Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation.

Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of Glial cells missing2 (Gcm2), we efficiently produced aparathyroid embryos for BC. In these embryos, mESCs differentiated into endocrinologically mature PTGs that rescued Gcm2-/- mice from neonatal death. The mESC-derived PTGs responded to extracellular calcium, restoring calcium homeostasis on transplantation into mice surgically rendered hypoparathyroid. We also successfully generated functional interspecies PTGs in Gcm2-/- rat neonates, an accomplishment with potential for future human PTG therapy using xenogeneic animal BC. Our results demonstrate that BC can produce functional endocrine organs and constitute a concept in treatment of hypoparathyroidism.

Feasibility of Autofluorescence Using Overlay Imaging for the Detection of Parathyroid Glands: Defining Standards.

BACKGROUND: The aim of this study is to define standards for the use of near-infrared autofluorescence (NIRAF)-based overlay imaging via EleVision IR (Medtronic, Dublin, Ireland) and to evaluate its clinical applicability. PATIENTS AND METHODS: This prospective study included 189 patients who had undergone open thyroid and/or parathyroid surgery and in whom EleVision IR was applied to visualize at least one parathyroid gland (PG) between January 2021 and May 2022 in a tertiary referral care center. Whether the PGs were first localized by the surgeon or by overlay imaging was noted. Handling of the device, application time and duration, distance, infrared intensity (IR%), and the angle of each measurement were analyzed. In thyroidectomies, the specimens were subsequently scanned for further PGs. NIRAF patterns and intensities were described. RESULTS: Overall, 543 PGs were analyzed in 158 (83.6%) surgeries of thyroid glands (TGs) and in 49 (25.9%) surgeries for hyperparathyroidism. In 111 (58.7%) patients, identical numbers of PGs were detected by the surgeon and by overlay imaging. While a larger number of PGs was identified by the surgeon in 48 (25.4%) patients, overlay imaging served to detect more PGs in 30 (15.9%) cases. In four (2.1%) patients, PGs were visualized post-thyroidectomy due to their autofluorescence on the specimen. NIRAF-based overlay imaging was applied to depict the PGs early on after exposure by the surgeon. The ideal distance for the measurement ranged between 8 and 12 cm with an angle of 90° and a mean IR% of 34.5% (± 17.6). CONCLUSIONS: Considering the standard operating procedures, NIRAF-based overlay imaging can be used as an adjunct tool for intraoperative localization.

An update on the use of near-infrared autofluorescence imaging in endocrine surgical procedures.

Over the past decade, near-infrared autofluorescence (NIRAF) imaging has been a major breakthrough in endocrine surgery. Although initial focus was directed at the parathyroid glands, subsequent work has also shown that non-parathyroid neuroendocrine tumors also possess autofluorescence properties. The aim of this review is to present an update and synopsis about NIRAF applications in various endocrine surgical procedures. Methodology includes a review of the literature supplemented with expert opinion. Overall, our review reveals that the use of NIRAF may provide the surgeon with adjunctive critical information that has the potential to change the conduct of many various endocrine surgical procedures.

Ultrasound characteristics of normal parathyroid glands and analysis of the factors affecting their display.

BACKGROUND: Parathyroid glands are important endocrine glands, and the identification of normal parathyroid glands is crucial for their protection. The aim of this study is to explore the sonographic characteristics of normal parathyroid glands and analyze the factors affecting their display. METHODS: Seven hundred three subjects who underwent physical examination at our hospital were included. The number, location, size, morphology, echogenicity and blood flow distribution of parathyroid glands were recorded. The ultrasound characteristics and display rate were also summarized. Meanwhile, shear wave elastography was performed in 50 cases to provide the stiffness measurements, and 26 cases received contrast-enhanced ultrasonography for the assessment of microcirculatory perfusion. Furthermore, we analyzed the factors affecting parathyroid display, including basic information of the subjects and ultrasound features of the thyroid. RESULTS: ① A total of 1038 parathyroid glands were detected, among which, 79.29% were hyperechoic, 20.71% were isoechoic, 88.15% were oval-shaped, and 86.71% had blood flow of grade 0-I. ② 81.79% of the subjects had at least one parathyroid gland detected. ③ The Emean, Emax, PI and AUC of the parathyroid glands were significantly lower than those of the adjacent thyroid tissue (P < 0.05). ④ The display of normal parathyroid glands was related to BMI, thyroid echogenicity and thyroid volume of the subjects (P < 0.05). CONCLUSIONS: Normal parathyroid glands tend to appear as oval-shaped hyperechoic nodules with blood flow of grade 0-I. BMI, thyroid echogenicity and thyroid volume are independent factors affecting the display of parathyroid glands.

