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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 -
Technology and Health Care : Official... Jun 2024Secondary hyperparathyroidism (SHPT) is one of the common complications of end-stage renal disease-uremia, and is mainly manifested as parathyroid hyperplasia and...
BACKGROUND
Secondary hyperparathyroidism (SHPT) is one of the common complications of end-stage renal disease-uremia, and is mainly manifested as parathyroid hyperplasia and abnormal secretion of parathyroid hormone (PTH).
OBJECTIVE
To investigate the value and advantages of contrast-enhanced ultrasound (CEUS) in evaluating the survival of autografts after parathyroidectomy + parathyroid autotransplantation.
METHODS
In this study, 125 patients with renal failure due to polycystic kidney disease, chronic nephritis, diabetic nephropathy, lupus nephritis, and atherosclerotic nephropathy were enrolled as the participants and each of them had 4 secondary hyperactive parathyroid glands and underwent parathyroid autotransplantation. One parathyroid gland was taken from each patient and equally divided into 4 parts and placed in the subcutaneous fat of one forearm for transplantation. CEUS was performed 14 days after the transplantation to observe the micro blood supply of the graft and assess the survival and secretory function of the transplanted parathyroid. The grafts were divided into the partial survival group and the total survival group based on the enhancement characteristics. The survival of the grafts was determined by comparing the parathyroid hormone level in bilateral elbow cephalic veins 1 month after surgery.
RESULTS
Among the 125 patients, 112 had linear or punctate enhancement of 2-4 parathyroid glands 14 days after surgery, and 13 patients had linear or punctate enhancement of 0-1 parathyroid gland. There were statistically significant differences in the perfusion pattern, enhancement uniformity, and parathyroid hormone levels in the cephalic veins at the elbow on both the graft and non-graft sides among all groups (P< 0.05).
CONCLUSION
Compared to the detection of the difference in the parathyroid hormone level in the cephalic vein of bilateral elbows 1 month after surgery, CEUS can reflect the parathyroid survival after transplantation more quickly and accurately 2 weeks later, and provide a more rapid and agile non-invasive clinical diagnosis method.
PubMed: 38905065
DOI: 10.3233/THC-231191 -
Journal of Hazardous Materials Jun 2024Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs...
Human exposure to micro- and nano-plastics (MNPs) primarily occurs through respiration and diet in the environment. However, the early effects and warning signs of MNPs exposure on vertebrates are unclear. Here we used intratracheal instillation and intragastric infusion to establish mouse models for MNPs exposure to systematically investigate the toxic mechanisms of MNPs on endocrine organs. Results showed that MNPs induced endocrine disruptions in short-term exposure by both dietary and respiratory pathways. Microplastics (MPs) exposed through dietary route were more toxic to thyroid gland, whereas nanoplastics (NPs) exhibited the highest level of toxicity to parathyroid gland through respiration. The transcriptome and validation of related functional genes revealed that MNPs affected the synthesis of thyroglobulin by interfering with the expressions of PAX8 and CREB. MNPs also impacted the levels of thyroid stimulating hormone, further mediating the secretion of thyroid hormones. Moreover, MNPs modulate the expression of Mafb, thereby exerting regulatory effects on parathyroid hormone (PTH) synthesis and growth development in parathyroid cells. Meanwhile, MNPs interfered with the expression of IP3R in the calcium signaling pathway, indirectly affecting the secretion of PTH. This study reveals the effects and mechanisms of MNPs on thyroid and parathyroid and highlights the significance of early warning of MNPs exposure.
PubMed: 38901250
DOI: 10.1016/j.jhazmat.2024.134960 -
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 -
Journal of Biophotonics Jun 2024The objective of this study was to discriminate thyroid and parathyroid tissues using Raman spectroscopy combined with an improved support vector machine (SVM)...
The objective of this study was to discriminate thyroid and parathyroid tissues using Raman spectroscopy combined with an improved support vector machine (SVM) algorithm. In thyroid surgery, there is a risk of inadvertently removing the parathyroid glands. At present, there is a lack of research on using Raman spectroscopy to discriminate parathyroid and thyroid tissues. In this article, samples were obtained from 43 individuals with thyroid and parathyroid tissues for Raman spectroscopy analysis. This study employed partial least squares (PLS) to reduce dimensions of data, and three optimization algorithms are used to improve the classification accuracy of SVM algorithm model in spectral analysis. The results show that PLS-GA-SVM algorithm has higher diagnostic accuracy and better reliability. The sensitivity of this algorithm is 94.67% and the accuracy is 94.44%. It can be concluded that Raman spectroscopy combined with the PLS-GA-SVM diagnostic algorithm has significant potential for discriminating thyroid and parathyroid tissues.
PubMed: 38890800
DOI: 10.1002/jbio.202400084 -
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