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The American Journal of the Medical... May 2017
Topics: Adenoma; Adolescent; Calcium; Female; Humans; Hypercalcemia; Hyperparathyroidism; Mediastinum; Parathyroid Hormone; Parathyroid Neoplasms; Radiography, Thoracic; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 28502343
DOI: 10.1016/j.amjms.2016.08.009 -
Endocrine-related Cancer Feb 2019Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by dysregulation of parathyroid hormone release. The large majority of PHPT cases are... (Review)
Review
Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by dysregulation of parathyroid hormone release. The large majority of PHPT cases are attributable to sporadic, single-gland parathyroid adenoma, in which MEN1 and CCND1/cyclin D1 are the most well-established drivers of tumorigenesis. Sporadic parathyroid carcinoma, which appears to mostly arise through molecular pathways distinct from those causing benign parathyroid tumors, is rare and is most frequently driven by mutational inactivation of the CDC73 (HRPT2) tumor suppressor gene. Targeted investigation of suspected tumor driver genes, as well as unbiased whole-genome or exome sequencing of small cohorts, have revealed additional novel candidate tumor genes in sporadic parathyroid neoplasia, generally at modest or low mutational frequencies consistent with marked molecular genetic heterogeneity from tumor to tumor. The ability of these additional candidates to participate in the pathogenic process of driving parathyroid tumorigenesis in vivo largely remains to be demonstrated experimentally. This review will summarize the molecular genetic abnormalities identified to date in sporadic PHPT and discuss the strength of evidence for their proposed roles in parathyroid tumor formation.
Topics: Adenoma; Animals; Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms
PubMed: 30475215
DOI: 10.1530/ERC-18-0304 -
Journal of the American Animal Hospital... Jan 2023A 10 yr old female spayed domestic shorthair was referred for an 11mo history of persistent total hypercalcemia and elevated ionized calcium with intermittent episodes...
A 10 yr old female spayed domestic shorthair was referred for an 11mo history of persistent total hypercalcemia and elevated ionized calcium with intermittent episodes of lethargy, vomiting, and diarrhea with a history of recurrent urinary tract infections and intermittently elevated kidney values. An abdominal ultrasound, thoracic radiographs, cervical ultrasound, and ionized calcium level, parathyroid hormone (PTH), and PTH-related peptide (PTHrp) levels were assessed. Results were consistent with chronic kidney disease, splenomegaly, diffuse thickening of small intestines, nodular lesions noted in the left thyroid and right parathyroid, and elevated ionized calcium, PTH, and elevated PTHrp levels. A left thyroidectomy and right cranial parathyroidectomy were performed. Hypocalcemia and anemia developed postoperatively, which were managed with calcium carbonate, calcitriol, and calcium gluconate and benign neglect of anemia. Histopathology was consistent with a left thyroid carcinoma and right cranial parathyroid adenoma. Thyroid carcinoma and parathyroid adenomas have not previously been reported to occur concurrently in domestic felines and should be considered when ionized calcium is elevated with both PTH and PTHrp levels increased in addition to ultrasonographic lesions.
Topics: Cats; Animals; Female; Parathyroid Hormone-Related Protein; Parathyroid Neoplasms; Calcium; Parathyroid Hormone; Hypercalcemia; Thyroid Neoplasms; Cat Diseases
PubMed: 36584312
DOI: 10.5326/JAAHA-MS-7299 -
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 -
Best Practice & Research. Clinical... Dec 2018Sporadic primary hyperparathyroidism (pHPT) is the commonest cause of hypercalcaemia in the ambulatory population. It has a female preponderance and its incidence is... (Review)
Review
Sporadic primary hyperparathyroidism (pHPT) is the commonest cause of hypercalcaemia in the ambulatory population. It has a female preponderance and its incidence is increasing. In 85% of cases it is caused by a single parathyroid adenoma, with four gland hyperplasia in up to 20%. Parathyroidectomy is the only cure and bilateral neck exploration remains the gold standard to achieve this. Several adjuncts have been developed to improve success rates or limit the extent of surgery. Pre-operative localisation permits planned targeted surgery. Ultrasound scanning and scintigraphy are the most commonly employed, although 4DCT has become a useful modality in complex cases. However, excellent rates of biochemical cure can be achieved in specialist centres when pre-operative imaging is negative. Pre-operative prediction models and intra-operative parathyroid hormone (ioPTH) assist, with high sensitivity, to predict single gland disease. Reoperations present a major challenge to the endocrine surgeon.
