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PubMed2006

Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats.

BACKGROUND: A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. METHODS: High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2) NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, <0.05%) for an additional 15 days. In each dietary group, one-half the rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)-1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. RESULTS: In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (P<0.05). But only in rats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (P<0.05). In the study of established hyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (P<0.05) ET-1 expression in rats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (P<0.05) than that in rats on the HPD sacrificed at 15 or 30 days. Bosentan did not reduce parathyroid cell proliferation or parathyroid gland weight in rats maintained on the HPD or further reduce these parameters beyond that obtained with dietary phosphorus restriction. PTH values were lowest in the VLPD group, intermediate in the NPD group, and highest in the HPD group, but in none of the three groups did bosentan decrease PTH values. CONCLUSIONS: In azotemic rats with developing hyperparathyroidism, bosentan resulted in a reduced increase in parathyroid gland weight when dietary phosphorus content was normal. Despite a reduction in ET-1 expression in rats on a HPD with developing or established hyperparathyroidism, bosentan did not reduce the increase in parathyroid cell proliferation, parathyroid gland growth or PTH values. Thus, ET-1 blockade with bosentan did not prevent parathyroid gland growth in the azotemic rat.

Animals↗

PubMed1998

Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands.

The thymus, thyroid, and parathyroid glands in vertebrates develop from the pharyngeal region, with contributions both from pharyngeal endoderm and from neural crest cells in the pharyngeal arches. Hoxa3 mutant homozygotes have defects in the development of all three organs. Roles for the Hoxa3 paralogs, Hoxb3 and Hoxd3, were investigated by examining various mutant combinations. The thyroid defects seen in Hoxa3 single mutants are exacerbated in double mutants with either of its paralogs, although none of the double-mutant combinations resulted in thyroid agenesis. The results indicate that the primary role of these genes in thyroid development is their effect on the development and migration of the ultimobranchial bodies, which contribute the parafollicular or C-cells to the thyroid. Hoxb3, Hoxd3 double mutants show no obvious defects in the thymus or parathyroids. However, the removal of one functional copy of Hoxa3 from the Hoxb3, Hoxd3 double mutants (Hoxa3 +/-, Hoxb3-/-, Hoxd3-/-) results in the failure of the thymus and parathyroid glands to migrate to their normal positions in the throat. Very little is known about the molecular mechanisms used to mediate the movement of tissues during development. These results indicate that Hoxa3, Hoxb3, and Hoxd3 have highly overlapping functions in mediating the migration of pharyngeal organ primordia. In addition, Hoxa3 has a unique function with respect to its paralogs in thymus, parathyroid, and thyroid development. This unique function may be conferred by the expression of Hoxa3, but not Hoxb3 nor Hoxd3, in the pharyngeal pouch endoderm.

Animals↗

PubMed1981

The parenchymal cell mass in normal human parathyroid glands.

The parenchymal cell mass in parathyroid glands from 368 autopsy cases without apparent parathyroid or kidney disease was investigated. By measuring the glandular density with a density gradient technique and the glandular weight, the parenchymal to fat cell ratio and the weight of the parenchymal cell mass could be determined. The mean parathyroid parenchymal cell weight was calculated to be 22 mg and the maximal normal parenchymal cell weight 39 mg. The glandular weight was evidently dependent on the body constitution, as the fat tissue content of the glands was related to the amount of fat tissue in the body as a whole. The parenchymal cell weight was much less variable. Also, the amount of fat tissue in the parathyroid glands was positively correlated to the size of glands. Thus, the amount of fat cells within parathyroid glands seems less adequate as a histological criterion and the parenchymal cell weight should be of greater value in the histological diagnosis that the weight of the whole gland. The age-and-sex-related variations of the parenchymal cell mass were slight and therefore a value of 39 mg may be considered an appropriate upper limit of the weight of this mass in parathyroid glands of adult persons.

Adipose Tissue↗

PubMed1970

Hormone synthesis and secretion by rat parathyroid glands in tissue culture.

