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Purpose: This study compares the efficacy of two different ranges of parathyroid transplantation weights with the aim of determining a preferable range for transplantation weight., Methods: From May 2018 to June 2023, 79 patients underwent total parathyroidectomy with autotransplantation. Demographic data, symptoms, and pre- or postoperative biochemical indicators were compared between two different ranges of parathyroid transplantation weights., Results: All 79 surgeries were successful, with a total of 316 parathyroid glands reported among the patients. The patients were diagnosed with parathyroid hyperplasia. Postoperatively, itching, bone pain, and muscle weakness disappeared, while serum parathyroid hormone and phosphate levels significantly decreased. With an average follow-up of 12 months, no transplant-dependent recurrence was observed., Conclusion: Parathyroid transplantation with a weight of 30-50 mg is a feasible, safe, and effective surgical approach., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted following the principles stated in the Declaration of Helsinki. This study is an observational, retrospective research. Patients’ written informed consent for using health data was obtained before operation. The experimental protocol approved by the ethics committee of Liaoyang Central Hospital (ethical number:2024080107). Consent for publication Not applicable. Clinical trial number Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Parathyroid gland (PG) surgery is often challenging due to the small size and indistinct nature of these glands. The introduction of intraoperative near-infrared autofluorescence (NIRAF) has shown promise in localizing parathyroid tissue. However, the NIRAF features of parathyroid adenomas remain unclear. The aim of this study is to assess the NIRAF pattern of parathyroid adenomas., Methods: Patients who underwent surgery for primary hyperparathyroidism at the University Hospital of Pisa, Endocrine Surgery Unit, between December 2021 and February 2022 were enrolled in this study. Intraoperative NIRAF patterns of suspected parathyroid adenomas were evaluated, with particular attention given to the presence of a bright cap., Results: A retrospective study was conducted on 11 patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution. Histopathological examination of the 15 resected specimens confirmed 14 parathyroid adenomas (12 chief cell parathyroid adenomas, 1 oxyphil cell parathyroid adenoma, and 1 mixed cell parathyroid adenoma) and one schwannoma. All adenomas exhibited a heterogeneous NIRAF pattern, distinct from the homogeneous pattern observed in the schwannoma. A bright cap was identified in 9 out of 14 (64.3%) parathyroid adenomas (all chief cell adenomas). On the contrary, all 9 macroscopically normal PGs identified during surgery presented an homogeneous pattern., Conclusion: Our findings support the integration of NIRAF into parathyroid surgical procedures. The heterogeneous NIRAF pattern observed in parathyroid adenomas, often accompanied by a bright cap, offers a promising intraoperative diagnostic tool to differentiate hyperfunctioning from normal parathyroid tissue. Larger-scale randomized trials are warranted to further validate these findings., (© 2024. The Author(s).)

Importance: The success of parathyroidectomy depends on accurate intraoperative localization and identification of all diseased glands in parathyroid exploration based on surgeon expertise to prevent persistent hyperparathyroidism. Near-infrared autofluorescence (NIRAF) imaging has recently emerged as a promising adjunctive intraoperative tool for localizing parathyroid glands; however, its potential utility in the assessment of parathyroid glands has yet to be established., Objective: To analyze the differences in NIRAF signatures of parathyroid glands in single vs multiple glands in primary hyperparathyroidism (pHPT)., Design, Setting, and Participants: This prospective diagnostic study analyzed in vivo NIRAF images of parathyroid glands obtained during parathyroidectomies between November 18, 2019, and December 31, 2023, at a single tertiary referral center. Pixel intensities of the images were measured using third-party software. Patients who underwent parathyroidectomy for sporadic pHPT using a second-generation NIRAF imaging device were included. Patients with multiple endocrine neoplasm disorders were excluded. In vivo NIRAF images obtained during the procedures were analyzed., Exposure: Near-infrared autofluorescence imaging during parathyroidectomy., Main Outcomes and Measures: The primary outcomes were the autofluorescence intensity and heterogeneity of single adenomas and multigland disease (ie, double adenomas and 3- or 4-gland hyperplasia) in sporadic pHPT. Normalized autofluorescence intensity was calculated by dividing the mean pixel intensity of the parathyroid gland by the background tissue. A heterogeneity index was calculated by dividing the standard deviation by the mean pixel intensity of the gland. The secondary outcome was the visibility of each parathyroid gland on NIRAF imaging before it became apparent to the naked eye during exploration., Results: A total of 1287 in vivo NIRAF images obtained from 377 patients (median [IQR] age, 66 [56-73] years; 299 female [79.3%]) were analyzed. Of all patients, 230 (61.0%) had a single adenoma, 91 (24.1%) had double adenomas, and 56 (14.9%) had 3- or 4-gland hyperplasia. A mean (SD) of 3.4 (1.1) parathyroid glands were identified in the procedures. A comparison of 581 diseased glands (45.1%) and 706 normal glands (54.9%) showed a lower median normalized autofluorescence intensity of 2.09 (95% CI, 1.07-4.01) vs 2.66 (95% CI, 1.43-4.20; effect size = 0.36) and higher heterogeneity index of 0.18 (95% CI, 0.07-0.41) vs 0.11 (95% CI, 0.01-0.27; effect size = 0.45), respectively. Of diseased glands, single adenomas (233 [40.1%]) vs double adenomas (187 [32.2%]) and 3- or 4-gland hyperplasia (161 [27.7%]) had a lower median autofluorescence intensity of 1.92 (95% CI, 1.02-4.44) vs 2.22 (95% CI, 1.10-3.97; effect size = 0.21), respectively. On receiver operating characteristic analysis, the optimal autofluorescence intensity threshold to differentiate between single adenomas vs multigland disease was 2.14, with a sensitivity of 64.4%, specificity of 58.1%, and area under the curve of 0.626., Conclusions and Relevance: These findings suggest that parathyroid glands in single- vs multigland disease may exhibit different autofluorescence characteristics. Although the effect size was modest, the differences identified should be kept in mind when assessing the parathyroid glands during surgical exploration.

