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Nuclear Medicine Review. Central &... 2019Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between...
BACKGROUND
Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between 99mTc MIBI accumulation and oxyphil cell content or parathyroid gland volume. The aim of our work was to assess the relationship between the pathological structure of parathyroids, their volume, oxyphil cell content and parathyroid 99mTc-MIBI retention.
MATERIAL AND METHODS
A total of 62 hyperfunctioning parathyroid glands in 46 patients were retrospectively analyzed. Preoperative 99mTc-MIBI scintigraphy was performed according to the double-phase and subtraction protocol. After surgery all glands were evaluated histologically, oxyphil cell content was assessed and volume of each excised gland was calculated.
RESULTS
Scintigraphy was positive in 41 of 62 parathyroid glands (66%). The median volume of positive glands was larger than that of negative glands (1.33 ml vs 0.7 ml, p = 0.015). Of the parathyroid lesions, there were 14 (22.6%) cases of nodular hyperplasia, 23 (37.1%) cases of diffuse hyperplasia, and 25 (40.3%) cases of adenomas. A high (≥ 25%) oxyphil cell content was found in 16 glands (25.8%) and a low ( < 25%) oxyphil cell content in 46 (74.2%) glands. Histopathology of parathyroid glands was related to the scintigraphy result (p = 0.002), but not to the 99mTc-MIBI uptake pattern (p = 0.868). The overall result of scintigraphy was not related to the oxyphil cell content (p = 0.797). 99mTc-MIBI uptake pattern wasn't related to the oxyphil cell content (p = 0.833). In general, parathyroid lesions with low oxyphil cell content were larger than parathyroid glands with high oxyphil cell content (1.33 ml vs 0.5 ml, respectively; p = 0.01). The median volume of parathyroids containing a high number of oxyphil cells and having a prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.62 ml vs 0.3 ml, respectively; p = 0.008). The median volume of parathyroids with low oxyphil cells content and showing prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.95 ml vs 1.07 ml, respectively; p = 0.014).
CONCLUSIONS
Our findings suggest that a positive scintigraphy result depends on parathyroid histopathology and gland volume and does not depend on the presence of oxyphil cells. Prolonged 99mTc-retention is not related to the parathyroid gland histopathology and the presence of oxyphil cells but to the gland volume.
Topics: Female; Humans; Male; Middle Aged; Organ Size; Oxyphil Cells; Parathyroid Glands; Radionuclide Imaging; Retrospective Studies; Technetium Tc 99m Sestamibi
PubMed: 31482540
DOI: 10.5603/NMR.2019.0005 -
PeerJ 2023Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify...
OBJECTIVE
Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify potential biomarkers that may be used to predict the progression of SHPT and to elucidate the molecular mechanisms of SHPT pathogenesis at the transcriptome level.
METHODS
We analyzed differentially expressed genes (DEGs) between diffuse and nodular parathyroid hyperplasia of SHPT patients from the GSE75886 dataset, and then verified DEG levels with the GSE83421 data file of primary hyperparathyroidism (PHPT) patients. Candidate gene sets were selected by machine learning screens of differential genes and immune cell infiltration was explored with the CIBERSORT algorithm. RcisTarget was used to predict transcription factors, and Cytoscape was used to construct a lncRNA-miRNA-mRNA network to identify possible molecular mechanisms. Immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the expression of screened genes in parathyroid tissues of SHPT patients and animal models.
RESULTS
A total of 614 DEGs in GSE75886 were obtained as candidate gene sets for further analysis. Five key genes (USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2) had significant expression differences between groups and were screened with the best ranking in the machine learning process. These genes were shown to be closely related to immune cell infiltration levels and play important roles in the immune microenvironment. Transcription factor ZBTB6 was identified as the master regulator, alongside multiple other transcription factors. Combined with qPCR and IHC assay of hyperplastic parathyroid tissues from SHPT patients and rats confirm differential expression of USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2, suggesting that they may play important roles in the proliferation and progression of SHPT.
CONCLUSION
USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2 have great potential both as biomarkers and as therapeutic targets in the proliferation of SHPT. These findings suggest novel potential targets and future directions for SHPT research.