Real-time imaging of ipsilateral parathyroid glands by retrograde injection of methylene blue into the superior thyroid artery: a new intraoperative parathyroid protection method.

BACKGROUND: Postoperative hypoparathyroidism caused by parathyroid injury is a problem faced by thyroid surgeons. The current technologies for parathyroid imaging all have some defects. METHODS: Patients with differentiated thyroid carcinoma (DTC) who underwent unilateral thyroidectomy plus ipsilateral central lymph node dissection were recruited. We dissected the main trunk of the superior thyroid artery entering the thyroid gland and placed the venous indwelling tube into the artery. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: A total of 132 patients enrolled in this single-arm clinical trial, 105 of them completed retrograde catheterization via the superior artery. The sensitivity was 69.23 and 83.33% respectively. The specificity was 72.91 and 64.89%. The accuracy was 72.91 and 64.89%. The PPV was 85.71 and 81.08%. The NPV was 22.58 and 45.45%. There were no patients with allergic reactions to the methylene blue, or methylene blue toxicity. CONCLUSIONS: Retrograde injection of methylene blue via the superior thyroid artery is an effective and safe method to visualize parathyroid glands. This method can accurately locate the target organ by ultraselecting the blood vessel and injecting the contrast agent while avoiding background contamination and reducing the amount of contrast agent. TRIAL REGISTRATION: Clinical trial registration numbers and date of registration: ChiCTR2300077263、02/11/2023.

Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma.

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.

Intraoperative indocyanine green angiography for predicting postoperative hypoparathyroidism.

BACKGROUND: Postoperative hypocalcemia is a common complication of thyroidectomy. This problem is most often associated with accidental devascularization or excision of the parathyroid glands (PG). AIM: Aim was to study near-infrared (NIR) fluorescent imaging with intraoperative PG indocyanine green (ICG) angiography to help identify and preserve PG during total thyroidectomy in order to avoid postoperative hypocalcemia. MATERIAL AND METHODS: From 2017 to 2022, a total of 92 patients underwent total thyroidectomy at Odessa Regional Hospital. Indications for surgery were multinodular goiter (n = 42), thyroid cancer (n = 43), and Graves' disease (n = 7). By randomization all patients were divided into two groups: in the control group, 48 patients underwent standard total thyroidectomy, and in the main group, 44 patients underwent NIR-assisted total thyroidectomy with ICG angiography. Serum calcium and parathyroid hormone levels were compared between the two groups of patients in 1, 7-15 days after surgery and then 3, 6 months later. RESULTS: In the control group, based on a visual assessment of the PG, autotransplantation of the PG was conducted in only five cases. In the second group, autotransplantation was performed in 16 patients. The transient postoperative hypocalcemia was observed in 8 patients of the control group (16, 70%) and in the 2 patients of ICG group (4, 50%) on 5-10 postoperative days. In the first group, 2 patients at 3 months after surgery had permanent hypocalcaemia. CONCLUSION: NIR fluorescent imaging with intraoperative PG ICG angiography is a safe and an easily repeatable method. This technique provides improved detecting and assessment of the perfusion of the PG. The need for autotransplantation of the PG can be determined more objectively using ICG imaging than simple visualization.

Experimental rat models for Hashimoto's thyroiditis.