Background: Preserving parathyroid function during thyroidectomy is crucial, but remains challenging. Real-time near-infrared autofluorescence (NIRAF) aids surgeons in intraoperative parathyroid gland (PTG) identification. However, its role in detecting PTGs unintentionally removed during surgery is unclear., Study Design: This prospective study included adult patients undergoing endoscopic thyroidectomy. Surgeons identified and documented PTGs visually. Excised specimens underwent visual inspection and NIRAF imaging (PDE-Neo II). All fluorescent tissues were dissected and pathologically evaluated (reference standard). One scanned image per lobe was chosen to quantify autofluorescence (AF) intensity., Results: Overall, 95 patients underwent endoscopic thyroidectomies, with NIRAF imaging applied to 152 excised lobes. Of these, 19 lobes displayed a total of 23 spots with increased intensity. 175 specimens were sent for pathological evaluation, and 7 were confirmed to be parathyroid tissue. NIRAF demonstrated 100.0 % sensitivity and 90.5 % specificity for predicting parathyroid tissue, with 30.4 % positive predictive value, 100.0 % negative predictive value of and 90.9 % accuracy. Quantitatively normalized, the AF signal intensity was significantly higher in NIRAF-positive tissues than negative (4.3 vs 1.2 times, p < 0.0001). Additionally, the AF signal intensity in regions pathologically confirmed of parathyroid tissue was higher than non-parathyroid tissue (9.1 vs 2.1 times, p < 0.0001)., Conclusion: This study suggests that NIRAF has high sensitivity and specificity for detecting inadvertently resected PTGs after endoscopic thyroidectomy, contributing to preservation efforts. However, NIRAF-positive tissues still require additional confirmation through multiple methods, emphasizing other examinations to verify that they are indeed parathyroid tissues. Further research is warranted to refine NIRAF imaging parameters., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Ectopic parathyroid carcinoma (EPC) is a rare clinical entity with multiple diagnostic pitfalls, making surgical cures challenging. We assessed the clinicopathological spectrum and outcome of EPCs., Methods: In this retrospective cohort study, 24 EPCs were identified from 133 PC patients treated at a tertiary referral center. The relationship between clinicopathological findings and locations was analyzed., Results: The locations of EPCs were predominantly intrathyroidal (62.5%), followed by 16.7% in the mediastinum, 8.3% in the retropharyngeal space, 8.3% in the carotid sheath, and 4.2% in the upper neck. Intrathyroidal EPC patients experienced higher serum calcium (p = 0.020), a higher rate of vascular invasion (p = 0.040), and a slightly higher incidence of non-R0 initial resection (p = 0.092) than those in other ectopic locations. Intrathyroidal EPC patients also suffered a trend of higher upper aerodigestive tract (UAT) invasion rate (p = 0.070) and higher risks of distant metastasis (p = 0.037) than the other PC patients. The 5-year disease-free survival rate after surgery was slightly compromised at 41.5% in intrathyroidal EPC patients compared with 77.8% among those in other ectopic locations (p = 0.143) and 59.7% among the other PC patients (log-rank = 3.194; p = 0.074), though without statistical significance., Conclusion: Intrathyroidal EPC might cause a more biochemically and invasively distinct PC picture compared with other PCs. Special caution should be exercised in the preoperative diagnosis and management of such cases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: 18 F-fluorocholine PET/CT is considered the imaging gold standard for detection of hyperfunctioning parathyroid glands . However, increased uptake might also occur in the thyroid gland. The aim of our study was to assess the incidence and significance of 18 F-fluorocholine uptake in the thyroid gland in patients with hyperparathyroidism., Materials and Methods: This retrospective study includes 195 consecutive patients with hyperparathyroidism, who underwent 18 F-fluorocholine PET/CT, for detection of hyperfunctioning parathyroid glands. PET/CT images were reviewed by two nuclear medicine physicians for the presence of focal or diffuse thyroid uptake. PET/CT results were compared with laboratory parameters, ultrasonography, EU-TIRADS classification in the presence of thyroid nodules, cytology, and final histology., Results: 25 patients (13%) showed 18 F-fluorocholine uptake in the thyroid gland: focal thyroid uptake (FTU) in 7 patients (4%), diffuse thyroid uptake (DTU) in 8 patients (4%), and combined uptake (FTU + DTU) in 10 patients (5%), with a total of 20 active thyroid nodules. There was no correlation between EU-TIRADS classification and PET parameters. One highly 18 F-fluorocholine active thyroid nodule and one isoactive thyroid nodule turned out to be papillary thyroid cancers in the final histology; 50% of the patients with DTU had Hashimoto's thyroiditis., Conclusion: Incidental 18 F-fluorocholine uptake in the thyroid gland was observed in 13% of patients. As reported for 18 F-FDG, focal 18 F-fluorocholine uptake might represent thyroid cancer and should be evaluated with ultrasound and, if indicated, with fine-needle aspiration cytology. Diffuse 18 F-fluorocholine uptake most likely represents multinodular goiter or Hashimoto's thyroiditis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In thyroidectomy and parathyroidectomy procedures, diagnostic dilemmas related to whether an index tissue is of parathyroid or nonparathyroid origin frequently arise. Current options of frozen section and parathyroid aspiration are time-consuming. Parathyroid glands appear brighter than surrounding tissues on near-infrared autofluorescence imaging. The aim of this study was to develop an artificial intelligence model differentiating parathyroid tissue on surgical specimens based on near-infrared autofluorescence., Methods: With institutional review board approval, an image library of ex vivo specimens obtained in thyroidectomy and parathyroidectomy procedures was created between November 2019 and April 2023 at a single academic center. Ex vivo autofluorescence images of surgically removed parathyroid glands, thyroid glands, lymph nodes, and thymic tissue were uploaded into an artificial intelligence platform. Two different models were trained, with the first model using autofluorescence images from all specimens, including thyroid, and the second model excluding thyroid, to prevent the effect of specimen size on the results. Deep-learning models were trained to detect autofluorescence signals specific to parathyroid glands. Randomly chosen 80% of data were used for training, 10% for validation, and 10% for testing. Recall, precision, and area under the curve of models were calculated., Results: Surgical procedures included 377 parathyroidectomies, 239 total thyroidectomies, 97 thyroid lobectomies, and 32 central neck dissections. For the development of the model, 1151 images from a total of 678 procedures were used. The dataset comprised 648 parathyroid, 379 thyroid, 104 lymph node, and 20 thymic tissue images. The overall precision, recall, and area under the curve of the model to detect parathyroid tissue were 96.5%, 96.5%, and 0.985, respectively. False negatives were related to dark and large parathyroid glands., Conclusion: The visual deep-learning model developed to identify parathyroid tissue in ex vivo specimens during thyroidectomy and parathyroidectomy demonstrated a high sensitivity and positive predictive value. This suggests potential utility of near-infrared autofluorescence imaging to improve intraoperative efficiency by reducing the need for frozen sections and parathyroid hormone aspirations to confirm parathyroid tissue., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Primary hyperparathyroidism represents the third most prevalent endocrine disease in the general population, consisting of an excessive secretion of parathyroid hormone from one or, more frequently, more of the parathyroid glands, leading to a dysregulation of calcium homeostasis. Schematically, its development occurs primarily by pathophysiological events with genetic mutation, at the germline and/or somatic level, that favor the neoplastic transformation of parathyroid cells and promote their aberrant proliferation, and mutations determining the shift in the PTH "set-point", thus interfering with the normal pathways of PTH secretion and leading to a "resetting" of Ca 2+ -dependent PTH secretion or to a secretion of PTH insensitive to changes in extracellular Ca 2+ levels. Familial syndromic and non-syndromic forms of primary hyperparathyroidism are responsible for approximately 2-5% of primary hyperparathyroidism cases and most of them are inherited forms. The history of the genetic/molecular studies of parathyroid tumorigenesis associated with multiple endocrine neoplasia type 1 syndrome (MEN1) represents an interesting model to understand genetic-epigenetic-molecular aspects underlying the pathophysiology of primary hyperparathyroidism, both in relation to syndromic and non-syndromic forms. This minireview aims to take a quick and simplified look at the MEN1-associated parathyroid tumorigenesis, focusing on the molecular underlying mechanisms. Clinical, epidemiological, and observational studies, as well as specific guidelines, molecular genetics studies, and reviews, have been considered. Only studies submitted to PubMed in the English language were included, without time constraints.

