Intact Parathyroid Hormone Assay Research Articles

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.

B-171 Comparison of Intact PTH and PTH Assays using LC-MS/MS Among Non-Dialysis Dependent Chronic Kidney Disease Patients

Abstract Background Parathyroid hormone (PTH) is an important regulator of calcium and phosphate homeostasis and bone remodeling. It is metabolized into PTH fragments, which are measured to a different extent by PTH assays of different generations because of differences in fragments recognized and lack of assay standardization. Therefore, we developed an LC-MS/MS method for 1-84 PTH and aimed to compare with immunoassay among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. Methods Blood samples were collected from 252 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation—PTH intact and immunocapture in situ digestion LC-MS/MS spectrometry assays. The severity of the kidney disease was based on the eGFR calculated by using the Modification of Diet in Renal Disease (MDRD) formula. Results Serum 1-84 PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r = 0.956, P &amp;lt; 0.0001). This finding was consistent among CKD stages 3 to 5. PTH concentrations by both assays (intact and 1-84 PTH) positively correlated with BUN (r = 0.613, r = 0.61; P &amp;lt; 0.0001, respectively), phosphorus (r = 0.423, r = 0.427; P &amp;lt; 0.0001, respectively) and negatively correlated with blood calcium (r = −0.355, r = −0.421; P &amp;lt; 0.0001, respectively), protein (r = −0.289, r = −0.305; respectively, P &amp;lt; 0.0001) and the estimated glomerular filtration rate (r = −0.468, r = −0.485; P &amp;lt; 0.0001, respectively). Conclusion Among patients with CKD stages 3 to 5 not on dialysis, the 1-84 PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. This LC-MS/MS method can provide accurate and precise PTH results in patients with severe chronic renal failure. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders are needed to determine whether 1-84 PTH assay results are better surrogate markers in these early stages of CKD.

A-042 Comparison of the Second-Generation Parathyroid Hormone Assays: ELSA-PTH and Alinity i Intact PTH

Abstract Background Measurement of parathyroid hormone (PTH) level is essential in diagnosing and treating hyper- and hypoparathyroidism. Because of the various presenting forms of PTH (biologically active full-length PTH and also PTH fragments) in the blood and the lack of standardization, there can be a difference in results between the assays even when the same assay generation is used. We compared the two second-generation PTH assays, ELSA-PTH and Alinity i Intact PTH, and evaluated the analytical performance of Alinity i Intact PTH, newly adopted in the laboratory. Methods For method comparison, 56 remnant samples of routinely ordered sera for the PTH test were collected. ESLA-PTH assay tested on Gamma-10 contains the anti-[39-84, amino acids] PTH antibody coated on the tube, which captures PTH in the sample and is measured by the radioactivity through the bound I125-labelled anti-[1-34] PTH antibody. Alinity i Intact PTH assay performed on Alinity i system uses the anti-[39-84] PTH antibody coated on a paramagnetic microparticle and is analyzed by the emitted light through the captured acridinium-labeled anti-[1-34] PTH antibody. The correlation between the two tests was evaluated. Additionally, precision, linearity, and reference range verification were analyzed to investigate the performance of the Alinity i Intact PTH assay. Results Of the 56 samples, 35 (62.5%) were requested by the Nephrology department for evaluating chronic kidney disease, 16 (28.6%) by the General surgery department during and after parathyroid and thyroid surgery, and 5 (8.9%) by other departments. 52.3% of the patients were female, and the median age was 61.5 years (interquartile range: 45.3–71). The median values of ELSA-PTH and Alinity i Intact PTH were 69.0 pg/mL and 101.9 pg/mL, respectively, and the PTH values of Alinity i Intact PTH were significantly higher (P &amp;lt; 0.0001) by the Wilcoxon test. The Pearson correlation coefficient (r) was 0.959, and the average difference between the two tests was 78.57 pg/mL. In Alinity i Intact PTH, the coefficient of variation obtained at each low (10.5 pg/mL), medium (66.6 pg/mL), high (254.6 pg/mL) levels were 1.9%, 2.4%, and 1.8% for repeatability, and 2.03%, 2.71%, and 2.65% for within-laboratory precision, respectively. Linearity was observed within the analytical measuring range of 3–3000 pg/mL. The reference range (15–68.3 pg/mL) recommended by the manufacturer was validated with 20 normal sera. Conclusion The PTH values of Alinity i Intact PTH were significantly higher than those of the ELSA-PTH, and both assays showed a strong correlation. Additionally, the Alinity i Intact PTH assay demonstrated acceptable analytical performance.

