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PubMed1990

Electron microscopic study of the parathyroid gland of the calcium-treated hamster subjected to hypergravity environment.

The ultrastructure of the parathyroid glands of calcium-treated golden hamsters subjected to 5 gravity environment was studied. In the calcium-treated animals exposed to hypergravity environment, the Golgi complexes and cisternae of the granular endoplasmic reticulum were significantly decreased compared with those of the animals exposed to hypergravity environment only and appeared to increase compared with those of the calcium-treated animals, but were almost similar to those of the control animals. In addition, many chief cells contained some prosecretory granules in the Golgi areas, some secretory granules situated close to the plasma membrane and many lysosomes. The morphology of the parathyroid glands in the calcium-treated animals exposed to hypergravity environment resembled that of the control animals. These results suggest that the parathyroid glands suppressed by treatment of calcium and stimulated in response to hypergravity environment may indicate the secretory activity of the parathyroid glands of the control animals.

Animals↗

PubMed1983

Polymorphism of parathyroid glands in patients with chronic renal failure and secondary hyperparathyroidism.

The excised parathyroid glands of twenty-one patients with secondary hyperparathyroidism due to chronic renal failure were submitted to careful histopathologic examinations including electron-microscopy. The previous history of these patients who had been on hemodialysis treatment for a certain period was relatively uniform with no association with primary hyperparathyroidism. Although eleven patients had four evenly enlarged parathyroid glands, eight patients showed four unevenly enlarged parathyroid glands with one or two glands weighing less than 100 mg. Histopathologic patterns of hyperplasia are easily divided into two distinctly different patterns, diffuse and nodular. Thirteen cases showed the same histopathological patterns of hyperplasia, either diffuse or nodular, in all excised glands. However, one or two out of four glands in eight patients evidenced a different histopathological pattern.

Adult↗

PubMed1999

The efficacy of technetium-99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands.

The efficacy of the technetium-99m-2-methoxyisobutylisonitrile (Tc-MIBI) scan and intraoperative methylene blue staining was analyzed in a consecutive series of 15 patients with primary hyperparathyroidism who underwent neck surgical exploration. A total of 17 abnormal parathyroid glands were removed, 7 of which were confirmed histologically as adenomas and 10 as hyperplasias. The Tc-MIBI scan and the thallium-201-technetium-99m subtraction (Tl/Tc) scan preoperatively localized 11 (69%) of 16, and 6 (40%) of 15 abnormal parathyroid glands, respectively. The Tc-MIBI scan correctly localized two ectopic abnormal parathyroid glands which were not localized by the Tl/Tc scan or ultrasonography (US). However, it also demonstrated false-positive accumulations caused by thyroid diseases in two patients. There were 4 abnormal parathyroid glands not detected by the preoperative imaging techniques, whereas all 17 abnormal parathyroid glands were stained with methylene blue, the infusion of which caused no adverse effects or toxicity. In conclusion, Tc-MIBI scanning and intraoperative methylene blue staining are effective techniques for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

Adenoma↗

PubMed1989

Direct demonstration of D1 dopamine receptors in the bovine parathyroid gland using the D1 selective antagonist [125I]-SCH 23982.

The presence of D1 dopamine receptors in the parathyroid gland has been proposed based on the demonstration of dopaminergic regulation of adenylate cyclase activity and parathyroid hormone release in dispersed bovine parathyroid cells. Using a radioiodinated D1 selective antagonist [125I]-SCH 23982, we have now directly labeled and characterized the D1 dopamine receptors in bovine parathyroid gland membranes. [125I]-SCH 23982 binds in a saturable manner with high affinity and low nonspecific binding to membranes prepared from bovine parathyroid glands. D1 dopamine receptors are present in this preparation at a concentration of approximately 130 fMoles/mg protein and [125I]-SCH 23982 binding increases with increasing protein concentration in a linear fashion. Determination of the Kd using the association (k1) and dissociation (k-1) rate constants revealed good agreement with the Kd determined by saturation analysis (390 pM vs. 682 pM, respectively). Inhibition of 0.3 nM [125I]-SCH 23982 binding by a series of dopaminergic antagonists verified the D1 nature of this binding site, exhibiting appropriate affinities and rank order of potency. The competition curves of all antagonists exhibited Hill coefficients that were not significantly different from 1. Inhibition of [125I]-SCH 23982 binding by dopamine and other dopaminergic agonists revealed the presence of high and low affinity agonist binding sites. Addition of 200 microM GppNHp effected a complete conversion of high affinity dopamine binding sites to a homogeneous population of low affinity dopamine sites. The D1 receptors identified in the parathyroid gland with [125I]-SCH 23982 appear to be pharmacologically identical with those previously characterized in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Innervation of the chicken parathyroid glands: immunohistochemical study with the TuJ1, galanin, VIP, substance P, CGRP and tyrosine hydroxylase antibodies.