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., (Copyright © 2024 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: This study aimed to explore the value of preoperative total parathyroid volume (TPV) as a marker for predict recurrence of renal secondary hyperparathyroidism (SHPT)., Methods: We identified 28 patients with recurrence and 128 without recurrence who underwent total parathyroidectomy with autotransplantation (tPTX + AT) at our institution between 2015 and 2022. The TPV and postoperative recurrence information of the patients were recorded. Within the intergroup comparison, data obtained from the recurrence and non-recurrence groups were evaluated using the t-test. Univariate and multivariate analyses were performed according to the regression model to determine factors that were significant in predicting postoperative recurrence. The cutoff value of TPV was determined using a receiver operating characteristic (ROC) curve., Results: The mean TPV of recurrence and no-recurrence groups were 2.99 ± 1.52 cm 3 and 1.73 ± 1.19 cm 3 , respectively ( p  = 0.007). In univariate analysis, female sex, total parathyroid volume > 1.99 cm 3 , serum PTH > 928.37 pg/mL and p  > 1.59 mmol/L were independent factors for SHPT recurrence. In multivariable analysis, TPV > 1.99 cm 3 , serum parathyroid hormone (PTH) > 928.37 pg/mL and p  > 1.59 mmol/L were independent factors for SHPT recurrence. The ability of TPV to distinguish between recurrence and non-recurrence was evaluated using the ROC curve. The cutoff value of TPV was estimated as 2.65 cm 3 . With this value, sensitivity was found as 60.70%, specificity was 89.80%, and AUC was 0.80 ( p  < 0.001, confidence interval =0.719-0.882)., Conclusion: According to the data in this study, it can be said that TPV can be used to distinguish recurrence from no-recurrence. Most importantly, TPV can be used to identify SHPT recurrence.

Purpose: To evaluate the potential benefit of adding a low frequency vascular probe to the conventional pre-operative ultrasound examination of patients with primary hyperparathyroidism., Methods: A prospective cohort of 136 patients with primary hyperparathyroidism underwent a conventional ultrasound examination of the neck with a high frequency ( > 10 MHz) linear ultrasound probe, followed by an add-on examination with a low frequency vascular probe. For each ultrasound probe, and for every potential parathyroid lesion, the presence of a feeding vessel, a polar placement of the feeding vessel, and the presence of a vascular arch was recorded., Results: A total of 146 ultrasound lesions were evaluated for vascularity by each probe. For both ultrasound probes, the odds of a hyperfunctioning parathyroid gland being correctly identified increased with the number of visible vascular features. The vascular probe identified a significantly higher number of vascular features among ultrasound true positive glands compared with the conventional probe (p < 0.0001). Among histopathologically verified pathological parathyroid glands, the vascular probe identified 20% more feeding vessels, 27% more polar placements of the feeding vessel, and 65% more vascular arches than the high frequency probe. However, the diagnostic confidence score for true positive glands did not differ significantly between the probes (p = 0.11)., Conclusion: The addition of a low frequency vascular probe increases the number of visible vascular features in hyperfunctioning parathyroid glands, which facilitates their preoperative detection. Whether or not this can increase the diagnostic confidence of ultrasound examiners has yet to be substantiated., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethics approval The study was carried out in accordance with the ethical principles of the 1964 Declaration of Helsinki and its later amendments. The study is registered at ClinicalTrials.gov (NCT04305561) and has been approved by the Regional Committees on Health Research Ethics for Southern Denmark (project ID S-20190077). Consent to participate Written informed consent was obtained from all participants in this study., (© 2024. The Author(s).)

Ectopic parathyroid adenomas are an uncommon etiology of primary hyperparathyroidism. We present a case of a patient admitted to the hospital with severe hypercalcemia and elevated parathyroid hormone levels, in whom imaging revealed two distinct parathyroid masses in the prevertebral space, representing a rare and atypical location for parathyroid tissue. This case highlights the importance of considering ectopic parathyroid adenomas as a potential cause of hyperparathyroidism and discusses the diagnostic challenges and management strategies associated with such cases., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. The Author(s).)

Background: Recognizing the parathyroid gland and distinguishing the parathyroid from thyroid lesions in fine needle aspiration (FNA) is challenging. This study aimed to identify cytomorphologic features suggestive of parathyroid origin and to assess the utility of cytopathology in conjunction with ancillary tests in the identification of parathyroid glands., Materials and Methods: Ultrasound (US) guided FNA of parathyroid gland and lesions in 81 patients were reviewed concerning clinical history and correlated to histopathologic findings in available cases. FNA smears were evaluated for cellularity, architectural patterns, cellular and nuclear features, and background of the smears. In 78 cases, FNA was supplemented by a measurement of parathormone (PTH) levels in the needle washout fluid (FNA-PTH assay) and/or GATA3/PTH/chromogranin-A immunostainings., Results: Sixty-four cases were diagnosed cytologically as parathyroid lesions in conjunction with FNA-PTH assay and/or immunocytochemical examinations. In an additional nine cases, a diagnosis of parathyroid lesions was rendered after repeated FNA with FNA-PTH assay. The histolopathologic diagnosis of surgically excised cases (n = 75) included parathyroid adenoma (60 cases), atypical parathyroid adenoma (4 cases), parathyroid hyperplasia (10 cases), and parathyroid carcinoma (1 case). Major cytological findings of parathyroid tissue included high cellularity, scattered naked nuclei, cribriform and three-dimensional clusters, stippled chromatin, and oxyphilic cytoplasm while papillary pattern or colloid-like material was identified in three cases respectively. No nuclear grooves or inclusions were seen in any case., Conclusions: High cellularity scattered naked nuclei, cribriform and three-dimensional patterns, stippled chromatin and oxyphilic cytoplasm are cytomorphologic features that favour parathyroid origin. A combination of these features with FNA-PTH assay and/or GATA3, PTH, and chromogranin-A immunostainings on cytologic specimens aid in the identification of parathyroid glands and the distinguishing of parathyroid from thyroid lesions., (© 2024 John Wiley & Sons Ltd.)

Objective: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm., Methods: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected., Results: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns., Conclusion: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.

This is a case of primary hyperparathyroidism in a female teenager with multiple fractures and severe bone manifestations. The histopathology revealed atypical parathyroid adenoma, an exceedingly rare form of hyperparathyroidism; its main differential diagnosis is parathyroid carcinoma, as it shares both clinical and histological characteristics with it, in addition to its still uncertain malignant potential., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperparathyroidism (HPT) is a disease caused by hypersecretion of one or more parathyroid glands, it can be associated with ectopic mediastinal parathyroid glands (MEPA) in 2% of cases. The use of video-assisted thoracoscopic surgery (VATS) for the surgical resection of these glands is a safe, cost-effective, and low morbidity option for patients with MEPA. We report a case series of patients with this disease managed with VATS, the first in Mexico and Latinamerica., Methods: From 2008 to 2022, a retrospective study involving patients with MEPA and treated by VATS approach was performed in a tertiary hospital in Mexico city. Relevant biochemical and clinical variables such as imaging studies, pre and postoperative laboratory results, surgical strategy, outcomes and pathological analysis were analyzed., Results: Four cases of mediastinal parathyroid adenomas causing HPT were included. All patients were female with a median age of 52.5 years-old (range 46-59 years), half of the patients had primary HPT and the others tertiary HPT after kidney transplant. 75% of cases had a MEPA in the medium mediastinum, all had a preoperative positive SPECT-CT 99mTc Sestamibi scan. Mean preoperative PTH was 621.3pg/mL (182-1382pg/mL). All patients successfully underwent parathyroidectomy with a VATS approach, no deaths were reported., Conclusions: VATS is a minimally invasive surgery that provides adequate access to mediastinal located glands, optimal visualization of mediastinal structures and has a high resection success rate with less complications and morbidity than open approaches., (© 2024. The Author(s).)

