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"Parathyroid Glands"
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Perspectives on the Parathyroid–Thymus Interconnection—A Literature Review
The parathyroid and thymus glands are key components of the endocrine and immune systems, respectively, with intriguing developmental, anatomical, and functional interrelationships. This study starts from the hypothesis that, given their shared embryological origin, it is plausible that the thymus and parathyroid glands interact functionally and may share pathological pathways. The present study explores the developmental pathways, spatial proximity, and potential cross-talk between these glands. Recent studies suggest that parathyroid hormone (PTH) may influence thymic function, including T-cell maturation and immune regulation, while thymic signaling molecules could impact calcium homeostasis and parathyroid activity. Understanding the functional and etiopathogenical relations between these endocrine glands offers new insights into endocrine–immunological crosstalk, and therapeutic approaches targeting disorders such as hypoparathyroidism, thymomas, myasthenia gravis and thymic hypoplasia. Perspectives and conclusion: Future research is essential to discover the molecular mechanisms underpinning this dynamic interrelation and its broader implications for health and disease. Because there is still very little data on this interaction, in-depth studies are necessary on large groups of patients. This research proposes a cross-study of the receptors for the main substances secreted by the two categories of endocrine glands. At the same time, it is essential to carry out an in-depth study on the cervico-pericardial ligaments through the lens of this glandular interaction. These ligaments could contain the main blood and nerve communication pathway between the parathyroids and the glands.
Journal Article
Efficacy of Ultrasound-guided Radiofrequency Ablation of Parathyroid Hyperplasia: Single Session vs. Two-Session for Effect on Hypocalcemia
To evaluate safety and efficacy of one- vs. two-session radiofrequency ablation (RFA) of parathyroid hyperplasia for patients with secondary hyperparathyroidism (SHPT) and to compare the outcome of both methods on hypocalcemia. Patients with secondary hyperparathyroidism underwent ultrasound guided RFA of parathyroid hyperplasia. Patients were alternately assigned to either group 1 (n = 28) with RFA of all 4 glands in one session or group 2 (n = 28) with RFA of 2 glands in a first session and other 2 glands in a second session. Serum parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) values were measured at a series of time points after RFA. RFA parameters, including operation duration and ablation time and hospitalization length and cost, were compared between the two groups. Mean PTH decreased in group 1 from 1865.18 ± 828.93 pg/ml to 145.72 ± 119.27 pg/ml at 1 day after RFA and in group 2 from 2256.64 ± 1021.72 pg/ml to 1388.13 ± 890.15 pg/ml at 1 day after first RFA and to 137.26 ± 107.12 pg/ml at 1 day after second RFA. Group 1’s calcium level decreased to 1.79 ± 0.31 mmol/L at day 1 after RFA and group 2 decreased to 1.89 ± 0.26 mmol/L at day 1 after second session RFA (P < 0.05). Multivariate analysis showed that hypocalcemia was related to serum ALP. Patients with ALP ≥ 566 U/L had lower calcium compared to patients with ALP < 566 U/L up to a month after RFA (P < 0.05). Group 1’s RFA time and hospitalization were shorter and had lower cost compared with Group 2. US-guided RFA of parathyroid hyperplasia is a safe and effective method for treating secondary hyperparathyroidism. Single-session RFA was more cost-effective and resulted in a shorter hospital stay compared to two sessions. However, patients with two-session RFA had less hypocalcemia, especially those with high ALP.
