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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 -
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 -
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... 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 -
Kidney International Aug 2008The identification of the calcium-sensing receptor (CaSR) and the clarification of its role as the major regulator of parathyroid gland function have important... (Review)
Review
The identification of the calcium-sensing receptor (CaSR) and the clarification of its role as the major regulator of parathyroid gland function have important implications for understanding the pathogenesis and evolution of secondary hyperthyroidism in chronic kidney disease (CKD). Signaling through the CaSR has direct effects on three discrete components of parathyroid gland function, which include parathyroid hormone (PTH) secretion, PTH synthesis, and parathyroid gland hyperplasia. Disturbances in calcium and vitamin D metabolism that arise owing to CKD diminish the level of activation of the CaSR, leading to increases in PTH secretion, PTH synthesis, and parathyroid gland hyperplasia. Each represents a physiological adaptive response by the parathyroid glands to maintain plasma calcium homeostasis. Studies of genetically modified mice indicate that signal transduction via the CaSR is a key determinant of parathyroid cell proliferation and parathyroid gland hyperplasia. Because enlargement of the parathyroid glands has important implications for disease progression and disease severity, it is possible that clinical management strategies that maintain adequate calcium-dependent signaling through the CaSR will ultimately prove useful in diminishing parathyroid gland hyperplasia and in modifying disease progression.
Topics: Animals; Disease Progression; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Mice; Parathyroid Glands; Parathyroid Hormone; Receptors, Calcium-Sensing; Signal Transduction
PubMed: 17568787
DOI: 10.1038/sj.ki.5002287 -
Kidney International Feb 2010Over the past few years there have been considerable advances in our understanding of the physiological regulation of mineral homeostasis. One of the most important... (Review)
Review
Over the past few years there have been considerable advances in our understanding of the physiological regulation of mineral homeostasis. One of the most important breakthroughs is the identification of fibroblastic growth factor 23 (FGF23) and its role as a key regulator of phosphate and 1,25-dihydroxyvitamin D metabolism. FGF23 exerts its biological functions by binding to its cognate receptor in the presence of Klotho as a cofactor. FGF23 principally acts on the kidney to induce urinary phosphate excretion and suppresses 1,25-dihydroxyvitamin D synthesis, thereby indirectly modulating parathyroid hormone secretion. FGF23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis and secretion. In patients with chronic kidney disease, FGF23 levels increase progressively to compensate for phosphate retention, but these elevated FGF23 levels fail to suppress the secretion of parathyroid hormone, particularly in the setting of uremia. Recent data suggest that this parathyroid resistance to FGF23 may be caused by decreased expression of Klotho-FGFR1 complex in hyperplastic parathyroid glands. This review summarizes recent insights into the role of FGF23 in mineral homeostasis and discusses the involvement of its direct and indirect interaction with the parathyroid gland, particularly focusing on the pathophysiology of secondary hyperparathyroidism in chronic kidney disease.
Topics: Animals; Chronic Disease; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperplasia; Kidney Diseases; Parathyroid Glands; Parathyroid Hormone; Uremia
PubMed: 20010546
DOI: 10.1038/ki.2009.466 -
Frontiers in Endocrinology 2023Parathyroid glands may be compromised during thyroid surgery which can lead to hypoparathyroidism and hypocalcemia. Identifying the parathyroid glands relies on the...
INTRODUCTION
Parathyroid glands may be compromised during thyroid surgery which can lead to hypoparathyroidism and hypocalcemia. Identifying the parathyroid glands relies on the surgeon's experience and the only way to confirm their presence was through tissue biopsy. Near infrared autofluorescence technology offers an opportunity for real-time, non-invasive identification of the parathyroid glands.
METHODS
We used a new research prototype (hANDY-I) developed by Optosurgical, LLC. It offers coaxial excitation light and a dual-Red Green Blue/Near Infrared sensor that guides anatomical landmarks and can aid in identification of parathyroid glands by showing a combined autofluorescence and colored image simultaneously.
RESULTS
We tested the imager during 23 thyroid surgery cases, where initial clinical feasibility data showed that out of 75 parathyroid glands inspected, 71 showed strong autofluorescence signal and were correctly identified (95% accuracy) by the imager.
