control delta (E/C). Normal bone responds to parathyroid hormone, E/C = 0.59 (P < 0.001). Protamine-treated bone loses this response, E/C = 0.9 (P = not significant [NS]). A parathyroid-hormone-induced osteoblast messenger was found. Protamine-treated bone continued to respond to this messenger, E/C = 0.42 (P < 0.001). Bone showed reversible loss of response to parathyroid hormone after incubation in magnesium-free solution, E/C = 0.93 (P = NS). With reincubation in magnesium, E/C = 0.69 (P < 0.01). Since protamine blocks parathyroid receptors, and magnesium depletion limits the bone's response to parathyroid hormone, this may explain the persistent hypocalcemia seen in some patients undergoing cardiopulmonary bypass.

Adult↗
PubMedDate not supplied

Clinical applications and technical aspects of parathyroid hormone measurements.

A review of human parathyroid hormone measurements is presented. Although parathyroid hormone was among the first hormones to be measured with the radioimmunoassay technique in 1963, there are even now still many pitfalls in both the technical aspects and clinical applicability of this assay. The main reasons for these difficulties are presented: firstly the complex intra- and extraglandular metabolism of parathyroid hormone results in the heterogeneity of the hormone in serum; secondly, the scarceness of pure human parathyroid hormone delays the development of a complete homologous human assay. The existing assays however have, despite their limitations, enormously contributed to our knowledge of parathyroid hormone secretion in both the normal state and in disease. The clinical applicability of these assays is reviewed and future technical improvements are suggested.

Humans↗
PubMed1992

Regulation of parathyroid hormone release in normal and pathological parathyroid cells exposed to modulators of protein kinase C.

Effects of the protein kinase C activating phorbol ester 12-O-tetradecanoyl phorbol 13-acetate and the inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) on parathyroid hormone (PTH) release were studied in normal bovine and pathological human parathyroid cells. An increase of extracellular Ca2+ from 0.5 to 3.0 mmol/l inhibited PTH release by 60% in the bovine cells with half maximal effect (ED50) at 1.31 mmol/l. This inhibition reached less than 50% in the cells from patients with primary and uremic hyperparathyroidism, and the ED50 values were 1.49 and 1.42 mmol/l, respectively. The phorbol ester (0.1 mumol/l) made secretion insensitive to changes of extracellular Ca2+, an action counteracted by H-7 (50 mumol/l) in the bovine cells, whereas H-7 alone had no effects. The phorbol ester and H-7 had opposite actions on regulation of PTH release also from cells from patients with hyperparathyroidism. However, in pathological cells H-7 alone improved Ca2+ inhibition of secretion by stimulating release in low Ca2+ concentrations and decreasing the ED50 values. The magnitude of changes in ED50 values by H-7 increased with the severity of the secretory disturbance of the pathological cells. The results indicate that increased protein kinase C activity may be a factor of importance in the pathophysiology of hyperparathyroidism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1975

The by-pass of tissue hormone stores during the secretion of newly synthesized parathyroid hormone.

Bovine parathyroid gland slices were incubated in Krebs' buffer with [3-H] leucine in order to assess the biosynthesis and secretion of parathyroid hormone (PTH). After incubation the particulate structures of the tissue were extracted with sodium deoxycholate to yield primarily newly synthesized (radioactive) PTH in the extract and preexisting granule PTH in the residue. In pulse-chase experiments radioactive PTH entered the granule fraction at a time when total tissue radioactive hormone was declining, which indicates that some newly-synthesized PTH was packaged into these granules. The specific radioactivity of the PTH in the incubation medium was from 20-fold to more than 80-fold greater than that of the granule PTH of the tissue, but was similar in magnitude to that of the tissue's newly synthesized hormone. Secretion of newly synthesized PTH was greater during incubation in buffer with 1.25 mM Ca than it was at 2.5 mM Ca which indicated that the hormone release was subject to physiological control. The PTH content of the tissue granule fraction was lower following incubation at 1.25 mM Ca than at 2.5 mM Ca. The possibility was excluded that the higher specific radioactivity of PT1 of incubation medium compared to that of the secretory granule fraction resulted from a diffusion gradient of [3-H] leucine into the tissue slices. These data indicate that a major portion of the newly synthesized PTH was secreted without prior equilibration with the hormone in the pool of secretory granules.

Amino Acids↗
PubMed2004

Intraoperative measurement of parathyroid hormone in minimally invasive surgery for parathyroid adenoma.

INTRODUCTION: In the past bilateral neck exploration was the gold standard for successful surgical management of primary hyperparathyroidism. More restricted procedures have been introduced recently thanks to imaging techniques and intraoperative parathyroid hormone assay confirming eradication of hyperfunctioning tissue. METHODS: Thirty patients operated for parathyroid adenoma were submitted to intraoperative PTH determination with Quick Pack immunochemiluminescent assay (Nichols lab.) prior to excision and 5, 10 and 20 minutes after removal of the presumed hyperactive gland. Eleven patients were operated on by a minimally invasive procedure with videoassistance. RESULTS: Response to excision of the hyperfunctioning gland was evidenced by a significant decrease of PTH levels (50% of initial value) in 26 patients. Plasma PTH levels decreased by at least 80% of pre-excisional value after 20 minutes, 70% after 10 minutes and by 50% after 5 minutes. In 2 cases, significant decrease of PTH was obtained after 45 and 60 minutes respectively. In 2 other cases, the adenoma could not be found and there was no decrease of PTH even after extensive exploration of the neck. In the 11 patients who underwent minimal invasive surgery, 2 were converted to open neck surgery: in one case the adenoma was not accessible in the upper part of the neck, in the other case the hyperfunctioning gland remained undiscovered. CONCLUSION: intraoperative measurement of PTH should be considered a reliable and reproducible method for evaluation of the secreting activity of a parathyroid gland. The Quick Pack method has the advantage of confirming that the hyperactive gland has really been eradicated and consequently of considerably reducing operating time and avoiding extensive exploration of the neck.

Adenoma↗
PubMed1988

Parathyroid hormone--quo vadis?

Parathyroid hormone is the most important calcium regulating hormone, especially in the process of aging. As a compensation for progressive calcium deficiency in aging, PTH secretion progressively rises. Heterogeneity of PTH in peripheral blood indicates the importance of understanding the degradation mechanism throughout the life cycle of the hormone. In addition to cathepsin B and D which degrades PTH in the liver, kidney and parathyroid gland, a new neutral PTH ase was found in the cytosolic fraction of rat kidney cells. PTH responsive bone and kidney cell lines, UMR-106 and OK cells, were found to degrade PTH by a chymotrypsin-like enzyme on the plasma membrane through a receptor mediated mechanism. This process was inhibited by cyclic AMP-A-kinase system and augmented by C-kinase system, suggesting an intimate relationship between PTH action and degradation and also a new physiological significance of PTH degradation.

Aging↗