PURPOSE: Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease characterized by T lymphocyte-mediated destruction of thyroid follicles. To study the pathogenesis of HT and the efficacy of new substances for its treatment, an easily obtained and adequate to the human disease experimental model is needed. The aim of our study was to find out whether it is possible to induce experimental autoimmune thyroiditis (EAT) similar to Hashimoto's thyroiditis by injecting with thyroglobulin (Tg) without using agents that enhance its thyroiditogenicity and without taking into account the genetic sensitivity of animals. METHODS: Wistar rats were immunized with freshly isolated rat Tg or porcine Tg. In 8 weeks, histological studies of the thyroid and parathyroid glands were performed. Thyroid function and total serum calcium level were also evaluated. RESULTS: Immunization with both rat and porcine freshly isolated Tg caused T lymphocytic infiltration of the thyroid gland, thyroid follicle atrophy and degradation in Wistar rats. EAT caused by porcine Tg was characterized by greater severity than EAT induced with rat Tg. In 55% of rats with porcine Tg-induced EAT, oxyphilic metaplasia was detected in the parathyroid glands. In addition, low total serum calcium was observed in these rats. CONCLUSION: Two rat models of autoimmune thyroiditis were obtained. EAT caused in Wistar rats by immunization with rat Tg is similar to Hashimoto's thyroiditis. EAT induced with porcine Tg was accompanied by oxyphil cell metaplasia in the parathyroids and hypocalcemia.

Effect of near infrared autofluorescence guided total thyroidectomy on postoperative hypoparathyroidism: a randomized clinical trial.

PURPOSE: The purpose of this single-blinded, 2-centre, randomized controlled trial was to test if near-infrared (NIR) autofluorescence image guidance for parathyroid gland (PG) detection during total thyroidectomy can reduce the incidence of hypoparathyroidism in both malignant and benign cases. METHOD: Patients admitted for primary or completion total thyroidectomy were randomized to either the NIR intervention group or the standard care NONIR (no near infrared) group. The primary endpoint was the rate of hypoparathyroidism at the 3-month follow-up, defined as hypocalcemia and inappropriately low parathyroid hormone levels and/or continuous treatment with active vitamin D. The secondary endpoint was the PG identification rate. RESULTS: A total of 147 patients were included of whom 73 were allocated to NIR. Primary or completion thyroidectomy was conducted in 84 and 63 cases, respectively. A total of 130 completed 3 months follow-up. Postoperative hypoparathyroidism in the NIR group at 12 h, 1 month and 3 months was, respectively, 31.8, 14.1, 6.5% compared with 35.9, 18.9, 11.8% in the NONIR group (all p > 0.46). In the NIR group, the identification rate of PGs was 69.5% (146 of 210 PGs), and 9% (19 of 210 PGs) were identified only due to additional use of NIR. For 15 out of 69 patients (21.7%) additionally PGs was found. CONCLUSION: Hypoparathyroidism was nominally less frequent in the NIR group, although not statistically significant. Further studies are needed to confirm if NIR may be a supportive PG identification tool to minimize the number of PG which would have been otherwise missed, especially during more complicated thyroid procedures. TRIAL REGISTRY: ClinicalTrials.gov: NCT04193332. Registration date: 16.08.2019.

The use of near-infrared autofluorescence during total laryngectomy with hemi- or total thyroidectomy.

PURPOSE: The aim of this study is to describe the use of near-infrared autofluorescence (NIR-AF) to identify and preserve parathyroid glands (PGs) in a group of patients with advanced hypopharyngeal/laryngeal cancer undergone total (pharyngo)laryngectomy with hemi- or total thyroidectomy. METHODS: At San Raffaele Hospital, Milan (Italy), from January 2021 to May 2021, 7 patients affected by cT4a laryngeal squamous cell carcinoma (SCC) underwent surgery using an autofluorescence detection system (Fluobeam-Fluoptics®). For proper surgical planning, the demolition phase envisaged extension of the intervention to 4 hemithyroidectomies and 3 total thyroidectomies associated, respectively, with homolateral or bilateral CCND. Serum calcium, ionized calcium, and parathyroid hormone (PTH) levels at post-operative day (POD) 1 and 2 and at 2 weeks after surgery were monitored. Finally, we compared the data obtained with a cohort of patients who underwent surgery without the adoption of NIR-AF. RESULTS: With the use of NIR-AF, 18/20 PGs were identified, of which 7/18 were preserved exclusively thanks to the use of autoflorescence. The technique also made it possible to identify and isolate three PGs from the surgical specimen, which were subsequently transplanted only after intraoperative histological confirmation. On POD-1, 3/7 patients (42.8%) were hypocalcemic; on POD-2 and after 2 weeks only 1/7 patient (14.2%) was hypocalcemic. Comparing the two groups, we highlighted that the utilization of NIR-AF was related to a significant decrease of median serum (p = 0.026) and ionized calcium levels (p = 0.017) 2 weeks after surgery. Using this new technology, in no case did definitive histological examination reveal the presence of PGs in the surgical specimen, reaching an accuracy of 100%. CONCLUSIONS: In our cohort of patients who underwent total (pharyngo)laryngectomy with hemi- or total thyroidectomy, the use of near-infrared autofluorescence improved medium term postoperative hypocalcemia rates. This new technology helps to achieve a better calcemic outcome compared to the standard naked eye approach, since it helps the surgeon to identify and preserve parathyroid glandular tissue with a lower incidence of post-operative hypocalcemia.