A-129 Analytical Performance Evaluation of Vitamin D, Intact Parathyroid Hormone, and Inorganic Phosphorus on the Atellica CI 1900 Analyzer

Abstract Background The Atellica® CI 1900 Analyzer is an automated, mid-throughput, integrated chemistry and immunoassay analyzer utilizing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica IM Vitamin D (VitD) and Intact Parathyroid Hormone (PTH) and Atellica CH Inorganic Phosphorus (IP) assays* on the Atellica CI 1900 Analyzer*. Methods The Atellica CI 1900 VitD, PTH, and IP assays use the same reagents and calibrators as the Atellica IM VitD and PTH and CH IP assays. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum (VitD and IP) or plasma (PTH) samples. One aliquot of each sample pool was tested in duplicate in two runs per day &amp;gt;2 h apart on each analyzer for &amp;gt;20 days. MC studies were performed according to CLSI EP09-A3. Native and contrived human samples were analyzed using the Atellica IM VitD and PTH assays on both the Atellica IM and Atellica CI 1900 Analyzers. For IP, native and contrived human samples were analyzed using the Atellica CH IP assay on both the Atellica CH and Atellica CI 1900 Analyzers. Results Representative precision and MC results for each assay across indicated sample ranges are listed in the table. For the three assays tested, repeatability and within-lab %CVs were &amp;lt;4.5% and &amp;lt;10%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1. Conclusion Evaluation of the Atellica IM VitD and PTH and Atellica CH IP assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on their respective Atellica IM and Atellica CH Analyzers. *The products/features mentioned are not commercially available in all countries. Their future availability cannot be guaranteed.

Inverse correlation of intact PTH, oxidized PTH as well as non-oxidized PTH with 25-hydroxyvitamin D3 in kidney transplant recipients.

25-hydroxyvitamin D (25(OH)D) and potentially also 1,25-dihydroxyvitamin D (1,25(OH)2D) inhibits the synthesis of parathyroid hormone (PTH) in the chief cells of the parathyroid gland. Clinical studies showing a negative correlation between (25(OH)D and PTH are in good agreement with these findings in basic science studies. However, PTH was measured in these studies with the currently clinically used 2nd or 3rd generation intact PTH (iPTH) assay systems. iPTH assays cannot distinguish between oxidized forms of PTH and non-oxidized PTH. Oxidized forms of PTH are the by far most abundant form of PTH in the circulation of patients with impaired kidney function. Oxidation of PTH causes a loss of function of PTH. Given that the clinical studies done so far were performed with an PTH assay systems that mainly detect oxidized forms of PTH, the real relationship between bioactive non-oxidized PTH and 25(OH)D as well as 1,25(OH)2D is still unknown. To address this topic, we compared for the first time the relationship between 25(OH)D as well as 1,25(OH)2D and iPTH, oxPTH as well as fully bioactive n-oxPTH in 531 stable kidney transplant recipients in the central clinical laboratories of the Charité. Samples were assessed either directly (iPTH) or after oxPTH (n-oxPTH) was removed using a column that used anti-human oxPTH monoclonal antibodies, a monoclonal rat/mouse parathyroid hormone antibody (MAB) was immobilized onto a column with 500 liters of plasma samples. Spearman correlation analysis and Multivariate linear regression were used to evaluate the correlations between the variables. There was an inverse correlation between 25(OH)D and all forms of PTH, including oxPTH (iPTH: r=-0.197, p<0.0001; oxPTH: r=-0.203, p<0.0001; n-oxPTH: r=-0.146, p=0.001). No significant correlation was observed between 1,25(OH)2D and all forms of PTH. Multiple linear regression analysis considering age, PTH (iPTH, oxPTH and n-oxPTH), serum calcium, serum phosphor, serum creatinine, fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), albumin, and sclerostin as confounding factors confirmed these findings. Subgroup analysis showed that our results are not affected by sex and age. In our study, all forms of PTH are inversely correlated with 25-hydroxyvitamin D (25(OH)D). This finding would be in line with an inhibition of the synthesis of all forms of PTH (bioactive n-oxPTH and oxidized forms of PTH with minor or no bioactivity) in the chief cells of the parathyroid glad.