Background: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited., Methods: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform., Findings: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia., Interpretation: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule., Funding: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to assess the diagnostic performance of 99m Tc-sestamibi SPECT/CT and 18 F-choline PET/CT in detecting hyperfunctioning parathyroid glands in patients undergoing surgery for primary hyperparathyroidism (PHPT)., Methods: A retrospective analysis was conducted on patients who underwent PHPT-related surgery between April 2019 and May 2022. The study focused on patients undergoing either 99m Tc-sestamibi SPECT/CT (81 patients) or 18 F-choline PET/CT (33 patients) scans before surgery to pinpoint hyperfunctioning parathyroid gland(s). In the majority of patients, 18 F-choline PET/CT was performed after negative or inconclusive findings on 99m Tc-sestamibi SPECT/CT. Pathohistological reports were utilized as the reference standard for evaluating the accuracy of the imaging findings., Results: The study encompassed 83 patients (70 females, 84.3%) with an average age of 57.2 years (24-80 years). The pathohistological analysis identified a total of 98 glands. In a per-lesion analysis, the detection rate of 99m Tc-sestamibi SPECT/CT was 57% (95% CI 45.3-68.1), while the detection rate of 18 F-choline PET/CT was 90.3% (95% CI 74.3-98.0)., Conclusion: The results of our study showed the significant usefulness of 18 F-choline PET/CT in patients with negative or inconclusive results of 99m Tc-sestamibi SPECT/CT in accurately locating hyperfunctioning parathyroid glands in PHPT patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To investigate the effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery. Methods: This study was a cross-sectional study. Patients who underwent surgery for papillary thyroid cancer (PTC) at the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University between January 2022 and September 2023 were included. All patients underwent thyroid lobectomy or total resection, and central lymph node dissection was performed at the same time. During the operation, tracing injection of mitoxantrone hydrochloride and 785 nm and 660 nm dual fluorescence imaging technique were used to measure the fluorescence intensity (FI) of parathyroid glands, central lymph nodes and background. After correcting to obtain the standardized FI, the paired t -test was used to compare the standardized FI of the parathyroid glands and central lymph nodes, and the Spearman's rank correlation analysis was used to analyze the relationship between the standardized FI and various clinical indicators. Results: The study included 30 patients (8 males and 22 females), with a mean age of (41.8±10.4) years. A total of 76 parathyroid glands and 234 central lymph nodes were identified under dual fluorescence imaging, and the standardized FI of parathyroid glands was less than that of central lymph nodes (44.7±16.8 vs 99.5±28.4, P <0.001). The visualization rate, false rate and miscut rate of parathyroid glands under 785 nm wavelength excitation light were 98.7% (76/77), 0 (0/77) and 1.3% (1/77), respectively (one case with no visualization and miscutting parathyroid gland was the encapsulated type). The visualization rate of central lymph nodes under 660 nm wavelength excitation light was 98.7% (234/237). There was no significant correlation between FI and clinical indicators such as gender, age, height, weight, body mass index, preoperative thyroid stimulating hormone, thyroglobulin antibody, thyroid microsomal antibody, serum calcium, parathyroid hormone level and surgical procedure (all P >0.05). Conclusion: Dual fluorescence imaging of central lymph nodes and parathyroid glands can improve the ability to identify parathyroid gland while assisting central lymph node dissection.

Background: The purpose of our study was to determine the frequency and management of intrathyroidal parathyroid glands in patients with primary hyperparathyroidism and evaluate whether intrathyroidal parathyroid glands were more often superior or inferior glands., Methods: A retrospective review of the prospective parathyroid database was completed to determine the number of patients with primary hyperparathyroidism and an intrathyroidal parathyroid gland. Demographic data, laboratory and localization studies, operative management, pathology, and outcome were determined for patients with an intrathyroidal parathyroid gland and were compared with patients with an extrathyroidal parathyroid gland., Results: From 1990-2023, 808 patients were operated on for primary hyperparathyroidism; 17 (2%) patients had an intrathyroidal parathyroid gland, an adenoma in 15 (88.2%), and a hyperplastic gland in 2 (11.8%). The mean age was 53 years; 16 (94%) patients were female. Mean calcium and parathyroid hormone was 12 mg/dL and 150 pg/mL, and there were no differences from the extrathyroidal parathyroid group. Ultrasound and Sestamibi imaging were valuable in identifying an intrathyroidal parathyroid gland in 10 of 13 patients and 13 of 17 patients, respectively. Local excision was performed in 9 (53%) patients and lobectomy in 8 (47%) patients. Intraoperative parathyroid hormone was measured and predictive of cure in 12 patients. The location of intrathyroidal parathyroid glands was determined in 15 patients and was inferior in 11 (73%). All patients were cured. No patient developed recurrent disease after a median 54-month follow-up., Conclusion: Intrathyroidal parathyroid glands are the cause of primary hyperparathyroidism in 2% of patients and are most often inferior glands. Local excision was accomplished in 53% of our patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Parathyroid carcinoma is a rare endocrine tumor. Parathyroid carcinoma in patients with secondary hyperparathyroidism due to chronic kidney disease is also rare. In addition, thyroid hemiagenesis is a rare congenital anomaly. We report an extremely rare case of parathyroid carcinoma in a patient with secondary hyperparathyroidism and thyroid hemiagenesis. We also present a review of the literature of this rare entity. We also discuss the surgical procedure performed for this patient. Our review of the literature found 34 case reports of parathyroid carcinoma in patients undergoing dialysis due to chronic renal failure; 14 reports of thyroid hemiagenesis with parathyroid disease; and no previous reports of thyroid hemiagenesis with secondary hyperparathyroidism and parathyroid carcinoma. Although surgical treatment of parathyroid carcinoma requires combined resection with the thyroid, peritracheal dissection with total parathyroidectomy, and monitoring intact parathyroid hormone as a tumor marker, our procedure preserved the patient's thyroid function. There has been no evidence of recurrence for over 8 years., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The parathyroid cell is a vital regulator of extracellular calcium levels, operating through the secretion of parathyroid hormone (PTH). Despite its importance, the regulation of PTH secretion remains complex and not fully understood, representing a unique interplay between extracellular and intracellular calcium, and hormone secretion. One significant challenge in parathyroid research has been the difficulty in maintaining cells ex vivo for in-depth cellular investigations. To address this issue, we introduce a novel platform for parathyroid cell transplantation and noninvasive in vivo imaging using the anterior chamber of the eye as a transplantation site. We found that parathyroid adenoma tissue transplanted into the mouse eye engrafted onto the iris, became vascularized, and retained cellular composition. Transplanted animals exhibited elevated PTH levels, indicating a functional graft. With in vivo confocal microscopy, we were able to repetitively monitor parathyroid graft morphology and vascularization. In summary, there is a pressing need for new methods to study complex cellular processes in parathyroid cells. Our study provides a novel approach for noninvasive in vivo investigations that can be applied to understand parathyroid physiology and pathology under physiological and pathological conditions. This innovative strategy can deepen our knowledge on parathyroid function and disease., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

