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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 -
World Journal of Clinical Cases Jun 2024Hypoparathyroidism is one of the main complications after total thyroidectomy, severely affecting patients' quality of life. How to effectively protect parathyroid... (Review)
Review
Hypoparathyroidism is one of the main complications after total thyroidectomy, severely affecting patients' quality of life. How to effectively protect parathyroid function after surgery and reduce the incidence of hypoparathyroidism has always been a key research area in thyroid surgery. Therefore, precise localization of parathyroid glands during surgery, effective imaging, and accurate surgical resection have become hot topics of concern for thyroid surgeons. In response to this clinical phenomenon, this study compared several different imaging methods for parathyroid surgery, including nanocarbon, indocyanine green, near-infrared imaging techniques, and technetium-99m methoxyisobutylisonitrile combined with gamma probe imaging technology. The advantages and disadvantages of each method were analyzed, providing scientific recommendations for future parathyroid imaging. In recent years, some related basic and clinical research has also been conducted in thyroid surgery. This article reviewed relevant literature and provided an overview of the practical application progress of various imaging techniques in parathyroid surgery.
PubMed: 38898826
DOI: 10.12998/wjcc.v12.i17.2946 -
Diagnostics (Basel, Switzerland) May 2024Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary...
Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.
PubMed: 38893652
DOI: 10.3390/diagnostics14111127 -
Journal of Clinical Medicine Jun 2024Transient hypoparathyroidism (TH) is the main post-thyroidectomy complication, significantly impacting surgical outcomes, hospitalization length, and perceived...
Transient hypoparathyroidism (TH) is the main post-thyroidectomy complication, significantly impacting surgical outcomes, hospitalization length, and perceived perceived quality of life understood as mental and physical well-being. This study aims to identify possible associated risk factors. We analyzed 238 thyroidectomies (2020-2022), excluding instances of partial surgery, primary hyperparathyroidism, neck irradiation history, and renal failure. The variables considered were as follows: demographics, histology, autoimmunity, thyroid function, pre- and postoperative Vitamin D levels (where available), type of surgery, number of incidentally removed parathyroid glands (IRP), and surgeons' experience (>1000 thyroidectomies, <500, in training). Univariate analysis applied: χ, Fisher's exact test for categorical variables, and Student's -test for continuous variables. Subsequently, logistic multivariate analysis with stepwise selection was performed. Univariate analysis did not yield statistically significant results for the considered variables. The 'No Complications' group displayed a mean age of 55 years, whereas the TH group showed a mean age of 51 (-value = 0.055). We considered this result to be marginally significant. Subsequently, we constructed a multivariate logistic model. This model (AIC = 245.02) indicated that the absence of incidental parathyroidectomy was associated with the age class >55 years, presenting an odds ratio (OR) of 9.015 (-value < 0.05). Simultaneously, the age class >55 years exhibited protective effects against TH, demonstrating an OR of 0.085 (-value < 0.01). Similarly, the absence of incidental parathyroidectomy was found to be protective against TH, with an OR of 0.208 (-value < 0.01). Multivariate analysis highlighted that having "No IRP" was protective against TH, while younger age was a risk factor. Surgeon experience does not seem to correlate with IRP or outcomes, assuming there is adequate tutoring and a case volume close to 500 to ensure good results. The effect of reimplantation has not been evident in transient hypoparathyroidism.
PubMed: 38893037
DOI: 10.3390/jcm13113326 -
Journal of Clinical Medicine May 2024: Thyroidectomy constitutes an important portion of endocrine surgery procedures and is associated with various complications such as bleeding, recurrent laryngeal nerve...
: Thyroidectomy constitutes an important portion of endocrine surgery procedures and is associated with various complications such as bleeding, recurrent laryngeal nerve injury, and postoperative hypoparathyroidsm. Effective parathyroid preservation during thyroid surgery is crucial for patient well-being, with current strategies heavily reliant on surgeon experience. Among various methods, Indocyanine Green Angiography (ICGA) offers a promising method for intraoperative assessment of parathyroid gland perfusion. : In a retrospective study, patients undergoing bilateral thyroidectomy from January 2021 to January 2023 were analyzed, excluding those with previous thyroidectomy, parathyroid disease, or chronic kidney disease. The study compared a control group ( = 175) with an ICGA group ( = 120), using propensity score matching for statistical analysis. Matched cohorts included 120 patients in each group. The primary outcome of this study was identified as temporary postoperative hypoparathyroidism, with secondary outcomes including the rate of parathyroid reimplantation and the incidence of permanent postoperative hypoparathyroidism. : The ICGA group showed significantly more parathyroid autotransplantations ( < 0.01). While not statistically significant, the control group had a higher incidence of temporary postoperative hypoparathyroidism ( < 0.09). Rates of hypocalcemia on postoperative day 1 and permanent hypocalcemia were similar. Subgroup analysis indicated more postoperative day 1 hypoparathyroidism in the control group during central neck dissections ( < 0.049). : Intraoperative ICGA use correlated with higher parathyroid autotransplantation and suggested reduced postoperative hypoparathyroidism. Changes in fluorescence intensity following a second ICG injection may provide an objective method to assess parathyroid perfusion. Further large-scale studies are needed to fully understand ICGA's impact on parathyroid preservation.
