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La Revue Du Praticien May 2024
Topics: Humans; Parathyroid Neoplasms; Adenoma; Female; Middle Aged; Male
PubMed: 38833234
DOI: No ID Found -
Calcified Tissue International Jun 2024Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to... (Review)
Review
Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.
PubMed: 38833001
DOI: 10.1007/s00223-024-01227-y -
Journal of Lipid and Atherosclerosis May 2024This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease...
OBJECTIVE
This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD).
METHODS
The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques.
RESULTS
CAC patients had considerably higher levels of TNF-α (<0.001), IL-6 (<0.001), hs-CRP (=0.006), TC, TG, parathyroid hormone (PTH) (<0.001) and phosphorus (<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (=0.046), age (=0.009), TNF-α (=0.027), IL-6 (=0.005), TG (=0.002), PTH (=0.002), and phosphorus (=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (=0.045).
CONCLUSION
Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.
PubMed: 38826181
DOI: 10.12997/jla.2024.13.2.194 -
Archives of Medical Research Jun 2024Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions...
BACKGROUND
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up.
OBJECTIVE
To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors.
METHODS
Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons.
RESULTS
Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine.
CONCLUSIONS
More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.
Topics: Humans; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Phenotype; Parathyroid Hormone; Phosphorus; Vitamin D; Renal Dialysis; Renal Insufficiency, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder; Calcium
PubMed: 38824883
DOI: 10.1016/j.arcmed.2024.103008 -
Nature Communications Jun 2024Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological...
Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling ("biased agonism") with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present an approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
Topics: Ligands; Humans; Receptor, Parathyroid Hormone, Type 1; Single-Domain Antibodies; HEK293 Cells; Signal Transduction; Receptors, G-Protein-Coupled; Protein Binding; Animals; Peptides
PubMed: 38824166
DOI: 10.1038/s41467-024-49068-5 -
Journal of Clinical Pathology May 2024This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and...
AIMS
This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and calcium levels.
METHODS
A historical cohort study was conducted on adult patients with solitary PTA removed in the Gold Coast Health Precinct, Australia, between 2017 and 2022.
RESULTS
PTA weight is correlated with the change in day 1 PTH level (r=0.26, p=0.036), the change in day 1 corrected calcium level (r=0.20, p=0.033), and the change in follow-up corrected calcium level (r=0.47, p<0.001). The largest dimension (size) of PTA is also correlated with the change in day 1 PTH (r=0.30, p=0.011) and the change in follow-up corrected calcium level (r=0.40, p<0.001). Adjusted for age and gender, a statistically significant negative correlation was found between day 1 PTH level and adenoma size, resulting in a 0.5% change in size for every percentage change in PTH level (equating to a 5.0% increase in variance explained, p=0.038). Similarly, a negative correlation was identified in day 1 corrected calcium levels and weight, with a 4.7% change in weight for every percentage of change in day 1 corrected calcium level (an increase of 5.6% variance explained, p=0.010). In addition, a negative correlation was identified, where every 3.1% change in size (an increase of 17.4% variance explained, p<0.001) and 7.6% change in weight (an increase of 22.7% variance explained, p<0.001) was seen with every percentage change in follow-up corrected calcium levels. Clear-cell PTA had the most significant percentage fall in day 1 corrected calcium levels compared with other PTA subtypes (p=0.007).
CONCLUSIONS
Preoperative calcium and PTH levels correlate with PTA weight and size. The degree of change in postoperative corrected calcium levels behaved differently in the clear-cell subtype.
PubMed: 38821854
DOI: 10.1136/jcp-2023-209340 -
Journal of the Pediatric Infectious... May 2024Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third trimester TDF exposure is associated with a 12% reduction in bone...
BACKGROUND
Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. Potential mechanisms underlying this observation are unknown.
METHODS
The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in third trimester versus none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4-30 days, to compare slopes by TDF exposure.
RESULTS
Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of -0.58 versus -0.08/day (difference -0.50/day [95%CI -0.88, -0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] versus 26 [22,37] ng/mL). No differences were observed for other biomarkers.
CONCLUSIONS
Third trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates.
PubMed: 38820092
DOI: 10.1093/jpids/piae054 -
The Journal of Surgical Research May 2024Total thyroidectomy (TTx) has been reported to be more challenging in patients with Graves' disease, especially in those who are hyperthyroid at the time of surgery. Our...
INTRODUCTION
Total thyroidectomy (TTx) has been reported to be more challenging in patients with Graves' disease, especially in those who are hyperthyroid at the time of surgery. Our aim was to compare outcomes in patients undergoing TTx for Graves' disease compared to other thyroid diseases at a large academic institution with high-volume fellowship-trained endocrine surgeons.