The innervation of the chicken parathyroid glands was studied by immunohistochemistry using various antibodies. The parathyroid glands, as well as the carotid body and ultimobranchial gland, received branches originating from the vagus nerve. Numerous nerve fibers immunolabeled with the monoclonal antibody (TuJ1) against neuron-specific class III beta-tubulin isotype were found in the connective tissue capsule and septa penetrating into the parathyroid parenchyma. They were also prominent in the wall of blood vessels. Peptidergic nerve fibers immunoreactive for galanin, vasoactive intestinal polypeptide (VIP), substance P and calcitonin gene-related peptide (CGRP) were densely distributed in the capsule, septa and blood vessel walls of the parathyroid glands. In addition, some TuJ1-, substance P- and CGRP-immunoreactive fibers were detected in close association with the parenchymal cells of parathyroid glands. Tyrosine hydroxylase-immunoreactive fibers were concentrated around blood vessels and also in connective tissue stroma.

Animals↗

PubMed1979

Effects of prostaglandin E1 on the metabolism in rat parathyroid gland in vitro.

We investigated some effects of prostaglandin E1 on the metabolism of rat parathyroid glands using a culture system containing basal Eagle's medium supplemented with 5--10% heat-inactivated rat serum. Rat parathyroid glands incorporate [3H]fucose and 14C-labeled amino acids into cellular glycoproteins and secrete some of these into the culture medium. Gel filtration chromatography separates these glycoproteins into three classes, the smallest of which (peak 3) is secreted with immunoreactive parathyroid hormone. In cultures of 48 h, prostaglandin E1 (1 microgram/ml) specifically inhibits the secretion of peak 3 and of parathyroid hormone but has no effect on the incorporation of [3H]fucose, 14C-labeled amino acids, or [3H]uridine into parathyroid glands. Cytochalasin B inhibits the secretion of parathyroid hormone and the incorporation of isotopic fucose and amino acids. Cortisol stimulates incorporation of [3H]fucose and the secretion of parathyroid hormone even in the presence of inhibitory doses of prostaglandin E1. It is concluded that, in organ culture, prostaglandin E1 inhibits the secretion of parathyroid hormone and of a specific glycoprotein the function of which may be related to the secretion of the hormone.

Amino Acids↗

PubMed1982

Cystic parathyroid gland hyperplasia--hyperparathyroidism presenting as a neck mass.

Hyperparathyroidism may occasionally present as a neck mass resulting from cystic change in a parathyroid adenoma. We report an unusual instance of hyperparathyroidism presenting as a palpable, but asymptomatic hyperplastic parathyroid gland cyst. We conclude that hyperplastic parathyroid glands may undergo cystic degeneration resulting in a palpable neck mass; and that all functional parathyroid gland cysts are not necessarily adenomas. Therefore, during parathyroidectomy procedures, biopsy material from at least one additional parathyroid gland should be obtained.

Aged↗

PubMed1996

Imaging of the parathyroid glands.

Primary hyperparathyroidism resulting in hypercalcemia is the most common presentation of parathyroid pathology and usually is related to a parathyroid adenoma and, less commonly, to hyperplasia. Imaging of the parathyroid glands focuses on the detection of adenomas in patients with primary hyperparathyroidism. The role of imaging (as well as the modality used) for preoperative localization of the parathyroid glands continues to be controversial. The embryology, anatomy, and physiology of the parathyroid glands are reviewed. The diagnostic utility of radiological imaging-including ultrasonography, CT, MR imaging, and nuclear scintigraphy-are discussed, particularly as it pertains to the evaluation of primary hyperparathyroidism.

Diagnostic Imaging↗

PubMed2000

A novel, noninvasive imaging technique for intraoperative assessment of parathyroid glands: confocal reflectance microscopy.