Rat parathyroid glands maintained in organ culture secrete biologically active parathyroid hormone (PTH) and synthesize and secrete labeled proteins from (3)H- or (14)C-labeled amino acids added to the medium. The amounts of biological activity and labeled protein in the medium are both inversely proportional to the calcium concentration. Some of the labeled low molecular weight protein was identified as PTH which had been synthesized and secreted in culture by preliminary isolation on Sephadex G-100 columns and further purification using an antibody to bovine PTH which cross-reacted with rat PTH. The cross-reacting antibody inhibited the biological effects of rat PTH and caused hypocalcemia in intact rats. The antibody bound some of the labeled low molecular weight protein of the medium at neutral pH so that it migrated as a large molecular weight complex on Sephadex. Biologically active, labeled PTH was recovered by dissociation of this complex in acid and rechromatography.

Amino Acids↗

PubMed1993

[Clinical applications of color-Doppler: the parathyroid glands].

The high-resolution appearance of enlarged parathyroid glands is well known. Thus, real-time gray-scale US alone fails to provide, in ENT surgery, adequate sensitivity and specificity rates to differentiate between parathyroid glands, hypoechoic thyroid adenomas and other hypoechoic neck masses. Since parathyroid tissue, in both normal and enlarged glands, is hypervascular, color-Doppler US is used as a sort of non-invasive angiography to identify parathyroid glands. The combined use of B-mode and color-Doppler US allows the vascular features of thyroid masses to be satisfactorily demonstrated, with easy differentiation between enlarged parathyroid glands, featuring diffuse internal vascularization, and thyroid adenomas characterized by rounded peripheral vessels and also lymph nodes and cysts exhibiting different vascular patterns. We studied 25 patients with clinical and biochemical signs of hyperparathyroidism (19 primary and 6 secondary) submitted to surgery in the last 20 months. Every patient was scanned with both B-mode and color-Doppler US. At surgery, 19 parathyroid adenomas were found--16 of them correctly identified preoperatively with color-Doppler US and 3 false negatives (retrotracheal glands). Moreover, 1 false positive was observed due to a small Plummer's adenoma misdiagnosed as an intrathyroid parathyroid adenoma: both lesions had the same vascular pattern on US images. Sensitivity was 84.5% and specificity 93.7%. In secondary HPT patients, 23 hyperplastic glands were found at surgery--21 of them correctly identified preoperatively by color-Doppler US, with 2 false negatives. No false positive was found. Sensitivity was 87.5% and specificity 100%. Sensitivity does not differ very much from what reported in literature. Specificity is clearly increased by the use of color-Doppler US. The possible source of error represented by Plummer's adenomas lead us to investigate pulsed Doppler capabilities in differentiating Plummer's adenomas from PT glands, since color-Doppler findings were similar in the two conditions. Peak velocities recorded with both color and pulsed Doppler showed velocity to range 6 to 40 cm/s in parathyroid glands (mean +/- SD: 14.6 +/- 11.7) and 38 to 120 cm/s in thyrotoxic nodules (mean +/- SD: 78.4 +/- 23). The statistical analysis of the results showed a highly significant difference between the two groups of velocities. Peak velocities as recorded in the main, vessels of the parathyroid glands with color and pulsed Doppler were correlated with the activity of the parathyroid glands.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗

PubMed2000

Thoracoscopic resection of ectopic parathyroid glands.

BACKGROUND: The vast majority of parathyroid glands in hyperparathyroidism can be resected through a cervical approach. In approximately 2% of the cases, the ectopic gland is in the mediastinum in a location that requires a thoracic approach. METHODS: We report 7 such cases that were resected using video-assisted thoracic surgery to avoid the need for an open surgical procedure. RESULTS: All glands were successfully identified preoperatively and subsequently resected. Hospital stay averaged less than 3 days with only one minor complication. CONCLUSIONS: Ectopic mediastinal parathyroid glands may be safely and accurately resected using video-assisted thoracic surgery to avoid open approaches.

Adenoma↗

PubMed1978

Function of the parathyroid glands after total thyroidectomy.

