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Sisli Etfal Hastanesi Tip Bulteni 2019Primary hyperparathyroidism (pHPT) is the third most frequently seen endocrine disease and it is the most common cause of hypercalcemia seen in ambulatory patients. PHPT... (Review)
Review
Primary hyperparathyroidism (pHPT) is the third most frequently seen endocrine disease and it is the most common cause of hypercalcemia seen in ambulatory patients. PHPT is most often (80%-85%) caused by a single parathyroid adenoma, followed by double adenoma (4%-5%), multiple gland hyperplasia (10%-15%), and parathyroid carcinoma (<1%). The diagnosis of pHPT is biochemically established and the only curative treatment is surgery. Since the cause of pHPT is typically single-gland disease, it is possible to determine the majority of pathological glands with preoperative localization methods and use the minimally invasive parathyroidectomy (MIP) approach. MIP has become the standard treatment for pHPT in selected patients. There are both noninvasive and invasive preoperative localization methods. Noninvasive methods currently used include ultrasonography (US), parathyroid scintigraphy, 4-dimensional computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT with 18F-fluoroquinolone and 11C-methionine. Preoperative invasive localization methods include parathyroid hormone (PTH) measurement with fine-needle aspiration biopsy, lateralization with PTH measurement via bilateral jugular vein sampling, selective venous sampling, and parathyroid arteriography. The aim of this study was to evaluate preoperative localization studies used in cases of pHPT.
PubMed: 33536819
DOI: 10.14744/SEMB.2019.78476 -
Best Practice & Research. Clinical... Dec 2018Parathyroid tumors represent an elusive endocrine neoplasia, which lead to primary hyperparathyroidism, pHPT, a common endocrine calcium disorder characterized by... (Review)
Review
Parathyroid tumors represent an elusive endocrine neoplasia, which lead to primary hyperparathyroidism, pHPT, a common endocrine calcium disorder characterized by hypercalcemia and normal-high parathormone secretion. Parathyroid tumours are benign adenomas or multiple glands hyperplasia in the vast majority (>99% of cases), while malignant neoplasms are rare (less than 1%). Despite pHPT is a common disorder, our knowledge about the genetic predisposition and molecular pathophysiology is limited to the familial syndromic forms of parathyroid tumour, that, however, represent not more than the 10% of all the cases; instead, the pathophysiology of sporadic forms remains an open field, although data about epigenetic mechanisms or private genes have been supposed. Here we present an overview of more recent acquisitions about the genetic causes along with their molecular mechanisms of benign, but also, malignant parathyroid tumours either in sporadic and familial presentation.
Topics: Adenoma; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroid Neoplasms
PubMed: 30477753
DOI: 10.1016/j.beem.2018.11.001 -
Molecular and Cellular Endocrinology Jul 2018Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism, a metabolic disorder characterized by parathormone hypersecretion.... (Review)
Review
Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism, a metabolic disorder characterized by parathormone hypersecretion. Parathyroid neoplasia are frequently benign adenomas or multiple glands hyperplasia, while malignancies are rare. The epigenetic scenario in parathyroid tumors has just begun to be decoded: DNA methylation, histones and chromatin modifiers expression have been investigated so far. The main findings suggest that DNA methylation and chromatin remodeling are active and deregulated in parathyroid tumors, cooperating with genetic alterations to drive the tumor phenotype: the tumor suppressors menin and parafibromin, involved in parathyroid tumorigenesis, interact with chromatin modifiers, defining distinct epigenetic derangements. Many epigenetic alterations identified in parathyroid tumors are common to those in human cancers; moreover, some aspects of the epigenetic profile resemble epigenetic features of embryonic stem cells. Epigenetic profile may contribute to define the heterogeneity of parathyroid tumors and to provide targets for new therapeutic approaches.
