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.

Background: 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. Methods: 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). Results: 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. Conclusion: 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.

Role of postoperative intact serum PTH as an early predictor of severe post-thyroidectomy hypocalcemia: a prospective study.

BACKGROUND: Post thyroidectomy hypocalcemia is a major sequel of thyroidectomy and continues to trouble the endocrinologists and the endocrine surgeons as there is no ideal predictive marker of hypocalcemia which has the potential to develop into a life-threatening complication. The role of early serum intact parathormone (iPTH) to predict post thyroidectomy hypocalcemia is becoming useful but the literature is still unclear regarding the optimal time of testing and the optimal cut-off value of serum iPTH. PATIENTS AND METHODS: This is a prospective cohort study of 111 patients who underwent total thyroidectomy in a tertiary care endocrine surgery referral unit. Serum iPTH was measured after 20 min and 4 h of surgery. Receiver-Operator characteristic Curve (ROC) was used to find out of the best cut-off value of S. iPTH 20 min and 4 h after surgery in predicting hypocalcemia. RESULTS: Hypocalcemia was noted in 60 (54%) out of 111 subjects who underwent total thyroidectomy. The best cut-off values of Serum iPTH to predict hypocalcemia was found to be 4.28 pmol/l at 20 min post total thyroidectomy with a sensitivity and specificity of 81.7% and 51%, respectively. In addition, patients with malignancy or central lymph nodal dissection were significantly over-represented in the hypocalcemia group with serum iPTH above the threshold level of 4.28 pmol/l. Below the cut off level, parenteral calcium supplementation was required in 23% (17/74) subjects while the rate was only 5.4% (2/37) patients when serum iPTH was above the cut-off level. CONCLUSIONS: The decline of serum iPTH below a specific level after surgery has predictive value together with other factors strictly related to patient, the thyroid disease itself and surgery. The risk of development of hypocalcemia and consequent need for calcium supplementation should be evaluated by clinical assessment along with serum PTH measurement.

Intraoperative parathyroid hormone (PTH) testing in patients with primary hyperparathyroidism and PTH levels in the normal range.

BACKGROUND: Primary hyperparathyroidism is a common endocrine disorder. Hypercalcemia with normal PTH levels is very unusual and can lead to diagnostic difficulties. There are very few very few studies in the literature and all with limited numerical samples. The goal of the present study was to determine the real incidence and characteristics of primary hyperparathyroidism with normal PTH and to evaluate if intraoperative PTH testing is useful in these patients. METHODS: We performed a retrospective review of 314 patients who had undergone parathyroidectomy to treat primary hyperparathyroidism between January 2002 and December 2016. Patients were divided in two groups according to biochemical preoperative findings: in Group A were included patients with normal serum PTH, in Group B those with increased serum PTH. RESULTS: Nine patients (3.7%) were included in group A and 235 in group B. Patients in group A were younger (51.5 ± 12.9 years vs 59.6 ± 12.5); preoperative serum calcium and the incidence of coexisting thyroid disease were similar between the two groups. Symptomatic patients were more frequent in Group A (77.8% vs 39.1%; p = 0.048). There were no significant differences regarding preoperative localization studies and surgical procedure. Intraoperative PTH determination demonstrated sensitivity of 86% in group A and 97% in group B, specificity and positive predictive value of 100% in both the groups, negative predictive value of 67% in group A and 79% in group B. Histopathological examination demonstrated a single gland disease in 8 (88.9%) patients in group A and a multi gland disease in 1 (11.1%), in group B single gland disease was found in 218 (92.8%) patients and multi gland disease in 17 (7.2%). Unsuccessful surgery with persistent or recurrent hyperparathyroidism occurred in 1 (11.1%) patient in group A and 4 (1.7%) in group B. CONCLUSIONS: Primary hyperparathyroidism with normal PTH is rare but physicians should be aware of this possibility in patients with hypercalcaemia. Patients with normal PTH levels are younger and more frequently symptomatic. Intraoperative PTH testing plays an important role in the operative management even in such patients.

Comparison of parathyroid hormone kinetics in endoscopic thyroidectomy via bilateral areola with open thyroidectomy.