Topics: Animals; Rats; Biomarkers; Cell Proliferation; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Hyperplasia; Parathyroid Glands; Humans
PubMed: 37456892
DOI: 10.7717/peerj.15633 -
Postepy Higieny I Medycyny... Nov 2010The sensitivity of parathyroid glands to a low calcium level in plasma results in parathyroid hormone (PTH) release in order to restore the normal Ca²+ concentration.... (Review)
Review
The sensitivity of parathyroid glands to a low calcium level in plasma results in parathyroid hormone (PTH) release in order to restore the normal Ca²+ concentration. Hyperparathyroidism is a common endocrinopathy, caused by uncontrolled growth of parathyroid cells. In primary hyperparathyroidism, hypercalcemia develops due to extensive autonomous secretion of PTH. Secondary hyperparathyroidism is a well-established complication of chronic renal insufficiency, where marked parathyroid hyperplasia occurs, especially in patients with long dialysis vintage. The elevated PTH level in the circulation is a direct result of renal function disturbances, vitamin D deficiency, and impaired calcium/phosphate metabolism. After successful kidney transplantation, the normalization of kidney function fails to normalize the secretion of PTH by parathyroid glands, which have become relatively autonomous and unresponsive to hypercalcemic conditions in the plasma. The development of tertiary hyperparathyroidism occurs in these conditions. The aim of our report is to present current views on the clinical, pathological and biochemical features of primary, secondary and tertiary hyperparathyroidism. The diagnostics of calcium/phosphate abnormalities in parathyroid gland disorders, as well as some aspects of hyperparathyroidism treatment, are briefly summarized.
Topics: Humans; Hypercalcemia; Hyperparathyroidism; Hyperphosphatemia
PubMed: 21109708
DOI: No ID Found -
American Journal of Physiology. Renal... Jun 2004The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate... (Review)
Review
The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range. Much has been learned in recent years about the diversity of signal transduction through the CaSR and the various factors that affect receptor expression. Beyond its classic role as a determinant of calcium-regulated PTH secretion, signaling through the CaSR also influences both gene transcription and cell proliferation in parathyroid cells. The CaSR thus serves a broad physiological role by integrating several distinct aspects of parathyroid gland function. The current review summarizes recent developments that enhance our understanding of the CaSR and its fundamental importance in parathyroid gland physiology.
Topics: Animals; Cell Cycle; Gene Expression Regulation; Humans; Hyperplasia; Parathyroid Glands; Parathyroid Hormone; Receptors, Calcium-Sensing; Signal Transduction
PubMed: 15130894
DOI: 10.1152/ajprenal.00013.2004 -
The Israel Medical Association Journal... Dec 2017Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used "gold...
BACKGROUND
Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used "gold standard" tests.
OBJECTIVES
To validate the accuracy of intraoperative measurements of parathyroid hormone levels in parathyroid adenomas.
METHODS
A prospective study included 22 patients diagnosed with primary hyperparathyroidism who underwent parathyroidectomy due to an adenoma or hyperplasia. Aspirations of tissues extracted from three adjacent areas (the pathological parathyroid, thyroid, and muscle tissues) were sent for rapid parathyroid hormone analysis. The assay values of these tissue aspirates were compared to the results of the pathology report based on frozen section analysis and the final pathology report.
RESULTS
All assay results were significantly higher for parathyroid tissue 16,800 to 1,097,986 pmol/L (median 26,600), than for either thyroid 1.7 to 415 pmol/L (median 6.5), P < 0.001, or muscle tissue 1.1 to 1230 pmol/L, (median 11.3), P < 0.001. All tissues showing high parathyroid assay values were also verified by pathology examinations: 7 had adenomas and 15 had a differential diagnosis of adenoma or hyperplasia. The frozen section identified all but one (false negative). Rapid intraoperative parathyroid levels > 1500 predicted parathyroid tissue with a 99% level of confidence, while levels between 1000 and 1500 predicted it with 95% confidence. The intraoperative parathyroid hormone assay showed > 70% decrease in 15/21 cases.
CONCLUSIONS
Rapid intraoperative parathyroid hormone analysis is a reliable and precise technique, equally accurate for frozen section analysis in predicting with high certainty intraoperative parathyroid tissue.
Topics: Biopsy, Needle; Clinical Chemistry Tests; Diagnosis, Differential; Female; Frozen Sections; Humans; Hyperparathyroidism, Primary; Hyperplasia; Intraoperative Care; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy; Predictive Value of Tests; Reproducibility of Results
PubMed: 29235733
DOI: No ID Found -
PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development.Breast Cancer Research : BCR Apr 2022Parathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar...