Agreement of Parathyroid Hormone Status Measured by Intact and Biointact Parathyroid Hormone Assays among Chronic Kidney Disease Patients and Its Correlation with Bone Turnover Parameters.

This study aimed to determine the agreement between intact parathyroid hormone (iPTH) and biointact parathyroid hormone (bio-PTH) assays and to correlate them with bone markers. This cross-sectional study included 180 patients with chronic kidney disease (CKD) stages 3b, 4 and 5D. We measured their iPTH, bio-PTH, 25-hydroxyvitaminD (25(OH)D), C-terminal telopeptide collagen (CTX), procollagen 1 intact N-terminal propeptide (P1NP), calcium, phosphate and alkaline phosphatase (ALP). Higher iPTH than bio-PTH concentrations were seen in CKD stages 3b, 4 and 5D (58[62] versus 55[67] pg/mL, 94[85] versus 85[76] pg/mL and 378[481] versus 252[280] pg/mL, respectively). Both PTH assays showed good agreement among all the subjects, with an intraclass correlation coefficient of 0.832 (P-value < 0.001). The Passing-Bablok showed that the equation for the bio-PTH was PTH = 0.64 iPTH + 15.80, with r = 0.99. The Bland-Altman plots showed increased bias with an increasing PTH concentration. Both PTH assays showed a high positive correlation with CTX and P1NP, a moderate correlation with phosphate, a low correlation with ALP and calcium, and a negligible correlation with phosphate and 25(OH)D. The iPTH and bio-PTH assays were in agreement, but their bias increased with the PTH concentration. The unacceptable large bias indicates that the two assays cannot be used interchangeably. They had a variable correlation with the bone parameters.

Full-length versus intact PTH concentrations in pseudohypoparathyroidism type 1 and primary hyperparathyroidism: clinical evaluation of immunoassays in individuals from China.

PurposeThe application of the third-generation parathyroid hormone (PTH) assay [PTH(1–84) assay] for evaluating PTH levels in patients with pseudohypoparathyroidism type-1 (PHP1) is less popular than the second-generation assay. Therefore, we aimed at examining the conformity between the PTH(1–84) assay and the intact PTH (iPTH) assay, specifically examining their performance in individuals with PHP1 versus individuals with primary hyperparathyroidism (PHPT), compared to healthy controls.MethodsPTH(1–84) and iPTH assay were performed in patients with PHP1, patients with PHPT, and healthy volunteers. ∆PTH%, PTH(1–84)/iPTH (3rd/2nd ratio), iPTH/upper limit of normal (ULN), and PTH (1–84)/ULN of each group were calculated for comparison. Linear regression, Kappa conformity test, and Bland–Altman analysis of ∆PTH/mean of iPTH and PTH(1–84) (percent bias) plotted against the mean of iPTH and PTH(1–84) were performed to determine the conformance of PTH(1–84) assay with iPTH assay.ResultsA total of 54 patients with PHP1, 127 patients with PHPT, and 65 healthy volunteers were enrolled in this study. All the three groups showed strong linear relationship between iPTH and PTH (1–84) (r2 = 0.9661, 0.7733, and 0.9575, respectively). No significant differences were noted in 3rd/2nd ratio (median 0.76 vs. 0.72) between the PHP1 and PHPT groups (p > 0.05). Conformity examination showed the Kappa value was 0.778 and 0.395 for PHP1 and PHPT groups respectively. No difference in the Kappa values was found between PHP1A and PHP1B subgroups. Bland–Altman plot demonstrated that the proportion of data points that were plotted within mean ± 1.96 SD in PHP1, PHPT and normal control groups were 96.3%, 93.7%, and 98.5%, respectively. The mean percent bias of the three groups were 26.1%, 31.2%, and 17.0%, respectively. The range of mean ± 1.96 SD of percent bias of the three groups were 2.2%–50.0%, −14.3%–76.6%, and 6.7%–27.2%, respectively.ConclusionAlthough iPTH and PTH(1–84) values were both lower in the present PHP1 cohort than in the PHPT cohort, there appear to be differences in the relative agreement between both immunoassays, and in the relationship between the two values, especially in comparison to healthy controls. Whether these differences are due to differential accumulation of C-terminal fragments or other factors requires further study.

