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International Journal of Molecular... Jun 2021As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were...
As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were isolated and characterized with mass spectrometry and binding of carbohydrate-recognizing ligands, with a focus on complex compounds. The glycosphingolipid patterns of the human parathyroid and thyroid glands were very similar. The major acid glycosphingolipids were sulfatide and the gangliosides GM3, GD3, GD1a, GD1b, GT1b and Neu5Ac-neolactotetraosylceramide, and the major non-acid glycosphingolipids were globotriaosylceramide and globoside. We also found neolactotetra- and neolactohexaosylceramide, the x glycosphingolipid, and complex glycosphingolipids with terminal blood group O and A determinants in both tissues. A glycosphingolipid with blood group Le determinant was identified in the thyroid gland, and the parathyroid sample had a glycosphingolipid with terminal blood group B determinant. Immunohistochemistry demonstrated the expression of blood group A antigens in both the thyroid and parathyroid glands. A weak cytoplasmatic expression of the GD1a ganglioside was present in the thyroid, while the parathyroid gland had a strong GD1a expression on the cell surface. Thus, the glycosylation of human thyroid and parathyroid glands is more complex than previously appreciated. Our findings provide a platform for further studies of alterations of cell surface glycosphingolipids in thyroid and parathyroid cancers.
Topics: Blood Group Antigens; Chromatography, Thin Layer; Gangliosides; Glycosphingolipids; Humans; Ligands; Mass Spectrometry; Organ Specificity; Parathyroid Glands; Thyroid Gland
PubMed: 34208903
DOI: 10.3390/ijms22137044 -
Frontiers in Endocrinology 2023The bone matrix protein osteocalcin (OC), secreted by osteoblasts, displays endocrine effects. We tested the hypothesis that OC modulates parathyroid tumor cell function.
INTRODUCTION
The bone matrix protein osteocalcin (OC), secreted by osteoblasts, displays endocrine effects. We tested the hypothesis that OC modulates parathyroid tumor cell function.
METHODS
Primary cell cultures derived from parathyroid adenomas (PAds) and HEK293 cells transiently transfected with the putative OC receptor GPRC6A or the calcium sensing receptor (CASR) were used as experimental models to investigate γ-carboxylated OC (GlaOC) or uncarboxylated OC (GluOC) modulation of intracellular signaling.
RESULTS
In primary cell cultures derived from PAds, incubation with GlaOC or GluOC modulated intracellular signaling, inhibiting pERK/ERK and increasing active β-catenin levels. GlaOC increased the expression of and , and reduced and . GluOC stimulated transcription of , and inhibited expression. Moreover, GlaOC and GluOC reduced staurosporin-induced caspase 3/7 activity. The putative OC receptor GPRC6A was detected in normal and tumor parathyroids at membrane or cytoplasmic level in cells scattered throughout the parenchyma. In PAds, the membrane expression levels of GPRC6A and its closest homolog CASR positively correlated; GPRC6A protein levels positively correlated with circulating ionized and total calcium, and PTH levels of the patients harboring the analyzed PAds. Using HEK293A transiently transfected with either GPRC6A or CASR, and PAds-derived cells silenced for , we showed that GlaOC and GluOC modulated pERK/ERK and active β-catenin mainly through CASR activation.
CONCLUSION
Parathyroid gland emerges as a novel target of the bone secreted hormone osteocalcin, which may modulate tumor parathyroid CASR sensitivity and parathyroid cell apoptosis.
Topics: Humans; Parathyroid Glands; Parathyroid Neoplasms; Osteocalcin; beta Catenin; HEK293 Cells; Receptors, Calcium-Sensing
PubMed: 37065733
DOI: 10.3389/fendo.2023.1129930 -
The Journal of Surgical Research Sep 2021Hypoparathyroidism is a common complication following thyroidectomy. There is a need for technology to aid surgeons in identifying the parathyroid glands. In contrast to... (Clinical Trial)
Clinical Trial
BACKGROUND
Hypoparathyroidism is a common complication following thyroidectomy. There is a need for technology to aid surgeons in identifying the parathyroid glands. In contrast to near infrared technologies, fluorescence lifetime imaging (FLIm) is not affected by ambient light and may be valuable in identifying parathyroid tissue, but has never been evaluated in this capacity.
