Intact Parathyroid Hormone Research Articles

Predictive analysis of severe hypocalcemia following total parathyroidectomy for renal secondary hyperparathyroidism.

This study aimed to evaluate the incidence and identify risk factors for severe hypocalcemia following total parathyroidectomy (TPTX) in patients with renal secondary hyperparathyroidism (SHPT). We included patients undergoing maintenance hemodialysis or peritoneal dialysis who underwent TPTX from January 1, 2018, to April 30, 2023. Participants were categorized into groups based on postoperative corrected serum calcium levels: severe hypocalcemia (<1.8 mmol/L) and non-severe hypocalcemia (≥1.8 mmol/L). We conducted univariate analyses of demographic and laboratory data to identify potential risk factors, which were further analyzed using a binary logistic regression model. Significant associations were observed with age, dialysis duration exceeding five years, type of dialysis (peritoneal dialysis), lower preoperative corrected serum calcium, elevated preoperative intact parathyroid hormone (iPTH), and increased preoperative alkaline phosphatase (ALP) levels (all p<0.05). Age, preoperative iPTH, and ALP levels were identified as independent risk factors for severe hypocalcemia post-TPTX. Younger patients with renal SHPT who have elevated preoperative iPTH and ALP levels are at an increased risk of experiencing severe hypocalcemia following TPTX. These findings underscore the importance of careful preoperative assessment and monitoring to mitigate the risk of this complication.

Relationship of calcium-sensing receptor gene polymorphism CASR rs 1042636, CASR rs 1802757, and cinacalcet response among Egyptian hemodialysis patients with secondary hyperparathyroidism

Introduction: Secondary hyperparathyroidism (SHPT) is a common complication associated with morbidity and mortality among hemodialysis (HD) patients. Objectives: The current study aims to evaluate the frequency of CASR gene polymorphism variants related to parathyroid hormone (PTH) regulation (CASR rs1042636 and CASR rs1802757) and to test the hypothesis that single nucleotide polymorphisms (SNPs) in the CASR gene alter the response to cinacalcet among Egyptian HD patients with SHPT. Patients and Methods: A case-control study that included 50 HD patients with intact parathyroid hormone (iPTH) ≥300 pg/mL treated with cinacalcet for a 6-month duration and 40 healthy volunteers as a control group. Eligible patients were recruited from Ain Shams university hospitals. Blood samples were collected from patients and controls to assess allele frequencies of CASR gene polymorphism variants using real-time polymerase chain reaction (PCR), corrected calcium (Ca), phosphorus (P), Ca×P product, iPTH level, and alkaline phosphatase before and after treatment. HD patients were categorized into two groups based on the reduction percentage; responders’ patients (iPTH ≥20%) and non-responders to cinacalcet treatment. Results: Of 50 HD patients, 48 (96%) carried the rs1042636 AA wild gene, while only two (4%) carried the rs1042636 AG mutant gene, 42 (87.5%) carried the rs1802757 CC wild genotype, and 6 (12.5%) carried the CT mutant genotype. The minor alleles T and G were (6.3% and 2%) respectively, with no statistically significant difference between the patient and control groups regarding the CASR genotypes or alleles distribution. There was no significant difference between responders and non-responder’s patient groups regarding CASR genotypes or allele frequencies. Moreover, no significant correlation between CASR genotypes or alleles to delta change of Ca, P, Ca×P product, or PTH was seen. However, CASR rs1802757 CT mutant genotype was associated with a significant reduction in alkaline phosphatase levels after treatment. Conclusion: There is no significant association between the gene polymorphism CASR rs1042636 or CASR rs1802757 and the reduction in PTH levels as a response to cinacalcet treatment among Egyptian HD patients with SHPT.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Only bioactive forms of PTH (n-oxPTH and Met18(ox)-PTH) inhibit synthesis of sclerostin – evidence from in vitro and human studies

