A comparative study of the int-2 gene product in primary and secondary parathyroid lesions

OBJECTIVE: The family of fibroblast growth factors stimulates proliferation of cells of mesenchymal, epithelial and neuroectodermal origin. One of the members of this family, the product of proto-oncogene int-2, fibroblast growth factor-3, has been found to stimulate mitosis of parathyroid cells in culture. Primary and secondary hyperparathyroidism have no clear differences with regard to the histopathological features of the diseased parathyroid glands. DESIGN: This study was undertaken in order to determine whether int-2 protein is immunohistochemically expressed in normal and abnormal parathyroid glands and to investigate whether there is a differential expression of the int-2 gene product between primary and secondary parathyroid disease. METHODS: A sheep anti-human int-2 antibody was applied to tissue sections from 37 samples of primary parathyroid disease (12 sporadic adenomas, 25 hyperplastic glands), from 30 samples of renal hyperparathyroidism, and from seven normal controls. Int-2 immunostaining was evaluated semi-quantitatively. RESULTS: None of the normal parathyroid glands stained positively. Int-2 immunopositive expression was more frequently detected in specimens of uraemic patients than in those of patients with primary parathyroid growth processes (P=0.029). The reason for this differential expression appears to be the higher proportion of oxyphilic cells growing in hyperplastic glands of patients with secondary hyperparathyroidism; the latter cells were specifically found to be int-2 immunoreactive. CONCLUSION: The int-2 gene product is likely to participate in the proliferation of this parathyroid cell subpopulation.

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Parathyroid Elastography―Elastography Evaluation Algorithm

Timisoara Medical Journal ◽

10.35995/tmj20200105 ◽

2020 ◽

Vol 2020 (1) ◽

pp. 1

Author(s):

Laura Cotoi ◽

Daniela Amzăr ◽

Ioan Sporea ◽

Andreea Borlea ◽

Oana Schiller ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Secondary Hyperparathyroidism ◽

Muscle Tissue ◽

Thyroid Tissue ◽

Parathyroid Tissue ◽

Parathyroid Glands ◽

Cervical Lymph Nodes ◽

Cardiovascular Morbidity And Mortality ◽

Parathyroid Lesions ◽

Parathyroid Disease

(1) Background: Primary hyperparathyroidism is a common disorder of the parathyroid glands and the third most frequent endocrinopathy, especially among elderly women. Secondary hyperparathyroidism is a common complication of chronic kidney disease, associated with high cardiovascular morbidity and mortality. In both primary and secondary hyperparathyroidism, the need to correctly identify the parathyroid glands is mandatory for a better outcome. Elastography can be an effective tool in the diagnosis of parathyroid lesions, by differentiating possible parathyroid lesions from thyroid disease, cervical lymph nodes, and other anatomical structures. There are currently no guidelines or recommendations and no established values on the elasticity of parathyroid lesions. (2) Material and Methods: In our studies, we have evaluated, by Shear Wave elastography (SWE), both primary and secondary hyperparathyroidism, determining that parathyroid glands have a higher elasticity index than both thyroid tissue and muscle tissue. (3) Results: For primary hyperparathyroidism, we have determined, using 2D-SWE, the parathyroid adenoma tissue (mean elasticity index (EI) measured by SWE 4.74 ± 2.74 kPa) with the thyroid tissue (11.718 ± 4.206 kPa) and with the surrounding muscle tissue (16.362 ± 3.829 kPa). For secondary hyperparathyroidism, by SWE elastographic evaluation, we have found that the mean EI in the parathyroid gland was 7.83 kPa, a median value in the thyroid parenchyma of 13.76 kPa, and a mean muscle EI value at 15.78 kPa. (4) Conclusions: Elastography can be a useful tool in localizing parathyroid disease, whether primary or secondary, by correctly identifying the parathyroid tissue. We have determined that an EI below 7 kPa in SWE elastography correctly identifies parathyroid tissue in primary hyperparathyroidism, and that a cut-off value of 9.98 kPa can be used in 2D-SWE to accurately diagnose parathyroid disease in secondary hyperparathyroidism.

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Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease

Kidney International ◽

10.1038/ki.2009.464 ◽

2010 ◽

Vol 77 (3) ◽

pp. 211-218 ◽

Cited By ~ 156

Author(s):

H. Galitzer ◽

I.Z. Ben-Dov ◽

Justin Silver ◽

Tally Naveh-Many

Keyword(s):

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Parathyroid Cell ◽

Fibroblast Growth ◽

Cell Resistance

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Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Scientific Reports ◽

10.1038/srep40534 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 23

Author(s):

Kazuki Kawakami ◽

Ai Takeshita ◽

Kenryo Furushima ◽

Masayasu Miyajima ◽

Ikuji Hatamura ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Parathyroid Glands ◽

Fibroblast Growth

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The In Vitro Effect of Calcitriol on Parathyroid Cell Proliferation and Apoptosis

Journal of the American Society of Nephrology ◽

10.1681/asn.v11101865 ◽

2000 ◽

Vol 11 (10) ◽

pp. 1865-1872

Author(s):

ANTONIO CANALEJO ◽

YOLANDA ALMADÉN ◽

VICENTE TORREGROSA ◽

JOSE C. GOMEZ-VILLAMANDOS ◽

BLANCA RAMOS ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Secondary Hyperparathyroidism ◽

