Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Temporal research trends in parathyroid surgery.

BACKGROUND: Progress has been observed in the pathophysiology of calcium homeostasis, localization studies, and intraoperative adjuncts in parathyroid surgery. The aim of this study is to gain a comprehensive perspective on the research landscape of parathyroid surgery over time. METHODS: A search of the Web of Science Core Collection was conducted to identify publications on parathyroid surgery from 1985 to 2024. Keywords were manually curated, and their frequencies were calculated based on the publication year. RESULTS: Publications on secondary hyperparathyroidism have decreased in recent years, but those on calcimimetics, tertiary hyperparathyroidism, and parathyroid cancer have increased. Publications related to sestamibi scans have decreased, while research on four-dimensional computed tomography and positron emission tomography has increased. Research on fluorescence and ablation treatment has recently been on the rise. The citation count per publication was positively correlated with the number of contributing institutions. CONCLUSION: We provide an overview of contemporary research themes and emerging topics related to parathyroid surgery. The endocrine surgery community could benefit from more inter-institutional partnerships to foster scientific progress.

Initial Experience With Ultra-High-Definition 3D Exoscope in Thyroid and Parathyroid Surgery.

BACKGROUND: Operation with a 3D exoscope has recently been introduced in clinical practice. The exoscope consists of two cameras placed in front of the operative field. Images are shown on a large 3D screen with high resolution. The system can be used to enhance precise dissection and provides new possibilities for improved ergonomics, fluorescence, and other optical-guided modalities. METHODS: Initial experience with the ultra-high-definition (4K) 3D exoscope in thyroid and parathyroid operations. The exoscope (OrbEyeTM) was mounted on a holding system (Olympus). RESULTS: We used the exoscope in parathyroidectomy (N = 6) and thyroidectomy (N = 6). Immediate advantages and disadvantages were discussed and recorded. The learning curve for use of the exoscope may be shorter for surgeons with training in endoscopic or robotic procedures. There may be improved ergonomics compared with normal open-neck operations. Further, the optical guided operations can be used with fluorescence and have potential for different on-lay techniques in the future. The 4 K 3D image quality is state-of-art and is highly appreciated during fine surgical dissection and eliminates the need for loupes. CONCLUSION: In several ways, using the ORBEYE™ in thyroid and parathyroid surgery provides the surgical team with a new and enhanced experience. This includes improved possibility for teaching, surgical ergonomics, and a 4K 3D camera with a powerful magnification system. However, it is not clear if utilization of these features would improve surgical outcomes. Furthermore, the ORBEYE™ lacks incorporation of parathyroid autofluorescence, and the current costs for the system do not facilitate general access to exoscope assisted operations.

Comparison of intraoperative imaging with a portable gamma camera with extemporaneous histology in minimally invasive surgery for primary hyperparathyroidism.

INTRODUCTION: The curative treatment of primary hyperparathyroidism (PPH) is surgical and today it can be performed by minimally invasive surgery (MIS) and also be radioguided (RG) if a radiopharmaceutical with affinity for the parathyroid tissue that can be detected with gamma-detector probes or with a portable gamma camera (PGC) is injected. AIM: The objective is to assess whether intraoperative scintigraphy (GGio) with PGC can replace intraoperative pathological anatomy (APio) to determine if the removed specimen is an abnormal parathyroid. MATERIAL AND METHOD: 92 patients underwent CMI RG--HPP with PGC after the administration of a dose of 99 mTc-MIBI. The information provided by the PGC in the analysis of the excised specimens is qualitatively compared (capture yes/no) with the result of the intraoperative pathological anatomy (APio). The Gold standard is the definitive histology. RESULTS: 120 excised pieces are evaluated with GGio and APio. There were 110 agreements (95TP and 15TN) and 10 disagreements (3FP and 7FN). Of the 120 lesions, 102 were parathyroid and 18 were non-parathyroid. There was good agreement between intraoperative scintigraphy imaging (GGio) and PA, 70.1% according to Cohen's Kappa index. The GGio presented the following values ​​of Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Positive Likelihood Ratio, Negative Likelihood Ratio and Overall Value of the Test (93.1%, 83.3%, 96.9%, 68.2%, 5.59, 0.08 and 0.92 respectively). CONCLUSION: GGio is a rapid and effective surgical aid technique to confirm/rule out the possible parathyroid nature of the lesions removed in PPH surgery, but it cannot replace histological study.