CONCLUSIONS
The hANDY-I prototype demonstrated promising results in this feasibility study by aiding in real-time visualization of the parathyroid glands. However, further testing by conducting randomized clinical trials with a bigger sample size is required to study the effect on levels of hypoparathyroidism and hypocalcemia.
Topics: Humans; Parathyroid Glands; Feasibility Studies; Thyroidectomy; Hypocalcemia; Optical Imaging; Hypoparathyroidism
PubMed: 37554762
DOI: 10.3389/fendo.2023.1190282 -
Medical Ultrasonography Mar 2011Thyroid ultrasound is easy to perform due to the superficial location of the thyroid gland, but appropriate equipment is mandatory with a linear high frequency...
Thyroid ultrasound is easy to perform due to the superficial location of the thyroid gland, but appropriate equipment is mandatory with a linear high frequency transducer (7.5 - 12) MHz. Some pathological aspects of the thyroid gland are easily diagnosed by ultrasound, like the enlargement of the thyroid volume (goiter) or the presence of nodules and cysts; while other aspects are more difficult and need more experience (diffuse changes in the structure, echogenicity and vascularization of the parenchyma, differential diagnosis of malignant nodules). Ultrasound has become the diagnostic procedure of choice in guidelines for the management of thyroid nodules; most structural abnormalities of the thyroid need evaluation and monitoring but not intervention. A good knowledge of the normal appearance of the thyroid gland is compulsory for an accurate ultrasound diagnosis.
Topics: Humans; Image Enhancement; Parathyroid Diseases; Parathyroid Glands; Thyroid Diseases; Thyroid Gland; Ultrasonography
PubMed: 21390348
DOI: No ID Found -
Problemy Endokrinologii Aug 2021Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied... (Review)
Review
Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism.The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. In view of the incidence of thyroid cancer, primary hyperparathyroidism and other pathologies of the neck organs, which radical treatment can lead to the parathyroid gland impairment, an increased number of patients with hypoparathyroidism is expected. Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. Autoimmune hypoparathyroidism usually occurs in childhood and is characterized by a severe course of the disease, especially in the case of concomitant malabsorption syndrome.Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.Timely diagnosis, rational medical therapy and management strategy may reduce the risks of short-term and long-term complications, frequency of hospitalizations and disability of patients, as well as improve the prognosis.This review covers the main issues of Russian guidelines for the management of chronic hypoparathyroidism, approved in 2021, including laboratory and instrumental evaluation, treatment approaches and follow-up. This guidelines also include the recommendations for special groups of patients: with acute hypocalcemia, hypoparathyroidism during pregnancy.
Topics: Humans; Hypocalcemia; Hypoparathyroidism; Parathyroid Glands; Parathyroid Hormone; Quality of Life
PubMed: 34533015
DOI: 10.14341/probl12800 -
Molecules (Basel, Switzerland) Jul 2019Injury to parathyroid glands during thyroid and parathyroid surgery is common and postoperative hypoparathyroidism represents a serious complication. Parathyroid glands...
Injury to parathyroid glands during thyroid and parathyroid surgery is common and postoperative hypoparathyroidism represents a serious complication. Parathyroid glands possess a unique autofluorescence in the near-infrared spectrum which could be used for their identification and protection at an early stage of the operation. In the present study parathyroid autofluorescence was visualized intraoperatively using a standard Storz laparoscopic near-infrared/indocyanine green (NIR/ICG) imaging system with minor modifications to the xenon light source (filtered to emit 690 nm to 790 nm light, less than 1% in the red and green above 470 nm and no blue light). During exposure to NIR light parathyroid tissue was expected to show autofluorescence at 820 nm, captured in the blue channel of the camera. Over a period of 5 years, we investigated 205 parathyroid glands from 117 patients. 179 (87.3%) glands were correctly identified by their autofluorescence. Surrounding structures such as thyroid, lymph nodes, muscle, or adipose tissue did not reveal substantial autofluorescence. We conclude that parathyroid glands can be identified by their unique autofluorescence at an early stage of the operation. This may help to preserve these fragile structures and their vascularization and lower the rate of postoperative hypocalcemia.
Topics: Humans; Intraoperative Care; Optical Imaging; Parathyroid Glands; Parathyroidectomy; Spectroscopy, Near-Infrared; Thyroid Gland; Thyroidectomy
PubMed: 31337096
DOI: 10.3390/molecules24142560