BACKGROUND: Successful surgical management of primary hyperparathyroidism requires the ability to identify and distinguish normal from abnormal parathyroid tissue. Microscopic pathologic confirmation often helps with the diagnoses and decisions regarding the extent of parathyroid resection. Confocal reflectance microscopy (CRM) is an optical method of noninvasively imaging tissue without fixation, sectioning, and staining as in standard histopathology. The goal of this study was to determine if CRM imaging could be used to distinguish normal from diseased parathyroid tissue intraoperatively. METHODS: In this study, 44 parathyroid glands from 21 patients undergoing operations for primary hyperparathyroidism were imaged immediately after excision. CRM images were compared with conventional hematoxylin-and-eosin stained sections obtained from the same gland. The percentage area occupied by fat cells was calculated in images of both normal and diseased glands. RESULTS: Characteristic microscopic features of parathyroid glands were distinguishable by CRM and correlated well with histopathology. The stromal fat content of normal and diseased glands could easily be determined. The percentage area occupied by fat cells differed significantly (P <.00001) in normal glands (average, 23.0% +/- 10.9%) and adenomatous glands (average, 0.4% +/- 0.7%). CONCLUSIONS: CRM imaging rapidly revealed microscopic features that reliably differentiated normal and diseased parathyroid glands. The success of this preliminary ex vivo study promotes interest in further development of an in situ probe for in vivo clinical diagnostic use.

Adenoma↗

PubMed1984

Effects of ovariectomy on the ultrastructure of the parathyroid gland of the golden hamster.

Ultrastructural changes of the parathyroid glands of ovariectomized golden hamsters were investigated. In the parathyroid glands there is a decrease in the area of each cell occupied by the Golgi complex, in the number of prosecretory granules and in the tortuosity of plasma membrane as compared with those of the control golden hamsters. In addition, the area occupied by lipid droplets appears to be increased and the number of secretory granules in the peripheral cytoplasm and large vacuolar body appears to be decreased compared to those of the control animals. These features suggest that the synthesis and release of parathyroid hormone may be suppressed in many chief cells of the ovariectomized golden hamsters.

Animals↗

PubMed1980

Effects of vagotomy on the ultrastructure of the parathyroid gland of the rabbit.

Ultrastructural changes of the parathyroid glands of vagotomized rabbits were examined. Many chief cells at 6, 12, 18 and 24 h after vagotomy are rich in free ribosomes compared to control rabbits. The main changes in the parathyroid glands of rabbits at 12, 18 and 24 h after vagotomy as compared with the control animals are a proliferation of the Golgi complexes, an increased number of secretory granules in the peripheral cytoplasm, and a frequent occurrence of enlarged intercellular spaces containing finely particulate substance. Large secretory granules, heterogeneously dense bodies, multivesicular bodies and lipid droplets apparently decrease in number in many chief cells at 12, 18 and 24 h after the operation. These alterations suggest that synthesis and release of parathyroid hormone are stimulated in many chief cells of the vagotomized rabbits. In addition, correlations of the occurrence of large secretory granules and various bodies are discussed.

Animals↗

PubMedDate not supplied

Assessment of proliferative activity of glandular cells in hyperfunctioning parathyroid gland using flow cytometric and immunohistochemical methods.

The proliferative activity of epithelial cells in hyperfunctioning parathyroid glands was estimated by flow cytometric and immunohistochemical procedures. A total of 30 parathyroid glands, 29 hyperfunctioning glands, and 1 normal gland were studied. The pathology of the 29 glands was determined to be hyperplasia in 19 and adenoma in 10. The S-phase cell population was expressed in terms of the S-phase fraction (%SPF) calculated from the histogram by DNA flow cytometry and in terms of the BrdU immunostaining labeling index (BrdU LI). Cells in all stages of the cell cycle were studied by Ki-67 immunostaining and expressed in terms of the labeling index (Ki-67 LI). Both BrdU LI and Ki-67 LI values were low, ranging from 0% to 0.58% and from 0.21% to 2.62%, respectively. The BrdU LIs were lower than the Ki-67 LIs, ranging from one-sixth to one-twelfth of the values depending on the disease. There were significant correlations between the two indices (p < 0.001). The %SPF determined by flow cytometry was consistently higher than both the BrdU LI and the Ki-67 LI. This discrepancy cannot be explained precisely, and further improvements are required for the flow cytometric analysis of %SPF. The cell cycle study by BrdU and Ki-67 immunohistochemistry suggested that the glandular cells of the hyperfunctioning parathyroid were characterized by low proliferative activity. No evidence of rapid cell turnover rate assumed from the flow cytometric study could be observed in the hyperfunctioning parathyroid gland.

