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Otolaryngologic Clinics of North America Feb 2024Secondary hyperparathyroidism (SHPT) does not initiate as a primary dysfunction of parathyroid glands resulting from an intrinsic defect or disease but is the... (Review)
Review
Secondary hyperparathyroidism (SHPT) does not initiate as a primary dysfunction of parathyroid glands resulting from an intrinsic defect or disease but is the physiologic response of parathyroids to metabolic changes elsewhere in the body occurring over time. SHPT is a manifestation of a chronic condition that classically occurs from chronic kidney disease. In fact, given the relatively recent transition of populations from outside (agrarian) to indoor (industrial, information technology, and so forth) employment and a consequent reduction in sun exposure, combined with diets of highly processed food, vitamin D and calcium deficiencies are now the leading causes of SHPT.
Topics: Humans; Parathyroid Hormone; Hyperparathyroidism, Secondary; Parathyroid Glands; Vitamin D; Vitamins
PubMed: 37634982
DOI: 10.1016/j.otc.2023.07.010 -
Minerva Endocrinology Dec 2022The main function of fibroblast growth factor 23 (FGF23) is the regulation of phosphate metabolism through its action on the sodium-dependent phosphate cotransporters in... (Review)
Review
The main function of fibroblast growth factor 23 (FGF23) is the regulation of phosphate metabolism through its action on the sodium-dependent phosphate cotransporters in the proximal renal tubules. Additionally, FGF23 interacts with vitamin D and parathyroid hormone in a complex metabolic pathway whose detailed mechanisms are still not clear in human physiology and disease. More recently, research has also focused on the understanding of mechanisms of FGF23 action on organs and system other than the kidneys and bone, as well as on its interaction with other metabolic pathways. Collectively, the new evidence are successfully used for the clinical evaluation and management of FGF23-related disorders, for which new therapies with many potential applications are now available.
Topics: Humans; Bone and Bones; Fibroblast Growth Factors; Parathyroid Hormone; Phosphates; Sodium-Phosphate Cotransporter Proteins; Vitamin D
PubMed: 33792238
DOI: 10.23736/S2724-6507.21.03378-2 -
Advances in Experimental Medicine and... 2020Parathyroid tumors are the second most common endocrine neoplasia, and it is almost always associated with hypersecretion of the parathormone (PTH), involved in calcium... (Review)
Review
Parathyroid tumors are the second most common endocrine neoplasia, and it is almost always associated with hypersecretion of the parathormone (PTH), involved in calcium homeostasis, causing primary hyperparathyroidism (PHPT). Parathyroid neoplasia has a stromal component particularly represented in atypical adenomatous and carcinomatous lesions. Recently, data about the features and the function of the parathyroid tumor microenvironment (TME) have been accumulated. Parathyroid TME includes heterogeneous cells: endothelial cells, myofibroblasts, lymphocytes and macrophages, and mesenchymal stem cells have been identified, each of them presenting a phenotype consistent with tumor-associated cells. Parathyroid tumors overexpress proangiogenic molecules including vascular endothelial growth factor (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietins that promote both recruitment and proliferation of endothelial cell precursors, thus resulting in a microvessel density higher than that detected in normal parathyroid glands. Moreover, parathyroid tumor endocrine cells operate multifaceted interactions with stromal cells, partly mediated by the CXCL12/CXCR4 pathway, while, at present, the immune landscape of parathyroid tumors has just begun to be investigated. Studies about TME in parathyroid adenomas provide an example of the role of TME in benign tumors, whose molecular mechanisms and functions comprehension are limited.
Topics: Humans; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Tumor Microenvironment
PubMed: 32030674
DOI: 10.1007/978-3-030-36214-0_3 -
Clinica Chimica Acta; International... Jul 2020Parathyroid hormone (PTH) is the key hormone regulating calcium homeostasis and, as such, is an important diagnostic and prognostic marker. Although the measurement of... (Review)
Review
Parathyroid hormone (PTH) is the key hormone regulating calcium homeostasis and, as such, is an important diagnostic and prognostic marker. Although the measurement of PTH has greatly improved over the past few decades, oxidation status thereof is unaccounted for in currently used assays. PTH can be oxidized on methionine residues located at amino acid positions 8 and 18. This is a relevant post-translational modification as, due to refolding of the molecule, it results in the decreased ability to activate the PTH1 receptor. Although this loss of activity after oxidation was observed as early as 1934, only recently a method was developed to measure and distinguish non-oxidized PTH (n-oxPTH) from oxidized PTH. This method creates exciting possibilities for studying more specifically the role of n-oxPTH in physiology and pathology. Therefore, it can now be explored what the clinical implications of measuring n-oxPTH will be. Herein, we review the available evidence of the effect of oxidation on the biological activity of PTH. We also discuss studies examining the mechanism of PTH oxidation in vivo and efforts to stabilize synthetic PTH ex vivo for therapeutic applications. Lastly, the available studies regarding the clinical significance of n-oxPTH are evaluated and future directions discussed.