M307 A comparison study between MAGLUMI and Abbott ARCHITECT intact parathyroid hormone (PTH) assay

M307 A comparison study between MAGLUMI and Abbott ARCHITECT intact parathyroid hormone (PTH) assay

POS-551 INTRAOPERATIVE PLASMA (1-84) PTH LEVELS ARE BETTER THAN INTACT PTH FOR ASSESSING THE SUCCESS OF PARATHYROIDECTOMY IN UREMIC HYPERPARATHYROIDISM PATIENTS

Parathyroidectomy (PTX) is the most effective treatment in severe secondary hyperparathyroidism (SHPT) patients with chronic kidney disease (CKD). Complete removal of all parathyroids is essential for successful PTX. Excessive or ectopic parathyroids are related with persistent SHPT, which occurs up to 25% of cases. Now the most commonly used second-generation intact parathyroid hormone (iPTH) assay can not only recognize (1-84)PTH, also named as whole PTH (wPTH), but also large C-terminal PTH. While the third-generation PTH assay can measure (1-84)PTH specifically. This provides a possibility of diagnostic accuracy for successful PTX by intraoperative (1-84)PTH because of its higher specificity and shorter half-life, however, there is no relevant report. Here we compared the predictive value of intraoperative plasma (1-84) PTH and iPTH levels in order to improve the safety and efficiency for PTX prospectively. We included 100 healthy controls, 162 stage 5 CKD patients without SHPT, 214 PTX patients because of SHPT. Plasma iPTH and (1-84)PTH levels were measured before incision (io-iPTH0, io-[1-84]PTH0), 10min (io-iPTH10, io-[1-84]PTH10) and 20min (io-iPTH20, io-[1-84]PTH20) after removing all parathyroids. Reduction percentage of PTH at 10min and 20min were calculated (io-iPTH10%, io-[1-84]PTH10%, io-iPTH20%, io-[1-84]PTH20%). Within one week after PTX, patients with serum iPTH<50pg/ml were classified as successful PTX, and patients with serum iPTH≥300pg/ml were defined as persistent SHPT. Patients would be followed up in 6 months when serum iPTH levels between 50-300pg/ml, serum iPTH＜300pg/ml subgroup was defined as successful PTX, and those whose serum iPTH≥300pg/ml were persistent SHPT(Fig.1). The receiver operating characteristic (ROC) curve was used to determine cut-off values for predicting surgical outcome. Accurate diagnosis was expressed by sensitivity, specificity, and area under the ROC curve (AUC). Baseline (1-84)PTH levels in controls, non-PTX and PTX patients were 22.10(15.36-31.31)pg/ml, 94.51(52.31-190.70)pg/ml and 850.90(595.00-1269.00)pg/ml. In PTX group, there were 187 successful PTX(87.38%), 19 persistent SHPT (8.88%), and 8 patients(3.74%) were lost to follow-up. In successful PTX subgroup, there were 5 patients had five parathyroids, 1 patient had two parathyroids, and 7 patients had three parathyroids. There was no significant difference between successful PTX and persistent SHPT subgroup on plasma io-iPTH10 levels. Compared with successful PTX group, persistent SHPT patients had higher io-(1-84)PTH10, io-iPTH20 and io-(1-84)PTH20 levels (P＜0.001). ROC curve revealed io-(1-84)PTH10%＞86.64% (AUC 0.77, sensitivity 55.10%, specificity 94.70%), and io- (1-84)PTH20%＞87.46% (AUC 0.92, sensitivity 84.00%, specificity 94.70%) could predict successful PTX. Sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the time-point of 10min. Compared with iPTH10% and iPTH20%, the predictive ability of io-(1-84)PTH10% and io-(1-84)PTH20% were higher (sensitivity: 55.10% vs 51.90% and 84.00% vs 73.30%; specificity: 94.70% vs 89.50% and 94.70% vs 89.50%)(Fig. 2). Intraoperative reduction percentage of plasma (1-84)PTH level is superior to iPTH for accurate evaluating successful PTX, especially at the time-point of 20min after all cervico-thoracic parathyroids were resected.

