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Polski Przeglad Chirurgiczny Mar 2024<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0-3.5 g...
<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0-3.5 g are called "large" or "giant" adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm<sup>3</sup> (control group). In both groups, the majority were women (81.5% - study group, 90.5% - control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3-0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>.
Topics: Humans; Hypercalcemia; Parathyroid Neoplasms; Female; Male; Middle Aged; Adenoma; Adult; Aged; Risk Factors; Hyperparathyroidism, Primary; Calcium; Parathyroidectomy
PubMed: 38940244
DOI: 10.5604/01.3001.0054.4440 -
Annals of Agricultural and... Jun 2024Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid...
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid adenomas, ganglioneuromas of the digestive tract, and musculoskeletal abnormalities. The case is presented of a 31-year-old male patient with numerous polyps in the colon described as ganglioneuromas which are ectodermal neoplasms emerging from a proliferation of ganglionic cells of the sympathetic nervous system. The results show elevated levels of normetanephrine, which is an endogenous catecholamine metabolite, and has high diagnostic sensitivity as well as specificity in pheochromocytoma detection. The patient underwent partial thyreoidectomy due to a nodular goiter. He was admitted to the Department of Gastroenterology to lead a diagnostic pathway towards MEN 2B.
Topics: Humans; Male; Adult; Multiple Endocrine Neoplasia Type 2b; Ganglioneuroma
PubMed: 38940117
DOI: 10.26444/aaem/171736 -
International Journal of Molecular... Jun 2024We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced... (Review)
Review
Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.
We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P ( = 9 studies, N = 1375) involved as a starting point parathyroid NETs ( = 7) or pancreatitis ( = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies ( = 7) included MEN1-related insulinomas ( = 2) or MEN1-associated PHP ( = 2) or analyses of genetic profile ( = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified ( = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome ( = 1). Normocalcemic and mildly symptomatic hyperparathyroidism ( = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.
Topics: Humans; Hyperparathyroidism, Primary; Insulin Resistance; Hypercalcemia; Pancreatitis; Female; Male; Proto-Oncogene Proteins; Pancreatic Neoplasms; Multiple Endocrine Neoplasia Type 1; Parathyroid Neoplasms; Adult; Parathyroidectomy; Neuroendocrine Tumors; Pancreas
PubMed: 38928056
DOI: 10.3390/ijms25126349 -
Cells Jun 2024Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the... (Review)
Review
Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasms. It also constitutes a summary of the current knowledge regarding the diagnosis of hypercalcemia and its management. Hypercalcemia of malignancy is estimated to affect over 40% of cancer patients and can be associated with both solid and blood cancers. Elevated calcium levels can be an indicator of developing cancer. The main mechanism of hypercalcemia development in tumors appears to be excessive production of parathyroid hormone-related peptides. Among the known treatment methods, bisphosphonates, calcitonin, steroids, and denosumab should be mentioned, but ongoing research promotes progress in pharmacotherapy. Given the rising global cancer prevalence, the problem of hypercalcemia is of high importance and requires attention.
Topics: Humans; Hypercalcemia; Neoplasms; Calcium
PubMed: 38920679
DOI: 10.3390/cells13121051 -
Medicina 2024Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are...
INTRODUCTION
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gastroenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phenotype and genotype of Argentinian patients with MEN1.
METHODS
A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation.
RESULTS
Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were missense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers.
CONCLUSION
The phenotype and genotype of Argentinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.
Topics: Humans; Argentina; Male; Multiple Endocrine Neoplasia Type 1; Phenotype; Female; Adult; Genotype; Middle Aged; Adolescent; Young Adult; Child; Aged; Mutation; Child, Preschool; Parathyroid Neoplasms; Proto-Oncogene Proteins
PubMed: 38907957
DOI: No ID Found -
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 -
Frontiers in Endocrinology 2024This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of F-AlF-NOTA-octreotide (F-OC)... (Review)
Review
INTRODUCTION
This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of F-AlF-NOTA-octreotide (F-OC) positron emission tomography/computed tomography (PET/CT).
METHODS
We analyzed TIO patients who underwent F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed.
RESULTS
6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm).
CONCLUSION
The implementation of whole-body F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of F-OC PET/CT in managing TIO.
Topics: Humans; Fibroblast Growth Factor-23; Fluorine Radioisotopes; Heterocyclic Compounds; Heterocyclic Compounds, 1-Ring; Neoplasms, Connective Tissue; Octreotide; Osteomalacia; Paraneoplastic Syndromes; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 38887276
DOI: 10.3389/fendo.2024.1400751 -
JBMR Plus Jul 2024Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview...
Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview of the secular trends in incidence, clinical characteristics, and treatment patterns of PHPT in South Korea. We used Korea's National Health Insurance Claim database (2005-2020) to identify newly diagnosed PHPT cases. Individuals with age below 19, fewer than 2 E21.0 diagnoses, fewer than 2 PTH measurements, secondary hyperparathyroidism, undergoing dialysis or kidney transplantation within a year of diagnosis, parathyroidectomy (PTX) within a year prior to the diagnosis code, and diagnosis of multiple endocrine neoplasm or parathyroid carcinoma were excluded from the analysis. A total of 6837 patients with PHPT (PTX, = 2989; non-surgery, = 3848) were compared with 1:10 age- and sex-matched controls ( = 68 370). The mean age of patients with PHPT was 56.0 years, with 77.4% being women. The annual incidence of PHPT increased from 0.23/100 000 persons in 2005 to 1.75 in 2020, with higher rate in women than in men. Compared with 2005-2010 ( = 675), the number of newly diagnosed PHPT cases increased up to 3.1-fold ( = 2119) in 2011-2015 and 6.0-fold ( = 4043) in 2016-2020 periods. Among all patients with PHPT, 43.7% of patients underwent PTX, with decrement of proportion of bilateral surgery among PTX group across time (11.9% in 2005-2010 to 8.9% in 2016-2020, for trend .033). Among all patients with PHPT, non-surgery group increased from 41.6% in 2005-2010 to 58.0% in 2016-2020 ( for trend <.001). Patients with PHPT had higher odds of osteoporosis (odds ratio [OR] 7.03), renal stones (OR 10.55), chronic kidney diseases (OR 7.42), and cardiovascular, metabolic, and neurological conditions after adjustment for comorbidity index. In summary, the incidence of PHPT increased from 2005 to 2020 with predominance of non-surgical treatment, which calls for research focus on improving non-surgical management.
PubMed: 38868595
DOI: 10.1093/jbmrpl/ziae065 -
Journal of the ASEAN Federation of... 2024Primary hyperparathyroidism (PHPT) is rare in pregnancy. This condition is challenging to diagnose and manage due to the limited diagnostic and therapeutic options that...
Primary hyperparathyroidism (PHPT) is rare in pregnancy. This condition is challenging to diagnose and manage due to the limited diagnostic and therapeutic options that are safe during pregnancy. If not diagnosed and managed in a timely manner, serious maternal and foetal complications may occur. We report two cases, one with surgical intervention and one without, to show the importance of timely surgical intervention and discuss the challenges in the management of PHPT in pregnancy.
Topics: Humans; Female; Pregnancy; Hyperparathyroidism, Primary; Adult; Pregnancy Complications; Parathyroid Neoplasms; Parathyroidectomy; Pregnancy Complications, Neoplastic; Adenoma; Treatment Outcome
PubMed: 38863924
DOI: 10.15605/jafes.039.01.17 -
Frontiers in Endocrinology 2024Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of...
Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of parathyroid lesions. We report here the case of a 30 year-old woman with a fortuitously discovered 2 cm cervical mass for which a parathyroid origin was originally suspected due to its retro-thyroidal localization and a personal history of nephrolithiasis. Normal serum calcium and parathyroid hormone (PTH) levels excluded primary hyperparathyroidism, raising suspicion of a non-functional parathyroid adenoma, and SPECT/CT imaging showed that the mass was Tc-sestamibi-avid. Fine-needle aspiration (FNA) was performed; cytology was non-diagnostic but the needle washout was negative for thyroglobulin, calcitonin and PTH, arguing against a thyroidal or parathyroidal origin of the mass. Core needle biopsy revealed a schwannoma, ostensibly originating from the recurrent laryngeal nerve; upon surgical resection, it was finally found to arise from the esophageal submucosa. This case illustrates the fact that endocrinologists, radiologists, nuclear medicine, head and neck, and other specialists investigating patients with cervical masses should be aware that schwannomas need to be considered in the differential diagnosis of focal Tc-sestamibi uptake in the neck region.
Topics: Humans; Female; Technetium Tc 99m Sestamibi; Parathyroid Neoplasms; Adult; Neurilemmoma; Diagnosis, Differential; Adenoma; Esophageal Neoplasms; Single Photon Emission Computed Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 38841301
DOI: 10.3389/fendo.2024.1258233