Journal Article
Preoperative and Intraoperative Methods of Parathyroid Gland Localization and the Diagnosis of Parathyroid Adenomas
Accurate pre-operative determination of parathyroid glands localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Its importance cannot be overemphasized as it helps to minimize the harmful side effects associated with damage to the parathyroid glands such as in hypocalcemia, severe hemorrhage or recurrent laryngeal nerve dysfunction. Preoperative and intraoperative methods decrease the incidence of mistakenly injuring the parathyroid glands and allow for the timely diagnosis of various abnormalities, including parathyroid adenomas. This article reviews 139 studies conducted between 1970 and 2020 (49 years). Studies that were reviewed focused on several techniques including application of carbon nanoparticles, carbon nanoparticles with technetium sestamibi (99m Tc-MIBI), Raman spectroscopy, near-infrared autofluorescence, dynamic optical contrast imaging, laser speckle contrast imaging, shear wave elastography, and indocyanine green to test their potential in providing proper parathyroid glands’ localization. Apart from reviewing the aforementioned techniques, this study focused on the applications that helped in the detection of parathyroid adenomas. Results suggest that applying all the reviewed techniques significantly improves the possibility of providing proper localization of parathyroid glands, and the application of indocyanine green has proven to be the ‘ideal’ approach for the diagnosis of parathyroid adenomas.
Journal Article
Comparing intraoperative parathyroid identification based on surgeon experience versus near infrared autofluorescence detection – A surgeon-blinded multi-centric study
Near infrared autofluorescence (NIRAF) detection has previously demonstrated significant potential for real-time parathyroid gland identification. However, the performance of a NIRAF detection device - PTeye® - remains to be evaluated relative to a surgeon's own ability to identify parathyroid glands.
Patients eligible for thyroidectomy and/or parathyroidectomy were enrolled under 6 endocrine surgeons at 3 high-volume institutions. Participating surgeons were categorized based on years of experience. All surgeons were blinded to output of PTeye® when identifying tissues. The surgeon's performance for parathyroid discrimination was then compared with PTeye®. Histology served as gold standard for excised specimens, while expert surgeon's opinion was used to validate in-situ tissues.
PTeye® achieved 92.7% accuracy across 167 patients recruited. Junior surgeons (<5 years of experience) were found to have lower confidence in parathyroid identification and higher tissue misclassification rate per specimen when compared to PTeye® and senior surgeons (>10 years of experience).
NIRAF detection with PTeye® can be a valuable intraoperative adjunct technology to aid in parathyroid identification for surgeons.
•Identifying parathyroid glands (PGs) during neck operations can be challenging.•This study compared the surgeons' ability in identifying PGs to a device PTeye®.•PTeye® achieved 92.7% accuracy across 167 patients recruited.•Junior surgeons had higher error rate in identifying PGs than seniors and PTeye®.•PTeye® can be a useful adjunct tool to intraoperatively identify PGs in real-time.
Journal Article
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.
Journal Article
Using ex vivo radioactivity measurement to differentiate parathyroid single-gland and multigland disease
Abstract
Background
Radioguided parathyroidectomy is based on the principle that hyperfunctioning parathyroid glands have increased radiotracer uptake, which can be measured instantaneously. We sought to determine if ex vivo radioactivity measurement could be used to predict parathyroid pathology and guide surgical decision-making in a time-efficient manner.
Materials and Methods: We retrospectively reviewed patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution (2000-2022). All patients received a preoperative injection of 10mCi of 99Tc. Intraoperatively, radioactivity was measured by a gamma counter within 5 seconds. The ratio of radioactive counts of resected parathyroid glands (ex vivo) to background thyroid tissue (radioactive ratio [RR]) was calculated. Patient demographics, preoperative laboratory measurements, and RRs were compared between patients with single-gland disease (SGD) versus multigland disease (MGD). The predictive threshold for SGD was subsequently validated on the following cohort of 115 patients.
Results
Of 2368 patients included, 1585 (66.9%) patients had SGD, and 783 (33.1%) had MGD. Patients with SGD had higher median (IQR) RRs than the MGD group (0.8 [0.5-1.3] vs 0.4 [0.3-0.7], P <.001). After adjusting for age, preoperative calcium and PTH, reoperative parathyroidectomy, and gland weight, the RR was an independent predictor (OR 2.155, P <.001) of SGD. A receiver operating characteristic curve was plotted using the RR to predict the likelihood of SGD. The positive predictive value (PPV) reached a plateau at 85.3% when RR was 1.2. When the threshold of 1.2 was used in the validation cohort, the PPV was 92.3%.