P0885THE RELATIONSHIP BETWEEN BONE REGULATORY MARKERS AND BONE TURNOVER IN RENAL OSTEODYSTROPHY

Abstract Background and Aims Renal osteodystrophy is common in advanced chronic kidney disease (CKD) patients and is characterized by abnormal bone turnover and mineralization. Parathyroid hormone (PTH) increases bone turnover through osteoblast and osteoclast activation. Osteoprotegerin (OPG) is a decoy receptor of receptor activator of nuclear factor kappa-β ligand and thus, inhibits osteoclast maturation. Meanwhile, sclerostin is an inhibitor of the Wnt signalling pathway and thus, inhibits osteoblast maturation. We aimed to assess the relationship between these bone regulatory markers and bone turnover as assessed by bone histomorphometry and bone turnover markers (BTMs). Method We recruited 43 CKD patients with eGFR&amp;lt;30ml/min/1.73m2 or on dialysis. Fasting serum samples were analysed using Immunodiagnostic Systems automated assays (Boldon, UK) for intact PTH (iPTH) and BTMs such as bone alkaline phosphatase (bALP) and intact procollagen type 1 N-terminal propeptide (intact PINP) which are bone formation markers, and tartrate-resistant acid phosphatase 5b (TRAP5b) which is a bone resorption marker. OPG and sclerostin were analysed using manual ELISA by Biomedica (Vienna, Austria). Trans-iliac bone biopsy was performed after tetracycline labelling. Bone samples were analysed using quantitative histomorphometry. Normal bone turnover was defined as bone formation rate/bone surface (BFR/BS) of 18 - 38µm3/µm2/year. Spearman rank correlation was used to test the relationship between the variables. Results Median BFR/BS was 32.12 (IQR 17.76 – 48.25) um3/um2/year. 26% of patients had low and 40% had high bone turnover. iPTH and OPG were positively correlated with BFR/BS (rho = 0.42, p&amp;lt;0.01 and rho = 0.36, p&amp;lt;0.05 respectively). Sclerostin was not correlated with BFR/BS. Furthermore, sclerostin did not correlate with bALP and intact PINP whereas OPG correlated with TRAP5b (rho = 0.43, p&amp;lt;0.01). iPTH correlated with bALP (rho = 0.62, p&amp;lt;0.001), intact PINP (rho = 0.62, p&amp;lt;0.001) and TRAP5b (rho = 0.50, p = 0.001). Conclusion Circulating levels of iPTH and OPG were modestly associated with bone turnover but sclerostin was not. There are likely to be bone regulators other than iPTH, OPG and sclerostin which regulate bone turnover in renal osteodystrophy.

PTH: Redefining Reference Ranges in a Healthy Population-The Role of Interfering Factors and the Type of Laboratory Assay.

Introduction. Parathyroid hormone (PTH) is a linear peptide constituted by 84 amino acids and active in its 1–84 form, but a wide range of PTH forms produced by its post-transcriptional modifications are present in blood. Many assays with different specificities are commercially available. The aim of our study was to compare a 2nd and 3rd generation in healthy population in order to better define the reference range in the healthy population residing in our region. Materials and Methods. 108 subjects (53 females and 55 males) referring to the transfusion donor were enrolled in the study centre in April 2016 and underwent PTH levels measurements with a 3rd generation kit (chemiluminescent immunoassay DiaSorin Liaison) and with a 2nd generation kit (immunoradiometric assay Total Intact PTH Assay (Coated Tube), Scantibodies). Also calcium, phosphate, creatinine, and 25OHD3 were measured. A questionnaire on lifestyle and dietary habits was obtained. Results The median PTH values obtained with the 2nd generation assay and the whole 3rd generation assay were 20.26 pg/ml and 23.11 pg/ml, respectively. Bland–Altman method showed substantial concordance between the two PTH assays, although with an overestimation of the 3rd generation method over the 2nd generation method. There was no correlation between 3rd generation PTH and 25OHD3 and creatinine. Calcium was negatively correlated with PTH only when measured with 3rd generation kit. Conclusions On the basis of our data, obtained from healthy subjects, we can conclude that the reference range used by our laboratory was too narrow and was necessary to reestablish normal ranges according to our population. This is useful to avoid hyperparathyroidism misdiagnosis.