Sclerostin (SOST) is produced by osteocytes and is known as a negative regulator of bone homeostasis. Parathyroid hormone (PTH) regulates calcium, phosphate as well as vitamin D metabolism, and is a strong inhibitor of SOST synthesis in vitro and in vivo. PTH has two methionine amino acids (positions 8 and 18) which can be oxidized. PTH oxidized at Met18 (Met18(ox)-PTH) continues to be bioactive, whereas PTH oxidized at Met8 (Met8(ox)-PTH) or PTH oxidized at Met8 and Met18 (Met8, Met18(di-ox)-PTH) has minor bioactivity. How non-oxidized PTH (n-oxPTH) and oxidized forms of PTH act on sclerostin synthesis is unknown. The effects of n-oxPTH and oxidized forms of PTH on SOST gene expression were evaluated in UMR106 osteoblast-like cells. Moreover, we analyzed the relationship of SOST with n-oxPTH and all forms of oxPTH in 516 stable kidney transplant recipients using an assay system that can distinguish in clinical samples between n-oxPTH and the sum of all oxidized PTH forms (Met8(ox)-PTH, Met18(ox)-PTH, and Met8, Met18(di-ox)-PTH). We found that both n-oxPTH and Met18(ox)-PTH at doses of 1, 3, 20, and 30 nmol/L significantly inhibit SOST gene expression in vitro, whereas Met8(ox)-PTH and Met8, Met18(di-ox)-PTH only have a weak inhibitory effect on SOST gene expression. In the clinical cohort, multivariate linear regression showed that only n-oxPTH, but not intact PTH (iPTH) nor oxPTH, is independently associated with circulating SOST after adjusting for known confounding factors. In conclusion, only bioactive PTH forms such as n-oxPTH and Met18(ox)-PTH, inhibit SOST synthesis.

Association of Low Vitamin D and Intact Parathyroid Hormone (iPTH) in Nepalese Population: When Does iPTH Exactly Rise?

Vitamin D deficiency is a global public health concern that provokes bone demineralization and weakening. In response to the decreased vitamin D level, calcium stores wear out. The homeostatic effect of compensatory hyperparathyroidism in vitamin D deficiency incites variable discrepancies in different populations. This study intends to decipher the transition point of PTH in relation to levels of vitamin D in a Nepalese population. A cross-sectional study was carried out at Tribhuvan University Teaching Hospital, Nepal. Serum calcium, phosphorus, intact PTH, and 25-hydroxy vitamin D levels were assayed in an Abbott ARCHITECT Integrated System. A correlation plot of PTH and vitamin D was analyzed in Statistical Package for Social Sciences version 22.0. Using a locally weighted scatter plot smoothing method, the relation between these variables was presented graphically. Among 281 individuals, 30.2% had vitamin D levels below 20 ng/mL. There was an archetypical transition in the PTH levels in concert with the decrease in vitamin D level marked by 2 inflection points (ie, 18.5 and 42.0 ng/mL). Our findings suggest that to augment overall health and avert weakness due to vitamin D deficiency, the levels of vitamin D should be maintained above 42.0 ng/mL in our population.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH)

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

The Efficacy and Safety of High-Dose Cholecalciferol Therapy in Hemodialysis Patients.

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00-17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL-the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

25 [OH] Vitamin D and Intact Parathyroid Hormone in Congolese Hemodialysis Patients: Evaluation of KDIGO Targets.

Data on 25 [OH] vitamin D and intact parathyroid hormone [iPTH] in hemodialysis patients are very limited in sub-Saharan African countries. The present study aimed to assess the magnitude of hypovitaminosis D, and to evaluate the achievement of iPTH KDIGO 2017 targets among chronic hemodialysis patients followed in Kinshasa. We conducted a multicenter cross-sectional study in 6 hospitals in Kinshasa. All patients followed on hemodialysis for more than 3 months were included. Hypovitaminosis D was defined as <30 ng/mL (insufficiency = 20-29 ng/mL; deficiency if <20 ng/mL) and the targets for iPTH values were based on the 2017 KDIGO guidelines. The determinants for hypovitaminosis D were evaluated by logistic regression. 251 patients [mean age 56 ± 14 years, 72.5% men, 63% hypertensive, 31% diabetic, 100% supplemented with native 25 [OH] vitamin D + CaCO3 were included. Hypovitaminosis D was found in 79.7% (deficiency 47.4%) and was associated with the male gender aOR 2.7 [1.4-5.2], p = 0.004, the low-permeability dialyzer 2.2 [1.1-4.2], p = 0.025 and anemia 3.9 [1.2-12.7], p = 0.022. Only 40% of patients with 25 [OH] vitamin D deficiency had iPTH according to KDIGO targets vs 6% of patients with severe hyperparathyroidism (iPTH > 600 pg/mL), 45% with levels between 16 and 150 pg/mL and 9% a iPTH ≤ 15 pg/mL. Despite a sunny environment, a large proportion of Congolese hemodialysis patients have hypovitaminosis D, in particular a deficiency. Among them, less than half have target iPTH values. These results show the benefit of regular monitoring of these parameters in order to optimize treatment.

