Reduced Parathyroid Hormone Levels Research Articles

The effect of local injections of a vitamin d receptor activator into the parathyroid glands on the level of parathyroid hormone and mineral metabolism in patients with secondary hyperparathyroidism in chronic kidney disease

Aim: to assess the dynamics of laboratory parameters (total calcium, inorganic phosphorus, albumin, and alkaline phosphatase levels) and parathyroid hormone (PTH) concentrations after administrating local injections of vitamin D receptor activators into the parathyroid glands of patients with secondary hyperparathyroidism in chronic kidney disease. The intial PTH concentration ranged from 300 to 600 pg/ml. This range was chosen to explore a more active strategy for managing the disease at its early stages and preventing the induction and progression of cardiovascular complications associated with secondary hyperparathyroidism.Methods: the study included 48 patients diagnosed with end-stage of chronic kidney disease, who were treated in the nephrology and dialysis department. The main group consisted of 34 patients who received two consecutive injections of a vitamin D receptor activator (Paricalcitol) into the most enlarged and technically accessible parathyroid gland under ultrasound guidance. The control group included 14 patients who continued with conservative treatment due to technical infeasibility of performing the injections. Effectiveness was assessed by comparing laboratory parameters before the intervention and six months after the injections in the main group, and among patients continuing standard medical therapy for secondary hyperparathyroidism.Results: the results showed a statistically significant reduction in parathyroid hormone levels after 3 and 6 months of treatment. In the control group, which continued to receive standard drug therapy, PTH and blood phosphate levels continued to rise. No undesirable effects or complications, such as hypocalcemia, bleeding, allergic reactions, and recurrent laryngeal nerve paralysis, were not observed throughout the observation period.Conclusion: this research confirms the efficacy of local injections of vitamin D receptor activators (Paricalcitol) in reducing PTH levels without significant complications or changes in calcium levels. This method could be employed to correct and prevent secondary hyperparathyroidism complications in early stages among patients with end-stage chronic kidney disease, offering a safer and more effective treatment option.

Extended-Release Calcifediol: A Data Journey from Phase 3 Studies to Real-World Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism.

Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D (25(OH)D) and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled phase 3 per-protocol populations, 74% of the ERC cohort were uptitrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. These data establish a "continuum" of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

Etelcalcetide use During Maintenance Hemodialysis and Incidence of Parathyroidectomy After Kidney Transplantation

Etelcalcetide is an i.v. calcimimetic agent, effectively reducing parathyroid hormone levels in patients on maintenance hemodialysis (HD). The clinical impact of discontinuing etelcalcetide at the time of kidney transplantation is unknown. We retrospectively reviewed all patients on HD meeting predefined criteria who received a kidney transplant at our institution between January 1, 2015, and December 12, 2022. The incidence of parathyroidectomy and the evolution of calcium, phosphate, and intact parathyroid hormone (iPTH) levels after transplantation was analyzed according to the type of calcimimetic treatment before transplantation (cinacalcet vs. etelcalcetide vs. none). Overall, 372 patients (aged 53 years; interquartile range [IQR]: 42-62 years) were included. At the time of transplantation, 35, 75, and 262 patients were under etelcalcetide, cinacalcet, or no calcimimetic, respectively. After 1064 (IQR: 367-1658) days, the incidences of parathyroidectomy in the etelcalcetide, cinacalcet, no calcimimetic groups were 29%, 12%, and 1%, respectively (P< 0.001). Etelcalcetide was associated with an increased incidence of parathyroidectomy after adjustment for age, sex, and HD vintage (hazard ratio [HR]: 97.0, 95% confidence interval [CI]: 19.1-493.9, P< 0.001). The incidence of parathyroidectomy was related to etelcalcetide dosage (6/11 [54.6%] in patients with≥ 10 mg vs. 4/24 [16.7%] in patients with< 10 mg, P= 0.02). Moreover, peak calcium levels were higher (P< 0.001) and parathyroidectomy was performed earlier (median 80 vs. 480 days, P< 0.001) in the etelcalcetide compared with the cinacalcet group. Long-term graft function, graft loss, and mortality were similar. Etelcalcetide use during maintenance HD is associated with an increased incidence of early parathyroidectomy after transplantation compared to cinacalcet or no calcimimetic.