Intraoperative detection of parathyroid glands using artificial intelligence: optimizing medical image training with data augmentation methods.

BACKGROUND: Postoperative hypoparathyroidism is a major complication of thyroidectomy, occurring when the parathyroid glands are inadvertently damaged during surgery. Although intraoperative images are rarely used to train artificial intelligence (AI) because of its complex nature, AI may be trained to intraoperatively detect parathyroid glands using various augmentation methods. The purpose of this study was to train an effective AI model to detect parathyroid glands during thyroidectomy. METHODS: Video clips of the parathyroid gland were collected during thyroid lobectomy procedures. Confirmed parathyroid images were used to train three types of datasets according to augmentation status: baseline, geometric transformation, and generative adversarial network-based image inpainting. The primary outcome was the average precision of the performance of AI in detecting parathyroid glands. RESULTS: 152 Fine-needle aspiration-confirmed parathyroid gland images were acquired from 150 patients who underwent unilateral lobectomy. The average precision of the AI model in detecting parathyroid glands based on baseline data was 77%. This performance was enhanced by applying both geometric transformation and image inpainting augmentation methods, with the geometric transformation data augmentation dataset showing a higher average precision (79%) than the image inpainting model (78.6%). When this model was subjected to external validation using a completely different thyroidectomy approach, the image inpainting method was more effective (46%) than both the geometric transformation (37%) and baseline (33%) methods. CONCLUSION: This AI model was found to be an effective and generalizable tool in the intraoperative identification of parathyroid glands during thyroidectomy, especially when aided by appropriate augmentation methods. Additional studies comparing model performance and surgeon identification, however, are needed to assess the true clinical relevance of this AI model.

[Indications and technique for transoral thyroid gland and parathyroid gland surgery]. / Indikation und Technik der transoralen Schilddrüsen­/Nebenschilddrüsenchirurgie.

The conventional Kocher collar incision is the standard access to the thyroid and parathyroid glands. Although the incision length has been significantly shortened in recent years with this approach, there is increasing interest among patients in a surgical technique without visible scars in the décolleté. Transoral endoscopic thyroid gland surgery via the vestibular approach (TOETVA) is a modern technique that can be learned relatively quickly and leaves no visible scars because it is carried out exclusively through a natural orifice (natural orifice transluminal endoscopic surgery, NOTES). For retrieval of larger specimens, the transoral approach can be combined with a retroauricular access and thus covers a larger range of indications. The indications must be strictly followed, analogous to conventional surgery. Once the transoral access has been established, the operation is carried out as in open surgery but strictly from cranial to caudal. The classical complications are comparable to the results of conventional surgery. Specific complications include perioral, mandibular or cervical dysesthesia and hypesthesia.

[Clinical practice guideline for robotic surgical system-assisted thyroid and parathyroid surgery (2024 edition)].

The use of robotic operating systems is an advancement of intelligent precision, minimally invasive surgery. It has been used in the field of thyroid surgery with satisfactory results. Robotic surgery system assisted thyroid and parathyroid surgical expert consensus(2016) as played an important role in the standardization and clinical popularization of robotic surgical system-assisted thyroid and parathyroid surgery. With the deepening of clinical practice, updates in minimally invasive concept, the replacement of robotic platforms and the continuous improvement of technology, robotic thyroid and parathyroid surgery has been further developed. Notably, it has made substantial progress in expanding indications and the training of robotic surgeons and teams. Based on the 2016 Chinese expert consensus, combined with recent related articles and clinical studies, the Clinical Practice Guideline for Robotic Surgical System-Assisted Thyroid and Parathyroid Surgery (2024 edition) was formed. The surgical team training, indications, preoperative evaluation, patient position and space establishment, thyroidectomy procedures, neck lymph node dissection skills were summarized and recommended. Furthermore, reasonable suggestions on reoperation, parathyroid surgery and management of postoperative complications were also put forward, aiming to better guide clinical practice.