METHODS
We used FLIm to measure the UV induced (355 nm) time-resolved autofluorescence signatures (average lifetimes in 3 spectral emission channels) of thyroid, parathyroid, lymphoid and adipose tissue in 21 patients undergoing thyroid and parathyroid surgery. The Mann-Whitney U test was used to assess the ability of FLIm to discriminate normocellular parathyroid from each of the other tissues. Various machine learning classifiers (random forests, neural network, support vector machine) were then evaluated to recognize parathyroid through a leave-one-out cross-validation.
RESULTS
Statistically significant differences in average lifetime were observed between parathyroid and each of the other tissue types in spectral channels 2 and 3 respectively. The largest change was observed between adipose tissue and parathyroid (P < 0.001), while less pronounced but still significant changes were observed when comparing parathyroid with lymphoid tissue (P < 0.05) and thyroid (P < 0.01). A random forest classifier trained on average lifetimes was found to detect parathyroid tissue with 100% sensitivity and 93% specificity at the acquisition run level.
CONCLUSION
We found that FLIm derived parameters can distinguish the parathyroid glands and other adjacent tissue types and has promise in scanning the surgical field to identify parathyroid tissue in real-time.
Topics: Adult; Aged; Female; Humans; Intraoperative Care; Male; Middle Aged; Optical Imaging; Parathyroid Glands; Parathyroidectomy; Pilot Projects; Thyroidectomy
PubMed: 33878575
DOI: 10.1016/j.jss.2021.03.023 -
Nutrients Dec 2018In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D)... (Review)
Review
In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D) synthesis; thereby increasing parathyroid hormone (PTH) production. FGF-23 acts on the parathyroid gland (PTG) to increase 1α-hydroxylase activity and results in increase intra-gland 1,25D production that attenuates PTH secretion efficiently if sufficient 25D are available. Interesting, calcimimetics can further increase PTG 1α-hydroxylase activity that emphasizes the demand for nutritional vitamin D (NVD) under high PTH status. In addition, the changes in hydroxylase enzyme activity highlight the greater parathyroid 25-hydroxyvitmain D (25D) requirement in secondary hyperparathyroidism (SHPT); the higher proportion of oxyphil cells as hyperplastic parathyroid progression; lower cytosolic vitamin D binding protein (DBP) content in the oxyphil cell; and calcitriol promote vitamin D degradation are all possible reasons supports nutritional vitamin D (NVD; e.g., Cholecalciferol) supplement is crucial in SHPT. Clinically, NVD can effectively restore serum 25D concentration and prevent the further increase in PTH level. Therefore, NVD might have the benefit of alleviating the development of SHPT in early CKD and further lowering PTH in moderate to severe SHPT in dialysis patients.
Topics: Dietary Supplements; Fibroblast Growth Factor-23; Humans; Hyperparathyroidism, Secondary; Parathyroid Glands; Renal Insufficiency, Chronic; Vitamin D
PubMed: 30513912
DOI: 10.3390/nu10121890 -
Endocrinology and Metabolism (Seoul,... Apr 2021We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission...
BACKGROUND
We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.
METHODS
The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.
RESULTS
Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.
CONCLUSION
Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.
Topics: Humans; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Radioactivity; Technetium Tc 99m Sestamibi
PubMed: 33820395
DOI: 10.3803/EnM.2020.823 -
Biomedical Engineering Online Jun 2022Near-infrared (NIR) autofluorescence detection is an effective method for identifying parathyroid glands (PGs) in thyroidectomy or parathyroidectomy. Fiber optical...
BACKGROUND
Near-infrared (NIR) autofluorescence detection is an effective method for identifying parathyroid glands (PGs) in thyroidectomy or parathyroidectomy. Fiber optical probes provide quantitative autofluorescence measurements for PG detection owing to its high sensitivity and high excitation light cut-off efficiency at a fixed detection distance. However, an optical fiber probe lacks the imaging capability and cannot map the autofluorescence distribution on top of normal tissue background. Therefore, there is a need for intraoperative mapping of PGs with high sensitivity and imaging resolution.
METHODS
We have developed a fluorescence scanning and projection (FSP) system that combines a scanning probe and a co-axial projector for intraoperative localization and in situ display of PGs. Some of the key performance characteristics, including spatial resolution and sensitivity for detection, spatial resolution for imaging, dynamic time latency, and PG localization capability, are characterized and verified by benchtop experiments. Clinical utility of the system is simulated by a fluorescence-guided PG localization surgery on a tissue-simulating phantom and validated in an ex vivo experiment.
