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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 -
Langenbeck's Archives of Surgery Jun 2024Over recent years, various advanced minimally invasive techniques have been developed for parathyroidectomy, and there was a universal acceptance of these less invasive... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Over recent years, various advanced minimally invasive techniques have been developed for parathyroidectomy, and there was a universal acceptance of these less invasive procedures by surgeons. This study is designed to compare overall outcomes between endoscopic versus focused, single gland parathyroidectomy using intraoperative rapid parathyroid hormone (ioPTH) changes under general anesthesia in primary hyperparathyroidism (PHPT) patients.
METHOD
In this randomized clinical trial, 96 patients diagnosed with PHPT were randomly assigned into two groups endoscopic and focused parathyroidectomy. Baseline clinical and demographical data were collected along with perioperative features. The success rate was evaluated based on ioPTH changes.
RESULTS
The ioPTH levels after five minutes in the endoscopic group were significantly lower than the focused group (P = 0.005). The success rate for endoscopic and the focused method was 95.3% and 77.1% during the first five minutes (P = 0.013) and 100% in both groups after ten minutes. A decrease in parathyroid hormone levels was significant in each group but not between each other. Postoperative calcium levels were significantly lower in the focused method (P = 0.042). The focused group also had a significantly shorter operation time than the endoscopic group (P < 0.001). Patient satisfaction with cosmetic outcome was significantly higher in the endoscopic group compared to the focused group.
CONCLUSION
The endoscopic technique was superior to the unilateral focused neck exploration parathyroidectomy in the management of single-gland PHPT. Influencing aspects included higher postoperative calcium levels, more rapid success achievement, and satisfactory cosmetic outcomes in the endoscopic group. However, patient selection and accurate adenoma localization are vital in this method.
Topics: Humans; Parathyroidectomy; Hyperparathyroidism, Primary; Male; Female; Middle Aged; Endoscopy; Treatment Outcome; Adult; Parathyroid Hormone; Aged; Operative Time
PubMed: 38907761
DOI: 10.1007/s00423-024-03390-0 -
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 -
Innere Medizin (Heidelberg, Germany) Jul 2024In the management of solid tumours, routine concepts are increasingly being transformed into individualized patient treatment. Endocrine surgery is traditionally... (Review)
Review
BACKGROUND
In the management of solid tumours, routine concepts are increasingly being transformed into individualized patient treatment. Endocrine surgery is traditionally characterized by resection strategies that are adapted to phenotype and genotype of the underlying disease. As complication rates in surgery correlate with the extent of resection, continuous efforts are made to identify selection criteria in order to limit the extent of surgery without compromising the oncological outcome. The aim is to design risk-stratified precision endocrine surgery.
MATERIALS AND METHODS
A search was carried out in PubMed for new and modern strategies and approaches for oncological endocrine surgery.
RESULTS
Several developments in surgical technique and technology, molecular pathology, medical therapy, and study data identify the potential to adapt the surgical strategy in all areas of endocrine surgery.
CONCLUSION
According to prevalent data, limited extent of resection in thyroid cancer surgery shows a reduction in complication rates while preserving oncological outcome when adequate selection criteria are implemented. New insights and innovative technologies also influence additional areas in oncological endocrine surgery for parathyroid, adrenal, and neuroendocrine neoplasia. However, the broad practice of these new concepts needs to be evaluated with regard to long-term oncological outcome.
Topics: Humans; Endocrine Gland Neoplasms; Endocrine Surgical Procedures; Thyroid Neoplasms; Adrenal Gland Neoplasms
PubMed: 38888613
DOI: 10.1007/s00108-024-01732-0 -
Khirurgiia 2024We present successful surgical treatment of a patient with chronic kidney disease (CKD) and hyperparathyroidism undergoing renal replacement therapy. At baseline,...
[Thoracoscopic resection of recurrent atypically located parathyroid adenoma of anterior mediastinum in a patient with hyperparathyroidism undergoing renal replacement therapy].
We present successful surgical treatment of a patient with chronic kidney disease (CKD) and hyperparathyroidism undergoing renal replacement therapy. At baseline, parathyroidectomy via cervical access was performed for parathyroid adenomas. After 6 years, clinical and laboratory relapse of disease required thoracoscopic resection of atypically located anterior mediastinal adenoma. This case demonstrates that this disease is one of the most difficult in modern medicine requiring a special approach in diagnosis and treatment. Patients with CKD and hyperparathyroidism need for follow-up, control of total and ionized serum calcium, inorganic phosphorus and parathormone, osteodensitometry, ultrasound and scintigraphy of thyroid and parathyroid glands, and, if necessary, CT or MRI of the neck and chest organs.
Topics: Humans; Parathyroid Neoplasms; Parathyroidectomy; Adenoma; Treatment Outcome; Neoplasm Recurrence, Local; Parathyroid Glands; Middle Aged; Thoracoscopy; Male; Female; Mediastinal Neoplasms; Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic; Mediastinum
PubMed: 38888023
DOI: 10.17116/hirurgia202406181 -
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 -
Nature Reviews. Endocrinology Jun 2024Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine... (Review)
Review
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies.
PubMed: 38886617
DOI: 10.1038/s41574-024-01005-8 -
Frontiers in Oncology 2024Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of...
Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of 60, and the clinical symptoms are consistent with those of hyperparathyroidism. This condition has a low occurrence, and its ultrasonographic signs are strikingly similar to thyroid malignant tumors, making it easily misdiagnosed. As a result, a case of APA ultrasonography misdiagnosis admitted to our hospital was recorded in order to serve as a reference point for APA diagnosis.
PubMed: 38884084
DOI: 10.3389/fonc.2024.1375373 -
The International Journal of Artificial... Jun 2024In this study, we investigated the effectiveness of regional citrate anticoagulation continuous renal replacement therapy (RCA-CRRT) in reducing blood calcium levels in...
In this study, we investigated the effectiveness of regional citrate anticoagulation continuous renal replacement therapy (RCA-CRRT) in reducing blood calcium levels in three patients with hypercalcemia crisis caused by different etiologies. The sodium citrate chelation of calcium ions was utilized as an anticoagulant for treating severely affected patients. By adjusting the citrate anticoagulant dose and monitoring treatment indicators, RCA-CRRT parameters were actively modified to alleviate the hypercalcemia crisis and provide time for surgery or specialized treatment. Two patients experienced rapid and effective reductions in blood calcium levels, allowing for further treatment, while the third patient exhibited a repeated increase in blood calcium, which eventually decreased after parathyroid adenoma resection, leading to clinical discharge. Our findings suggest that RCA-CRRT can help alleviate hypercalcemia crisis, stabilize the patient's internal environment, and provide valuable time for clinical treatment in cases of various medical conditions causing abnormal blood calcium elevations.
PubMed: 38869042
DOI: 10.1177/03913988241259963 -
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