Topics: Adenoma; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy; Radionuclide Imaging; Ultrasonography
PubMed: 30551990
DOI: 10.1016/j.beem.2018.12.001 -
Endocrine Mar 2020Recently, it has been demonstrated that Raman spectroscopy is able to differentiate between healthy parathyroid tissues and parathyroid adenoma based on the basis of a...
PURPOSE
Recently, it has been demonstrated that Raman spectroscopy is able to differentiate between healthy parathyroid tissues and parathyroid adenoma based on the basis of a specific molecular fingerprint. However, to our knowledge, no previous studies have been performed to evaluate the metabolic profile of parathyroid adenoma. Therefore, we designed a proof of concept study aimed to investigate the glucose/fatty acid metabolisms, in addition to the mitochondrial changes, in solitary parathyroid adenoma and in healthy parathyroid glands.
METHODS
Nine females with primary hyperparathyroidism due to a solitary parathyroid adenoma and formal surgical indication for parathyroidectomy have been enrolled. At the time of surgery, the removed specimens were immediately submitted unfixed and a tissue slice of about 0.5 cm in diameter was obtained from the nodular lesion. The expression of selected metabolic enzymes and proteins has been evaluated by western blot analysis, using human parathyroid whole tissue lysates as control.
RESULTS
Data obtained highlighted an increase, compared with the healthy group, of: (i) the glucose uptake by the GLUT-1 receptor and its phosphorylation by hexokinase II (HXKII); (ii) the expression of 3-phosphoglycerate dehydrogenase (3-PGDH) and glucose-6-phosphate dehydrogenase (G6PD); (iii) lipids biosynthesis; and (iv) cytochrome c expression.
CONCLUSIONS
Our findings highlight for the first time the parathyroid adenoma metabolic hallmarks that could represent potential molecular targets usable for the development of new pharmacological treatments, allowing to reduce surgical parathyroidectomy.
Topics: Adenoma; Female; Humans; Metabolome; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy
PubMed: 31786773
DOI: 10.1007/s12020-019-02146-x -
Clinical and Translational Medicine Jun 2024Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
BACKGROUND
Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
METHODS
Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations.
RESULTS
There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues.
CONCLUSIONS
We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications.
HIGHLIGHTS
Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.
Topics: Humans; Parathyroid Neoplasms; Adenoma; Inflammation; Histone-Lysine N-Methyltransferase; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogene Mas; Cell Proliferation
PubMed: 38888967
DOI: 10.1002/ctm2.1734 -
Medicine Nov 2022Most patients with parathyroid adenomas are asymptomatic and rarely present with chronic pancreatitis (CP). Several studies have reported a positive association between... (Review)
Review
BACKGROUND
Most patients with parathyroid adenomas are asymptomatic and rarely present with chronic pancreatitis (CP). Several studies have reported a positive association between primary hyperparathyroidism (PHPT) and pancreatitis. Parathyroidectomy is the definitive treatment for PHPT. IV bisphosphonates can be considered the drug of choice for bridge to surgery.
METHODS
We reported a 57-year-old female patient was admitted to the emergency room with left upper quadrant abdominal pain and a diagnosis of recurrent pancreatitis. Magnetic Resonance Cholangiopancreatography confirmed the diagnosis of CP. The patient had no common etiology of pancreatitis. Persistent hypercalcemia was noted despite administering intravenous fluids, and Calcitonin. Intravenous Pamidronate, a Bisphosphonate derivative, was also administered. Although calcium levels initially decreased, they were later found to rebound to previous levels.
RESULTS
A diagnosis of parathyroid adenoma and PHPT was made based on the elevated parathyroid hormone levels and cervical ultrasonography indicated right inferior parathyroid adenoma. Technetium-99m methoxy-isobutyl-isonitrile scintigraphy revealed a focal hot spot of tracer accumulation at the right lower thyroid bed. The patient underwent right lower parathyroidectomy smoothly and successfully. After right lower parathyroidectomy, she had normal serum calcium levels (9.2 mg/dL) and parathyroid hormone (16.1 pg/mL). There was no recurrent abdominal pain after the operation.