Parathyroid Hormone Measurement in Chronic Kidney Disease: From Basics to Clinical Implications.

Accurate measurement of parathyroid hormone (PTH) is crucial for therapeutic decision-making in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The second-generation PTH assays, often referred to as “intact PTH” assays, are the current standard and most available assays in clinical practice. However, intact PTH assays measure both full-length biologically active PTH and heterogeneous PTH fragments in the circulation, providing the equivocal value of PTH measurement in patients with CKD-MBD. Due to the variability of PTH assays, preanalytical sample errors, and the phenomenon of end-organ PTH hyporesponsiveness, current CKD-MBD guidelines recommend a wide range for serum PTH targets (2–9 the upper normal limit of the intact PTH assay) in dialysis patients to diminish the risk of developing adynamic bone disease. Nevertheless, a sizeable proportion of CKD patients still experience renal osteodystrophy despite having serum PTH levels within the recommended range. The primary cause of this inconsistency is the analytical interference of various PTH fragments and oxidized PTH forms that considerably accumulate in CKD patients. Therefore, a new mass spectrometry-based assay, which is capable of specifically measuring the whole spectra of PTH fragments, can potentially improve diagnostic accuracy for renal osteodystrophy. However, the effects of different PTH fragments on bone metabolism, vascular calcification, and mortality in CKD patients warrant further research.

SUN-272 Changes in whole PTH/intact PTH ratio in patients with chronic kidney disease

Serum parathyroid hormone (PTH) levels increase with decreasing kidney function. Two types of assays for the measurement, the intact PTH (iPTH) assay and the whole PTH (wPTH) assay, are routinely used in clinical settings. Although we usually measure serum iPTH levels because there are many evidences on clinical practice, the iPTH assay detect not only PTH (1-84), which is a physiologically active hormone, but also PTH (7-84), which is a PTH fragment. Whereas, the wPTH assay can mainly detect PTH (1-84). Therefore, Japanese Society of Dialysis Therapy guidelines proposed that estimated iPTH is wPTH multiplied by approximately 1.7 in chronic dialysis patients. However, wPTH/iPTH ratio in non-dialysis chronic kidney disease (CKD) patients remains unclear. Therefore, the aim of the present study was to examine the relationship between wPTH/iPTH ratio and kidney function and other factors affecting wPTH/iPTH ratio. We conducted a cross-sectional observational study including 874 CKD patients (CKD stage 1-5; n=773, CKD stage 5D; n=101) who visited our department from December 2014 to December 2015. We measured serum iPTH and wPTH levels using the Elecsys Intact PTH assay and Elecsys PTH (1-84) assay (Roche Diagnostics). Other laboratory data and clinical characteristics were also evaluated and compared among five CKD stage groups (CKD1-2, CKD3, CKD4, CKD5, and CKD5D). We assessed wPTH/iPTH ratio and the correlation of wPTH/iPTH with various clinical factors. Furthermore, we determined the inflection points of these correlation lines using multiple linear regression analysis. Between five CKD stages groups, there were significant differences in age, past history of coronary artery disease, chronic heart failure, use of calcium carbonate and bisphosphonate, wPTH/iPTH ratio, wPTH, iPTH, calcium, phosphate, alkaline phosphatase, hemoglobin, and blood urea nitrogen levels. Diabetes mellitus, medication of vitamin D, total protein, and HbA1c levels were comparable between the groups. Among each CKD stage groups, wPTH/iPTH ratio was 0.85, 0.81, 0.78, 0.59, and 0.69, respectively. wPTH/iPTH ratio was significantly correlated with serum calcium and phosphate levels only in the CKD5 group, and with the GFR and age in the CKD3, CKD4 and CKD5 group. In addition, an inflection point of the correlation lines between eGFR and wPTH/iPTH ratio was 24.1 mL/min/1.73m2. Similarly, an inflection point for serum calcium levels was 20.0 mL/min/1.73m2 and for serum phosphate levels was 18.0 mL/min/1.73m2, respectively. Our study demonstrated that wPTH/iPTH ratio was lowering with decreasing kidney function possibly due to increasing PTH synthesis and metabolization and accumulation of PTH fragments.