Topics: Animals; Humans; Oxidation-Reduction; Parathyroid Hormone
PubMed: 32178977
DOI: 10.1016/j.cca.2020.03.020 -
Surgical Oncology Clinics of North... Jan 2023Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation... (Review)
Review
Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation of thyroid lobectomy for well-selected patients with low-risk disease; minimally invasive parathyroidectomy with, and potentially without, intraoperative parathyroid hormone monitoring for patients with well-localized primary hyperparathyroidism; improvement in the management of parathyroid cancer with the incorporation of immune checkpoint blockade and/or targeted therapies; and the incorporation of minimally invasive techniques in the management of patients with benign tumors and selected secondary malignancies of the adrenal gland.
Topics: Humans; Monitoring, Intraoperative; Parathyroid Hormone; Parathyroidectomy; Endocrine System
PubMed: 36410918
DOI: 10.1016/j.soc.2022.08.004 -
Casopis Lekaru Ceskych 2023Hypoparathyroidism is a rare endocrine disease caused by an absence or insufficient production of parathormone. Parathormone deficiency leads to lower serum calcium...
Hypoparathyroidism is a rare endocrine disease caused by an absence or insufficient production of parathormone. Parathormone deficiency leads to lower serum calcium concentration that is responsible for patients' neuromuscular symptoms. Conventional treatment consists of calcium and active vitamin D metabolites administration but doesn't constitute an adequate substitution of missing parathormone. Although the treatment substantially alleviates patients' troubles, chronic complications may develop because of hyperphosphatemia and conventional medication. Solution to this resides in recombinant parathormone administration, however the only one drug available is being now recalled from the market. The mainstay of hypoparathyroidism prevention is the judicious indication of total thyroidectomy representing the main cause of the disease.
Topics: Humans; Calcium; Hypoparathyroidism; Parathyroid Hormone; Rare Diseases
PubMed: 37734939
DOI: No ID Found -
Nature Feb 2024Many peptide hormones form an α-helix on binding their receptors, and sensitive methods for their detection could contribute to better clinical management of disease....
Many peptide hormones form an α-helix on binding their receptors, and sensitive methods for their detection could contribute to better clinical management of disease. De novo protein design can now generate binders with high affinity and specificity to structured proteins. However, the design of interactions between proteins and short peptides with helical propensity is an unmet challenge. Here we describe parametric generation and deep learning-based methods for designing proteins to address this challenge. We show that by extending RFdiffusion to enable binder design to flexible targets, and to refining input structure models by successive noising and denoising (partial diffusion), picomolar-affinity binders can be generated to helical peptide targets by either refining designs generated with other methods, or completely de novo starting from random noise distributions without any subsequent experimental optimization. The RFdiffusion designs enable the enrichment and subsequent detection of parathyroid hormone and glucagon by mass spectrometry, and the construction of bioluminescence-based protein biosensors. The ability to design binders to conformationally variable targets, and to optimize by partial diffusion both natural and designed proteins, should be broadly useful.
