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Journal of Bone and Mineral Research :... May 2024Although parathyroid hormone (PTH) is best known for its role as a regulator of skeletal remodelling and calcium homeostasis, more recent evidence supports a role for it... (Review)
Review
Although parathyroid hormone (PTH) is best known for its role as a regulator of skeletal remodelling and calcium homeostasis, more recent evidence supports a role for it in energy metabolism and other non-classical targets. In this report, we summarize evidence for an effect of PTH on adipocytes. This review is based upon all peer-reviewed papers, published in the English language with PubMed as the primary search engine. Recent preclinical studies have documented an effect of PTH to stimulate lipolysis in both adipocytes and liver cells and to cause browning of adipocytes. PTH also reduces bone marrow adiposity and hepatic steatosis. Although clinical studies are limited, disease models of PTH excess and PTH deficiency lend support to these preclinical findings. This review supports the concept of PTH as a polyfunctional hormone that influences energy metabolism as well as bone metabolism.
Topics: Humans; Parathyroid Hormone; Adiposity; Animals; Adipocytes; Energy Metabolism; Lipolysis
PubMed: 38637302
DOI: 10.1093/jbmr/zjae056 -
Endocrinology and Metabolism (Seoul,... Dec 2019Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized... (Review)
Review
Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or ">50% intraoperative PTH drop" criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.
Topics: Humans; Hyperparathyroidism, Primary; Monitoring, Intraoperative; Parathyroid Hormone; Parathyroidectomy; Point-of-Care Systems
PubMed: 31884732
DOI: 10.3803/EnM.2019.34.4.327 -
The FEBS Journal Jul 2020Parathyroid hormone (PTH) regulates serum calcium levels and bone strength. Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD)... (Review)
Review
Parathyroid hormone (PTH) regulates serum calcium levels and bone strength. Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality. In experimental SHP, the increased PTH gene expression is due to increased PTH mRNA stability and is mediated by protein-PTH mRNA interactions. Adenosine-uridine-rich binding factor 1 (AUF1) stabilizes and K-homology splicing regulatory protein (KSRP) destabilizes PTH mRNA. The peptidyl-prolyl cis/trans isomerase Pin1 acts on target proteins, including mRNA-binding proteins. Pin1 leads to KSRP dephosphorylation, but in SHP, parathyroid Pin1 activity is decreased and phosphorylated KSRP fails to bind PTH mRNA, leading to increased PTH mRNA stability and levels. A further level of post-transcriptional regulation occurs through microRNA (miRNA). Dicer mediates the final step of miRNA maturation. Parathyroid-specific Dicer knockout mice that lack miRNAs in the parathyroid develop normally. Surprisingly, these mice fail to increase serum PTH in response to both hypocalcemia and CKD, indicating that parathyroid Dicer and miRNAs are essential for stimulation of the parathyroid. Human and rodent parathyroids share similar miRNA profiles that are altered in hyperparathyroidism. The evolutionary conservation of abundant miRNAs and their regulation in hyperparathyroidism indicate their significance in parathyroid physiology and pathophysiology. let-7 and miR-148 antagonism modifies PTH secretion in vivo and in vitro, suggesting roles for specific miRNAs in parathyroid function. This review summarizes the current knowledge on the post-transcriptional mechanisms of PTH gene expression in SHP and the central contribution of miRNAs to the high serum PTH levels of both primary hyperparathyroidism and SHP.
Topics: Animals; Gene Expression Regulation; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; RNA Processing, Post-Transcriptional; Renal Insufficiency, Chronic
PubMed: 32191397
DOI: 10.1111/febs.15300 -
Endocrine Practice : Official Journal... Jan 2022Calcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland...
Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients.
OBJECTIVE
Calcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration.
METHODS
Two thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H).
RESULTS
There were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm, DA = 1.43 cm, and H = 1.27 cm; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001).
CONCLUSION
This is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.
Topics: Calcium; Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Retrospective Studies
PubMed: 34403781
DOI: 10.1016/j.eprac.2021.08.003 -
Cardiovascular & Hematological... 2023Calcium homeostasis is regulated by the dyad of parathyroid hormone and calcitriol, whereas kidney, intestine, and bone are the primary target sites. Elevation of serum... (Review)
Review
Calcium homeostasis is regulated by the dyad of parathyroid hormone and calcitriol, whereas kidney, intestine, and bone are the primary target sites. Elevation of serum calcium levels and hypercalcemia are likely markers of pathological conditions, particularly malignancy and hyperparathyroidism. Similarly, several dysfunctions within the body can direct hypercalcemia. Furthermore, chemicals and drugs can also drive this condition. Owing to the significant role of the kidney in calcium homeostasis, renal abnormalities lead to hypercalcemia and increased calcium levels can have pathological effects on the kidney. This review is designed to highlight some of the commonly known causes of hypercalcemia and their effects on the kidney.