METHODS
In our retrospective analysis from December 2015 to May 2023, patients undergoing TTx for Graves' disease were compared to those undergoing TTx for all other indications excluding advanced malignancy (poorly differentiated thyroid cancer and concomitant neck dissections). Patient demographics, biochemical values, and postoperative outcomes were compared. A subgroup analysis was performed comparing hyperthyroid to euthyroid patients at the time of surgery.
RESULTS
There were 589 patients who underwent TTx, of which 227 (38.5%) had Graves' disease compared to 362 (61.5%) without. Intraoperatively in Graves' patients, nerve monitoring was used more frequently (65.6% versus 57.1%; P = 0.04) and there was a higher rate of parathyroid autotransplantation (32.0% versus 14.4%; P < 0.01). Postoperatively, transient voice hoarseness occurred less frequently (4.8% versus 13.6%; P < 0.01) and there was no difference in temporary hypocalcemia rates or hematoma rates. In our subgroup analysis, 83 (36%) of Graves' patients were hyperthyroid (thyroid-stimulating hormone < 0.45 and free T4 > 1.64) at the time of surgery and there were no differences in postoperative complications compared to those who were euthyroid.
CONCLUSIONS
At a high-volume endocrine surgery center, TTx for Graves' disease can be performed safely without significant differences in postoperative outcomes. Hyperthyroid patients demonstrated no differences in postoperative outcomes.
PubMed: 38805845
DOI: 10.1016/j.jss.2024.04.070 -
Current Opinion in Endocrinology,... Aug 2024Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making... (Review)
Review
PURPOSE OF REVIEW
Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making these conditions a major public health concern. Due to the limited use of bone histomorphometry in clinical practice, the gold standard for assessing bone turnover, extensive efforts have been made to identify bone turnover markers (BTMs) as noninvasive surrogates. Since the identification of certain commonly used markers several decades ago, considerable experience has been acquired regarding their clinical utility in such bone disorders.
RECENT FINDINGS
Mounting evidence suggested that BTMs represent a simple, low-risk, rapid and convenient way to obtain data on the skeletal health and that they may be useful in guiding therapeutic choices and monitoring the response to treatment.
SUMMARY
BTMs could provide clinicians with useful information, independent from, and often complementary to bone mineral density (BMD) measurements. They have proven valuable for monitoring the effectiveness of osteoporosis therapy, as well as promising for discriminating low and high turnover states. Improved performance is observed when BTMs are combined, which may be useful for selecting treatments for chronic kidney disease-bone mineral disorders (CKD-MBD).
Topics: Humans; Biomarkers; Osteoporosis; Bone Remodeling; Renal Insufficiency, Chronic; Bone Density; Chronic Kidney Disease-Mineral and Bone Disorder; Bone and Bones
PubMed: 38804196
DOI: 10.1097/MED.0000000000000869 -
Frontiers in Endocrinology 2024Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of...
INTRODUCTION
Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)D on calcium (Ca) concentrations after total thyroidectomy.
METHODS
Serum Ca, parathyroid hormone (PTH), and 1,25(OH)D levels were measured in 82 patients with thyroid disease before and after surgery.
RESULTS
Serum Ca, PTH, and 1,25(OH)D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p<0.0001), with 28% of patients showing increases in 1,25(OH)D. The only factor predicting a postoperative 1,25(OH)D decrease was a high preoperative 1,25(OH)D concentration. Postoperative 1,25(OH)D concentrations, as well as the magnitude and rate of decrease from preoperative levels, showed strong positive correlations with preoperative 1,25(OH)D concentrations (p<0.0001 for all three variables) but not with PTH concentrations. These findings suggest that 1,25(OH)D concentrations after thyroidectomy were more strongly dependent on preoperative concentrations than on the effect of PTH decrease and were relatively preserved, possibly preventing sudden severe postoperative hypocalcemia. A high 1,25(OH)D level was the most important preoperative factor for hypocalcemia (<2 mmol/L; p<0.05) on the first postoperative day; however, only PTH decrease was statistically significant (p<0.001) when intraoperative factors were added. In the PTH >10 pg/mL group, the decrease in 1,25(OH)D levels was significantly associated with postoperative hypocalcemia (p<0.05). Similarly, in the PTH levels >15 pg/mL group, a decrease in 1,25(OH)D concentration was a significant factor, and the amount of PTH decrease was no longer significant.
CONCLUSION
1,25(OH)D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.
Topics: Humans; Thyroidectomy; Female; Male; Middle Aged; Vitamin D; Prospective Studies; Calcium; Adult; Parathyroid Hormone; Hypocalcemia; Aged; Postoperative Complications; Postoperative Period; Thyroid Diseases
PubMed: 38803480
DOI: 10.3389/fendo.2024.1360464