Background: Near-infrared autofluorescence imaging is an adjunct to parathyroid identification. As it does not show perfusion, it is important to study its impact during thyroidectomy by measuring quantifiable data on parathyroid detection rather than function. The aim of this study was to compare incidental parathyroidectomy rates in patients undergoing total thyroidectomy with or without near-infrared autofluorescence., Methods: Retrospective study of patients who underwent total thyroidectomy between 2014 and 2022 at one center. Clinical parameters, including rates of incidental parathyroid tissue on pathology reports, were compared between near-infrared autofluorescence and non-near-infrared autofluorescence groups. Near-infrared autofluorescence was used to guide dissection (identification) and/or to confirm tissue as parathyroid (confirmation). Statistical analysis was done with Wilcoxon rank sum test and χ 2 analysis., Results: There were 300 patients in the near-infrared autofluorescence and 750 patients in the non-near-infrared autofluorescence group. The rate of incidental parathyroid tissue detection on final pathology was 13.3% (n = 40) in the near-infrared autofluorescence and 23.2% (n = 174) in the non-near-infrared autofluorescence group (P < .001). The rate of incidental parathyroid tissue detected on pathology with near-infrared autofluorescence decreased when used for identification and confirmation of parathyroid tissue (30.0% to 13.4%, P < .001), but not when used for confirmation only (19.6% to 18.5%, P = .89). Impact of near-infra red autofluorescence in decreasing the rate of incidental parathyroid tissue was more profound for early (38.5% to 17.1%) versus mid-late career surgeons (20% to 13%)., Conclusion: Our results suggest that the use of near-infrared autofluorescence may help decrease the rate of incidental parathyroid tissue detected on final pathology if used for both identification and confirmation of parathyroid glands during thyroidectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic MGD is more common and affects a similar patient profile as single gland parathyroid disease (SGD). The distinction between SGD and MGD is of great clinical importance, especially for the strategy of parathyroidectomy. Based on the limited knowledge available, MGD is likely to be a genetically heterogeneous disease resulting from the interaction of germline and somatic DNA mutations together with epigenetic alterations. Furthermore, these events may combine and occur independently in parathyroid tumors within the same individual with MGD. Gene expression profiling has shown that SGD and MGD may represent distinct entities in parathyroid tumorigenesis. We are waiting for studies to analyze exactly which genes are different in SGD and MGD in order to identify potential biomarkers that can distinguish between the two forms of the disease.

Spontaneous or fine-needle aspiration (FNA)-induced remission of primary hyperparathyroidism (PHPT) is an extremely rare phenomenon with variable outcomes. We report a 75-year-old Male who initially presented with left ureteric calculi and was found to have PHPT. Imaging studies including ultrasound neck, parathyroid sestamibi scan and computed tomography of thorax, abdomen, and pelvis failed to identify the culprit lesion and exploratory parathyroidectomy was planned. Before surgery, he underwent FNA for cytology of a right cold thyroid nodule which was complicated with a large neck haematoma and dysphagia. The cytology of the aspirated fluid was consistent with a benign cyst. One month after the procedure, serum calcium and phosphate normalised along with resolution of haematoma. He remained in biochemical remission at 1-year follow-up with the latest ultrasound of neck showing resolution of a large colloid nodule that was previously seen occupying the right thyroid lobe., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism. In this study, we developed a new method of parathyroid cell differentiation from human induced pluripotent stem (iPS) cells. Parathyroid cell differentiation occurred in accordance with embryologic development. Differentiated cells, which expressed the parathyroid hormone, adopted unique cell aggregation similar to the parathyroid gland. In addition, these differentiated cells were identified as calcium-sensing receptor (CaSR)/epithelial cell adhesion molecule (EpCAM) double-positive cells. Interestingly, stimulation with transforming growth factor-α (TGF-α), which is considered a causative molecule of parathyroid hyperplasia, increased the CaSR/EpCAM double-positive cells, but this effect was suppressed by erlotinib, which is an epidermal growth factor receptor (EGFR) inhibitor. These results suggest that TGF-α/EGFR signaling promotes parathyroid cell differentiation from iPS cells in a similar manner to parathyroid hyperplasia.

Background: Parathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery are challenging. We describe a rare case of recurrent hyperparathyroidism due to synchronous parathyroid carcinoma and parathyromatosis., Case Presentation: A 46-year-old Chinese woman was diagnosed with end-stage renal disease and received regular hemodialysis. Four years later, she experienced discomfort due to itching and was diagnosed with drug-resistant secondary hyperparathyroidism. Parathyroidectomy was performed, and her parathyroid hormone (PTH) levels were reduced. The pathology also revealed that the four nodules were parathyroid nodular hyperplasia without evidence of malignancy. Five years after surgery, the right subcutaneous nodule and left inferior nodule were detected by multiple imaging modalities, and the nodules were accompanied by recurrence itching and elevation of PHT. A complete resection of two nodules was performed, and the patient was diagnosed with parathyroid carcinoma and parathyromatosis. At 8 months postsurgery, her PHT and serum calcium levels were stable, and there were no signs of recurrence., Conclusions: This is a rare case of synchronous parathyroid carcinoma and parathyromatosis in a patient with secondary hyperparathyroidism after parathyroidectomy. We suggest meticulous handling of parathyroid hyperplasia to avoid rupture and spillage during surgery, and precise pro-operation location by multiple imaging modalities is crucial for successful parathyroidectomy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Secondary hyperparathyroidism (sHPT) is a compensatory complication of chronic kidney disease. The aim of this study was to compare PS findings in pediatric and adult patients with sHPT., Methods: This study included 50 pediatric and 50 adult patients with sHPT. Parathyroid scintigraphy was performed with Tc-99m sestamibi. After radiopharmaceutical injection, early-phase (15 min) and late-phase (60-90 min) images were acquired. Planar images were interpreted visually for the presence / number of active foci compatible with a parathyroid lesion, the presence and degree of uptake in skeletal structures, and the degree of thyroid sestamibi uptake. Parathyroid surgery was performed in 21 pediatric and 28 adult patients., Results: Serum PTH and ALP values were significantly higher in pediatric than in adult patients ( P < 0.05 for each). In operated patients, on a lesion-based analysis, the sensitivity of PS in pediatric and adult patients were 40% and 71%, respectively. A nonlocalizing scan was observed in 24% of pediatric patients. Pediatric patients had a higher incidence of reduced thyroid sestamibi uptake (42% versus 2%). Skeletal sestamibi uptake was detected in 40% of pediatric and 30% of adult patients and the degree of uptake was higher in pediatric patients., Conclusions: The results revealed more significant changes in the biochemical profile of pediatric compared with adult patients with sHPT. The sensitivity of PS was lower, and the likelihood of a nonlocalizing scan was higher in pediatric patients. The results may also suggest more severe skeletal findings in pediatric patients. Reduced thyroid sestamibi uptake in children needs further evaluation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Primary hyperparathyroidism is a common endocrine disorder. Interestingly, the majority (75%) of parathyroid tumors are localized to the inferior parathyroid glands. To date, the reason for this natural bias has not been investigated. We assessed the global gene expression profile of superior and inferior glands obtained from forensic autopsies. The genes with significant differential expression between superior and inferior parathyroids were further assessed by RT-PCR in 19 pairs. As an iterative approach, additional genes with an established role in parathyroid disorders, i.e., CASR, MAFB, PAX9, TBCE, TBX1, VDR, MEN1, CCND1, and CDC73 were also evaluated by RT-PCR in all 19 pairs of superior and inferior parathyroid glands. Seven homeobox genes, namely HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, and one encoding for ALDH1A2 showed a lower expression in the inferior parathyroid glands than in the superior. Conversely, SLC6A1 showed a higher expression in the inferior glands. Of the nine genes with significant differential mRNA expression among superior and inferior glands HOXB9, HOXB4 and IRX1 could be detected by western blotting/mass spectrometry. The study is the first to show the differential expression of nine genes HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, ALDH1A2, and SLC6A1 in inferior versus the superior parathyroid glands. This could have potential implications for the preferential localization of parathyroid tumors to the inferior parathyroid glands as observed in patients with primary hyperparathyroidism., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine syndrome caused by the mutation in the tumor suppressor gene MEN1 . The recurrence rate of primary hyperparathyroidism (PHPT) in patients with MEN1 after parathyroidectomy remains high, and the management of recurrent hyperparathyroidism is still challenging., Case Presentation: We reported a 44-year-old woman with MEN1 combined with PHPT who was diagnosed through genetic screening of the patient and her family members. After parathyroidectomy to remove one parathyroid gland, the patient suffered from persistent high levels of serum calcium and parathyroid hormone, which returned to normal at up to 8 months after ultrasound-guided microwave ablation (MWA) for bilateral parathyroid glands, suggesting an acceptable short-term prognosis., Conclusion: Ultrasound-guided MWA for parathyroid nodules may be an effective therapeutic strategy for recurrent PHPT in MEN1 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhao, Han, Hu, Zhang, Xu, Chen, Liu and Xu.)