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.

PTH levels, sleep quality, and cognitive function in primary hyperparathyroidism.

Cognitive function in patients with primary hyperparathyroidism (PHPT) may be affected and be identified to have been linked to the level of parathyroid hormone (PTH). Previous studies have suggested that patients with PHPT present poor sleep quality, which might interact with cognitive decline. The purpose of this study was to determine whether sleep quality mediates the association between PTH level and cognitive function and investigate whether surgery improves sleep quality and cognition in PHPT patients. Between June 2019 and August 2022, we recruited 146 patients diagnosed with PHPT (n = 146). We collected clinical data from medical records and evaluated sleep quality and cognition preoperatively and 2 months postoperatively by using the Pittsburgh Sleep Quality Index and Min-Mental State Examination. We examined the mediation effects of sleep disturbance and latency on correlations between PTH level and cognitive impairment by using the Bootstrap method. The sleep quality and cognitive function were correlated with PTH level before surgery. Sleep latency or sleep disturbance exhibited a partial mediating effect on the association between PTH level and MMSE scores in PHPT patients (p < 0.05). In PHPT patients, there was a significant decline in PTH levels and an improvement in cognitive function post-surgery compared to pre-surgery, but no significant differences in sleep quality. Sleep disturbance and sleep latency may mediate the association between PTH level and cognitive impairment in PHPT before surgery. The surgery could reduce PTH levels and improve cognition, but might not improve sleep quality in PHPT patients.

The rationale for intermittent administration of PTH in the management of mineral and bone disorder of chronic kidney disease.

A major complication of chronic kidney disease is the derangement of mineral metabolism, leading to increased risk of fractures and cardiovascular mortality. Current therapeutic regimens are focused on reducing parathyroid hormone levels caused by secondary hyperparathyroidism, and the active vitamin D metabolite l,25(OH)2D, with limited success. It may be a more effective approach, however, if we could target the delayed response of parathyroid hormone in the early retention of phosphate following loss of renal function.We propose intermittent administration (even in stage 2 chronic kidney disease) of parathyroid hormone, known for its bone anabolic effects compared to the catabolic effects of the continuously elevated parathyroid hormone associated with the hyperparathyroid state, to mitigate the retention of phosphate. This approach may prevent the compensatory responses of the other two major calcium- and phosphate-regulating hormones (FGF-23 and l,25(OH)2D) that lead to further worsening of the derangement of mineral metabolism.In addition to its strong theoretical basis, there are data supporting the need for further research focused on the use of intermittent parathyroid hormone in the management of chronic kidney disease-mineral bone disorder.

Cost-effectiveness analysis of intravenous paricalcitol vs. oral calcitriol in the treatment of hyperparathyroidism secondary to chronic kidney disease.

Hyperparathyroidism (SHPT) secondary to chronic kidney disease (CKD) is characterized by high levels of parathyroid hormone (PTH), hyperplasia of the parathyroid glands and cardiovascular disease. Selective and non-selective and selective vitamin D-receptor activators, calcimimetics, are available in the Brazilian market to reduce PTH levels. To develop a cost-effectiveness (C/E) and budgetary impact (BI) analysis of intravenous paricalcitol vs. oral calcitriol for patients on dialysis with SHPT, from the perspective of the Brazilian Public Health Care System (SUS). We built a decision-tree model to analyze C/E, which considered the outcome of avoided death and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of demand and one of epidemiological approach, based on data from the Brazilian Society of Nephrology. The analysis showed that the C/E ratio was R$ 1,213.68 per year, and an incremental effectiveness of 0.032, referring to avoided death. The incremental C/E ratio was R$37,927.50 per death averted by paricalcitol. It was estimated that the incremental BI with the expansion of paricalcitol use will be between R$1,600,202.28 and R$4,128,565.65 in the first year, considering the main and epidemiological scenarios. At the end of 5 years after the expansion of its use, an incremental BI was estimated between R$ 48,596,855.50 and R$ 62,90,555.73. Intravenous paricalcitol has superior efficacy and similar safety to oral calcitriol, reducing the overall mortality of dialysis patients, although it implies a higher cost.