Parathyroid function, defined as the ability to maintain normocalcemia without substitution, was evaluated in 36 patients following total thyroidectomy for carcinoma. In 16 patients, all visualized parathyroid tissue was sliced and autotransplanted into muscle pockets; one year after the operation, 11 patients had substitution for lack of parathyroid function. In 20 patients, the parathyroid glands were preserved in situ with intact vascular supply; one year postoperatively, three patients had evidence of persistent hypoparathyroidism. The difference in the parathyroid insufficiency rate is significant, p less than 0.005. We conclude that parathyroid autotransplantation has been a failure io preserve the parathyroids in situ whenever this is feasible, autotransplantation being reserved for parathyroids unfortunately removed or devascularized.

Adenocarcinoma↗

PubMed1995

The roles of calcium and 1,25-dihydroxyvitamin D3 in the regulation of vitamin D receptor expression by rat parathyroid glands.

Expression of the vitamin D receptor (VDR) in the parathyroid glands is decreased in secondary hyperparathyroidism associated with chronic renal failure by undefined mechanisms. In the present study, we examined the effects of hyperparathyroidism and dietary calcium and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on the expression of VDR in rat parathyroid glands. Vitamin D-deficient rats were maintained on diets containing 0.02% Ca (-D, LCD), 0.4% Ca (-D, NCD), or 2.0% Ca (-D, HCD) for 6 weeks. Serum ionized Ca (ICa) in the rats on the three diets ranged from 2.5-5.2 mg/dl. Serum PTH ranged from 22-590 pg/ml and correlated inversely with ICa (r = -0.835; P < 0.001). Rats with the highest ICa had normal PTH values, suggesting that vitamin D deficiency per se does not lead to hyperparathyroidism. VDR messenger RNA (mRNA) levels in the parathyroid glands correlated positively with ICa (r = 0.845; P < 0.001) and negatively with PTH (r = -0.716; P < 0.001). VDR mRNA levels in the rats fed the -D, HCD were 6 times higher than those receiving -D, LCD and the same as those in rats fed a normal (Purina) diet. Thus, prevention of hyperparathyroidism with high dietary calcium prevented the drop in VDR expression. Treatment of the rats on all three diets with 0, 25, or 100 ng 1,25-(OH)2D3, ip, 48 and 12 h before death dose dependently increased ICa and decreased PTH, as expected, and also increased parathyroid gland VDR mRNA. This coordinate regulation of VDR mRNA by calcium and 1,25-(OH)2D3 was also observed in the kidney, but intestinal VDR mRNA was not stimulated by dietary calcium or 1,25-(OH)2D3. Analysis of covariance for parathyroid gland VDR mRNA and ICa for the three doses of 1,25-(OH)2D3 revealed no significant independent effect of 1,25-(OH)2D3 on VDR mRNA, suggesting that the up-regulation of VDR expression by 1,25-(OH)2D3 in the parathyroid glands may be mediated primarily by increasing serum calcium.

Animals↗

PubMed1983

Excision of mediastinal parathyroid gland by mediastinoscopy.

Mediastinal parathyroid tissue continues to be a significant problem in patients with recurrent or persistent hypercalcemia after parathyroid surgery. In two such cases, we used mediastinoscopy to locate and remove mediastinal parathyroid glands, thus avoiding the morbidity of median sternotomy.

Humans↗

PubMed2004

Age-related changes of the ultrastructure in the cardiomyopathic hamster (UM-X7.1 Syrian hamster) parathyroid gland.

We qualitatively and quantitatively investigated parathyroid glands of the UM-X7.1 cardiomyopathic hamster at 1, 2, 6 and 12 months of age to compare them with those of the normal hamster. We found that at 1 month of age in the UM-X7.1 hamster, the Golgi apparatus, lipid droplets and secretory granules decreased. There were no significant differences between the UM-X7.1 hamster and the control hamster at 2 months of age. At 6 months of age, the Golgi apparatus, rER and the secretory granules significantly increased in the UM-X7.1 hamster. At 12 months of age, the Golgi apparatus and lysosomes increased, while the secretory granules decreased. Ultrastructurally, we consider that in the UM-X7.1 hamster, the synthesis and release of the parathyroid at 6 months of age may be activated by an excessive amount of circulating catecholamine, and the functional activity of the parathyroid glands at 12 months of age may be depressed by the increased plasma calcium level. These findings suggest that the activities of the synthesis and release of the parathyroid hormone were the highest at 6 months of age in the UM-X7.1 hamster.