Topics: Humans; Hypercalcemia; Calcium; Kidney; Parathyroid Hormone; Calcitriol
PubMed: 36475333
DOI: 10.2174/1871529X23666221205143041 -
Endocrinologia, Diabetes Y Nutricion 2021To evaluate the safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate (PTH-FNA) in patients with primary hyperparathyroidism and... (Observational Study)
Observational Study
OBJECTIVE
To evaluate the safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate (PTH-FNA) in patients with primary hyperparathyroidism and suspicious parathyroid adenomas.
METHODOLOGY
A retrospective observational study was performed in 47 patients (57.7 ± 11.2 years of average age, 74% women) attending an endocrinology clinic for primary hyperparathyroidism (average calcemia: 11.6 ± 1.6 mg/dl and PTH: 276 ± 477 pg/mL) in which PTH-FNA was made. Sensibility, specificity, positive predictive value and negative predictive value were calculated in all surgical patients.
RESULTS
Forty-seven lesions were punctured (mean adenoma maximum diameter: 1.8 ± 2.6 cm): negative image in the sestamibi scan (26 patients); the discordance between ultrasonography and the sestamibi scan (6 patients); possible intrathyroidal adenomas (4 patients); a positive sestamibi scan in 2 or more localizations (4 patients); ectopic adenoma (3 patients); persistent primary hyperparathyroidism (2 patients) and atypical adenomas (2 patients). Mean PTH-FNA was 2853 ± 3957 pg/mL and 68% were considered positive (PTH-FNA ≥ 100 pg/mL). No complications were detected during or after the puncture. Thirty-seven patients were operated on, 95% were cured and no parathyromatosis cases were detected. PTH-FNA ≥ 100 pg/mL as a diagnostic test had a sensitivity of 93.7%, a specificity of 100%, a positive predictive value of 100% and an negative predictive value of 71.4%.
CONCLUSION
PTH-FNA is an easy and safe diagnostic test and has a high sensitivity and specificity for differentiating between parathyroid adenomas and other cervical masses in patients with primary hyperparathyroidism.
Topics: Adenoma; Aged; Biopsy, Fine-Needle; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms
PubMed: 34863413
DOI: 10.1016/j.endien.2020.07.004 -
Frontiers in Endocrinology 2021After the initial signaling action of parathyroid hormone (PTH) on bone was shown to be activation of adenylyl cyclase, its target was found to be cells of the... (Review)
Review
After the initial signaling action of parathyroid hormone (PTH) on bone was shown to be activation of adenylyl cyclase, its target was found to be cells of the osteoblast lineage, to the exclusion of osteoclasts and their precursors. This led to the view that the osteoblast lineage regulated osteoclast formation, a proposal that was established when the molecular mechanisms of osteoclast formation were discovered. This is in addition to the effect of PTH1Rv signaling throughout the osteoblast differentiation process to favour the formation of bone-forming osteoblasts. Initial signaling in the PTH target cells through cAMP and protein kinase A (PKA) activation is extremely rapid, and marked by an amplification process in which the later event, PKA activation, precedes cAMP accumulation in time and is achieved at lower concentrations. All of this is consistent with the existence of "spare receptors", as is the case with several other peptide hormones. PTH-related protein (PTHrP), that was discovered as a cancer product, shares structural similarity with PTH in the amino-terminal domain that allows the hormone, PTH, and the autocrine/paracrine agent, PTHrP, to share actions upon a common G protein coupled receptor, PTH1R, through which they activate adenylyl cyclase with equivalent potencies. Studies of ligand-receptor kinetics have revealed that the PTH/PTH1R ligand-receptor complex, after initial binding and adenylyl cyclase activation at the plasma membrane, is translocated to the endosome, where adenylyl cyclase activation persists for a further short period. This behavior of the PTH1R resembles that of a number of hormones and other agonists that undergo such endosomal translocation. It remains to be determined whether and to what extent the cellular effects through the PTH1R might be influenced when endosomal is added to plasma membrane activation.
Topics: Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Osteoblasts; Parathyroid Hormone; Receptor, Parathyroid Hormone, Type 1
PubMed: 35126319
DOI: 10.3389/fendo.2021.833221 -
Endocrine Apr 2021Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term...
PURPOSE
Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1-84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment.