Level of parathyroid hormone in the early postoperative period as a prognostic factor for persistent manifestations of clinical hypocalcemia

Objective — to determine the level of parathyroid hormone (PTH) in the early postoperative period in patients after the thyroid gland surgery, which enables to define the risk of persistent postoperative hypoparathyroidism with clinical manifestations of hypocalcemia.&#x0D; Materials and methods. The study involved 303 patients who were operated in the Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organ and Tissue due to various thyroid pathologies in the period of January, 2020 through June, 2021. The scope of the operation was thyroidectomy with/without lymph node dissection. The PTH level in blood serum was determined for all patients in the morning after the surgery (16 — 22 hours later). Clinical signs of hypocalcemia due to hypoparathyroidism (PTH level &lt; 15 pg/ml) were revealed in 147 (48.5 %) subjects. Moving forward, such patients were examined for blood serum PTH levels after 3 months (first stage of examinations) and 6 months (second stage of examinations).&#x0D; Results. After 3 months, normalization of PTH levels and no clinical hypocalcemia manifestations were defined in 126 patients (85.7 %); 21 patients (14.3 %) had low PTH levels (&lt; 15 pg/ml) with clinical manifestations of hypocalcemia. The use of ROC‑analysis to predict the normalization of PTH levels after 3 months revealed the cut‑off threshold 2.8 pg/ ml. After 6 months, normalization of PTH levels and no clinical hypocalcemia manifestations were defined in 136 (92.5 %) patients, whereas 11 (7.4 %) subjects demonstrated the reduced PTH levels and clinical manifestations of hypocalcemia. Results of ROC‑analysis prediction of the normalization of PTH levels after 6 months post‑surgery, the cut‑off threshold 1.6 pg/ml.&#x0D; Conclusions. Postoperative PTH levels &gt; 2.8 pg/ml after 3 months after surgery and &gt; 1.6 pg/ml after 6 months established to be a predictor of normalization serum PTH levels. A PTH level &lt; 1.6 pg/ml can be considered a predictor of persistent hypoparathyroidism, and allows the physician to recognize patients with possible long‑term specific treatment.

Non-Additive Effects of Combined NOX1/4 Inhibition and Calcimimetic Treatment on a Rat Model of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

ABSTRACTChronic kidney disease‐mineral and bone disorder (CKD‐MBD) increases cardiovascular calcification and skeletal fragility in part by increasing systemic oxidative stress and disrupting mineral homeostasis through secondary hyperparathyroidism. We hypothesized that treatments to reduce reactive oxygen species formation and reduce parathyroid hormone (PTH) levels would have additive beneficial effects to prevent cardiovascular calcification and deleterious bone architecture and mechanics before end‐stage kidney disease. To test this hypothesis, we treated a naturally progressive model of CKD‐MBD, the Cy/+ rat, beginning early in CKD with the NADPH oxidase (NOX1/4) inhibitor GKT‐137831 (GKT), the preclinical analogue of the calcimimetic etelcalcetide, KP‐2326 (KP), and their combination. The results demonstrated that CKD animals had elevated blood urea nitrogen, PTH, fibroblast growth factor 23 (FGF23), and phosphorus. Treatment with KP reduced PTH levels compared with CKD animals, whereas GKT treatment increased C‐terminal FGF23 levels without altering intact FGF23. GKT treatment alone reduced aortic calcification and NOX4 expression but did not alter the oxidative stress marker 8‐OHdG in the serum or aorta. KP treatment reduced aortic 8‐OHdG and inhibited the ability for GKT to reduce aortic calcification. Treatments did not alter heart calcification or left ventricular mass. In the skeleton, CKD animals had reduced trabecular bone volume fraction and trabecular number with increased trabecular spacing that were not improved with either treatment. The cortical bone was not altered by CKD or by treatments at this early stage of CKD. These results suggest that GKT reduces aortic calcification while KP reduces aortic oxidative stress and reduces PTH, but the combination was not additive. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol

Introduction: The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee^®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC’s efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population. Materials and Methods: Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations. Results: The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (p < 0.001) with nominal changes of 0.1 mg/dL (p > 0.05) in serum calcium (Ca) and phosphorus (P) levels. Discussion/Conclusion: Analysis of postlaunch data confirmed ERC’s effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.