Purpose: To assess the added value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging over dual-phase scintigraphy in the diagnosis of secondary hyperparathyroidism (SHPT)., Methods: This retrospective study included 23 patients with SHPT. The diagnostic efficacy of 99m Tc-MIBI dual-phase scintigraphy and SPECT/CT fusion imaging was analyzed and compared based on the result of postoperative pathology and follow-up. To evaluate the diagnostic ability of 99m Tc-MIBI dual-phase scintigraphy, the volume and radioactive count of parathyroid lesions were assessed using the region of interest method., Results: A total of 79 hyperplastic parathyroid glands and two thyroid tissues were surgically removed from 23 SHPT patients and 13 normal parathyroid glands were preserved. 99m Tc-MIBI SPECT/CT fusion imaging showed higher sensitivity and accuracy than 99m Tc-MIBI dual-phase scintigraphy [sensitivity, 77.2% (61/79) vs 46.8% (37/79); accuracy, 80.4% (74/92) vs 54.3% (50/92), respectively], but comparable specificity [100% (13/13)). Among 61 positive lesions detected by 99m Tc-MIBI SPECT/CT fusion imaging, 37 were dual-phase scintigraphy positive and 24 were dual-phase scintigraphy false negative. The radioactivity counts and radioactivity per unit volume in dual-phase scintigraphy positive were higher than that in dual-phase scintigraphy false negative ( P  < 0.05), but the volume of parathyroid lesions between the two groups had no significant difference ( P  > 0.05)., Conclusion: Compared with 99m Tc-MIBI dual-phase scintigraphy, 99m Tc-MIBI SPECT/CT fusion imaging has incremental value in the diagnosis of SHPT. The low uptake of MIBI in the whole gland and low MIBI uptake per unit volume are easy to cause dual-phase scintigraphy false negative., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND. Existing gaps in primary hyperparathyroidism (PHPT) diagnosis and treatment have prompted calls for systemic change in the approach to this disease. One proposed change is opportunistic assessment for enlarged parathyroid glands on routine CT examinations, to target biochemical testing to individuals most likely to have un-diagnosed PHPT. OBJECTIVE. The purpose of our study was to assess the utility of a radiologist recommendation for biochemical testing in patients with a suspected enlarged parathyroid gland on routine CT for identifying previously undiagnosed PHPT. METHODS. This retrospective study included patients without known or suspected PHPT who underwent routine CT (i.e., performed for reasons other than known or suspected parathyroid disease) between August 2019 and September 2021 in which the clinical CT report included a radiologist recommendation for biochemical testing to evaluate for possible PHPT because of a suspected enlarged parathyroid gland. Neuroradiologists at the study institution included this recommendation on the basis of individual judgment without formal criteria. The EHR was reviewed to identify patients who underwent subsequent laboratory evaluation for PHPT. An endocrine surgeon used available laboratory results and clinical data to classify patients as having PHPT, secondary hyper-parathyroidism, or no parathyroid disorder independent of the CT findings. RESULTS. The sample comprised 39 patients (median age, 68 years; 20 women, 19 men) who received the radiologist recommendation for biochemical evaluation. Of these patients, 13 (33.3%) received the recommended biochemical evaluation. Of the 13 tested patients, three (23.1%) were classified as having PHPT, four (30.8%) as having secondary hyperparathyroidism, and six (46.2%) as having no parathyroid disorder. Thus, the number of patients needing to receive a radiologist recommendation for biochemical testing per correct PHPT diagnosis was 13.0, and the number of patients needing to undergo laboratory testing per correct PHPT diagnosis was 4.3. One of the three patients classified as having PHPT underwent surgical resection of the lesion identified by CT, which was shown on histopathologic evaluation to represent hypercellular parathyroid tissue. CONCLUSION. Radiologist recommendations for biochemical testing in patients with suspected enlarged parathyroid glands on routine CT helped to identify individuals with undiagnosed PHPT. CLINICAL IMPACT. Opportunistic assessment for enlarged parathyroid glands on routine CT may facilitate PHPT diagnosis.

Objective: Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify potential biomarkers that may be used to predict the progression of SHPT and to elucidate the molecular mechanisms of SHPT pathogenesis at the transcriptome level., Methods: We analyzed differentially expressed genes (DEGs) between diffuse and nodular parathyroid hyperplasia of SHPT patients from the GSE75886 dataset, and then verified DEG levels with the GSE83421 data file of primary hyperparathyroidism (PHPT) patients. Candidate gene sets were selected by machine learning screens of differential genes and immune cell infiltration was explored with the CIBERSORT algorithm. RcisTarget was used to predict transcription factors, and Cytoscape was used to construct a lncRNA-miRNA-mRNA network to identify possible molecular mechanisms. Immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the expression of screened genes in parathyroid tissues of SHPT patients and animal models., Results: A total of 614 DEGs in GSE75886 were obtained as candidate gene sets for further analysis. Five key genes (USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2) had significant expression differences between groups and were screened with the best ranking in the machine learning process. These genes were shown to be closely related to immune cell infiltration levels and play important roles in the immune microenvironment. Transcription factor ZBTB6 was identified as the master regulator, alongside multiple other transcription factors. Combined with qPCR and IHC assay of hyperplastic parathyroid tissues from SHPT patients and rats confirm differential expression of USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2, suggesting that they may play important roles in the proliferation and progression of SHPT., Conclusion: USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2 have great potential both as biomarkers and as therapeutic targets in the proliferation of SHPT. These findings suggest novel potential targets and future directions for SHPT research., Competing Interests: The authors declare that they have no competing interests., (© 2023 Shen et al.)