CONCLUSION
CP is a rare manifestation of parathyroid adenoma. When patients with a history of recurrent pancreatitis, without common causes of pancreatitis, present persistent elevated serum calcium levels, PHPT could be suspected.
Topics: Humans; Female; Middle Aged; Parathyroid Neoplasms; Calcium; Pancreatitis, Chronic; Hypercalcemia; Parathyroid Hormone; Abdominal Pain
PubMed: 36401406
DOI: 10.1097/MD.0000000000031750 -
Journal of Endocrinological... Jun 2023This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on...
PURPOSE
This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on for primary hyperparathyroidism (PHPT) with uniglandular parathyroid adenomas in other localizations.
METHODS
The data of PHPT patients who underwent parathyroidectomy in our institution were assessed retrospectively. Abnormal gland localization was confirmed by operative and pathology reports as well as normocalcemia that lasted for at least 6 months postoperatively. The relationships of biochemical and clinical findings of patients with confirmed adenoma localizations were analyzed. In order to determine independent factors that can predict EPAs, binary logistic regression was used.
RESULTS
Among 421 patients (83.4% female, mean age 49 ± 13.2 years) enrolled in the study, the most common adenoma localization was the lower left parathyroid gland (36.1%; p < 0.001). Parathyroid adenomas were more common in lower localizations compared to upper localizations and were smaller in size (p < 0.001 and p = 0.004, respectively). In univariate analysis, serum intact parathyroid hormone and calcium levels were found to be higher (p = 0.004 and p = 0.002, respectively), moderate/severe hypercalcemia was more common (p = 0.024), phosphorus levels were lower (p = 0.04), and postoperative transient hypocalcemia was more common (p = 0.013) in cases of EPAs than other localizations. There was no significant difference in adenoma size between EPAs and other classical localizations. In multivariate analysis, only a high serum calcium level was an independent predictor of EPAs (OR 2.017, 95% CI 1.142-3.564, p = 0.016). Receiver-operating characteristic curve analysis yielded an optimal cutoff value of 12.25 mg/dL for serum calcium (88% sensitivity, 63% specificity, and area under the curve: 0.861).
CONCLUSION
EPAs can cause a more biochemically distinct PHPT picture compared to parathyroid adenomas in classical localizations. A high calcium level at diagnosis may be a clinical predictor for EPAs and may affect the clinical approach and imaging technique choices. Due to the increased risk of transient hypocalcemia in patients with EPAs, caution should be exercised in postoperative follow-up. Furthermore, in the event of negative preoperative imaging, starting the parathyroid exploration from the lower left region may be a good option for the surgeon.
Topics: Humans; Female; Adult; Middle Aged; Male; Parathyroid Neoplasms; Hypocalcemia; Calcium; Retrospective Studies; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Adenoma; Hyperparathyroidism, Primary
PubMed: 36510103
DOI: 10.1007/s40618-022-01986-1 -
Journal of Medical Case Reports Apr 2022Giant parathyroid adenoma is a type of parathyroid adenoma weighing > 3.5 g and having a size of more than 2 cm.
BACKGROUND
Giant parathyroid adenoma is a type of parathyroid adenoma weighing > 3.5 g and having a size of more than 2 cm.
CASE PRESENTATION
This report describes giant primary parathyroid adenoma with reference to the literature. We report the case of a 48-year-old Persian man referred to the clinic with knee and lower back pain. He had a history of mitral valve replacement and several episodes of bilateral nephrolithiasis. After a thorough assessment, a neck mass with a possible thyroid origin was detected, but further assessment showed it was of parathyroid origin. The resected mass was 9 × 6× 4 cm and weighed 122 g, and histopathology showed a giant parathyroid adenoma.
CONCLUSION
Giant parathyroid adenomas that weigh more than 110 g and are larger than 8 cm can lead to significant hypercalcemia. Despite giant parathyroid adenomas and high parathyroid hormone levels, a calcium crisis may not always occur in these patients, and the masses may be initially misdiagnosed as a thyroid mass.
Topics: Adenoma; Humans; Hypercalcemia; Male; Middle Aged; Parathyroid Hormone; Parathyroid Neoplasms; Thyroid Gland
PubMed: 35414046
DOI: 10.1186/s13256-022-03401-y