Topics: Animals; DNA Methylation; Histones; Humans; Parathyroid Neoplasms; Promoter Regions, Genetic; Protein Processing, Post-Translational
PubMed: 28501573
DOI: 10.1016/j.mce.2017.05.010 -
Therapeutic Apheresis and Dialysis :... Feb 2018The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of... (Review)
Review
The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of calcium and vitamin D, to arrest or reverse the parathyroid hyperplasia. However, when nodular hyperplasia or an autonomous adenoma develops, surgery may be indicated. We reviewed the literature with the aim of defining if the echographic criteria predictive of unresponsiveness of SHPT to calcitriol therapy are valid also in the cinacalcet era and if drug therapy may reverse nodular hyperplasia of parathyroid gland (PTG). The responsiveness to therapy and regression of the nodular hyperplasia of PTG remains an open question in the calcimimetic era as well as the cutoff between medical and surgical therapy. Prospective studies are needed in order to clarify if an earlier use of cinacalcet in moderate SHPT might arrest the progression of parathyroid growth and stabilize SHPT.
Topics: Calcimimetic Agents; Calcitriol; Calcium Channel Agonists; Cinacalcet; Humans; Hyperparathyroidism, Secondary; Hyperplasia; Parathyroid Glands; Treatment Outcome
PubMed: 28980761
DOI: 10.1111/1744-9987.12604 -
Annales D'endocrinologie Aug 2022Parathyroid hormone (PTH) is a hypercalcemic hormone acting on kidneys, bone and intestine. PTH promotes calcium release from the bone, renal calcium reabsorption and... (Review)
Review
Parathyroid hormone (PTH) is a hypercalcemic hormone acting on kidneys, bone and intestine. PTH promotes calcium release from the bone, renal calcium reabsorption and phosphate excretion, and conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D-3. Hyperparathyroidism consists in PTH elevation, which may be adapted (secondary hyperparathyroidism) or non-adapted to calcemia levels (primary hyperparathyroidism, familial hypercalcemia/hypocalciuria, tertiary hyperparathyroidism). Primary hyperparathyroidism (PHP) features hypercalcemia and elevated or inappropriate PTH elevation. PHP may be revealed by biological abnormalities such as hypercalcemia and can be accompanied by renal complications (hypercalciuria, nephrolithiasis, nephrocalcinosis) and/or osteoporosis. However, it can also be normocalcemic and calcium loading will be necessary to diagnosis it. The differential diagnosis of PHP is familial hypocalciuric hypercalcemia (FHH), a dominant autosomal disease implicating a calcium sensing receptor-inactivating mutation. It impairs parathyroid cell sensitivity to calcemia elevation and thus induces excessive PTH stimulation, leading to hypercalcemia. Secondary HP (SHP) consists in PTH elevation secondary to a stimulus that needs to be corrected. 25 OHvitD deficiency, kidney failure, renal hypercalciuria, malabsorption and some drugs can induce SHP. Tertiary HP (THP) consists in autonomous PTH secretion by the parathyroid glands after prolonged stimulation under SHP, of whatever cause. This parathyroid autonomy results from the polyclonal hyperplasia observed in SHP progressing toward monoclonal nodular proliferation, leading to nodular hyperplasia or parathyroid adenoma (or, exceptionally, carcinoma), with reduced expression of CaSR and vitamin D receptor. In patients under dialysis, the frontier between SHP and THP is a matter of debate. This review will focus on the pathophysiology of calcium, diagnosis, and management of hyperparathyroidism.
Topics: Bone Density Conservation Agents; Calcium; Homeostasis; Humans; Hypercalcemia; Hypercalciuria; Hyperparathyroidism, Primary; Hyperplasia; Parathyroid Hormone; Receptors, Calcium-Sensing
PubMed: 35598638
DOI: 10.1016/j.ando.2022.05.003 -
Nuclear Medicine and Biology 2021Parathyroid hyperplasia is a disease characterized by overactive parathyroid glands secreting increased levels of parathyroid hormone. Surgical removal of the...
INTRODUCTION
Parathyroid hyperplasia is a disease characterized by overactive parathyroid glands secreting increased levels of parathyroid hormone. Surgical removal of the parathyroid glands is the standard treatment but requires precise pre-operative localization of the glands. However, currently available imaging modalities show limited sensitivity. Since positron emission tomography (PET) is a molecular imaging technique with high accuracy and sensitivity, our aim was to develop a new PET tracer for overactive parathyroid glands imaging by radiolabelling cinacalcet, a drug binding to the calcium-sensing receptor of the parathyroid glands.