Influence of hydroxyurea on tubular phosphate handling in sickle cell nephropathy

ObjectiveThis study aims to evaluate the markers of tubular phosphate handling in adults with sickle cell anemia (SCA) and the influence of hydroxyurea (HU), the degree of anemia and Hb F concentration on these markers. MethodsEighty-eight steady state SCA patients in outpatient follow-up in Fortaleza, Ceara, Brazil and 31 healthy individuals were included in this study. Vitamin D (25OHD) was measured by enzyme-bound fluorescence assay, intact parathyroid hormone (iPTH) by electrochemiluminescence, and serum and urinary phosphate and creatinine by colorimetric methods. Details of Hb F and HU use were obtained from clinical records. Tubular reabsorption of phosphate (TRP) and maximum tubular reabsorption of phosphate (MTRP) were calculated. SCA patients were stratified according to the use of HU, degree of anemia and percentage of Hb F. The significance level was set for p-values <0.05. ResultsCompared to controls the 25OHD level (25 ± 11 vs. 30 ± 9 pg/mL) was lower in SCA, while serum phosphate and MTRP were higher (3.86 ± 0.94 vs. 3.46 ± 0.72 and 3.6 ± 1.21 vs. 3.21 ± 0.53, respectively). There was no significant difference in iPTH, TRP and phosphaturia. Serum phosphate showed correlation with TRP (r = 0.32; p-value = 0.008) and MTRP (r = 0.9; p-value <0.001) in SCA. Patients taking HU, especially those with Hb F >10 % presented reduced serum phosphate levels, and TRP and MTRP rates. Those with mild anemia presented reduced serum phosphate levels and MTRP rates. ConclusionSerum phosphate levels and renal phosphate reabsorption rate were increased in SCA. HU use, high Hb F concentration and total Hb were associated with better control of tubular phosphate handling markers.

Analysis of risk factors for late arteriovenous fistula failure and patency rates after angioplasty in hemodialysis patients: a retrospective cohort study.

The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing worldwide. Hemodialysis (HD) is the mainstay of renal replacement therapy for patients with ESKD. Risk factors associated with late arteriovenous fistula (AVF) failure in HD patients are poorly investigated. Therefore, the aim of this study was to identify factors associated with late AVF failure in HD patients. Patients with end-stage renal disease (ESRD) who underwent forearm or upper arm AVF angioplasty at Second Affiliated Hospital of Chongqing Medical University between September 2009 and August 2018 were included. Patients were followed up for 36 months. Baseline characteristics were collected using electronic medical records (EMRs). Variables associated with late AVF failure were identified using Cox proportional hazards models. There were 137 patients (64% male, 36% female) included in this study, with 50 (36.5%) experiencing AVF failure. Univariable log-rank analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), intact parathyroid hormone (iPTH), albumin (ALB), and AVF patency rate were significantly different between patients who did and did not experience AVF failure. Cox regression analysis showed that CRP [P=0.002, hazard ratio (HR) =2.719, 95% confidence interval (CI) for HR: 1.432-5.164], ESR (P=0.030, HR =2.431, 95% CI: 1.088-5.434), iPTH (P=0.013, HR =0.325, 95% CI: 0.133-0.793), and ALB (P=0.040, HR =0.539, 95% CI: 0.299-0.972) were independently associated with AVF failure. Kaplan-Meier survival analysis showed that the cumulative patency rates of AVF at 6, 12, 18, 24, 30, and 36 months were 84%, 74%, 69%, 64%, 64%, and 64%, respectively. CRP, ESR, iPTH, and ALB were associated with AVF failure and should be used as reference in clinical practice.