Ultrasound-guided bilateral superficial cervical plexus block enhances the quality of recovery of uremia patients with secondary hyperparathyroidism following parathyroidectomy: a randomized controlled trial

BackgroundParathyroidectomy has been proposed as a method for reducing parathyroid hormone levels. We evaluated the effects of ultrasound-guided bilateral superficial cervical plexus block (BSCPB) on the quality of recovery of uremia patients with secondary hyperparathyroidism (SHPT) following parathyroidectomy.MethodsEighty-two uremia patients who underwent parathyroidectomy and exhibited SHPT were randomly allocated to the BSCPB group or the control group (CON group). The patients received ultrasound-guided BSCPB with 7.5 ml of ropivacaine 0.5% on each side (BSCPB group) or equal amount of 0.9% normal saline (CON group). The primary outcome of the Quality of Recovery-40(QoR-40) score was recorded on the day before surgery and postoperative day 1(POD1). Secondary outcomes including total consumption of remifentanil, time to first required rescue analgesia, number of patients requiring rescue analgesia, and total consumption of tramadol during the first 24 h after surgery were recorded. The occurrence of postoperative nausea or vomiting (PONV) and the visual analogue scale (VAS) scores were assessed and recorded.ResultsThe scores on the pain and emotional state dimensions of the QoR-40 and the total QoR-40 score were higher in the BSCPB group than in the CON group on POD1 (P = 0.000). Compared with the CON group, the total consumption of remifentanil was significantly decreased in the BSCPB group (P = 0.000). The BSCPB group exhibited longer time to first required rescue analgesia (P = 0.018), fewer patients requiring rescue analgesia (P = 0.000), and lower postoperative total consumption of tramadol during the first 24 h after surgery (P = 0.000) than the CON group. The incidence of PONV was significantly lower in the BSCPB group than in the CON group (P = 0.013). The VAS scores in the BSCPB group were lower than those in the CON group at all time-points after surgery (P = 0.000).ConclusionUltrasound-guided BSCPB with ropivacaine 0.5% can enhance the quality of recovery, postoperative analgesia, and reduce the incidence of PONV in uremia patients with SHPT following parathyroidectomy.Trial registrationChiCTR1900027185. (Prospective registered). Initial registration date was 04/11/2019.

Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors

ObjectivePatients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency. MethodsWe enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed. ResultsAldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism. ConclusionPTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.

Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease–Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients

Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April2017. New-user design within prospective cohort. 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium< 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.

How should we define cure after parathyroidectomy for normocalcemic primary hyperparathyroidism? A retrospective cohort study.

Cure after surgery for normocalcemic primary hyperparathyroidism (NHPT) is defined as parathyroid hormone (PTH) normalization. However, an increase of PTH is frequently observed in cured patients with hypercalcemic primary hyperparathyroidism (HHPT). Therefore, this criterion must be redefined. A single-center retrospective study was performed including all patients who underwent surgery for Primary Hyperparathyroidism from 2013 to 2019. Cure rates of different types of hyperparathyroidism were analyzed. PTH reduction was studied as a possible criterion to define cure in patients with NHPT. One-hundred and eighty-six patients were included: 173 with HHPT and 13 with NHPT. After a mean follow-up of 33.4months, 174 (93.6%) patients were considered cured. Cure was more frequent in the group of patients with HHPT (97.1% vs. 46.2%, p < 0.001). In the multivariate analysis, surgical failure was associated with NHPT and multiglandular disease. Forty-nine (30.1%) cured patients with HHPT had an increased PTH during the follow-up. When decline of PTH levels was studied in patients with HHPT to define cure, the area under curve was 0.92. A cut-off value of 40% in PTH reduction achieved a sensitivity and specificity of 83.4% and 80.0%. If cure was defined as a 40% reduction of PTH, cure rate in the group of patients with NHPT would increase to 69.2%. Patients with NHPT had a lower cure rate than patients with HHPT. A significant number of cured patients with HHPT had an increased PTH during follow-up. A 40% reduction in PTH levels is proposed as an alternative definition for cure in patients with NHPT.