High-Definition 3D Exoscope in Thyroid Surgery.

BACKGROUND: The high-definition 3D exoscope is an innovative and promising tool that was recently introduced in the clinical practice. It may be used during open surgical procedures to enhance the ability to perform precise dissection of fine structures. We describe our preliminary experience with the 3D exoscope in thyroid surgery, discussing potential advantages of this system. METHODS: A high-definition 3D exoscope (3D VITOM®) mounted on the VERSACRANETM holding system (Karl Storz, Tuttlingen, Germany) was used to perform open thyroid surgery. RESULTS: The 3D exoscope was used in three patients without significant intra-operative delay or complications. Both thyroidectomy and central compartment dissection were performed. The 3D exoscope allows to perform precise dissection in the identification and preservation of the recurrent laryngeal nerve and the parathyroid glands. CONCLUSIONS: 3D exoscope-assisted thyroid surgery seems to be feasible and safe. Further studies should be encouraged to analyze potential clinical benefit in the post-operative period.

Telocytes/CD34+ Stromal Cells in the Normal, Hyperplastic, and Adenomatous Human Parathyroid Glands.

Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not been explored. Using immunological and ultrastructural procedures, we assess the location, arrangement, and behavior of TCs/CD34+ SCs in normal human parathyroids, during their development and in their most frequent pathologic conditions. In normal parathyroids, TCs/CD34+ SCs show a small somatic body and long thin processes with a moniliform aspect, form labyrinthine systems, connect other neighboring TCs/CD34+ SCs, vessels, adipocytes, and parenchymal cells directly or by extracellular vesicles, and associate with collagen I. TCs/CD34+ SCs and collagen I are absent around vessels and adipocytes within parenchymal clusters. In developing parathyroids, TCs/CD34+ SC surround small parenchymal nests and adipocytes. In hyperplastic parathyroids, TCs/CD34+ SCs are prominent in some thickened internodular septa and surround small extraglandular parenchymal cell nests. TCs/CD34+ SCs are present in delimiting regions with compressed parathyroids and their capsule in adenomas but absent in most adenomatous tissue. In conclusion, TCs/CD34+ SCs are an important cellular component in the human parathyroid stroma, except around vessels within parenchymal nests. They show typical characteristics, including those of connecting cells, are present in developing parathyroids, and participate in the most frequent parathyroid pathology, including hyperplastic and adenomatous parathyroids.

Surgical treatment of hyperparathyroidism with a pathologically changed parathyroid gland found in the mediastinum.

The most common indication for surgical treatment of parathyroid gland pathology is primary hyperparathyroidism where extirpation of the pathologically changed parathyroid gland is the first-choice treatment. Embryonic development of the lower pair of parathyroid glands is quite complex and is closely related to the tissue of the thymus; for this reason it is not uncommon for a parathyroid adenoma to be located in the mediastinum or directly in the tissue of the thymus. The treatment of primary hyperparathyroidism is becoming a multidisciplinary issue in which radiodiagnostics and nuclear medicine methods play a significant role as they are needed to accurately localize the affected gland and to plan an adequate surgery. In case of intrathoracic localization of parathyroid adenoma, the therapy belongs in the hands of thoracic surgery. At our department, the endocrine surgery program, including parathyroid gland surgery, has a long tradition, and complicated patients are concentrated here, often patients with refractory hyperparathyroidism after a previous procedure. In the last 10 years, almost 2,300 procedures for parathyroid pathology have been performed at the IIIrd Department of Surgery of the 1st Faculty of Medicine, Charles University and University Hospital in Motol, of which some pathologies with mediastinal localization were managed using minimally invasive methods, i.e. videothoracoscopy or robotic-assisted surgery.