Conclusions
Ex vivo radioactivity measurement provides an instantaneous and reliable prediction of parathyroid pathology, which could be used as an adjunct to guide surgical decision-making during parathyroidectomy.
Journal Article
Intraoperative near-infrared autofluorescence imaging of parathyroid glands
Objective
To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light.
Methods
Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690–770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically.
Results
In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence.
Conclusion
Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.
Journal Article
Usefulness of ICG Angiography-Guided Thyroidectomy for Preserving Parathyroid Function
Introduction
Hypoparathyroidism is the most frequent complication after total thyroidectomy and, when permanent, it becomes a severe chronic disease. We assessed the usefulness of indocyanine green (ICG) angiography-guided thyroidectomy to reduce the postoperative hypocalcemia.
Methods
Prospective study with two consecutive cohorts of patients who underwent total thyroidectomy: historical control group (CG) and angiography-guided thyroidectomy group (AG). In all patients, ICG-angiography was performed at the end of the surgery to predict immediate parathyroid gland (PG) function. In the AG, ICG-angiography was also done after PG identification to show their vascular supply. We compared the rate of postoperative hypocalcemia (calcium supplementation needed due to hypocalcemia symptoms or calcium levels < 1.8 mmol/L on the first postoperative day) and permanent hypocalcemia (need of calcium ± vitamin D supplementation 12 months after thyroidectomy).
Results
We included 120 consecutive patients (84 CG; 36 AG). Thyroid cancer was the most common diagnostic (63.1% CG–69.4% AG;
p
= 0.646) and central neck dissection was also frequent (54.8% CG–64.3% AG;
p
= 0.468). The AG developed a lower rate of postoperative (26.2–5.6%;
p
= 0.011) and permanent hypocalcemia (11.9–0%;
p
= 0.032). The OR for permanent hypocalcemia was 0.673 (95% CI 0.591–0.766). A significant higher rate of well vascularized PG at the end of the surgery (score 2) in the AG (39.2–52.9%;
p
= 0.018) was also seen.
Conclusion
ICG angiography-guided thyroidectomy is a useful tool to identify PG vascularization, allowing a better PG preservation and a significant decrease in hypocalcemia rates.
Journal Article
Increased identification of parathyroid glands using near infrared light during thyroid and parathyroid surgery
Background
Parathyroid gland (PG) identification during thyroid and parathyroid surgery is challenging. Accidental parathyroidectomy increases the rate of postoperative hypocalcaemia. Recently, autofluorescence with near infrared light (NIRL) has been described for PG visualization. The aim of this study is to analyze the increased rate of visualization of PGs with the use of NIRL compared to white light (WL).
Materials and methods
All patients undergoing thyroid and parathyroid surgery were included in this study. PGs were identified with both NIRL and WL by experienced head and neck surgeons. The number of PGs identified with NIRL and WL were compared. The identification of PGs was correlated to age, sex, and histopathological diagnosis.
Results
Seventy-four patients were included in the study. The mean age was 48.4 (SD ±13.5) years old. Mean PG fluorescence intensity (47.60) was significantly higher compared to the thyroid gland (22.32) and background (9.27) (
p
< 0.0001). The mean number of PGs identified with NIRL and WL were 3.7 and 2.5 PG, respectively (
p
< 0.001). The difference in the number of PGs identified with NIRL and WL and fluorescence intensity was not related to age, sex, or histopathological diagnosis, with the exception of the diagnosis of thyroiditis, in which there was a significant increase in the number of PGs visualized with NIRL (
p
= 0.026).
Conclusion
The use of NIRL for PG visualization significantly increased the number of PGs identified during thyroid and parathyroid surgery, and the differences in fluorescent intensity among PGs, thyroid glands, and background were not affected by age, sex, and histopathological diagnosis.
Journal Article