Parathyroid Gland ◽

Parathyroid Glands ◽

Parathyroid Cell ◽

Proliferation And Apoptosis ◽

High Concentrations ◽

Dose Dependent

Abstract. Calcitriol treatment is used to reduce parathyroid hormone levels in azotemic patients with secondary hyperparathyroidism (HPT). Whether long-term calcitriol administration reduces parathyroid gland size in patients with severe secondary hyperparathyroidism is not clear. The aim of the study was to evaluate in vitro the effect of calcitriol on parathyroid cell proliferation and apoptosis in normal parathyroid glands and in adenomatous and hyperplastic human parathyroid glands. Freshly harvested parathyroid glands from normal dogs and hyperplastic and adenomatous glands from patients with secondary (2°) and primary (1°) HPT undergoing parathyroidectomy were studied. Flow cytometry was used to quantify the cell cycle and apoptosis of parathyroid cells. Apoptosis was also evaluated by DNA electrophoresis and light and electron microscopy. In normal dog parathyroid glands, culture with calcitriol (10-10 to 10-7 M) for 24 h produced a dose-dependent inhibitory effect on the progression of cells into the cell cycle and into apoptosis. When glands from patients with 2°HPT were cultured for 24 h, only high calcitriol concentrations (10-7 M) inhibited the progression through the cell cycle and the induction of apoptosis. In parathyroid adenomas (1°HPT), even a high concentration of calcitriol (10-7 M) had no significant effect on the cell cycle or apoptosis. The present study shows that in vitro, calcitriol inhibits in a dose-dependent manner in normal parathyroid glands both parathyroid cell proliferation and apoptosis. However, in secondary hyperplasia, only high concentrations of calcitriol inhibited cell proliferation and apoptosis. In 1°HPT, even high concentrations of calcitriol had no effect. Because calcitriol simultaneously inhibits both cell proliferation and apoptosis, a reduction in the parathyroid gland mass may not occur as a direct effect of calcitriol treatment.

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Differential Expression of Fibroblast Growth Factor Family Members in a Progestin-Dependent BT-474 Human Breast Cancer Cell Xenograft Model.

10.1210/endo-meetings.2010.part2.p2.p2-54 ◽

2010 ◽

pp. P2-54-P2-54

Author(s):

FR Lopez ◽

C Besch-Williford ◽

Y Liang ◽

SM Hyder

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Differential Expression ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Human Breast Cancer ◽

Xenograft Model ◽

Human Breast Cancer Cell ◽

Fibroblast Growth

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SURGICAL ANATOMY OF PARATHYROID GLANDS IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM

HERALD of North-Western State Medical University named after I I Mechnikov ◽

10.17816/mechnikov20157323-28 ◽

2015 ◽

Vol 7 (3) ◽

pp. 23-28 ◽

Cited By ~ 1

Author(s):

K Yu Novokshonov ◽

Y N Fedotov ◽

V Y Karelin ◽

T S Pridvizhkin ◽

R A Chernikov ◽

...

Keyword(s):

Secondary Hyperparathyroidism ◽

Surgical Anatomy ◽

Parathyroid Glands ◽

Total Parathyroidectomy ◽

Thyroid Lobe ◽

Subtotal Parathyroidectomy ◽

Carotid Sheath ◽

Treat Ment ◽

Gland Tissue ◽

Surgical Failure

Ectopic or supernumerary parathyroid glands (PTg) can be the reason of surgical failure in treat- ment of secondary hyperparathyroidism in patients, who underwent dialysis. The aim of this study is to estimate the number and localization of PTgs in patients with secondary hyperparathyroidism. We included 165 patients, who underwent total parathyroidectomy with heterotopic autotransplantation of parathyroid gland tissue or subtotal parathyroidectomy. All identified PTgs were separated in two groups: eutopic and ectopic. Preoperative localization was performed by multispiral computed tomog- raphy of neck and mediastinum, neck ultrasonography, two-isotope Tc99 MIBI of PTgs. In postopera- tive period, we estimated the level of parathyroid hormone in the serum and performed morphological verification. There were found 659 PTgs. 12 (7,2%) patients had 3 parathyroid glands, and 11 (6.7%)had 5 PTgs. 4 Ptgs were found in 142 (86,1%) patients. 520 (78,9%) PTgs were eutopic, 139 (21,1%) - ectopic. The most common ectopic place for upper PTgs were paraesophageal and retrotracheal spaces, carotid sheath. Ectopic lower PTgs were most commonly located in the horns of the thymus. All super- numerary PTg were ectopic and often located in area between lower pole of the thyroid lobe and the thymus.Conclusion. During the operation in case when ectopy is suspected, upper PTgs should be located in in paraesophageal and paratracheal areas or in carotid sheath, if it necessary. If lower PTgs is absence, surgery should be completed cervical thymectomy.

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Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions

Acta Endocrinologica ◽

10.1530/eje.0.1480081 ◽

2003 ◽

pp. 81-87 ◽

Cited By ~ 9

Author(s):

GE Thomopoulou ◽

S Tseleni-Balafouta ◽

AC Lazaris ◽

H Koutselini ◽

N Kavantzas ◽

...

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Cell Cycle Control ◽

Parathyroid Glands ◽

Considerable Proportion ◽

Parathyroid Cell ◽

Apoptotic Cells ◽

Cell Cycle Regulators ◽

Suppressor Activity ◽

Fhit Protein

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

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Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism

Acta Endocrinologica ◽

10.1530/eje.1.02007 ◽

2005 ◽

Vol 153 (4) ◽

pp. 587-594 ◽

Cited By ~ 28

Author(s):

Takehisa Kawata ◽

Yasuo Imanishi ◽

Keisuke Kobayashi ◽

Takao Kenko ◽

Michihito Wada ◽

...

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Secondary Hyperparathyroidism ◽

Murine Model ◽

Hormone Secretion ◽

Suppressive Effect ◽

Receptor Expression ◽

Parathyroid Glands ◽

Calcium Sensing Receptor ◽

Calcium Sensing

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

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