PubMed: 38892750
DOI: 10.3390/jcm13113038 -
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 -
Endocrinology and Metabolism (Seoul,... Jun 2024Patients with permanent hypoparathyroidism require lifelong treatment. Current replacement therapies sometimes have adverse effects (e.g., hypercalciuria and chronic...
Patients with permanent hypoparathyroidism require lifelong treatment. Current replacement therapies sometimes have adverse effects (e.g., hypercalciuria and chronic kidney disease). Generating parathyroid glands (PTGs) from the patient's own induced pluripotent stem cells (PSCs), with transplantation of these PTGs, would be an effective treatment option. Multiple methods for generating PTGs from PSCs have been reported. One major trend is in vitro differentiation of PSCs into PTGs. Another is in vivo generation of PSC-derived PTGs by injecting PSCs into PTG-deficient embryos. This review discusses current achievements and challenges in present and future PTG regenerative medicine.
PubMed: 38853617
DOI: 10.3803/EnM.2024.1989 -
Asian Journal of Surgery Jun 2024
PubMed: 38849247
DOI: 10.1016/j.asjsur.2024.05.125 -
Scientific Reports Jun 2024Thyroid surgery often results in ischemia-reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain...
Thyroid surgery often results in ischemia-reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain incompletely explored. Our study identifies a polyphenolic herbal extract-gallic acid (GA)-with antioxidative properties against IRI. Through flow cytometry and CCK8 assays, we investigate the protective effects of GA pretreatment on a parathyroid IRI model and decode its potential mechanisms via RNA-seq and bioinformatics analysis. Results reveal increased apoptosis, pronounced G1 phase arrest, and significantly reduced cell proliferation in the hypoxia/reoxygenation group compared to the hypoxia group, which GA pretreatment mitigates. RNA-seq and bioinformatics analysis indicate GA's modulation of various signaling pathways, including IL-17, AMPK, MAPK, transient receptor potential channels, cAMP, and Rap1. In summary, GA pretreatment demonstrates potential in protecting parathyroid cells from IRI by influencing various genes and signaling pathways. These findings offer a promising therapeutic strategy for hypoparathyroidism treatment.
Topics: Signal Transduction; Reperfusion Injury; Gallic Acid; Animals; Apoptosis; Parathyroid Glands; Cell Proliferation; Humans; Mice
PubMed: 38839854
DOI: 10.1038/s41598-024-63470-5 -
Frontiers in Oncology 2024We previously made a detailed expansion to the gasless transaxillary endoscopic thyroidectomy(GTET) procedure described in the previous literatures. In this study, we...
INTRODUCTION
We previously made a detailed expansion to the gasless transaxillary endoscopic thyroidectomy(GTET) procedure described in the previous literatures. In this study, we optimized the procedure focused on the limitation of the approach in terms of trauma and lymph node dissection and made a comparison with the early procedure.
MATERIALS AND METHODS
This paper gave a detailed description of the updated procedure and prospectively collected data about patients with papillary thyroid carcinoma(PTC) performed by the two procedures from December 2020 to April 2023. The differences in surgical outcome, surgical trauma and parathyroid gland(PG) function protection were analyzed.
RESULTS
Of the 302 patients, 184 underwent with early procedure(EP), and 118 underwent with updated procedure(UP). The surgical outcomes of operative time, time of thyroidectomy and central neck dissection, blood loss, drainage and postoperative hospital stay were shorter in UP than that of the EP. The mean number of lymph nodes retrieved and weight of dissection lymphatic tissue in the UP were significantly more than that in EP without increasing the mean number of metastatic lymph nodes. Postoperative complications did not differ between the two procedures. The UP had more advantages in the identification and preservation of the superior parathyroid gland, however, it did not improve the preservation of the inferior parathyroid gland. The visual analog scale score for pain and the changes among inflammation factors was lower in the UP.
CONCLUSION
The UP of GTET could perform safely and efficiently while reducing surgical trauma in selected patients.
PubMed: 38800390
DOI: 10.3389/fonc.2024.1377878