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Frontiers in Bioscience (Landmark... Aug 2023Parathyroid hormone (PTH) is an endocrine peptide found exclusively in the parathyroid glands, whereas parathyroid hormone-related protein (PTHrP) is expressed in a wide... (Review)
Review
Parathyroid hormone (PTH) is an endocrine peptide found exclusively in the parathyroid glands, whereas parathyroid hormone-related protein (PTHrP) is expressed in a wide range of tissues and organs and exerts endocrine, paracrine, and autocrine actions. PTH and PTHrP have a similar homology, sharing the initial 13 amino acid residues at the N-terminus and binding to the same type 1 PTH receptor (PTH1R), which regulates calcium homeostasis. An abnormal increase in PTH production can occur in primary and secondary hyperparathyroidism, whereas PTHrP can be produced in large quantities by malignant cancer cells from solid organs. In addition to increased bone resorption and hypercalcemia, recent evidence suggests that excess PTH and PTHrP can result in protein-energy wasting, malnutrition, and cachexia. Through binding to PTH1R and activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A in white adipose tissue, PTH and PTHrP can stimulate the expression of thermogenic genes causing adipose tissue browning. This change results in an increase in resting energy expenditure, loss of muscle and fat mass, and weight loss. These findings provide a mechanistic link for the long-established relationship between hyperparathyroidism and myopathy, as well as cancer and cachexia. The purpose of this review is to provide a summary of the emerging evidence from both experimental and clinical studies on the role of PTH and PTHrP in protein-energy malnutrition.
Topics: Humans; Adipose Tissue; Cachexia; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Protein-Energy Malnutrition
PubMed: 37664938
DOI: 10.31083/j.fbl2808167 -
The Journal of Clinical Endocrinology... Nov 2023Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding...
CONTEXT
Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease.
OBJECTIVE
(1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss.
DESIGN
Retrospective study of patients with HPT-JT syndrome (genetically confirmed or affected first-degree relatives). Independent review of uterine tumor from 2 patients and staining for parafibromin on parathyroid tumors from 19 patients (13 adenomas, 6 carcinomas) was performed. RNA-sequencing was performed in 21 parathyroid samples (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas, and 7 sporadic carcinomas with wild-type CDC73).
RESULTS
We identified 68 patients from 29 kindreds with HPT-JT with median age at last follow-up of 39 [interquartile range, 29-53] years. A total of 55/68 (81%) developed primary hyperparathyroidism; 17/55 (31%) had parathyroid carcinoma. Twelve of 32 (38%) females developed uterine tumors. Of the 11 patients who had surgical resection for uterine tumors, 12/24 (50%) tumors were rare mixed epithelial mesenchymal polypoid lesions. Four of 68 patients (6%) developed solid kidney tumors; 3/4 had a CDC73 variant at p.M1 residue. Parafibromin staining of parathyroid tumors did not correlate with tumor histology or genotype. RNA-sequencing showed a significant association of HPT-JT-related parathyroid tumors with transmembrane receptor protein tyrosine kinase signaling pathway, mesodermal commitment pathway, and cell-cell adhesion.
CONCLUSIONS
Multiple, recurrent atypical adenomyomatous uterine polyps appear to be enriched in women with HPT-JT and appear characteristic of the disease. Patients with CDC73 variants at p.M1 residue appear predisposed to kidney tumors.
CLINICAL TRIAL NUMBER
NCT04969926.
Topics: Humans; Female; Adult; Middle Aged; Male; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Retrospective Studies; Jaw Neoplasms; Adenoma; Transcription Factors; Carcinoma; Uterine Neoplasms; Kidney Neoplasms; RNA
PubMed: 37339334
DOI: 10.1210/clinem/dgad368 -
Medicine Sep 2023The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing...