Localized 131 I Uptake in the Deltoid Muscle Bilaterally After Parathyroid Transplantation.

ABSTRACT: A 49-year-old woman patient with thyroid cancer accepted thyroidectomy and parathyroid transplantation. One month later, localized 131 I uptake in the deltoid muscle bilaterally was detected by 131 I whole-body imaging performed in 2 days after 131 I administration.

[Endoscopic assisted parathyroid surgery via a subclavian approach].

Objective:To explore the safety and efficacy of airless endoscopic surgery in the treatment of parathyroid diseases. Methods:By retrospective comparison, clinical treatment of 26 patients with primary hyperparathyroidism admitted to the Department of Otolaryngology and Head and Neck Surgery of the Hospital, Sun Yat-sen University from January 2018 to January 2023 were collected. They were divided into traditional group（13 cases） and endoscopic group（13 cases） according to the surgical method. The traditional group underwent traditional open parathyroid surgery, and the endoscopic group underwent airless endoscopic surgery through the subclavian approach. The efficacy, postoperative incision pain, incidence of adverse events, and aesthetic effects of the two groups were evaluated. Results:A total of 26 patients were included, including 13 patients in the traditional group and 13 patients in the endoscopic group. There was no significant difference in the incidence of hypocalcemia and transient hypoparathyroidism on the first day after surgery between the two groups（P>0.05）. No patients with incision pain（>3 points） or swallowing pain were found in both groups after the operation, and they were afraid or unwilling to cough and expel phlegm. There were no significant differences in the amount of blood loss, duration of operation, incidence of temporary recurrent laryngeal nerve palsy and transient hypocalcemia, and postoperative pain score between the two groups. The endoscopic group's scar evaluation score and aesthetic effect satisfaction score at 6 months after surgery were higher than those of the traditional group（P<0.01）. Conclusion:Airless Endoscopic parathyroid surgery via the subclavian approach has good effectiveness and safety, which did not significantly increase the risk of surgery. It can safely remove the lesion and leave no surgical scar on the anterior neck, which has the advantage of a good cosmetic effect. It is a safe and feasible endoscopic parathyroid surgery and can be used as a new choice for patients undergoing parathyroid surgery.

Is intraoperative parathyroid monitoring during minimally invasive parathyroidectomy still justified?

Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. With parathyroidectomy, a cure rate of over 95% at initial surgery is reported. Localization of the abnormal parathyroid gland is critical for the operation to be successful. The aim of this study is to analyze data of patients with single gland disease (SGD) and positive concordant localization imaging undergoing minimally invasive parathyroidectomy (MIP) and intraoperative parathyroid hormone monitoring (IOPTH) to evaluate if IOPTH is still justified in patients with localized SGD. Methods: A retrospective database analysis of all minimally invasive operations with IOPTH for PHPT and positive concordant localization in ultrasound (US) and 99mTc-sestamibi scintigraphy (MIBI) between 2016-2021. When both US and MIBI were negative, patients underwent either choline or methionine PET-CT. The patients were also analyzed a second time without applying IOPTH. Results: In total, 198 patients were included in the study. The sensitivity of US, MIBI and PET-CT was 96%, 94% and 100%, respectively. Positive predictive value was 88%, 89% and 94% with US, MIBI and PET-CT, respectively. IOPTH was true positive in 185 (93.4%) patients. In 13 (6.6%) patients, no adequate IOPTH decline was observed after localizing and extirpating the assumed enlarged parathyroid gland. Without IOPTH, the cure rate decreased from 195 (98.5%) to 182 (92%) patients and the rate of persisting disease increased from 2 (1.0%) to 15 (7.5%) patients. Conclusion: Discontinuing IOPTH significantly increases the persistence rate by a factor of 7.5 in patients with concordantly localized adenoma. Therefore, IOPTH appears to remain necessary even for this group of patients.

Development and Validation of an Explainable Machine Learning Model for Identification of Hyper-Functioning Parathyroid Glands from High-Frequency Ultrasonographic Images.