Aging↗

PubMed1991

[Lectins expression of parathyroid glands with primary hyperparathyroidism].

The binding sites of lectins in parathyroid glands were determined by an immunohistochemical method in normal parathyroid gland, hyperplasia, adenoma and carcinoma, the used lectins were commercially available Glycine max (SBA), Concanavalin enciformis (Con A), Triticum vulgaris (WGA), Richinus communis (RCA), Banderiaea simplicifolia II (BSA II) and Arachis hypogaea (PNA). For normal parathyroid glands (2 cases) and hyperplasia (2 cases), WGA and BSA II were stained in cytoplasma and cell membrane. For carcinoma (1 cases), all lectins but BSA II were positively stained. In particular, SBA revealed more stronger stain than any other hystological types. From the staining patterns of lectins, it was suggested that adenomas (22 cases) be divided into one group similar to carcinoma and the others to normal parathyroid gland and hyperplasia. But there was no difference in clinical data of patients between the two groups.

Adenoma↗

PubMed1995

Calcium-activated proteases in the bovine parathyroid gland: potential role in degradation of parathyroid hormone to peptide fragments.

Our studies suggest that protein kinase C is involved in low calcium (Ca2+)-stimulated secretion of parathyroid hormone (PTH) but not directly in high Ca(2+)-stimulated intracellular degradation of PTH to secreted carboxyl-terminal fragments (C-PTH), an important component of Ca(2+)-regulated PTH secretion. The present study was undertaken to determine the presence of calcium-activated proteases, 84 kDa (micro)-calpain and 80 kDa (milli)-calpain, in the bovine parathyroid, and whether they could degrade PTH to C-terminal fragments. Immunocytochemistry of bovine parathyroid tissue using antibodies raised against bovine heart micro- and milli-calpain detected both isoforms of calpain. Western blotting of total bovine parathyroid cell protein prepared from primary cell cultures confirmed the presence of both isoforms of calpain, demonstrated by specific milli- and micro-calpain bands. Purified bovine PTH (bPTH) was incubated in vitro with human erythrocyte micro-calpain and the cleavage products were separated by reverse-phase HPLC. Eluant fractions were assayed with an RIA with equimolar sensitivity to C-PTH and bPTH, and peak areas integrated. Micro-calpain produced a C-PTH peak from bPTH which co-eluted with the major C-PTH secreted by parathyroid cells in culture. C-PTH production by micro-calpain, expressed as per cent area under the curve, increased from 0% in the absence of either micro-calpain or Ca2+, to 71.5% when a 5:1 molar ratio of bPTH to calpain was used. Amino acid sequencing and analysis of the immunoreactive PTH cleavage products indicated the presence of two fragments of bPTH in the C-PTH peak, bPTH47-48 and bPTH69-84. In summary, both isoforms of calpain are present in the bovine parathyroid and calpains may play a role in the Ca(2+)-dependent degradation of PTH to secreted C-terminal fragments.

Amino Acid Sequence↗

PubMed1971

[Ultrastructural comparison of human parathyroid glands in secondary hyperparathyroidism and primary parathyroid adenoma].

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Adenoma↗

PubMed1986

Concomitant thyroid disease in hyperparathyroidism. Reasons for unsatisfactory ultrasonographical localization of parathyroid glands.

Ultrasonic localization of enlarged parathyroid glands has been attempted in a consecutive series of 23 patients with primary hyperparathyroidism. Seven of 15 patients with operatively verified diagnosis, had predictive ultrasound scans (47% consistency) and 10 of 16 adenomas were identified (63%). A possible explanation for these unsatisfactory results could be a high incidence of coexisting nodular thyroid lesions, and significantly enlarged thyroid glands in these patients.