BACKGROUND: In this study, we aimed to compare the kinetics of intact parathyroid hormone (iPTH) during the perioperative period of endoscopic thyroidectomy via bilateral areola approach (ETBAA) in the same period, following a traditional open thyroidectomy approach (OTA). METHODS: We conducted a prospective observational study of patients who were undergoing thyroidectomy and level VI clearance. Patients who had been affected by papillary thyroid cancer (PTC) were stratified into three groups: those eligible for endoscopic treatment (ETBAA); patients who were eligible for ETBAA but had opted for OTA (OTA-L); and patients who were not suitable for endoscopic intervention (OTA-H). A process for locating parathyroid glands was utilized to stratify gland dissection laboriousness. In Type A, the gland is firmly fixed to thyroid gland. This type can be sub-classified into three subtypes. A1: the parathyroid gland is attached to the inherent thyroid capsule. A2: the gland is partially embedded in the thyroid gland. A3: the gland is located in the thyroid tissue. Type B is defined as a gland which is separated from the thyroid gland. The iPTH was sampled at wound closure. RESULTS: There were 100 patients in each group. We found a significant difference between the ETBAA and OTA-H groups for type A2, as well as a loss of parathyroid glands and a number of parathyroid transplantation procedures. The endoscopic group was treated during an earlier stage of thyroid cancer. The iPTH profile of each group decreased, although this was the most consistent in the OTA-H group. A comparison of ETBAA with OTA-L demonstrates that the iPTH level change is similar. CONCLUSION: There is no advantage of endoscopic treatment for preserving parathyroid function.

Low serum intact parathyroid hormone level is an independent risk factor for overall mortality and major adverse cardiac and cerebrovascular events in incident dialysis patients.

UNLABELLED: Abnormal bone dynamics is a major risk factor for cardiovascular disease in patients with chronic kidney disease. The level of serum intact parathyroid hormone (iPTH) is widely used as a bone dynamic marker. We investigated the effect of the mean level of serum iPTH on overall mortality and cardiovascular outcomes in incident dialysis patients. PURPOSE: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major risk factor for cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). CKD-MBD is classified as low- or high-turnover bone disease according to the bone dynamics; both are related to vascular calcification in ESRD. To evaluate the prognostic value of abnormal serum parathyroid hormone (PTH) levels on ESRD patients, we investigated the effects of time-averaged serum intact PTH (TA-iPTH) levels on overall mortality and major adverse cardiac and cerebrovascular events (MACCEs) in incident dialysis patients. METHODS: Four hundred thirteen patients who started dialysis between January 2009 and September 2013 at Yonsei University Health System were enrolled. The patients were divided into three groups according to TA-iPTH levels during the 12 months after the initiation of dialysis: group 1, <65 pg/ml; group 2, 65-300 pg/ml; and group 3, >300 pg/ml. Cox regression analyses were performed to determine the prognostic value of TA-iPTH for overall mortality and MACCEs. RESULTS: The mean age of the patients was 57 ± 15 years, and 222 patients (54 %) were men. During the median follow-up of 40.8 ± 29.3 months, 49 patients (12 %) died, and MACCEs occurred in 55 patients (13 %). The multivariate Cox regression analyses demonstrated that a low TA-iPTH level was an independent risk factor for both overall mortality (group 2 as reference; group 1: hazard ratio (HR) = 2.06, 95 % confidence interval (CI) = 1.11-3.83, P = 0.023) and MACCEs (HR = 1.82, 95 % CI = 1.04-3.20, P = 0.036) in incident dialysis patients after adjustment for confounding factors. CONCLUSION: Low serum TA-iPTH is a useful clinical marker of both overall mortality and MACCEs in patients undergoing incident dialysis, mediated by vascular calcification.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

[Clinical value of two methods to measure parathyroid hormone in chronic renal insufficiency, considering vitamin D metabolism]. / Kétféle parathormonmérési módszer klinikai értékének vizsgálata krónikus veseelégtelenségben a D-vitamin-ellátottság figyelembevételével.

INTRODUCTION: Parathyroid hormone levels provide important information in chronic renal failure. AIM: To compare parathyroid hormone levels measured by two assays in correlation with vitamin D supply. METHOD: Parathyroid hormone and 25-hydroxi-vitamin-D were determined in 104 patients (31 patients with chronic renal failure without renal replacement therapy, 36 patients treated with peritoneal dialysis and 37 patients treated with hemodialysis). RESULTS: Good correlation was found between results of the two parathyroid hormone methods, but the intact parathyroid hormone levels were higher than the biointact values. 87% and 13% of the patients had vitamin-D deficiency and insufficiency, respectively. The frequency of serious vitamin-D deficiency was higher in the peritoneal dialysis than in the hemodialysis group. Intact parathyroid hormone levels were different in dialysed patients having vitamin-D-deficiency and insufficiency, and the difference was higher for the biointact than intact values. Negative correlation was detected between biointact parathyroid hormone and 25-hydroxivitamin-D in the hemodialysis group. CONCLUSIONS: Biointact parathyroid hormone levels better reflect the vitamin D supply and bone metabolism than intact levels, especially in hemodialysed patients.