RESULTS
The system is able to detect indocyanine green (ICG) solution of 5 pM at a high signal-to-noise ratio (SNR). Additionally, it has a maximal projection error of 0.92 mm, an averaged projection error of 0.5 ± 0.23 mm, and an imaging resolution of 748 μm at a working distance ranging from 35 to 55 cm. The dynamic testing yields a short latency of 153 ± 54 ms, allowing for intraoperative scanning on target tissue during a surgical intervention. The simulated fluorescence-guided PG localization surgery has validated the system's capability to locate PG phantom with operating room ambient light interference. The simulation experiment on the PG phantom yields a position detection bias of 0.36 ± 0.17 mm, and an area intersection over unit (IoU) of 76.6% ± 6.4%. Fluorescence intensity attenuates exponentially with the thickness of covered tissue over the PG phantom, indicating the need to remove surrounding tissue in order to reveal the weak autofluorescence signal from PGs. The ex vivo experiment demonstrates the technical feasibility of the FSP system for intraoperative PG localization with accuracy.
CONCLUSION
We have developed a novel probe-based imaging and navigation system with high sensitivity for fluorescence detection, capability for fluorescence image reconstruction, multimodal image fusion and in situ PG display function. Our studies have demonstrated its clinical potential for intraoperative localization and in situ display of PGs in thyroidectomy or parathyroidectomy.
Topics: Optical Imaging; Parathyroid Glands; Parathyroidectomy; Surgery, Computer-Assisted; Thyroidectomy
PubMed: 35710423
DOI: 10.1186/s12938-022-01004-8 -
Frontiers in Endocrinology 2023The accurate detection of parathyroid glands (PGs) during surgery is of great significance in thyroidectomy and parathyroidectomy, which protects the function of normal... (Review)
Review
The accurate detection of parathyroid glands (PGs) during surgery is of great significance in thyroidectomy and parathyroidectomy, which protects the function of normal PGs to prevent postoperative hypoparathyroidism and the thorough removal of parathyroid lesions. Existing conventional imaging techniques have certain limitations in the real-time exploration of PGs. In recent years, a new, real-time, and non-invasive imaging system known as the near-infrared autofluorescence (NIRAF) imaging system has been developed to detect PGs. Several studies have confirmed that this system has a high parathyroid recognition rate and can reduce the occurrence of transient hypoparathyroidism after surgery. The NIRAF imaging system, like a magic mirror, can monitor the PGs during surgery in real time, thus providing great support for surgeries. In addition, the NIRAF imaging system can evaluate the blood supply of PGs by utilizing indocyanine green (ICG) to guide surgical strategies. The NIRAF imaging system and ICG complement each other to protect normal parathyroid function and reduce postoperative complications. This article reviews the effectiveness of the NIRAF imaging system in thyroidectomies and parathyroidectomies and briefly discusses some existing problems and prospects for the future.
Topics: Humans; Parathyroid Glands; Optical Imaging; Parathyroidectomy; Hypoparathyroidism; Indocyanine Green; Monitoring, Intraoperative
PubMed: 37284221
DOI: 10.3389/fendo.2023.1160902 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Nov 2022To evaluate the clinical effect of reoperation in persistent hyperparathyroidism (PHPT) patients after operation of parathyroidectomy combined with...