Carotid Intima-Media Thickness in Children with Chronic Kidney Disease as an Early Predictor of Cardiovascular Diseases

Aim: Cardiovascular problems are very common in children with chronic kidney disease (CKD). To examine early cardiovascular risk factors, notably carotid intima-media thickness (CIMT) and pulse wave velocity (PWV). Material and Method: Case-control study was conducted in the Department of Pediatric Nephrology Sindh Institute of Urology and Transplantation Karachi from 1stFebruary 2023 to 31st July 2023. Forty two children were enrolled. CIMT and PWV were measured using ultrasonography and pulse wave analysis respectively. The following clinical parameters were also assessed: blood pressure, age, gender, etiology, duration of chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), serum albumin, calcium-phosphate product, and intact parathyroid hormone (PTH), and vitamin D levels. Results: The average age was 10.2±3.6 years, with a higher proportion of boys in the cases group (69% versus 47.6%, p-value 0.04). Most patients had normal blood pressure (78.6%), and congenital anomalies were the most common CKD etiology (57.1%). Median eGFR was 30.5 ml/min/1.73 m2, with stages 3 and 4 CKD most prevalent. Serum albumin was normal (mean 4.45±0.68), but some cases had a high calcium-phosphate product (7%) and low vitamin D levels (52%). CIMT and PWV did not differ significantly between cases and controls. Echocardiography revealed mild cardiac abnormalities in some cases. Practical implication: Some patients showed minor left ventricular expansion, while others had mildly depressed GLS and decreased LVEF. Further research should focus on longitudinal studies and explore new biomarkers for early cardiovascular risk detection. Conclusion: The various clinical characteristics such as blood pressure, mineral and bone diseases, and cardiac abnormalities are common in children with chronic kidney diseases. There were no significant changes in carotid intima-media thickness and pulse wave velocity between the cases and controls. Keywords: Chronic kidney disease, Carotid intima-media thickness, Cardiovascular disease, Pulse wave velocity

Features of cardiovascular magnetic resonance native T1 mapping in maintenance hemodialysis patients and their related factors

Purpose Increased myocardial T1 values on cardiovascular MRI (CMRI) have been shown to be a surrogate marker for myocardial fibrosis. The use of CMRI in patients on hemodialysis (HD) remains limited. This research aimed to explore the characteristics of native T1 values in HD patients and identify factors related to T1 values. Methods A total of thirty-two patients on HD and fourteen healthy controls were included in this study. All participants underwent CMRI. Using modified Look-Locker inversion recovery (MOLLI) sequence, native T1 mapping was achieved. Native CMRI T1 values were compared between the two groups. In order to analyze the relationship between T1 values and clinical parameters, correlation analysis was performed in patients on HD. Results Patients on HD exhibited elevated global native T1 values compared to control subjects. In the HD group, the global native T1 value correlated positively with intact parathyroid hormone (iPTH) (r = 0.418, p = 0.017) and negatively with triglycerides (r= −0.366, p = 0.039). Moreover, the global native T1 value exhibited a positive correlation with the left ventricular end-diastolic volume indexed to body surface area (BSA; r = 0.528, p = 0.014), left ventricular end-systolic volume indexed to BSA (r = 0.506, p = 0.019), and left ventricular mass indexed to BSA (r = 0.600, p = 0.005). A negative correlation was observed between the global native T1 value and ejection fraction (r = 0.-0.551, p = 0.010). Conclusion The global native T1 value was prolonged in HD patients compared with controls. In the HD group, the global T1 value correlated strongly with iPTH, triglycerides, and cardiac structural and functional parameters.

Left ventricular remodeling and its association with mineral and bone disorder in kidney transplant recipients

Background The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors. Methods Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed. Results One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. ΔLVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. ΔLVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with ΔLVMI and positively associated with ΔLVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling. Conclusions LV remodeling partially improved after KT, showing a close relationship with MBD.

Comparative efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of vascular calcification in patients with haemodialysis: a systematic review and network meta-analysis

BackgroundUp to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification.MethodsA comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software.ResultsIn total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD − 0.59; 95% CI [–0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD − 1.20; 95% CI [–2.08, − 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level.ConclusionsThis network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice.Systematic Review Registration[http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022379965].

Age-specific Reference Intervals of Abbott Intact PTH-Potential Impacts on Clinical Care.