Analysis of intraoperative laboratory measurements and imaging techniques such as Tc-99 m-MIBI SPECT/CT, 18F-fluorocholine PET/CT and ultrasound in patients operated with prediagnosis of parathyroid adenoma.

AIM: The aim of this study is to determine accurately the localization of the adenoma with the imaging methods in the patients, who are planned to be operated on with prediagnosis of parathyroid adenoma. METHOD: In our study, the files of the patients who were considered to have parathyroid adenoma and underwent operation between 2012 and 2020 with the methods such as Tc99m-MIBI SPECT/CT, 18F-fluorocholine PET/CT, and ultrasound, and biochemical examinations were examined retrospectively. RESULTS: In this study, 31 (18.2%) male and 139 (81.8%) female adult patients were included. The sensitivities of localization methods were 82.6% for ultrasound and 78.4% for scintigraphy. Adenoma was localised in the right place in 14 of 15 (93.3%) patients with the 18F-fluorocholine PET/CT method. A statistically significant correlation was found between the sensitivity of scintigraphy, the gland weights (p: 0.002), and phosphor values (p: 0.039). A statistically significant improvement was observed in the intact PTH value (p: 0.001) 15 min after the removal of adenoma. A statistically significant improvement was observed in the serum PTH value (p: 0.001), the serum phosphorus value (p: 0.001), and the serum calcium (p: 0.001) in the first 3 months after the operation. CONCLUSION: Determining localization accurately for the patients enables performing operations with minimally invasive surgery successfully in a shorter time. Also, fewer complications and faster recovery are seen in the patients. It was concluded that studying intraoperative intact PTH and using 18F-fluorocholine PET/CT method for localization give more accurate results for localization and allow having more successful operation outcomes.

Effect of vitamin D deficiency on surgical outcomes of degenerative cervical myelopathy.

Background: Due to its association with bone metabolic status and muscle strength/mass, vitamin D deficiency has the potential to affect neurological symptom recovery after surgery for degenerative cervical myelopathy (DCM). However, few studies have investigated the effects of vitamin D deficiency (serum 25(OH)D <20 ng/mL) on surgical outcomes in DCM patients. Herein, we investigated the prevalence of vitamin D deficiency in patients with DCM, and determined whether vitamin D deficiency affects surgical outcomes for DCM. Methods: In this retrospective observational study we assessed the recovery rate 1 year after surgery in 91 patients diagnosed with DCM who underwent surgery. First, we analyzed the correlation between vitamin D levels and various background factors. Then, patients were divided into 2 groups according to vitamin D sufficiency, and univariate analysis was performed on vitamin D and surgical outcomes. Finally, Spearman correlation analyses were performed to identify factors correlated with recovery rate after surgery for DCM. Results: The average Japanese Orthopedic Association score for the assessment of cervical myelopathy (C-JOA score) improved postoperatively. Age was positively correlated with vitamin D levels, and parathyroid hormone levels were negatively correlated with vitamin D levels. Among the 91 patients, 79.1% of patients were diagnosed with vitamin D deficiency. No significant differences in recovery rate were found between the vitamin D-deficient and vitamin D-sufficient groups. Finally, the Spearman correlation analysis showed a positive correlation between the preoperative C-JOA motor dysfunction score in the lower extremities and the recovery rate, while age demonstrated a negative correlation with recovery rate. Conclusions: No association was found between vitamin D deficiency and clinical outcomes after surgery for DCM. The results of this study do not support the need to normalize vitamin D levels for achieving neurological improvements in patients with DCM.

Intraoperative intact parathyroid hormone monitoring and frozen section diagnosis are essential for successful parathyroidectomy in secondary hyperparathyroidism.