To evaluate the clinical effect of reoperation in persistent hyperparathyroidism (PHPT) patients after operation of parathyroidectomy combined with autotransplantation(PTX+AT) on secondary hyperparathyroidism (SHPT) . 18 PHPT patients who treated with reoperation after PTX+AT were enrolled in this study during the period from Aug 2012 to Dec 2021 in the Department of Otolaryngology Head and Neck Surgery of Peking University Civil Aviation School of Clinical Medicine, Civil Aviation General Hospital. The remaining parathyroid glands were located by preoperative colour Doppler ultrasonography, radionuclide imaging, enhanced CT and MR imaging in the neck region . Based on the imaging findings, the remaining parathyroid glands were removed in situ, and the missed ectopic or extra parathyroid glands were resected with an extended surgical scope according to the parathyroid dissection method. The surgical effect was evaluated by the changes of clinical symptoms, the dynamic change of serum intact paramyroidhomone(i-PTH) between preoperative and postoperative periods and the surgical complications. All the 18 patients accepted successful operation. 30 parathyroid glands were resected confirmed by postoperative pathology, including 16 in situ and 14 ectopic glands(5 in superior mediastinum, 4 in thymus, 2 in posterior mediastinum ,2 in thyroid glands, 1 in carotid sheath).Osteoarthropathy and skin itching were significantly relieved or even disappeared at 6 h after surgery. The levels of serum i-PTH, calcium and phosphorus reached the standards and muscle weakness was significantly improved 1 week after surgery. 16 patients presented hypocalcemia and returned to normal after supplement of calcium. Hoarseness due to temporary injury of laryngeal nerve was found in 6 cases. No serious complications or death occurred after the operation.There was no recurrence after 1 year follow-up. Reoperation is the first choice for SHPT patients complicated with persistent hyperparathyroidism. Multiple imaging examinations are used to locate the residual parathyroid, especially the ectopic gland. Expanded surgical scope is applied to resect all the residual parathyroid glands(ectopic, in situ and concealed parathyroid) according to the concept of dissection parathyroidectomy. The surgery is effective and safe. Patients'quality of life and long-term survival rate is improved.
Topics: Humans; Reoperation; Calcium; Quality of Life; Hyperparathyroidism, Secondary; Parathyroidectomy; Parathyroid Glands; Postoperative Period; Parathyroid Hormone
PubMed: 36347573
DOI: 10.13201/j.issn.2096-7993.2022.11.003 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... May 2022The main causes of hypoparathyroidism are unintentional parathyroidectomy and/or impaired blood supply. Therefore, accurate identification and preservation of... (Review)
Review
The main causes of hypoparathyroidism are unintentional parathyroidectomy and/or impaired blood supply. Therefore, accurate identification and preservation of parathyroid glands in situ during thyroid or parathyroid surgery has become one of the problems that plague endocrine surgeons. In recent years, near-infrared autofluorescence imaging technology has gradually attracted more and more attention from surgeons because of its simplicity, safety, accuracy, real-time, no-contrast agent, and non-invasiveness. This article reviews the development history, clinical application, and application prospects of the parathyroid gland autofluorescence imaging technology in recent years.
Topics: Humans; Hypoparathyroidism; Optical Imaging; Parathyroid Glands; Parathyroidectomy; Thyroidectomy
PubMed: 35483695
DOI: 10.13201/j.issn.2096-7993.2022.05.016 -
Acta Otorrinolaringologica Espanola 2017To evaluate the incidence and predictive factors for transient and permanent hypocalcemia and hypoparathyroidism following thyroidectomy.
OBJECTIVE
To evaluate the incidence and predictive factors for transient and permanent hypocalcemia and hypoparathyroidism following thyroidectomy.
METHOD
We studied all the 162 patients that underwent thyroid surgery in the ENT department of the Centro Hospitalar Vila Nova Gaia/Espinho from January 2005 to December 2014. We reviewed pre-operative, 6h and 12h after surgery ionized calcium and PTH levels. All patients were reviewed and evaluated according to the following criteria: gender, age, thyroid function, histologic diagnosis of the specimen, surgery extension and presence or absence of hypoparathyroidism.
RESULTS
There were 31 (19.1%) cases of transient hypoparathyroidism and 8 (5%) of permanent hypoparathyroidism. No significant difference was found for transient hypoparathyroidism when patients were analyzed by gender. However, all cases of permanent hypoparathyroidism were observed in female individuals. Comparing hemithyroidectomy with all other surgical procedures, we found that extension of surgery was a great predictor of transient (p=0.0001) and permanent (p=0.001) hypoparathyroidism. Diagnosis of malignancy was a strong predictor of transient hypoparathyroidism (p=0.002). It was also associated with permanent hypoparathyroidism, although differences did not reach statistical significance (p=0.096).
CONCLUSION
Extension of surgery (total thyroidectomy) and diagnosis of malignancy are predictors of transient and permanent hypoparathyroidism.
Topics: Adult; Aged; Aged, 80 and over; Calcium; Female; Humans; Hypocalcemia; Hypoparathyroidism; Incidence; Intraoperative Complications; Male; Middle Aged; Neck Dissection; Parathyroid Glands; Parathyroid Hormone; Retrospective Studies; Risk Factors; Sex Factors; Thyroid Diseases; Thyroid Neoplasms; Thyroidectomy; Young Adult
PubMed: 27776803
DOI: 10.1016/j.otorri.2016.06.008