OBJECTIVE: To develop and validate a machine learning (ML) model based on high-frequency ultrasound (HFUS) images with the aim to identify the functional status of parathyroid glands (PTGs) in secondary hyper-parathyroidism (SHPT) patients. METHODS: This retrospective study enrolled 60 SHPT patients (27 female, 33 male; mean age: 51.2 years) with 184 PTGs detected from February 2016 to June 2022. All enrollments underwent single-photon emission computed tomography/computed tomography and contrast-enhanced ultrasound examinations. The PTGs were randomly divided into training (n = 147) and testing datasets (n = 37). Four effective ML classifiers were used and combined models incorporating multi-modal HFUS visual signs and radiomics features was constructed based on the optimal classifier. Model performance was compared in terms of discrimination, calibration and clinical utility. The Shapley additive explanation method was used to explain and visualize the main predictors of the optimal model. RESULTS: This model, using a random forest classifier algorithm, outperformed other classifiers. Based on optimal classifier features, the model constructed from ultrasound visual and ML features achieved a favorable performance in the prediction of hyper-functioning PTGs. Compared with the traditional visual model, the ultrasound-based ML model achieved significant (p = 0.03) improvement (area under the curve: 0.859 vs. 0.629) and higher sensitivity (100.0% vs. 94.1%) and accuracy (86.5% vs. 67.6%). Among the predictors attributed to model development, large size and high echogenic heterogeneity of PTGs in ultrasonographic images were more often associated with high risk of hyper-functioning PTGs. CONCLUSION: The ultrasound-based ML model for identifying hyper-functioning PTGs in SHPT patients showed good performance and interpretability using high-frequency ultrasonographic images, which may facilitate clinical management.

Comparison of opioid-free and opioid-inclusive propofol anaesthesia for thyroid and parathyroid surgery: a randomised controlled trial.

BACKGROUND: Postoperative nausea and vomiting occur frequently following thyroid and parathyroid surgery and are associated with worse patient outcomes. We hypothesised that opioid-free propofol anaesthesia would reduce the incidence of postoperative nausea and vomiting compared with opioid-inclusive propofol anaesthesia in patients undergoing these procedures. METHODS: We conducted a randomised, double-blinded controlled trial in adult patients scheduled to undergo thyroid and parathyroid surgery at two medical centres in mainland China. Patients were allocated randomly (1:1, stratified by sex and trial site) to an opioid-free anaesthesia group (esketamine, lidocaine, dexmedetomidine and propofol) or an opioid-inclusive group (sufentanil and propofol). Propofol infusions were titrated to bispectral index 45-55. Patients received prophylaxis for nausea and vomiting using dexamethasone and ondansetron and multimodal analgesia with paracetamol and flurbiprofen axetil. The primary outcome was the incidence of postoperative nausea and vomiting in the first 48 h after surgery. RESULTS: We assessed 557 patients for eligibility and 394 completed this trial. The incidence of postoperative nausea and vomiting in the first postoperative 48 h was lower in the opioid-free anaesthesia group (10/197, 5%) compared with opioid-inclusive group (47/197, 24%) (OR (95%CI) 0.17 (0.08-0.35), p < 0.001), yielding a number needed to treat of 5.3. Additionally, opioid-free propofol anaesthesia was associated with a reduced need for rescue anti-emetics, lower rates of hypotension and desaturation after tracheal extubation, and higher patient satisfaction. Time to tracheal extubation was prolonged slightly in the opioid-free group. The two groups had similar postoperative pain scores and 30-day outcomes. DISCUSSION: Opioid-free propofol anaesthesia reduced postoperative nausea and vomiting in patients undergoing thyroid and parathyroid surgery. An opioid-free anaesthetic regimen can optimise anaesthetic care during thyroid and parathyroid surgery.

Parathyroid Adenoma Orientation for Gland Embryologic Origin on Ultrasonography.