PTH assays are not standardized; therefore, method-specific PTH reference intervals are required for interpretation of results. PTH increases with age in adults but age-related reference intervals for the Abbott intact PTH (iPTH) assay are not available. Deidentified serum PTH results from September 2015 to November 2022 were retrieved from the laboratory information system of a laboratory serving a cosmopolitan population in central-west England for individuals aged 18 years and older if the estimated glomerular filtration rate was ≥60 mL/min, serum 25-hydroxyvitamin D was >50 nmol/L, and serum albumin-adjusted calcium and serum phosphate were within reference intervals. Age-specific reference intervals for Abbott iPTH were derived by an indirect method using the refineR algorithm. PTH increased with age and correlated with age when controlled for 25-hydroxyvitamin D, estimated glomerular filtration rate, and adjusted calcium (r = 0.093, P < .001). The iPTH age-specific reference intervals for 4 age partitions of 18 to 45 years, 46 to 60 years, 61 to 80 years, and 81 to 95 years were 1.6 to 8.6 pmol/L, 1.8 to 9.5 pmol/L, 2.0 to 11.3 pmol/L, and 2.3 to 12.3 pmol/L, respectively. PTH was higher in women compared with men (P < .001). Sex-specific age-related reference intervals could not be derived because of the limited sample size. Age-specific Abbott iPTH reference intervals were derived. Application of age-specific reference intervals will impact the diagnosis and management of normocalcemic hyperparathyroidism, based on current definitions, and secondary hyperparathyroidism. Additional studies are required to clarify the effect of sex and ethnicity on PTH.

The refractory secondary hyperparathyroidism presenting with retro-orbital brown tumor: a case report

BackgroundTertiary hyperparathyroidism describes the autonomous and excessive secretion of parathyroid hormone (PTH) by the parathyroid glands after longstanding secondary hyperparathyroidism in chronic kidney disease. Brown tumors are a sign of uncontrolled hyperparathyroidism. In this case, we have reported a refractory and destructive hyperparathyroidism storm. Also, it presented with atypical onset and unexpected adenoma location.Case presentationA 37-year-old man was diagnosed with end-stage kidney disease 22 years ago. He has been undergoing dialysis treatment since that time. Recently, he was admitted to the ophthalmology department due to the unilateral anterior bulging of the right eye and drooping of the eyelid. Magnetic resonance imaging exhibited an extraconal mass lesion located in the right orbital posterior superolateral position. Computerized tomography scans considered expansile bone lesion with peripheral calcification and originating from the sphenoid wing. The bone mass lesion was resected via craniotomy due to the compressive effect. The pathological findings were consistent with brown tumors. Plasma intact PTH level was 4557 pg/mL. The patient informed that he underwent parathyroidectomy and two leg fractures operation in a medical query. Parathyroid scintigraphy determined three distinct foci consistent with adenomas and one of them was in mediastenum. Second parathyroidectomy was recommended to the patient but the patient refused surgery. Despite his medication and dialysis regimen being revised, PTH levels were maintained at higher levels in follow-up.ConclusionsWe presented a hyperparathyroidism case that was resistant to all treatments and exhibited all the severe complications in a long-term dialysis patient. Furthermore, this case has revealed the importance and difficulty of secondary hyperparathyroidism management.

The Plasma Neurofilament Light Chain, Brain-Derived Neurotrophic Factor, and Risk of Depression in Chronic Hemodialysis Patients.

Depression is highly prevalent among hemodialysis patients. Understanding the relationship between the plasma neurofilament light chain (NfL) and brain-derived neurotrophic factor (BDNF) may help us to better understand the mechanisms of depression. This study determined their impact, alongside that of other factors, on the risk of depression in hemodialysis patients. The study enrolled 82 patients undergoing chronic hemodialysis. Serum NfL, BDNF, uric acid, urea, potassium, calcium, phosphorus, intact parathyroid hormone, and C-reactive protein (CRP) levels were measured. The patients completed the Beck Depression Inventory (BDI). Blood pressure values, body mass before and after hemodialysis, and weekly duration of hemodialysis in hours were assessed. For 19-month survival analysis, the patients were stratified according to baseline BDI scores. Based on the BDI score, 18.3% of the patients had an increased risk of depression. Lower scores were associated with significantly longer duration of hemodialysis treatment (37.5 (25-57) 24 (14-37) months, p = 0.01). Within the 19-month survival analysis, 31.7% of patients died. The patients with BDI scores above the median had significantly lower survival than those below the median (log-rank test p = 0.02). No significant differences in serum BDNF levels (192.7 [125.2-278.2]; 207.7 [142.8-265.8] pg/mL, p = 0.40), or NfL concentrations (1431.5 [1182.6-1625.7]; 1494.6 [1335.7-1667] kDa, p = 0.52) were found between patients with lower and higher risk of depression. Patients with BDI scores above the median had significantly higher levels of CRP (9.6 [4.4-14]) than those with scores below the median (3.6 [2.2-7.5], p = 0.01). A significant positive correlation was found between the BDI score and serum CRP level (r = 0.38, p = 0.01). A significant negative correlation was observed between the BDI score and URR% value (r = -0.36, p = 0.02). Patients with lower BDI scores had a longer dialysis duration, indicating a potential negative association between depression risk and length of dialysis treatment. Neither serum NfL nor BDNF levels can serve as markers of depression risk in the dialysis population.