Analytical verification and method comparison of the Atellica IM intact parathyroid hormone assay

Analytical verification and method comparison of the Atellica IM intact parathyroid hormone assay

A comparison of canine whole and intact parathyroid hormone concentrations as measured by different assays.

To compare an intact immunoradiometric parathyroid hormone assay with (1) a non-isotopic technique; and, (2) a whole parathyroid hormone immunoradiometric assay. Intact parathyroid hormone concentrations were measured using immunoradiometric (Scantibodies) and chemiluminescent (Immulite 2000) assays. Whole parathyroid hormone concentration was measured using an immunoradiometric assay (Scantibodies). A total of 48 and 47 samples, respectively, were used to compare immunoradiometric and chemiluminescent intact parathyroid concentrations and intact and whole parathyroid hormone concentrations by immunoradiometric assays. Using chemiluminescence, 39 (81.3%) samples had intact parathyroid hormone concentrations at or below the reported limit of detection of the assay (0.3pmol/L). Intact [6.3 (2.0 to 95.5) pmol/L] and whole [3.3 (0.8 to 125.2) pmol/L] immunoradiometric parathyroid hormone concentrations exhibited excellent correlation. Not all parathyroid hormone assays perform similarly. The chemiluminescent assay in this study cannot be recommended for use in dogs. The immunoradiometric intact parathyroid hormone assay proved to be a more reliable method. Given the correlation between intact and whole parathyroid hormone concentrations, it remains unclear which one is superior for routine clinical decision-making.

Effects of Parathyroidectomy on Plasma iPTH and (1-84) PTH Levels in Patients with Stage 5 Chronic Kidney Disease.

Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1-84)PTH levels, respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1-84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5 (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.

Management of undetectable and lost parathyroid adenoma

The introduction of new technologies and the improvement of localization diagnostics have led to a change of strategy in the surgery of primary hyperparathyroidism (pHPT). Focused approach to a preoperatively located parathyroid adenoma and the use of intraoperative parathyroid hormone (IOPTH) determination improve the quality of the surgical procedure and reduce morbidity. Nevertheless, the success rate of approximately 95–99% in the initial intervention could not be improved by the new or further developed technologies. The parathyroid adenoma, which cannot be found intraoperatively, is still a surgical problem today. Advances in preoperative imaging and use of IOPTH levels are even more important for the approach to re-operative parathyroidectomy. Diagnosis of persistent and recurrent pHPT is dependent on the quality and duration of follow-up, as well as the availability of biochemical data in centralized repositories. The consequence are the high cost to the patient of missed or inadequate initial operation, physical effects of remaining hyperparathyroid, additional time off work, potentially invasive localization testing, reoperative surgery, increased risk of complication and expense. To reduced failure rate is essential the correct indication, timing and type of surgery, availability of intact parathyroid hormone (iPTH) assay and the improvement of preoperative localizing studies.

Analytical verification and method comparison of the ADVIA Centaur® Intact Parathyroid Hormone assay

ObjectivesThis study is the first verification of the novel iPTH Siemens ADVIA Centaur® Intact Parathyroid Hormone (iPTHm) chemiluminescence immunoassay based on monoclonal antibodies. We also compared the iPTH results obtained using this assay with the previous ADVIA Centaur® Parathyroid Hormone assay (iPTHp) based on polyclonal antibodies. Design and methodsThe analytical performance study of iPTHm assay included LoD, LoQ, intra- and inter-assay reproducibility, and linearity. A comparison study was performed on 369 routine plasma samples. The results were analyzed independently for patients with normal and abnormal GFR, as well as patients on hemodialysis. In addition, clinical concordance between assays was assessed. Finally, we studied PTH stability of plasma samples at 4°C. ResultsFor the iPTHm assay LoD and LoQ were 0.03pmol/L and 0.10pmol/L, respectively. Intra- and inter-assay CV were between 2.3% and 6.2%. Linearity was correct in the range from 3.82 to 203.08pmol/L. Correlation studies showed a good correlation (r=0.99) between iPTHm and iPTHp, with bias of −2.55% (IC −3.48% to −1.62%) in the range from 0.32 to 117.07pmol/L. Clinical concordance, assessed by Kappa Index, was 0.874. The stability study showed that differences compared to basal iPTH concentration did not exceed 20% in any of the samples analyzed. ConclusionsThe iPTHm assay demonstrated acceptable performance and a very good clinical concordance with iPTHp assay, currently used in our laboratory. Thus, the novel iPTHm assay can replace the previous iPTHp assay, since results provided by both assays are very similar. In our study, the stability of iPTH is not affected by storage up to 14days.