Importance: Accurate preoperative localization is critical to success in targeted parathyroidectomy for primary hyperparathyroidism. Objective: To determine if the association between the long axis of a parathyroid adenoma (PTA) candidate and strap musculature on sagittal ultrasonography (US) can be used to predict the embryologic origin of the gland. Design, Setting, and Participants: This diagnostic study was performed using the Stanford Research Repository. Patients 18 years or older with primary hyperparathyroidism who underwent parathyroidectomy between January 2009 and October 2021 were considered. Additional inclusion criteria were having clear sagittal view of the adenoma candidate on US, confirmation of the gland of origin intraoperatively, and confirmation of hypercellular parathyroid on final pathology. Data were analyzed from October 2021 to June 2022. Exposures: B-mode US and surgical parathyroidectomy. Main Outcomes and Measures: The index test was using US to measure the angle between the long axis of an adenoma candidate and the strap musculature in the sagittal plane. This angle was used to test whether inferior and superior PTAs could be accurately assigned. The hypothesis was formulated prior to data collection. Results: A total of 426 patients (mean [range] age, 61.1 [20-96] years; 316 [74.2%] female) with 442 adenomas met inclusion criteria. Of the 442 adenomas, 314 (71.0%) had measurable angles, of which 204 (46.2%) were assigned a superior origin, 238 (53.8%) were assigned an inferior origin, and 128 (29%) were indeterminate. Of the surgically identified superior PTAs, 144 (70.6%) had a definable angle, and of the surgically identified inferior PTAs, 170 (71.4%) had a definable angle. The receiver operating characteristic analysis found 94° as the optimized angle for differentiating true negatives from true positives, with an overall sensitivity of 74% and specificity of 72%. This supported using 90° as a break point for US review. True positives were considered superior adenomas with an angle greater than 90°; true negatives were inferior adenomas with an angle less than 90°. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of angulation analysis for determining PTA origin were 72.2% (95% CI, 64.9%-79.5%), 73.5% (95% CI, 66.9%-80.1%), 69.8% (95% CI, 62.5%-77.1%), 75.8% (95% CI, 69.3%-82.3%), and 72.9%, respectively. A subgroup analysis of 426 adenomas using the posterior carotid artery border on transverse US as a surrogate for predicting gland origin showed the following for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy: 49.5% (95% CI, 42.6%-56.4%), 82.3% (95% CI, 77.3%-87.3%), 71.4% (95% CI, 63.9%-78.9%), 64.6% (95% CI, 59.1%-70.1%), and 66.9%, respectively. Conclusions and Relevance: This diagnostic study showed that PTA angulation on sagittal plane US can be used to predict gland of origin and guide surgery. The relationship between adenoma and posterior carotid artery border on transverse US can also be used to predict gland origin. These easy-to-apply US-based tests can be used in conjunction with other imaging modalities to guide targeted parathyroidectomy.

The role of parathyroid autotransplantation for hypoparathyroidism following total thyroidectomy with bilateral central neck dissection.

Background: Hypoparathyroidism is the most common complication for patients who undergo total thyroidectomy (TT) with bilateral central lymph node dissection (BCLND). The objective of this retrospective study was to investigate the relationship between parathyroid autotransplantation (PA) and postoperative hypoparathyroidism. Materials and Methods: Four hundred and sixty-five patients with papillary thyroid carcinoma (PTC) who underwent TT with BCLND (including prophylactic and therapeutic BCLND) by the same surgeon were enrolled in this retrospective study. They were divided into five groups based on the number of PAs. Group 0 was defined as no PA, while Group 1, 2, 3, and 4 were considered as 1, 2, 3, and 4 PAs during TT with BCLND, respectively. Results: Transient and permanent hypoparathyroidism occurred in 83 (17.8%) and 2 (0.4%) patients who underwent TT and BCLND, respectively. The incidence of transient hypoparathyroidism increased gradually with an increase in the number of PAs. Compared with the previous group, Groups 2 and 3 had significantly more cases of transient hypoparathyroidism (p=0.03 and p=0.04, respectively). All cases of permanent hypoparathyroidism occurred in the patients without PA. Compared with Group 0, there were more removed central lymph nodes (RCLNs) in patients with one PA. Furthermore, Group 2 had more metastatic central lymph nodes(MCLNs) and RCLNs than Group 1.The number of PAs was the only identified risk factor for transient hypoparathyroidism after the multivariate logistic regression analysis. The median parathyroid hormone level recovered to the normal range within 1 month after surgery. Conclusion: With an increasing number of PAs, the possibility of transient hypoparathyroidism also increases in patients with PTC who undergo TT and BCLND. Considering the rapid recovery of transient hypoparathyroidism in 1 month, two PAs during TT and BCLND could be a good choice, leading to an increase in the central lymph node yield and no permanent hypoparathyroidism. However, this conclusion should be validated in future multicenter prospective studies.