Ectopic PTH-producing parathyroid cyst inside the thymus: a case report.

BACKGROUND: The hallmark of hyperparathyroidism is hypersecretion of parathyroid hormone (PTH) which results in hypercalcemia and hypophosphatemia. While hypercalcemia due to malignancy is often brought about by PTH-related protein in adults, PTH-producing tumors are quite rare in clinical practice. Additionally, from the point of embryology, it is very difficult to examine ectopic PTH-producing tissue such as ectopic parathyroid glands. Furthermore, clear histopathological criteria are not present. CASE PRESENTATION: A 57-year-old woman was referred to our hospital for hypercalcemia. Her parathyroid hormone (PTH) level was elevated, but there were no enlarged parathyroid glands. Although 99mTc-MIBI confirmed a localized and slightly hyperfunctioning parathyroid tissue in the anterior mediastinum, it was not typical as hyperfunctioning parathyroid. We finally diagnosed her as ectopic PTH-producing cyst-like tumor with venous sampling of PTH. She underwent anterosuperior mediastinal ectopic PTH-producing cyst-like tumor resection. It is noted that intact-PTH concentration of the fluid in the cyst was very high (19,960,000 pg/mL). Based on histopathological findings, we finally diagnosed her as ectopic PTH-producing parathyroid cyst inside the thymus. After resection of anterosuperior mediastinal thymus including ectopic PTH-producing parathyroid cyst, calcium and intact-PTH levels were decreased, and this patient was discharged without any sequelae. CONCLUSIONS: We should know the possibility of superior mediastinal ectopic PTH-producing parathyroid cyst inside the thymus among subjects with ectopic PTH-producing parathyroid glands. Particularly when the cyst is present in the superior mediastinum, it is necessary to do careful diagnosis based on not only positive but also negative findings in 99mTc-MIBI. It is noted that the patient's bloody fluid in the cyst contained 19,960,000 pg/mL of intact-PTH, and its overflow into blood stream resulted in hyperparathyroidism and hypercalcemia. Moreover, in such cases, the diagnosis is usually confirmed after through histological examination of ectopic PTH-producing parathyroid glands. We think that it is very meaningful to let clinicians know this case.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

Ultrasound-guided thermal ablation for hyperparathyroidism: current status and prospects.

BACKGROUND: Hyperparathyroidism (HPT) is classified into primary HPT (PHPT), secondary HPT (SHPT), tertiary HPT (THPT), and pseudohyperparathyroidism. Parathyroid surgery is generally reserved for patients with symptomatic PHPT and asymptomatic patients who meet the surgical guideline criteria. However, the risk of complications and mortality after parathyroid gland surgery increases with increasing patient age. AIM: This study aimed to review existing research on laser ablation, radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound in the treatment of HPT and analyze its application prospects. CONCLUSIONS: Thermal ablation is a good alternative treatment for patients with parathyroid hyperplasia who do not meet the criteria or decline surgery. Being a type of minimally invasive treatment, ultrasound-guided thermal ablation has the advantages of easy operation, rapid recovery, and reusability and is used widely.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation.

OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

Autofluorescence of parathyroid glands during endocrine surgery with minimally invasive technique.