METHODS
The study was a Phase III, open-label, non-comparative, clinical investigation (study period: 3 months), at a tertiary care clinical research center. Thirty patients with chronic hypoparathyroidism were screened, and 12 started teriparatide. After the optimization phase (0-4 weeks), calcium and calcitriol supplements were progressively reduced, while teriparatide 20 µg once daily was administered (5-7 weeks), and then could be titrated up to 20 µg twice daily (7-17 weeks). The main outcome measures included serum and urinary biochemical exams and Rand 36-Item Short Form Health Survey.
RESULTS
This study showed that teriparatide 20 µg once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal serum calcium concentrations. Conversely, for more than half of patients treated with teriparatide 20 µg twice daily, calcium and calcitriol administration was avoidable, but in some cases at the expense of serum calcium and phosphate oscillations.
CONCLUSIONS
Since intervention trials evaluating the efficacy and safety of teriparatide in hypoparathyroid patients are not yet available, the routine use of this molecule poses some doubts.
Topics: Adult; Calcitriol; Calcium; Hormone Replacement Therapy; Humans; Hypoparathyroidism; Parathyroid Hormone; Teriparatide
PubMed: 33538953
DOI: 10.1007/s12020-020-02577-x -
Biotechnic & Histochemistry : Official... Nov 2022Bone healing deficiencies are challenging for orthopedic practice. The use of stem cells with scaffolds to treat bone tissue losses currently is popular for promoting...
Bone healing deficiencies are challenging for orthopedic practice. The use of stem cells with scaffolds to treat bone tissue losses currently is popular for promoting regeneration of tissue. Programmable cells of monocytic origin (PCMO) may differentiate into three germ layers and may be a promising alternative treatment due to their stem cell-like properties. Parathyroid hormone (PTH) participates in bone metabolism. Intermittent administration of PTH promotes osteogenic activity of mesenchymal stem cdells (MSC). We investigated the osteogenic effects of continuous and intermittent administration of PTH on PCMO. Mononuclear cells were harvested from the peripheral blood of healthy donors. Isolated cells were cultured for six days in a de-differentiation medium. Indirect immunocytochemistry using anti-CD14, anti-CD45 and anti-CD90 primary antibodies, as well as electron microscopy were used to detect PCMO. PCMO then were cultured in an osteogenic differentiation medium supplemented with continuous or intermittent 50 ng/ml PTH. The PTH-free control group (CG), intermittent PTH treated group (IPG) and continuous PTH treated group (CPG) were cultured and assessed for their differentiation into osteogenic lineage cells by indirect immunocytochemistry using anti-collagen I, anti-osteonectin and anti-osteocalcin primary antibodies. Osteoblast-like cells obtained by continuous or intermittent PTH administration exhibited increased levels of collagen I, osteonectin and osteocalcin immunoreactivity. We found that continuous and intermittent PTH administration to PCMO enhanced their differentiation to osteogenic lineage cells and increased osteoblastic activity.
Topics: Osteogenesis; Parathyroid Hormone; Cell Differentiation; Osteoblasts; Stem Cells
PubMed: 35473476
DOI: 10.1080/10520295.2022.2049876 -
Otolaryngology--head and Neck Surgery :... Dec 2019Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative...
OBJECTIVE
Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative PTH and calcium drop can confirm the resection of all parathyroid tissues.
STUDY DESIGN
Case series with planned data collection.
SETTING
Tertiary referral medical center.
SUBJECTS AND METHODS
The study assessed patients with tertiary hyperparathyroidism who were treated at the Hospital of the State University of Campinas from 2007 to 2015. All patients underwent total parathyroidectomy with autotransplantation of parathyroid fragments. PTH and calcium were collected during the preoperative period; at 10, 20, and 240 minutes after resection of the glands; and at 1 year after the procedure. Data were analyzed by analysis of variance and logistic regression analysis with statistical values of < .05.
RESULTS
Thirty-five patients were assessed: 17 women (48.57%) and 18 men (51.43%). The percentage of PTH drop was statistically significant at all times, unlike the calcium analysis, but only PTH collected at 20 minutes was able to confirm the removal of all parathyroid tissues ( = .029). Based on the receiver operating characteristic curve, the 71.2% drop obtained high sensitivity and specificity ( = .028).
CONCLUSIONS
Treatment success can be predicted by analyzing the decrease of intraoperative PTH and not by calcium. The 71.2% PTH drop at 20 minutes after parathyroidectomy had high sensitivity and specificity to predict surgical cure.
Topics: Adult; Aged; Calcium; Cohort Studies; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Monitoring, Intraoperative; Parathyroid Hormone; Parathyroidectomy; Predictive Value of Tests; ROC Curve; Treatment Outcome
PubMed: 31359817
DOI: 10.1177/0194599819866819