Background: Additional studies may be needed when evaluating parathyroid fine needle aspirates (FNA) due to cytomorphologic similarities. The liquid-based cytology (LBC) is an effective cytology method which provides additional slides for ancillary techniques. We aimed to examine the immunocytochemical (ICC) GATA 3, TTF-1, which chromogranin and PTH expressions and to determine their diagnostic importance in parathyroid FNAs which were prepared via LBC technique., Methods: In total, 45 parathyroid FNA cases were examined in our laboratory for 12-month period. Thirty five cases without cell blocks were included in the study. Ten cases were excluded from study (five cases were nondiagnostic, five cases had cell blocks). For main LBC cytology slides SurePath pap test kit was used. For ICC study 4 PAP-stained LBC slides were obtained from each case's residual material. The slides were then stained with GATA 3, TTF-1, PTH and chromogranin., Results: Of 35 cases, 8 were male and 27 were female. The mean age of the cases was 52.25 ± 11.44 (range 27-72). The mean diameter of the lesions was 18.54 ± 7.66 mm (range 6-32 mm).The most used antibody was TTF-1 (in all 35 cases). The positivity rates were 84.8%, 83.9% and 81.8% for GATA 3, PTH and chromogranin, respectively. TTF-1 was completely negative in 100% of cases. All patients had high PTH washout values (29 patients, PTH washout value was >5000 pg/mL). In 30 cases, histopathologic follow-up was available. The cyto-histological correlation was 100%. Based on the PTH washout values for cases without resection, the diagnostic accuracy of FNA was determined as 100% in detecting the parathyroid origin. Among the antibodies, the most specific and sensitive antibody was TTF-1 (100%). The sensitivity values of the antibodies indicating parathyroid origin for GATA3, PTH and chromogranin were 86.67%, 83.33% and 81.82%, respectively., Conclusion: The addition of ICC studies applied to LBC slides is also very helpful in diagnosis, especially in FNAs with limited material such as parathyroid. GATA3 is a more reliable ICC marker determining parathyroid origin. In differentiation from thyroid origin, the addition of TTF-1 to the ICC panel increases the diagnostic accuracy to 96.67%. Although PTH and chromogranin have lower sensitivity, they are still reliable markers to detect parathyroid origin., (© 2023 Wiley Periodicals LLC.)

Purpose: This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on for primary hyperparathyroidism (PHPT) with uniglandular parathyroid adenomas in other localizations., Methods: The data of PHPT patients who underwent parathyroidectomy in our institution were assessed retrospectively. Abnormal gland localization was confirmed by operative and pathology reports as well as normocalcemia that lasted for at least 6 months postoperatively. The relationships of biochemical and clinical findings of patients with confirmed adenoma localizations were analyzed. In order to determine independent factors that can predict EPAs, binary logistic regression was used., Results: Among 421 patients (83.4% female, mean age 49 ± 13.2 years) enrolled in the study, the most common adenoma localization was the lower left parathyroid gland (36.1%; p < 0.001). Parathyroid adenomas were more common in lower localizations compared to upper localizations and were smaller in size (p < 0.001 and p = 0.004, respectively). In univariate analysis, serum intact parathyroid hormone and calcium levels were found to be higher (p = 0.004 and p = 0.002, respectively), moderate/severe hypercalcemia was more common (p = 0.024), phosphorus levels were lower (p = 0.04), and postoperative transient hypocalcemia was more common (p = 0.013) in cases of EPAs than other localizations. There was no significant difference in adenoma size between EPAs and other classical localizations. In multivariate analysis, only a high serum calcium level was an independent predictor of EPAs (OR 2.017, 95% CI 1.142-3.564, p = 0.016). Receiver-operating characteristic curve analysis yielded an optimal cutoff value of 12.25 mg/dL for serum calcium (88% sensitivity, 63% specificity, and area under the curve: 0.861)., Conclusion: EPAs can cause a more biochemically distinct PHPT picture compared to parathyroid adenomas in classical localizations. A high calcium level at diagnosis may be a clinical predictor for EPAs and may affect the clinical approach and imaging technique choices. Due to the increased risk of transient hypocalcemia in patients with EPAs, caution should be exercised in postoperative follow-up. Furthermore, in the event of negative preoperative imaging, starting the parathyroid exploration from the lower left region may be a good option for the surgeon., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Rationale and Objectives: Gaps in primary hyperparathyroidism diagnosis are well-documented. End-organ damage correlates with disease duration and often occurs before diagnosis. We hypothesize that opportunistic parathyroid gland assessment on routine CT could decrease existing diagnosis gaps. Our purpose is to assess for enlarged parathyroid glands on contrast-enhanced CT acquired prior to biochemical screening and subsequent development of related morbidity., Materials and Methods: This retrospective study included consecutive patients with primary hyperparathyroidism undergoing parathyroidectomy with contrast-enhanced CT including the lower neck and upper chest acquired prior to biochemical screening. One neuroradiologist retrospectively evaluated all CTs for enlarged (estimated weight greater than 60 mg) parathyroid glands. Gold standard operative and pathology reports were correlated with CT findings, and medical records were reviewed for development of primary hyperparathyroidism-related comorbidities., Results: The sample comprised 38 patients (30 women, 8 men, median age 60 years) with 70 CTs of interest. The neuroradiologist identified 32 putative enlarged parathyroid glands (median estimated weight 307 mg) in 29 (76%) patients on CTs predating biochemical screening by a median of 30 months. Putative enlarged parathyroid glands on CT corresponded to pathologically proven parathyroid lesions in 26 (90%) patients. Of 26 patients with retrospectively identified pathologically proven parathyroid lesions, 12 (46%) developed at least 1 renal, bone, or neurocognitive comorbidity between CT and subsequent biochemical screening., Conclusion: Enlarged parathyroid glands are frequently visible on routine CTs acquired years prior to primary hyperparathyroidism diagnosis. Biochemical screening based on enlarged glands could potentially prevent associated morbidity in almost half of such patients., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: Accurate preoperative localization is imperative to facilitate a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). This study aims to compare the diagnostic value of standard-of-care localization techniques (ultrasound [US] and 99m Technetium ( 99m Tc) -sestamibi scintigraphy) to [F-18]-fluorocholine positron emission tomography/magnetic resonance imaging (FCH-PET/MRI) to determine the additional clinical usefulness of PET/MRI in a Canadian cohort., Methods: We conducted a prospective, appropriately powered, study to compare the diagnostic value of -FCH PET/MRI to that of the US and 99m Tc-sestamibi scintigraphy for localization of parathyroid adenomas in a patient with pHPT. The primary outcome was the per-lesion sensitivity and positive predictive value (PPV) of FCH-PET/MRI, US, and 99m Tc-sestamibi scintigraphy. Intraoperative surgeon localization, parathormone levels, and histopathological findings were used as reference standards., Results: Forty-one patients underwent FCH-PET/MRI of which 36 patients had parathyroidectomy. In these 36 patients, 41 parathyroid lesions were histologically confirmed as adenomas or hyperplastic glands. Per-lesion sensitivity of FCH-PET/MRI was 82.9% and of US and 99m Tc-sestamibi scintigraphy combined at 50.0%, respectively. The sensitivity of FCH-PET/MRI was superior to that of US and 99m Tc-sestamibi scintigraphy (p = 0.002). In the 19 patients in whom both US and 99m Tc-sestamibi scintigraphy were negative, PET/MRI correctly identified the parathyroid adenoma in 13 patients (68%)., Conclusions: FCH-PET/MRI is a highly accurate imaging modality for localization of parathyroid adenomas in a tertiary center in North America. It is a superior functional imaging modality to 99m Tc-sestamibi scintigraphy alone and more sensitive for localization of parathyroid lesions than US and 99m Tc-sestamibi scintigraphy combined. This imaging modality could become the most valuable preoperative localization study given its superior performance in localizing parathyroid adenomas., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Apart from being a rare endocrine tumor, parathyroid carcinoma is also one of the rarest malignancies in human beings. Parathyroid carcinoma is even more uncommon in haemodialysis patients with end-stage renal disease. The pathogenesis of parathyroid hyperplasia in haemodialysis patients is well known, but the mechanism of development of parathyroid carcinoma in these patients remains unclear., Methods: Three cases of parathyroid carcinoma in haemodialysis patients are presented in this study: a 69-year-old male patient and two female patients (67 and 61 years old). In all cases parathyroid carcinoma infiltrated the ipsilateral thyroid lobe and in one patient the right laryngeal nerve was involved as well. One patient underwent three surgical procedures., Results: After surgical treatment, all patients were normocalcaemic and showed a significant reduction in PTH levels., Conclusion: In patients with secondary hyperparathyroidism, who develop parathyroid carcinoma, surgical resection is the only viable treatment option.