PURPOSE: Accidental injury to the parathyroid glands (PTGs) is common during thyroid and parathyroid surgery. To overcome the limitation of naked eye in identifying the PTGs, intraoperative autofluorescence imaging has been embraced by an increasing number of surgeons. The aim of our study was to describe the technique and assess its utility in clinical practice. METHODS: Near-infrared (NIR) autofluorescence imaging was carried out during open parathyroid and thyroid surgery in 25 patients (NIR group), while other 26 patients underwent traditional PTG detection based on naked eye alone (NO-NIR group). Primary variables assessed for correlation between traditional approach and autofluorescence were number of PTGs identified and incidence of postoperative hypoparathyroidism (hypoPT). RESULTS: 81.9% of PTGs were detected by means of fluorescence imaging and 74.5% with visual inspection alone, with an average of 2.72 PTGs visualized per patient using NIR imaging versus approximately 2.4 per patient using naked eye (p = 0.38). Considering only the more complex total thyroidectomies (TTs), the difference was almost statistically significant (p = 0.06). Although not statistically significant, the observed postoperative hypoPT rate was lower in the NIR group. CONCLUSION: Despite the limitations and technical aspects still to be investigated, fluorescence seems to reduce this complication rate by improving the intraoperative detection of the PTGs.

Near-infrared autofluorescence-based parathyroid glands identification in the thyroidectomy or parathyroidectomy: a systematic review and meta-analysis.

PURPOSE: To evaluate the diagnostic accuracy of near-infrared autofluorescence-based identification in the identification of parathyroid glands during thyroidectomy or parathyroidectomy. METHODS: The clinical studies were retrieved from PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, SCOPUS, and Google Scholar. The study protocol was registered on Open Science Framework ( https://osf.io/um8rj/ ). The search period ranged from the date of each database's inception to May 2021. Cohort studies dealing with patients of whom parathyroid glands were detected by near-infrared autofluorescence and confirmed clinically or pathologically during thyroidectomy or parathyroidectomy were included. Editorials, letters, "how-I-do-it" descriptions, other site head and neck tumors, and articles with lack of diagnostic identification data were excluded. True positive, true negative, false positive, and false negative were extracted. The QUDAS ver. 2 was used to evaluate the methodological quality. RESULTS: Seventeen studies with 1198 participants were evaluated in this analysis. Near-infrared autofluorescence-based identification of parathyroid glands showed a diagnostic odds ratio of 228.8759 (95% confidence interval, 134.1099; 390.6063). The area under the summary receiver operating characteristic curve was 0.967. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.9693 (0.9491; 0.9816), 0.9248 (0.8885; 0.9499), 0.9517 (0.8981; 0.9778), and 0.9488 (0.9167; 0.9689), respectively. Subgroup analyses were performed to compare two autofluorescence detection methods, because there was high heterogeneity in the outcomes. The diagnostic accuracy was higher in probe-based detection than in image-based detection. CONCLUSIONS: Near-infrared autofluorescence-based identification is valuable for identifying the parathyroid glands of patients during thyroidectomy or parathyroidectomy.

The anatomical basis for preserving the blood supply to the parathyroids during thyroid surgery, and a review of current technologic advances.

BACKGROUND: Devascularization of the parathyroid glands is generally accepted as the most common mechanism for iatrogenic hypocalcemia, a frequently seen complication of both total and completion thyroidectomy procedures. Much has been written about iatrogenic hypoparathyroidism, but few papers have precisely delineated the arterial supply of the parathyroid glands and the common anatomical variations that may impact parathyroid preservation during thyroid surgery. METHODS: We offer an illustrated review and discussion of the only two anatomic studies published in the medical literature focusing on parathyroid vasculature. In addition, we examine current techniques of parathyroid identification, preservation, and classification. FINDINGS: A surgical technique that preserves the parathyroid arteries is vital to preserving the viability of the parathyroid gland(s) during thyroid surgery. In 1907, Halsted and Evans described a technique of ligating the distal branches of the thyroid arteries beyond the origin of the parathyroid arteries, a technique termed ultra-ligation. In 1982, Flament et al.. reported three distinct anatomical variations of the parathyroid arteries which place the parathyroid blood supply at risk for devascularization during thyroid surgery. Our review also highlights novel techniques that aid surgeons in identification and assessment of the parathyroid glands. CONCLUSIONS: Recognition of the variations of parathyroid anatomy and their potential to lead to devascularization aids thyroid surgeons in their pursuit of parathyroid preservation. An awareness of the variety of novel parathyroid identification and preservation techniques can assist surgeons to achieve this goal.