Topics: Biosensing Techniques; Computer-Aided Design; Deep Learning; Diffusion; Glucagon; Luminescent Measurements; Mass Spectrometry; Parathyroid Hormone; Peptides; Protein Structure, Secondary; Proteins; Substrate Specificity; Models, Molecular
PubMed: 38109936
DOI: 10.1038/s41586-023-06953-1 -
Annales D'endocrinologie Jun 2021Cardiovascular diseases remain the leading cause of non-communicable chronic diseases, are related to high morbidity and mortality and are associated to a huge impact on... (Review)
Review
Cardiovascular diseases remain the leading cause of non-communicable chronic diseases, are related to high morbidity and mortality and are associated to a huge impact on healthcare budgets. Biomarkers play an important role for the diagnosis and prognosis of cardiovascular diseases and are recognized tools for value-based care. Parathyroid hormone (PTH) is a major systemic calcium-regulating hormone and an important regulator of bone and mineral homeostasis. PTH 1-84, the biologically active hormone produced by the parathyroid glands and secreted into the systemic circulation, exerts its biological effects through the interaction of its first 34 amino acids with PTH receptors. PTH levels are raised in several cardio-renal disorders and hyperparathyroidism have detrimental effects on the heart and cardiac cells such as cardiac hypertrophy, remodeling and arrhythmias. High circulating PTH levels, through an increase in intracellular calcium, contribute also to the impairment of mitochondrial function and ATP production and to oxidative stress as well as inflammation states and, at the end, to cardiomyocytes necrosis. The interplay between PTH, fibroblast growth factor 23 and aldosterone is also detrimental for cardiovascular system and participate to endothelial dysfunction. Measurement of PTH levels could be therefore relevant in high risk individuals and could provide added value to established cardiac biomarkers for the sub-phenotyping of patients and treatment selection.
Topics: Calcium; Cardiovascular Diseases; Heart Disease Risk Factors; Heart Diseases; Humans; Hyperparathyroidism; Parathyroid Hormone; Risk Factors
PubMed: 32192791
DOI: 10.1016/j.ando.2020.02.005 -
FP Essentials Mar 2022Parathyroid hormone (PTH) helps regulate calcium homeostasis in a complex relationship with the gastrointestinal tract, kidneys, bone, and parathyroid glands....
Parathyroid hormone (PTH) helps regulate calcium homeostasis in a complex relationship with the gastrointestinal tract, kidneys, bone, and parathyroid glands. Abnormalities in PTH production can result in many conditions, including hypoparathyroidism, and primary, secondary, and tertiary hyperparathyroidism. Management of each abnormality centers on maintaining normal or near-normal serum calcium values to prevent complications. Most cases of hypoparathyroidism are caused by neck surgery and may result in acute hypocalcemia. Patients with chronic hypoparathyroidism are treated with a combination of calcium, vitamin D analogs, and, occasionally, exogenous PTH. A single parathyroid adenoma causes most cases of primary hyperparathyroidism, with multiglandular disease and cancer as other possible etiologies. All patients with symptomatic primary hyperparathyroidism and many with asymptomatic hyperparathyroidism undergo partial or full parathyroidectomy to correct the underlying condition. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is the most common cause of secondary and tertiary hyperparathyroidism, in which hypocalcemia stimulates PTH production. Most patients with CKD-MBD are treated medically with phosphate binders, vitamin D analogs, and calcimimetics, but rare cases are managed with parathyroidectomy. Severe calcium or vitamin D deficiency also causes secondary hyperparathyroidism and is managed with calcium and vitamin D replacement.
Topics: Calcium; Humans; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Thyroid Gland; Vitamin D
PubMed: 35235284
DOI: No ID Found -
Archives of Endocrinology and Metabolism Nov 2022Hypoparathyroidism remains the single endocrine deficiency disease that is not habitually treated with the missing hormone. In this article, we aim to provide a review... (Review)
Review
Hypoparathyroidism remains the single endocrine deficiency disease that is not habitually treated with the missing hormone. In this article, we aim to provide a review of the conventional approach and the novel therapies as well as an overview of the perspectives on the treatment of this rare condition. We conducted a literature review on the conventional therapy using vitamin D analogs and calcium salts, indications for thiazide diuretics and phosphorus binders, PTH analogs history and usage, and the drugs that are currently being tested in clinical trials. Conventional treatment involves calcium salts and vitamin D analogs. Thiazide diuretics can be used to reduce hypercalciuria in some cases. A low-phosphate diet is recommended, and phosphate binders are rarely needed. During pregnancy, a careful approach is necessary. The use of PTH analogs is a new approach despite the limitation of high cost. Studies have included modified PTH molecules, calcilytics, microencapsulation of human parathyroid cells, and allotransplantation.
Topics: Humans; Parathyroid Hormone; Calcium; Sodium Chloride Symporter Inhibitors; Salts; Hypoparathyroidism; Vitamin D; Phosphates
PubMed: 36382754
DOI: 10.20945/2359-3997000000554