The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing the links between the various research components (authors, journals, institutions, countries) of the academic outputs, it was aimed to summarize the intellectual structure of PHPT, identify recent research trends, and determine the global productivity. Three thousand nine hundred fifty-four articles on PHPT published between 1980 and 2022 were pulled from the Web of Science database and analyzed using bibliometric approaches. Bibliometric network visualization maps were used to identify trending topics, citation analysis, and international collaborations. Spearman correlation coefficient was used for correlation analysis. The 3 most prolific authors are Bilezikian JP. (n = 87), Silverberg SJ. (n = 72) and Akerstrom G. (n = 57). The top 3 most productive institutions were Columbia University (n = 133), Udice French Research Universities (n = 127) and Uppsala University (n = 98). The top 3 most productive journals were Surgery (n = 216), Journal of Clinical Endocrinology and Metabolism (n = 201) and World Journal of Surgery (n = 148). The top 3 contributing countries to the PHPT literature were United States of America (n = 1062, 26.8%), Italy (346, 8.7%) and United Kingdom (274, 6.9%). The most studied topics from past to present are parathyroidectomy, hypercalcemia, parathyroid hormone/adenoma/glands, calcium/calcimimetics, scintigraphy/sestamibi, bone mineral density, ultrasound, vitamin D, osteoporosis, minimally invasive parathyroidectomy, brown tumor, nephrocalcinosis/nephrolithiasis, multiple endocrine neoplasia type 1, normocalcemia, pregnancy, imaging/preoperative imaging, parathyroid cancer/carcinoma, asymptomatic primary hyperparathyroidism, and cinacalcet. The trending topics in recent years were normocalcemic primary hyperparathyroidism, trabecular bone score, children, CDC73, microwave ablation, radiofrequency ablation, denosumab, cinacalcet, preoperative imaging, imaging, diagnosis, CT, PET, PET/CT, 4D/CT, SPECT/CT, F-18-fluorocholine, quality of life, fractures, and metabolic syndrome. We can say that there will be an increasing research trend on PHPT in the coming years. In addition to the Western countries such as the United States and European countries with large economies, Japan and Turkey were also identified as leading countries in the development of the PHPT literature. This study provides significant information about the intellectual structure and global productivity of PHPT to clinicians and other researchers interested on PHPT.
Topics: Child; Female; Pregnancy; Humans; Cinacalcet; Hyperparathyroidism, Primary; Positron Emission Tomography Computed Tomography; Quality of Life; Bibliometrics
PubMed: 37657020
DOI: 10.1097/MD.0000000000034622 -
Endocrine Connections May 2024In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative... (Review)
Review
In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative predictors. Primary hyperparathyroidism (PHPT) is the third-most common endocrine disorder, and multiglandular parathyroid disease (MGD) is a cause of PHPT. Hereditary MGD can be definitively diagnosed with detailed family history and genetic testing, whereas sporadic MGD presents a greater challenge in clinical practice, and parathyroidectomy for MGD is associated with a higher risk of surgical failure than single gland disease (SGD). Therefore, it is crucial to be able to predict the presence of sporadic MGD in a timely manner, either preoperatively or intraoperatively. Various predictive methods cannot accurately identify all cases of sporadic MGD, but they can greatly optimize the management of MGD diagnosis and treatment and optimize the cure rate. Future research will urge us to investigate more integrative predictive models as well as increase our understanding of MGD pathogenesis.
PubMed: 38513354
DOI: 10.1530/EC-23-0492 -
Frontiers in Endocrinology 2023Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary...
INTRODUCTION
Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies.
METHODS
838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688).
RESULTS
There were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2.
DISCUSSION
The present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT.