Adenoma↗

PubMed1990

Morphometric evaluation of intracytoplasmic lipid in normal and pathological parathyroid glands.

The chief morphological criterion for classifying parathyroid glands as 'normal', 'suppressed', or 'activated' is the lipid content of the cytoplasm. In particular, cytoplasm lipid deposit is scanty in the active parathyroid cell, according to many authors. In this paper we present the results of a morphometrical study of ten normal parathyroid glands from patients undergoing thyroidectomy, 20 enlarged 'adenomatous' glands from patients with primary hyperparathyroidism, and 20 glands of normal size from the same hyperparathyroid patients. We aimed at assessing the content of intracytoplasmic lipid of secretory cells in all these conditions. The results show that secretory cells of adenomatous glands have less lipid than those from normal glands; however, there was considerable overlapping of the data in the two groups. The mean lipid content of cells in glands of normal size taken from hyperparathyroid patients was not significantly different from the mean value of normal cells, even when ultrastructural evidence of activation was present in the former. These data suggest that caution has to be exercised in assessing the functional status of parathyroid glands on the basis of lipid content of secretory cells, mainly when differentiating between adenoma and hyperplasia.

Cytoplasm↗

PubMed2006

Surgical anatomy of parathyroid glands with emphasis on parathyroidectomy.

Number, location and surrounding structures of parathyroid glands with emphasis on parathyroidectomy were studied on 101 cadaverous bodies. Number of collected samples from all known locations of parathyroid glands varied from three to five in one individual, with mean 3.71 +/- 0.62. We identified 80% of samples as parathyroid glands. Mean number of correctly identified parathyroid glands in one individual was 2.77 +/- 1.06. The rest 20% of collected samples were lymph nodes, fat particles and thyroid or lipothymic tissue. Almost 30% more of inferior parathyroid glands were found in abnormal position in lipothymic tissue in comparison with their superior counterparts. We found several abnormities of vessels and cervical extensions of thymus. We also present case of brachiocephalic trunk, reaching the inferior pole of thyroid gland. We recommend beginning of parathyroidectomy in circumscribed area 2 cm in diameter, 1 cm cranially to the intersection of the inferior thyroid artery and recurrent laryngeal nerve followed by preparation on dorsal surface of thyroid gland, along the course of inferior thyroid artery and recurrent laryngeal nerve, in cervical extensions of thymus and in paraoesophageal and retropharyngeal region. Success of parathyroidectomy is based on the knowledge and experience of surgeon.

Adult↗

PubMedDate not supplied

Ultrasonically guided fine needle aspiration of suggested enlarged parathyroid glands.

Ultrasonically guided fine needle aspiration from 22 ultrasonically suspect enlarged parathyroid glands was performed in 21 consecutive patients with biochemically confirmed hyperparathyroidism. Histologic examination revealed parathyroid tissue in 20 and thyroid tissue in 2 of the 22 ultrasonically suspect parathyroid glands. The aspirated material (21 patients) was analysed for PTH content and compared with the PTH content in aspirates from corresponding thyroid tissue. In all but one, a higher PTH content was found in aspirates from parathyroid glands. Further, the aspirated material (16 patients) was cytologically examined for parathyroid cells. In 10 of 14 histologically confirmed parathyroid glands cells of parathyroid origin were found, but in 4 cases only cells of endocrine origin were seen. The results and the use of fine needle aspiration in relation to the ultrasonic findings are discussed.

Adult↗

PubMed1978

Seasonal variations in the parathyroid gland of the lizard, Uromastix hardwickii (Gray).

Morphology, histology and seasonal changes in the parathyroid gland of the lizard, Uromastix hardwickii are reported. The lizard possesses a pair of glands consisting of a single type of cells. Parathyroid gland undergoes well defined seasonal changes. During breeding season (Summer) gland showed hyperactivity, whereas in winter, when lizard is quiescent, parathyroid gland shows degenerative changes. Though parathyroid gland from both male and female exhibited hyperactive phase during summer, plasma calcium and phosphorus concentration of female only has increased during this period suggesting that the changes in the parathyroid gland are not due to the endogenous circulating calcium level.

Animals↗