METHODS
[F]Cinacalcet was synthesized by copper-catalysed [F]trifluoromethylation of a boronic acid precursor using high molar activity [F]fluoroform. Ex vivo biodistribution and metabolism were evaluated in 12 healthy male Wistar rats at 5, 15, 45 and 90 min. PET scans were performed at baseline and after blocking with NPS R-568.
RESULTS
[F]Cinacalcet was obtained in an overall radiosynthesis time of 1 h with a radiochemical purity of 98 ± 1%, a radiochemical yield of 8 ± 4% (overall, n = 7, corrected for decay) and a molar activity of 40 ± 11 GBq/μmol (n = 7, at EOS). The ex vivo biodistribution showed uptake in the thyroid and parathyroid glands as well as in other glands such as adrenals, salivary glands and pancreas. The tracer was rapidly cleared from the blood via liver and kidneys and showed fast metabolism. PET images confirmed uptake in the target organ. However, in a blocking study with NPS R-568 specific binding of [F]cinacalcet to the CaSR could not be confirmed.
CONCLUSIONS
[F]Cinacalcet was successfully synthesized. First in vivo experiments in healthy rats showed uptake of the tracer in the target organ and fast metabolism, encouraging further in vivo evaluation of this tracer.
Topics: Cinacalcet
PubMed: 34743064
DOI: 10.1016/j.nucmedbio.2021.10.003 -
Journal of Investigative Surgery : the... Aug 2018Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD),...
Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis.
Topics: Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Humans; Hyperparathyroidism, Primary; Hyperplasia; Parathyroid Glands; Parathyroid Neoplasms
PubMed: 28362510
DOI: 10.1080/08941939.2017.1303101 -
Metabolites Jan 2022Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that induces morbidity and mortality in patients. How CKD stimulates the... (Review)
Review
Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that induces morbidity and mortality in patients. How CKD stimulates the parathyroid to increase parathyroid hormone (PTH) secretion, gene expression and cell proliferation remains an open question. In experimental SHP, the increased gene expression is post-transcriptional and mediated by PTH mRNA-protein interactions that promote PTH mRNA stability. These interactions are orchestrated by the isomerase Pin1. Pin1 participates in conformational change-based regulation of target proteins, including mRNA-binding proteins. In SHP, Pin1 isomerase activity is decreased, and thus, the Pin1 target and PTH mRNA destabilizing protein KSRP fails to bind PTH mRNA, increasing PTH mRNA stability and levels. An additional level of post-transcriptional regulation is mediated by microRNA (miRNA). Mice with parathyroid-specific knockout of Dicer, which facilitates the final step in miRNA maturation, lack parathyroid miRNAs but have normal PTH and calcium levels. Surprisingly, these mice fail to increase serum PTH in response to hypocalcemia or uremia, indicating a role for miRNAs in parathyroid stimulation. SHP often leads to parathyroid hyperplasia. Reduced expressions of parathyroid regulating receptors, activation of transforming growth factor α-epidermal growth factor receptor, cyclooxygenase 2-prostaglandin E2 and mTOR signaling all contribute to the enhanced parathyroid cell proliferation. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. This review summarizes the current knowledge on the mechanisms that stimulate the parathyroid cell at multiple levels in SHP.
PubMed: 35208186
DOI: 10.3390/metabo12020111 -
Frontiers in Pharmacology 2022A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary... (Review)
Review
A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.
PubMed: 36267284
DOI: 10.3389/fphar.2022.1020858 -
Frontiers in Nephrology 2022Altered parathyroid gland biology is a major driver of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients with chronic kidney disease. CKD-MBD is... (Review)
Review
Altered parathyroid gland biology is a major driver of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients with chronic kidney disease. CKD-MBD is associated with a high risk of vascular calcification and cardiovascular events. A hallmark of CKD-MBD is secondary hyperparathyroidism with increased parathyroid hormone (PTH) synthesis and release and reduced expression of calcium-sensing receptors on the surface of parathyroid cells and eventually hyperplasia of parathyroid gland cells. The KDIGO guidelines strongly recommend the control of PTH in hemodialysis patients. Due to the complexity of parathyroid gland biology, mathematical models have been employed to study the interaction of PTH regulators and PTH plasma concentrations. Here, we present an overview of various model approaches and discuss the impact of different model structures and complexities on the clinical use of these models.
PubMed: 37674998
DOI: 10.3389/fneph.2022.893391