Purpose: The present study discussed the effects of accidental parathyroid resection on hypoparathyroidism and investigated the risk factors associated with accidental parathyroid resection., Methods: Clinical data from patients who have undergone thyroidectomy at a university hospital in the period from November 2018 and October 2020 were entered into the database and analyzed. Risk factors for accidental parathyroid resection were recorded., Results: A total of 1775 cases were included in this study. The analysis showed that lymph-node dissection (p < 0.001), T staging (p = 0.037), and treatment group (p < 0.001) were independent risk factors for accidental parathyroid resection. Different treatment groups were important risk factors for accidental parathyroid resection. There were significant differences between the professional and non-professional groups in the following aspects: accidental parathyroid resection (p < 0.001), Scope (p < 0.001), T stage (p = 0.009), N stage (p < 0.001), range of lymph-node dissection (p < 0.001), number of lymph nodes dissected in central area (p < 0.001), and number of lymph-node metastases in the central region (p < 0.001)., Conclusions: The causes of accidental parathyroid resection are multifactorial. The predictors for accidental parathyroid resection include lymph-node dissection in the central region, T staging, as well as the operating surgeons' experience., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Management of the inferior parathyroid gland using total thyroidectomy (TT) with central lymph node dissection (CLND) is still controversial. Therefore, we evaluated the safety and effectiveness of single inferior parathyroid autotransplantation., Methods: The clinical data of patients with papillary thyroid carcinoma (PTC) who underwent TT with bilateral CLND from January 2018 to December 2020 were collected. Quality of life (QoL) was assessed using the Chinese version of the EORTC QLQ-C30 and THYCA-QOL. The patients were divided into an autotransplantation group and a preservation group according to whether a single inferior parathyroid gland was transplanted. The incidence of permanent hypoparathyroidism, the number of resected central lymph nodes (CLNs), the rate of recurrence reoperation, the rate of radioactive iodine (RAI) treatment, and the QoL score were compared between the two groups., Results: A total of 296 patients were included in the study; there were 99 patients in the autotransplantation group and 197 in the preservation group. The incidence of permanent hypoparathyroidism was 3.0% (3/99) and 4.6% (9/197) in the autotransplantation and preservation groups, respectively (P = 0.532). The median number of resected CLNs was 12 (8-17) and 10 (6-14) in the autotransplantation and preservation groups, respectively (P = 0.015). No reoperations were performed for patients with CLN recurrence, and the rates of lateral lymph node (LLN) recurrence reoperation were 2.0% (2/99) and 3.6% (7/197) in the autotransplantation and preservation groups, respectively (P = 0.473). The RAI treatment rates were 12.1% (12/99) and 22.3% (44/197) in the autotransplantation and preservation groups, respectively (P = 0.034). A total of 276 questionnaires were recovered, including 84 in the autotransplantation group and 192 in the preservation group. The QoL of the two groups of patients is similar (P > 0.05)., Conclusion: Single inferior parathyroid autotransplantation during thyroidectomy can be used to prevent permanent hypoparathyroidism and can enable more extensive CLND., (© 2023. The Author(s).)

Introduction: Parathyromatosis is a rare cause of primitive hyperparathyroidism characterized by the presence of numerous parathyroid tissue foci in the neck/mediastinum, due to hyperplasia of parathyroid embryologic residues (primary-form) or to local parathyroid tissue implantation (secondary-form). 63 cases have been described in the literature. In our patient parathyromatosis was due to a combination of two mutations., Case Report: A 36-years-old woman was diagnosed with osteoporosis secondary to primary hyperparathyroidism. Subsequent right parathyroidectomy showed a parathyroid adenoma. The follow-up was negative but after 10 years she had a relapse. The genetic screening showed a rare intronic mutation of the MEN1 gene and a heterozygous mutation never described in exon 8 of the CASR gene, coding for the calcium receptor. Calcemia and PTH increased over the years with the onset of nephrocalcinosis and the worsening of osteoporosis despite the therapy with Cinacalcet, bisphosphonates and Vitamin D. She had therefore two additional surgical procedures (parathyroid tissue without malignancy). At follow-up she showed elevated levels of PTH (>1000 pg/ml) and calcium (11.2 mg/dl) and CT scans multiple subcentimetric nodules in the neck/upper mediastinum. Since the 68 Ga-DOTATATE showed an increased uptake in the neck/mediastinum, lanreotide was added. After two months there was a significant biochemical response but, unfortunately, after six months, the patient showed a new worsening., Conclusions: a rare case of parathyromatosis due to a combination of two genetic alterations never described. The main issues concern the diagnosis and the radical treatment. Somatostatin analogues may have a useful role in both diagnosis and therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sapuppo, Giusti, Aricò, Masucci, Tavarelli, Russo and Pellegriti.)

Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively, making diagnosis and treatment challenging. Current data on IPAs are sparse and fragmented in the literature. This makes it difficult to compare the effectiveness of different imaging and surgical techniques. To address this issue, this scoping review maps the literature on IPAs, focusing on four domains: clinical presentation, current localization methods, different surgical techniques, and histopathological features. A search of MEDLINE, Embase, and the Cochrane Library was conducted, with 19 studies meeting the inclusion criteria. The characteristics of IPAs on ultrasound, fine-needle aspiration, CT, MRI, sestamibi-based techniques, and selective venous sampling are summarized. Emerging imaging modalities, including autofluorescence, are introduced. Surgical methods and intraoperative factors that correlate with high success rates for removal are highlighted. This review also identifies gaps in knowledge to guide further research into this area., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Parathyroid disease typically presents with parathyroid hyperfunction as result of neoplasia or a consequence of non-neoplastic systemic disease. Given the parathyroid gland is a hormonally active organ with broad physiologic implications and serologically accessible markers for monitoring, the diagnosis of parathyroid disease is predominantly a clinical pathologic correlation. We provide the current pathological correlates of parathyroid disease and discuss preoperative, intraoperative, and postoperative pathology consultative practice for optimal patient care., (Copyright © 2022 Elsevier Inc. All rights reserved.)