Safety and efficacy of common vitamin D supplementation in primary hyperparathyroidism and coexistent vitamin D deficiency and insufficiency: a systematic review and meta-analysis.

Primary hyperparathyroidism (PHPT) is characterized by excessive secretion of parathyroid hormone (PTH). Vitamin D deficiency can stimulate parathyroid secretion. However, whether to correct vitamin D deficiency in patients with PHPT is controversial. We aimed to evaluate the safety and efficacy of vitamin D replacement in patients with PHPT. We searched PubMed, Cochrane Library, and Embase. The relevant data were extracted from the included documents. The methodological items for non-randomized studies score entries were used for evaluation of quality. Review Manager 5.3 and Stata 12.0 were used for statistical analysis. A total of 11 articles were included with a total of 388 patients. The serum calcium mean difference (MD) was -0.06mg/dL [95% confidence interval (95% CI) -0.16, 0.04]. Subgroup analysis showed that serum calcium levels did not change if the intervention time exceeded 1month. The 24-h urinary calcium MD was 36.78mg/day (95% CI -37.15, 110.71), which indicated that there was no significant effect of vitamin D supplementation on 24-h urinary calcium levels. The MD of PTH was -16.01pg/mL (95% CI -28.79, -3.24). Subgroup analysis according to the intervention time showed that vitamin D intervention for more than 1month significantly reduced PTH levels. The ALP MD was -10.81 U/L (95% CI -13.98, -7.63), which indicated Vitamin D supplementation reduced its level. The MD of 25-hydroxyvitamin D was 22.09μg/L (95% CI 15.01, 29.17), and no source of heterogeneity was found. Vitamin D supplementation in patients with PHPT and vitamin D deficiency significantly reduces PTH and ALP levels without causing hypercalcemia and hypercalciuria.

Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial.

ABSTRACTVitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post‐transplant, we randomized 193 patients to an 11‐month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25‐hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between‐group difference of −15%; 95% confidence interval [CI] −25 to −3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (p int < 0.05). The percent change in lumbar spine (LS) BMD from before KTx to 12 months post‐transplant was −0.2% (95% CI −1.4 to 0.9) in the cholecalciferol group and −1.9% (95% CI −3.0 to −0.8) in the placebo group, with a significant between‐group difference (1.7%; 95% CI 0.1 to 3.3). The beneficial effect of cholecalciferol on LS BMD was prominent in patients with low bone mass p int < 0.05). Changes in serum calcium, phosphate, bone metabolic markers, and BMD at the distal radius were not different between groups. In mediation analyses, change in whole PTH levels explained 39% of treatment effects on BMD change. In conclusion, 4000 IU/d cholecalciferol significantly reduced PTH levels and attenuated LS BMD loss after KTx. This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells.

Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005-50µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. In eight of the fourteen parathyroid cell cultures, extracellular Ca2+ reduced parathyroid hormone levels. In four of the eight parathyroid cell cultures which responded extracellular Ca2+, etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells.

Calcimimetic Use in Dialysis-Dependent Medicare Fee-for-Service Beneficiaries and Implications for Bundled Payment.