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol

IntroductionCoronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics...

Idiopathic Hypoparathyroidism Presenting with Erythrodermic Psoriasis and Fahr’s Syndrome: A Case Report

Idiopathic hypoparathyroidism may remain asymptomatic or present with hypocalcaemic neuromuscular manifestations. Dermatological manifestations like exfoliative dermatitis, pustular psoriasis and symmetrical brain calcification known as Fahr’s syndrome are uncommon in clinical practice. Even in absence of neuromuscular symptoms, hypocalcaemia associated with exfoliative skin lesions and symmetrical brain calcification should prompt investigation for hypoparathyroidism. A 40-year-old male presented with diffuse erythematous pruritic plaques and fever of 10 days duration. Auspitz sign was positive on examination. Investigations showed leucocytosis with neutrophilic predominance. He was admitted with a diagnosis of erythrodermic psoriasis with secondary infection. On the second day of admission he developed an episode of generalised tonic clonic seizure for the first time. Investigations into the cause of seizure revealed low serum calcium while computerised tomography of head revealed symmetrical calcification of bilateral basal ganglia. Further, he was found to have a low level of intact Parathyroid Hormone (PTH) level and hyperphosphataemia. Based on clinical, biochemical and radiological findings, a diagnosis of idiopathic hypoparathyroidism, psoriasis and Fahr’s syndrome was made. Serum calcium was corrected with infusions of calcium gluconate followed by oral calcium carbonate. The patient was kept under observation for seizure recurrence. Calcium and vitamin D supplements and hydrochlorothiazide were started and psoriasis treatment was continued. His skin lesions resolved over the next two weeks, serum calcium levels returned to normal level and no seizure episodes were reported over three months of follow-up.

Ultrasound-Guided Radiofrequency Ablation in Tertiary Hyperparathyroidism: A Prospective Study.

To prospectively evaluate the outcomes of ultrasound (US)-guided radiofrequency ablation (RFA) in tertiary hyperparathyroidism (THPT). Patients with THPT underwent RFA between September 2017 and January 2022. Laboratory parameters, including serum intact parathyroid hormone (iPTH) levels, were monitored for 48 months after RFA and compared with the levels at baseline. Complications related to RFA and changes in hyperparathyroidism-related clinical symptoms were recorded before and after RFA. A total of 42 patients with THPT were recruited for this study. Ultimately, 36 patients with renal failure and 2 patients who underwent successful renal transplantation (male:female, 17:21; median age, 54.5 years) were enrolled. The follow-up time was 21.5 ± 19.0 months in the 36 patients with renal failure. In these 36 patients, iPTH levels were significantly decreased to 261.1 pg/mL at 48 months compared with the baseline value of 1284.9 pg/mL (P = 0.012). Persistent hyperparathyroidism, defined as iPTH levels maintained at > 585.0 pg/mL for 6 months after treatment, occurred in 4.0% of patients (1/25). Recurrent hyperparathyroidism, defined as iPTH levels > 585.0 pg/mL after 6 months, were 4.0% (1/25) and 0.0% (0/9) at 6 months and 4 years after treatment, respectively. In two patients with THPT after successful renal transplantation, iPTH decreased from the baseline value of 242.5 and 115.9 pg/mL to 171.0 and 62.0 pg/mL at 6 months after treatment. All complications resolved within 6 months of ablation without medical intervention, except in 10.5% (4/38) patients with permanent hypocalcemia. The overall symptom recovery rate was 58.8% (10/17). The severity scores for bone pain, arthralgia, and itchy skin associated with hyperparathyroidism improved after treatment (P < 0.05). US-guided RFA is an effective and safe alternative to surgery in the treatment of patients with TPTH and improves hyperparathyroidism-related clinical symptoms.