In vitro diagnostic company recalls and medical laboratory practices: an Italian case.

IntroductionIn vitro human diagnostic (IVD) company recalls are a common practice aimed to either minimize a potential error or eliminate an existing failure. In this case report, we aim to provide a critical analysis of a recent IVD recall and to provide a practical framework about what to do when an IVD company recalls product(s) based on the International Organization for Standardization - ISO 15189:2012 standard.Case reportIn 2014, Abbott Laboratories® (Green Oaks, IL) published an urgent field safety notice regarding a product recall (Architect Intact parathyroid hormone (PTH) Assay List Number 8K25) with immediate action required. The IVD company explained the reasons for the recall as follows: i) Abbott has confirmed that a performance shift in the Architect Intact PTH assay has the potential to generate falsely elevated results on patient samples; ii) results generated with impacted lots may demonstrate a positive shift relative to those generated with previous reagent and/or calibrator lots. This issue may also impact established Architect Intact PTH reference ranges; iii) the magnitude of shift averages approximately 13% to 45%; iv) Abbott Architect Intact PTH controls do not detect the shift; and v) all current reagent, calibrator, and control inventory are impacted. The recall could have resulted in ~40,000 inaccurate laboratory tests reported by 18 laboratories from Italy (Lombardy region).ConclusionIVD company recalls have a serious impact on the patient safety and require a thorough investigation and responsible approach to minimize the possible damage. Medical laboratories accredited according to the ISO 15189 standard have procedures in place to manage such situations and ensure that patient safety is maintained when such recalls are issued.

Intact parathyroid hormone and whole parathyroid hormone assay results disagree in hemodialysis patients under cinacalcet hydrochloride therapy.

BackgroundThe parathyroid gland secretes 1-84 and 7-84 parathyroid hormone (PTH) fragments, and its regulation is dependent on stimulation of the extracellular calcium-sensing receptor. While the intact PTH system detects both PTH fragments, the whole PTH system detects the 1-84PTH but not the 7-84PTH. Cinacalcet hydrochloride (CH) binds to calcium-sensing receptor as a calcimimetic. Here we investigated the role of CH treatment in the assessment of parathyroid gland function.MethodsStable adult dialysis patients for whom CH therapy was planned were included. Patients for whom CH therapy was not planned were simultaneously included as the control group.ResultsThe CH group (n = 44) showed significantly higher circulating levels of Ca, intact PTH, and whole PTH, before the CH treatment than the control group (n = 112). The Ca, intact PTH, and whole PTH levels decreased along with the CH therapy, and the Ca levels became comparable in the 8th week of treatment and thereafter. The CH group in the 8th week and thereafter showed significantly lower whole/intact PTH ratios than the control group, while the whole/intact PTH ratio was not significantly different between before and during the CH therapy. A multiple regression analysis revealed that the whole/intact PTH ratio was almost constant, but both the serum Ca level and a CH therapy could potentially modify the fixed number. When the whole PTH levels were estimated by intact PTH levels using the relationship between them in the control group, the levels were clearly overestimated in the CH group.ConclusionsAlthough the direct effect of CH on the whole/intact PTH ratio is masked by its hypocalcemic action, we could successfully demonstrate that the ratio in CH users is lower than that in the non-users with comparable levels of serum Ca. Evaluating parathyroid function with intact PTH according to the clinical practice guidelines in patients being treated with CH may lead to significant overestimation and subsequent overtreatment.