Adenoma↗

PubMed1992

Oestrogen, progesterone, and glucocorticoid receptors in normal and neoplastic parathyroid glands.

OBJECTIVE: To verify the presence or absence of steroid receptors in the parathyroid glands of patients undergoing operations on the parathyroid and thyroid glands. DESIGN: Open experimental study. SETTING: Karolinska Hospital, Stockholm, Sweden. MATERIAL: 165 parathyroid glands from 137 patients, 108 of whom underwent operations on the parathyroid glands and 29 on the thyroid gland. INTERVENTIONS: Normal and neoplastic parathyroid tissue was analysed for its content of oestrogen and progesterone and glucocorticoid receptors using either ligand binding or antibodies raised against oestrogen and progesterone receptors. RESULTS: Positive reactions to female sex steroid receptors (defined as > 0.05 fmol/microgram DNA) were uncommon (9%) regardless of the morphological classification of the glands or the age, sex, and menopausal status of the patients. Glucocorticoid receptors were detected in 107/163 (66%) of all glands analysed (mean value 0.43 fmol/micrograms DNA, range 0-44). Seventy of the 96 diseased glands (73%) contained receptors, as did 27/67 normal glands from patients with primary hyperparathyroidism or those undergoing thyroid operations. The difference was again not associated with age, sex, and menopausal status. CONCLUSIONS: It seems unlikely that sex steroid hormones play a physiological part in the secretion of parathyroid hormone, but our finding of glucocorticoid receptors in normal as well as diseased parathyroid tissue suggests that they may have a role in the regulation of parathyroid function.

Adult↗

PubMed2002

Loss of heterozygosity in parathyroid glands of familial hypercalcemia with hypercalciuria and point mutation in calcium receptor.

Development of sporadic parathyroid tumors is accompanied by loss of heterozygosity (LOH) on several chromosomes like 1p, 1q, 6q, 11q, and 15q. Here, we investigate a unique variant of familial hypercalcemia, unrelated to multiple endocrine neoplasia and hyperparathyroidism-jaw tumor syndromes, with hypercalcemia due to a point mutation in the intracellular part of the calcium receptor (CaR) gene. The hypercalcemia and hypercalciuria of the family is accompanied by age-related growth of the parathyroid glands and transition from diffuse to nodular parathyroid hyperplasia. Genome-wide screening for allelic loss was performed on nine enlarged parathyroid glands (weighing 40-680 mg) from eight parathyroidectomized members of the family (aged 22-66 yr). Using 139 fluorescent- or (32)P-labeled microsatellite markers, informative results were obtained on all examined chromosome arms and 1p, 1q, 6q, 11q, and 15q were investigated more closely. All parathyroid glands displayed allelic loss on at least one chromosomal arm (range 1-7). Most of the common loci for allelic loss corresponded to findings in sporadic parathyroid tumors, but the unique variant of familial hypercalcemia also exhibited frequent LOH on 12q (67%) and 7q (44%). LOH could not be detected at 3q, where the CaR gene is located, and additional somatic mutations in exons 2-7 of the CaR gene was not found by sequencing. The point mutation resulting in alteration of the intracellular portion of CaR seems to cause sensitivity to secondary genetic hits, with increased frequency of allelic loss (P < 0.01, r(2) = 0.66) and weight of parathyroid tumors with age in this family.

Adult↗

PubMed1987

Quantitative autoradiography of parathyroid glands in rats with carbon-14-labeled amino acids.

We have utilized a quantitative autoradiographic method as a means of evaluating amino acid uptake of the rat parathyroid gland for the ultimate purpose of finding agents potentially suitable for position emission tomographic scanning of parathyroid glands. L-[1-14C]leucine and L-[guanido-14C]arginine were evaluated because of their relatively high content in the synthetic products of the parathyroid glands compared with other neck tissues, thyroid gland, and muscle. Carbon-14 leucine disappeared rapidly from plasma following intravenous injection and there was relatively selective uptake of the [14C]leucine and [14C]arginine by the parathyroid glands when compared with uptake by the thyroid gland and neck muscle. These data suggest that both agents warrant further investigation for their potential utility in positron emission tomographic scanning of the parathyroid gland.