[The role of immunohistochemical examination in the differential diagnosis of atypical tumors and carcinomas of parathyroid glands]. / Rol' immunogistokhimicheskogo analiza v differentsial'noi diagnostike atipicheskikh opukholei i kartsinom okoloshchitovidnykh zhelez.

Differential diagnosis of atypical parathyroid tumors (APT) and parathyroid carcinomas (PC) is important in determining further management and prognosis. Morphologic diagnosis is sometimes difficult, in which case it is supplemented by immunohistochemical (IHC) examination. OBJECTIVE: Studying the role of IHC analysis in the differential diagnosis of APT and PC. MATERIAL AND METHODS: The study included 44 patients with morphologic diagnosis of the APT established after surgical treatment for primary hyperparathyroidism on the basis of Endocrinology Research Centre during 2018-2023. All cases underwent IHC examination with evaluation of CD31/CD34 and parathormone (PTH) expression for identification of vascular invasion, Ki-67, parafibromin. RESULTS: According to the results of IHC analysis in 8/44 patients (18.2%) the diagnosis of APT was revised in favor of the PC: in 7 of them vascular invasion was detected; in 1 patient the additional series of slices in the surrounding fatty tissue revealed foci of tumor growth, confirmed by positive reaction with antibodies to PTH. According to IHC results, the material was divided into 2 groups: APT and PC. There were no differences in clinical and morphological characteristics, Ki-67% level and parafibromin expression between the groups. CONCLUSION: Assessment of clinical and laboratory-instrumental data at the preoperative stage does not allow differentiating APT from PC. In case of APT diagnosis and detection of suspicious morphological features, it is necessary to perform IHC examination to exclude PC.

Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue.

Studies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adult M. mulatta reveals a continuous trajectory of epithelial cell states. Pseudotime analysis based on transcriptomic signatures suggests a progression from GCM2 hi progenitors to mature parathyroid hormone (PTH)-expressing epithelial cells with increasing core mitochondrial transcript abundance along pseudotime. We sequenced, as a comparator, four histologically characterized hyperfunctioning human parathyroids with varying oxyphil and chief cell abundance and leveraged advanced computational techniques to highlight similarities and differences from non-human primate parathyroid expression dynamics. Predicted cell-cell communication analysis reveals abundant endothelial cell interactions in the parathyroid cell microenvironment in both human and NHP parathyroid glands. We show abundant RARRES2 transcripts in both human adenoma and normal primate parathyroid cells and use coimmunostaining to reveal high levels of RARRES2 protein (also known as chemerin) in PTH-expressing cells, which could indicate that RARRES2 plays an unrecognized role in parathyroid endocrine function. The data obtained are the first single-cell RNA transcriptome to characterize nondiseased parathyroid cell signatures and to show a transcriptomic progression of cell states within normal parathyroid glands, which can be used to better understand parathyroid cell biology.

Primary hyperparathyroidism caused by a tiny mediastinal parathyroid adenoma with non-localising imaging studies.

Variations in parathyroid gland positions often cause failure in initial parathyroid adenoma surgery, especially when imaging fails to localise the adenoma. This report describes a female patient with primary hyperparathyroidism for which preoperative localisation studies did not determine the position of the hyperfunctioning gland. The initial approach with bilateral cervical exploration and intraoperative parathyroid hormone monitoring was performed unsuccessfully. A mediastinal adenoma was suspected due to meticulous negative neck exploration and repeated negative images for a neck adenoma. Subsequently, a second approach involving mediastinal exploration was performed. After the removal of remnant thymic tissue in the mediastinal space, a significant drop in intraoperative parathyroid hormone levels was achieved. The pathological result confirmed the presence of a tiny pathological parathyroid adenoma within the thymus. At 6 months follow-up, postoperative biochemical assessment was consistent with normal calcium and parathyroid hormone levels.

Parathyroid Gland Generation from Pluripotent Stem Cells.

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.

Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration.

The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack in vivo similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.