Topics: Humans; Middle Aged; Aged; Hyperparathyroidism, Primary; Diabetes Mellitus, Type 2; Risk Factors; Hypertension; Cardiovascular Diseases
PubMed: 37842310
DOI: 10.3389/fendo.2023.1266728 -
Journal of Clinical Medicine Dec 2023This review investigates the intricate relationship between hyperparathyroidism (HPT) and thyroid carcinoma (TC), aiming to elucidate their coexistence, potential... (Review)
Review
This review investigates the intricate relationship between hyperparathyroidism (HPT) and thyroid carcinoma (TC), aiming to elucidate their coexistence, potential pathogenetic mechanisms, and clinical implications. A systematic search strategy, employing the MeSH terms 'Hyperparathyroidism' and 'Thyroid Carcinoma', spanned publications from 2013 to 2023 across the PubMed, Web of Science, and Scopus databases. Fifteen selected articles were analyzed. Studies unanimously confirm the notable association between primary hyperparathyroidism (PHPT) and thyroid nodules/cancer, with incidences ranging from 2.8% to 47.1%. Key findings reveal a predilection for papillary thyroid carcinoma (PTC) in this association, showcasing varying tumor characteristics and gender disparities. Lower preoperative serum parathyroid hormone (PTH) levels are a potential risk factor for thyroid cancer in PHPT patients. Diverse surgical approaches and tumor characteristics between PHPT and secondary hyperparathyroidism (SHPT) cases were noted. Moreover, this review underscores the scarcity of definitive guidelines in managing concurrent PHPT and thyroid conditions, advocating for comprehensive assessments to enhance diagnostic accuracy and refine therapeutic interventions. Rare coincidental associations, as highlighted by case reports, shed light on unique clinical scenarios. In essence, this review amalgamates evidence to deepen the understanding of the interplay between HPT and TC, emphasizing the need for further research to elucidate underlying mechanisms and guide clinical management.
PubMed: 38202152
DOI: 10.3390/jcm13010147 -
Journal of Bone and Mineral Research :... Jul 2023Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the...
Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single-cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast-musculature cells and endocrine cells. PC development may be stimulated by fibroblast-endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Parathyroid Neoplasms; Transcriptome; Endothelial Cells; Adenoma; Carcinogenesis; Tumor Microenvironment
PubMed: 37191193
DOI: 10.1002/jbmr.4824 -
Physiological Research Dec 2023Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic... (Review)
Review
Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic MGD is more common and affects a similar patient profile as single gland parathyroid disease (SGD). The distinction between SGD and MGD is of great clinical importance, especially for the strategy of parathyroidectomy. Based on the limited knowledge available, MGD is likely to be a genetically heterogeneous disease resulting from the interaction of germline and somatic DNA mutations together with epigenetic alterations. Furthermore, these events may combine and occur independently in parathyroid tumors within the same individual with MGD. Gene expression profiling has shown that SGD and MGD may represent distinct entities in parathyroid tumorigenesis. We are waiting for studies to analyze exactly which genes are different in SGD and MGD in order to identify potential biomarkers that can distinguish between the two forms of the disease.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Hormone; Retrospective Studies; Parathyroid Glands; Molecular Biology
PubMed: 38116772
DOI: 10.33549/physiolres.935253 -
International Journal of Molecular... Apr 2024Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established...
Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.
Topics: Humans; TRPC Cation Channels; Hyperparathyroidism, Primary; Parathyroid Glands; Female; Male; TRPC6 Cation Channel; Down-Regulation; Middle Aged; Aged; Adult; Immunohistochemistry; Parathyroid Hormone
PubMed: 38673977
DOI: 10.3390/ijms25084392 -
TouchREVIEWS in Endocrinology Jul 2023Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge... (Review)
Review
Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge due to the high rate of local recurrence of the tumour. We report the case of a middle-aged north Indian woman who presented with recurrent primary hyperparathyroidism due to parathyroid carcinoma. She presented with a recurrent palpable hard neck mass and underwent radical dissection of the neck six times. At the time of writing this report, she was referred for external beam radiotherapy to the neck. Parathyroid carcinoma is a rare malignancy with an indolent but tenacious course. Complete resection at the time of initial surgery determines the prognosis of the neoplasm. Chemotherapy and radiotherapy are usually ineffective. Hypercalcaemia needs to be aggressively managed. A multidisciplinary team is required to effectively manage parathyroid carcinoma.
PubMed: 38046185
DOI: 10.17925/EE.2023.19.2.6