Amino Acids↗

PubMed1982

[Functional morphology and pathology of the parathyroid glands. Secretion study using tissue culture, electron microscopy, ultrahistochemistry, immunohistochemistry, morphometry and radioimmunoassay].

The subject of this volume provides an overview on current investigational trends in parathyroid research comprising morphology, function, and regulation of function. After describing calcium homoeostasis and disorders induced by parathyroid hypo- or hyperfunction, problems associated with surgical pathology and morphological diagnostics of parathyroid tissue from hyperparathyroid patients and of tumors with paraneoplastic PTH secretion are discussed. Experimental investigations by the author using tissue culture techniques have revealed details of structure, regulation, and secretion of PTH in human and porcine parathyroid glands drawing special attention to the secretory and morphological differences between normal and adenomatous parathyroid tissues. The combined application of methods available in morphology (electron microscopy, immunohistochemistry, ultrahistochemistry, morphometry) and biochemistry (radioimmunoassay, gel-filtration) allows the direct correlation of structure and function in the organ culture system, resulting in a functional morphology and pathology of parathyroid glands. Clinical pathology of primary hyperparathyroidism. The quantitative distribution of 220 operatively obtained parathyroid tumors consisting of 90% adenomas, 8.6% hyperplasias, and 1.4% carcinomas is in agreement with published data of the literature. The intraoperative discrimination between parathyroid and non-parathyroid tissue, necessary for successful search, is a prerequisite for the adequate therapy. A summary of macroscopical criteria will be helpful in improving the intraoparative first-look diagnostics. Problems arising with rapid intraoperative frozen section diagnostics and histological discrimination between adenoma, hyperplasia, and carcinoma are described. Functional morphology and pathomorphology of the parathyroid glands Cellular distribution of PTH and calcium. The chief cells of normal parathyroid glands often cannot be distinguished from those of adenomas if only conventional light- or electron microscopy are applied. However, by using immuno- and ultrahistochemistry evidence was established that adenomatous chief cells contain less PTH than normal chief cells, and that tumor cells are in an activated state. The intracellular calcium content of tumor cells was distinctly lower than in normal parathyroid chief cells, although in primary hyperparathyroidism the extracellular calcium concentration is elevated. The increased amounts of extracellular calcium finds a correlation in the accumulation of calcium deposits in the intercellular space and at the plasmalemma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗

PubMed1991

Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1.

OBJECTIVE: We wished to determine whether there was size heterogeneity of the parathyroid glands in patients with familial multiple endocrine neoplasia type 1 (FMEN1) and primary hyperparathyroidism. DESIGN: At the National Institutes of Health we performed a retrospective analysis of parathyroid gland volume either from initial or repeat parathyroid exploration. PATIENTS: We studied subjects with FMEN1 and primary hyperparathyroidism. MEASUREMENTS: The parathyroid gland volume was estimated from recorded orthogonal diameters. Volume could also be estimated conservatively in many glands for which one or more diameters were not recorded. Reproducibility of volume measurements was tested with a series of clay gland models. Indices of variability (among glands at an operation or among replicate measurements of a clay model) were the ratio of maximum volume/minimum volume and the average standard deviation of the log volume. RESULTS: The most complete data were from eight initial operations with three dimensions recorded for all four glands. Volume heterogeneity was indicated by the average ratio of 9.6 for the maximum/minimum gland volume within an operation. The size heterogeneity was even greater among other subgroups. For example, the average ratio of maximum/minimum gland volume within an operation was 17 among five initial operations with four glands removed, but lacking measurements of three dimensions for some glands. Little of this size heterogeneity could be attributed to measurement error since eight replicate measurements on a model gland yielded a maximum/minimum volume ratio of 1.45. CONCLUSIONS: There is a wide heterogeneity in size of the parathyroid glands in the patients with FMEN1 and primary hyperparathyroidism.

Humans↗

PubMed1980

Beta adrenergic receptors in the parathyroid glands.

The location of beta-adrenoceptors in human parathyroid gland was studied using an immunohistochemical method. Frozen sections of human parathyroid glands, taken from surgical samples, were treated with (-)-alprenolol, washed and exposed to (-)-alprenolol antibodies conjugated with fluorescent dyes. The (-)-alprenolol was bound to the parathyroid principal cells and to the main blood vessels. On the contrary, adrenergic nerve fibres, demonstrated with formaldehyde fluorescence technique, were only located within the walls of main blood vessels. The findings are discussed.

Alprenolol↗