BACKGROUND
Parathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar epithelial cells and secreted into the maternal circulation to mobilize skeletal calcium used for milk production. PTHrP is also produced by breast cancers, and GWAS studies suggest that it influences breast cancer risk. However, the exact functions of PTHrP in breast cancer biology remain unsettled.
METHODS
We developed a tetracycline-regulated, MMTV (mouse mammary tumor virus)-driven model of PTHrP overexpression in mammary epithelial cells (Tet-PTHrP mice) and bred these mice with the MMTV-PyMT (polyoma middle tumor-antigen) breast cancer model to analyze the impact of PTHrP overexpression on normal mammary gland biology and in breast cancer progression.
RESULTS
Overexpression of PTHrP in luminal epithelial cells caused alveolar hyperplasia and secretory differentiation of the mammary epithelium with milk production. This was accompanied by activation of Stat5 and increased expression of E74-like factor-5 (Elf5) as well as a delay in post-lactation involution. In MMTV-PyMT mice, overexpression of PTHrP (Tet-PTHrP;PyMT mice) shortened tumor latency and accelerated tumor growth, ultimately reducing overall survival. Tumors overproducing PTHrP also displayed increased expression of nuclear pSTAT5 and Elf5, increased expression of markers of secretory differentiation and milk constituents, and histologically resembled secretory carcinomas of the breast. Overexpression of PTHrP within cells isolated from tumors, but not PTHrP exogenously added to cell culture media, led to activation of STAT5 and milk protein gene expression. In addition, neither ablating the Type 1 PTH/PTHrP receptor (PTH1R) in epithelial cells nor treating Tet-PTHrP;PyMT mice with an anti-PTH1R antibody prevented secretory differentiation or altered tumor latency. These data suggest that PTHrP acts in a cell-autonomous, intracrine manner. Finally, expression of PTHrP in human breast cancers is associated with expression of genes involved in milk production and STAT5 signaling.
CONCLUSIONS
Our study suggests that PTHrP promotes pathways leading to secretory differentiation and proliferation in both normal mammary epithelial cells and in breast tumor cells.
Topics: Animals; Breast Neoplasms; Female; Humans; Lactation; Mammary Glands, Animal; Mammary Neoplasms, Animal; Mice; Parathyroid Hormone-Related Protein; STAT5 Transcription Factor
PubMed: 35440032
DOI: 10.1186/s13058-022-01523-1 -
Medicine Nov 2022Secondary parathyroid hyperplasia canceration is very rare and thus easily be overlooked during parathyroid ultrasound examination. However, secondary parathyroid...
INTRODUCTION
Secondary parathyroid hyperplasia canceration is very rare and thus easily be overlooked during parathyroid ultrasound examination. However, secondary parathyroid hyperplasia still has the possibility of canceration, and it is still important to be alert to its occurrence when performing ultrasound examinations and clinical treatment.
PATIENT CONCERNS
A 49-years-old man visited our outpatient department with generalized weakness and pain in both lower extremities a month ago.
DIAGNOSIS
Hyperparathyroidism secondary to chronic renal failure.
INTERVENTIONS
The patient underwent ultrasound and other preoperative examinations. The preoperative ultrasound showed 3 parathyroid enlargements, 2 on the left and 1 on the right. The patient then underwent surgical treatment.
OUTCOMES
Ultrasonography suggested the presence of 3 parathyroid hyperplasias, and ectopic right inferior parathyroid gland was visible during intraoperative examination. 10 days after surgery, the patient's Parathyroid Hormone returned to the normal range.
CONCLUSION
Secondary parathyroid hyperplasia has the potential to become cancerous, so doctors should be alert to its occurrence when conducting ultrasound examinations. Ultrasound examination is the key to its diagnosis and subsequent treatment.
Topics: Humans; Male; Middle Aged; Hyperplasia; Parathyroid Neoplasms; Parathyroid Glands; Hyperparathyroidism, Primary; Carcinoma
PubMed: 36401397
DOI: 10.1097/MD.0000000000031362 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Apr 2021The prevalence of asymptomatic primary hyperparathyroidism (PHPT) in China is lower than that in European and American countries and the study about the characteristics...
OBJECTIVES
The prevalence of asymptomatic primary hyperparathyroidism (PHPT) in China is lower than that in European and American countries and the study about the characteristics of asymptomatic PHPT was rare in China. This study aims to explore the characteristics of asymptomatic PHPT.