Patients who are dialysis dependent and have secondary hyperparathyroidism (SHPT) may require calcimimetics to reduce parathyroid hormone levels to treatment goals. Medicare currently uses the Transitional Drug Add-on Payment Adjustment (TDAPA) designation under the ESKD Prospective Payment System ("bundled payment") to pay for calcimimetics (the first products eligible for the adjustment); this payment designation for calcimimetics is expected to conclude after 2020. This study explores variability in calcimimetic use across key patient characteristics and its potential effect on policy options for incorporating calcimimetics permanently into the bundle. This descriptive analysis used the 100% sample of Medicare FFS Part B (outpatient) 2018 claims to describe national-, regional-, and patient-level variation (including race, dual eligibility, and dialysis vintage) in calcimimetic use among beneficiaries who are dialysis dependent. A total of 373,874 beneficiaries were analyzed, 28% had ≥90 days of calcimimetic use during 2018. At the national level, the proportion of patients on dialysis using calcimimetics was roughly 80% higher in Black versus non-Black patients on dialysis, 30% higher in patients on dialysis who were dual eligible versus non-dual eligible, and three times higher in patients with a dialysis vintage ≥3 years versus <3 years (all results unadjusted). Calcimimetic use was similar across census regions, however, substantial variation in calcimimetic use was observed at the facility level. Medicare spending for calcimimetic therapies as a proportion of total Medicare dialysis spending was >10% in approximately 20% of dialysis facilities. Although less than a third of beneficiaries use calcimimetics, certain patient-level characteristics are associated with higher rates of maintenance calcimimetic use. Due to the financial pressure many dialysis facilities face, how calcimimetics are incorporated into the bundle may have a direct effect on facility reimbursement for, and patient access to, therapy. Careful consideration will be required to ensure patients who are vulnerable and require treatment for SHPT do not face barriers to appropriate care.

Reassessing vitamin D supplementation in preterm infants: a prospective study and review of the literature.

Objectives Recommendations for vitamin D (VitD) intake and target serum levels of 25(OH)D in preterm infants are diverse. We hypothesized that preterm infants with low birth weight (BW) have low dietary intake of VitD and therefore should be supplemented with higher amounts of VitD. Methods Infants with BW<2kg were supplemented with 600 units of VitD a day during the first 2-6weeks of life, whereas infants with BW>2kg continued with the routine supplementation of 400 units of VitD daily. Serum levels of 25(OH)D, calcium, phosphorous, alkaline phosphatase (AP) and parathyroid hormone (PTH) were assessed 24h after birth and before discharge. The total daily intake of vitD was calculated in each infant. Results Sixty-two infants were enrolled, 49 with BW<2kg. After birth, only 24% had sufficient levels of 25(OH)D, whereas before discharge 45 of 54 infants (83%) available for analysis reached sufficient levels of 25(OH)D. All 54 infants demonstrated significant elevation in serum levels of calcium, phosphorous, AP and significant reduction in PTH levels. The total daily intake of VitD was lower than recommended (800-1000IU/d) in 16 of 45 infants with BW<2kg (36%) and in all nine infants with BW>2kg. Nevertheless, only 2 of 25 infants with insufficient intake of VitD demonstrated insufficient levels of serum 25(OH)D. No case of vitamin D excess was recorded. Conclusions Increased supplementation of VitD (600IU/d) for premature newborns with BW<2kg is effective in increasing both total daily intake of VitD and serum levels of 25(OH)D.

The coexistence of hypercalcemia, osteoporosis and thymic enlargement in graves\u2019 disease: a case report

BackgroundHyperthyroidism-induced hypercalcemia has been reported previously, but hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement in patients with hyperthyroidism is quite rare. We report the coexistence of hypercalcemia, osteoporosis and thymic enlargement in a patient with Graves’ disease.Case presentationA 22-year-old female was diagnosed as Graves’ disease with obviously elevated serum calcium and reduced parathyroid hormone levels. Dual-energy x-ray absorptiometry and chest enhanced computer tomography (CT) revealed severe osteoporosis and a significant enlargement of thymus. After the successful control of hyperthyroidism with methimazole, hypercalcemia was corrected, bone mineral density was improved and thymus also shrank obviously.ConclusionThis is a very rare case of hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement induced by Graves’ disease. In clinical practice, examination of thymus and bone density should be considered when a patient with Graves’ disease was present with hypercalcemia.