METHODS
Clinical data of 150 patients with PHPT confirmed by operation and pathological examination were retrospectively analyzed. The patients were assigned into a symptomatic PHPT group (=124) and an asymptomatic PHPT group (=26).
RESULTS
The proportion of adenomas was higher than that of adenocarcinoma in the asymptomatic PHPT group. The proportion of the first diagnosis due to hypercalcemia found via biochemical examination in the asymptomatic PHPT group was higher than that in the symptomatic PHPT group (76.92% vs 25.81%, <0.001). The duration was shorter in the asymptomatic PHPT patients than that in the symptomatic PHPT patients (median 12 months vs 24 months, =0.004). The serum calcium, the albumin-corrected serum calcium, and parathyroid hormone (PTH) were lower in the asymptomatic PHPT patients than those in the symptomatic PHPT (=0.003, =0.006, and =0.042, respectively). The serum 1,25-dihydroxyvitamin D was higher (<0.001), the diameter was shorter (=0.028), and the bone mineral densities (BMD) of L and femoral neck were higher in the asymptomatic PHPT patients than those in the symptomatic PHPT patients (both <0.001).
CONCLUSIONS
Only a minority of PHPT patients are asymptomatic. Compared with the symptomatic PHPT patients, the primary cause of diagnosis is hypercalcemia, the duration of diagnosis and the diameter of parathyroid gland are shorter, the levels of serum calcium, and PTH are lower, the proportion of adenomas, vitamin D, and the BMD of L and femoral neck are higher, and the pathological type is benign in the asymptomatic PHPT patients.
Topics: Calcium; China; Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Hormone; Retrospective Studies
PubMed: 33967082
DOI: 10.11817/j.issn.1672-7347.2021.200356 -
Current Gastroenterology Reports Dec 2012Proton pump inhibitors (PPIs) have been widely used since their introduction in the late 1980s because they are highly effective for acid-related conditions. However,... (Review)
Review
Proton pump inhibitors (PPIs) have been widely used since their introduction in the late 1980s because they are highly effective for acid-related conditions. However, some recent epidemiological studies have suggested a positive association between PPI therapy and the risk of osteoporotic fractures. The potential mechanisms underlying this association may be related to the physiologic effects of chronic acid suppression on calcium metabolism. First, chronic hypergastrinemia induced by PPI therapy may lead to parathyroid hyperplasia, resulting in increased loss of calcium from the bone. Second, profound gastric acid suppression may reduce the bioavailability of calcium for intestinal absorption. I will review the published evidence regarding these potential links and discuss their clinical implications.
Topics: Bone and Bones; Calcium; Humans; Hyperparathyroidism; Osteoporotic Fractures; Parathyroid Glands; Proton Pump Inhibitors
PubMed: 23054811
DOI: 10.1007/s11894-012-0290-4 -
Telocytes/CD34+ Stromal Cells in the Normal, Hyperplastic, and Adenomatous Human Parathyroid Glands.International Journal of Molecular... Jul 2023Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not...
Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not been explored. Using immunological and ultrastructural procedures, we assess the location, arrangement, and behavior of TCs/CD34+ SCs in normal human parathyroids, during their development and in their most frequent pathologic conditions. In normal parathyroids, TCs/CD34+ SCs show a small somatic body and long thin processes with a moniliform aspect, form labyrinthine systems, connect other neighboring TCs/CD34+ SCs, vessels, adipocytes, and parenchymal cells directly or by extracellular vesicles, and associate with collagen I. TCs/CD34+ SCs and collagen I are absent around vessels and adipocytes within parenchymal clusters. In developing parathyroids, TCs/CD34+ SC surround small parenchymal nests and adipocytes. In hyperplastic parathyroids, TCs/CD34+ SCs are prominent in some thickened internodular septa and surround small extraglandular parenchymal cell nests. TCs/CD34+ SCs are present in delimiting regions with compressed parathyroids and their capsule in adenomas but absent in most adenomatous tissue. In conclusion, TCs/CD34+ SCs are an important cellular component in the human parathyroid stroma, except around vessels within parenchymal nests. They show typical characteristics, including those of connecting cells, are present in developing parathyroids, and participate in the most frequent parathyroid pathology, including hyperplastic and adenomatous parathyroids.
Topics: Humans; Parathyroid Glands; Stromal Cells; Telocytes; Antigens, CD34; Parathyroid Neoplasms; Hyperplasia; Cell Adhesion Molecules; Adenoma; Collagen
PubMed: 37569493
DOI: 10.3390/ijms241512118