Background: Total parathyroidectomy (PTx) is often performed to treat secondary hyperparathyroidism (SHPT). Successful PTx is essential to prevent recurrent and persistent SHPT because remnant parathyroid glands (PTGs) in the neck can be stimulated and may secrete excessive parathyroid hormone (PTH) in end-stage renal disease. However, to date, few studies have investigated factors contributing to successful PTx before the completion of surgery. Materials and methods: Between August 2010 and February 2020, 344 patients underwent total PTx, transcervical thymectomy, and forearm autograft for SHPT at our institute. Factors contributing to successful PTx before the completion of surgery were investigated. Preoperative imaging diagnoses, including computed tomography, ultrasonography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, intraoperative intact PTH (IOIPTH) monitoring, and frozen section histologic diagnosis, were performed. Successful PTx was defined as intact PTH level < 60 pg/mL on postoperative day 1. A sufficient decrease in IOIPTH level was defined as > 70% decrease in intact PTH levels measured 10 min after total PTx and transcervical thymectomy compared to intact PTH levels measured before skin incision. Logistic regression analysis was conducted to investigate factors contributing to PTx success. Results: Univariate analysis showed that the number of all PTGs identified preoperatively by imaging modalities and the specimens submitted for frozen section diagnosis, which surgeon presumed to be PTGs, were not significant factors contributing to successful PTx. However, multivariate analysis revealed that the number of PTGs identified by frozen section diagnosis (P < 0.001, odds ratio [OR] 4.356, 95% confidence interval [CI] 2.499-7.592) and sufficient decrease in IOIPTH levels (P = 0.001, OR 7.847, 95% CI 2.443-25.204) significantly contributed to successful PTx. Conclusion: Sufficient intact PTH level decrease observed on IOIPTH monitoring and the number of PTGs identified by frozen section diagnosis contributed to successful PTx for SHPT. IOIPTH monitoring and frozen section diagnosis are essential for achieving successful PTx for SHPT.

Changes in the whole/intact parathyroid hormone ratio and their clinical implications in patients with chronic kidney disease.

BACKGROUND: Although a previous study has reported the relationship between intact parathyroid hormone (iPTH) and whole parathyroid hormone (wPTH) levels in patients undergoing dialysis, the w/i PTH ratio (whole/intact PTH ratio) among predialysis chronic kidney disease (CKD) patients remains unclear. The present study therefore aimed to examine the relationship between w/i PTH ratio and kidney function and determine other factors affecting the w/i PTH ratio. METHODS: An observational study including 773 predialysis CKD patients was conducted. The correlation between w/i PTH ratio and kidney function, as well as clinical factors at different CKD stages, were assessed using univariate and multivariate analyses. In addition, the relationship between w/i PTH ratio and composite renal outcome [kidney transplantation, dialysis, and 30% decline in estimated glomerular filtration rate (eGFR)] was examined. RESULTS: The w/i PTH ratio decreased as the CKD stage progressed. Patients in each CKD stage (1/2, 3, 4, and 5) had a w/i PTH ratio of 0.85, 0.81, 0.78, and 0.59, respectively. The inflection point in the correlation lines between eGFR and w/i PTH ratio was 24.1 mL/min/1.73 m2. In multivariate analysis, the w/i PTH ratio was significantly correlated with serum calcium levels only in the CKD5 group and with eGFR in the CKD3, CKD4 and CKD5 group. Furthermore, w/i PTH ratio, eGFR, serum phosphate levels, and urinary protein/creatinine ratio were determined to be significant independent predictors for composite renal outcome. CONCLUSIONS: Our study demonstrated that changes in the w/i PTH ratio were associated with kidney function, abnormal mineral metabolism, and renal outcome.

Parathormone decline levels are better markers of symptomatic hypocalcemia following total thyroidectomy than parathormone alone.

Background: We aimed to assess the predictive value of the absolute and relative intact parathormone (iPTH) decline levels as reliable markers of postoperative hypocalcemia. Materials & methods: iPTH levels were measured 4 h after surgery and the following morning after surgery (postoperative day 1). iPTH, absolute iPTH decline (ΔPTH) and relative iPTH decline (ΔPTH%) were calculated and correlated with symptomatic hypocalcemia. Results: Of the 95 patients, 20% of patients (n = 19) developed symptomatic hypocalcemia. The ΔPTH (U = 206; p < 0.001) and ΔPTH% (U = 127; p < 0.001) were significantly higher in patients with symptomatic hypocalcemia. A ΔPTH% of 20% (sensitivity of 84%; specificity of 91%); and an absolute iPTH decline of 3.75 pg/ml (sensitivity of 74%; specificity of 87%) were highly predictive of symptomatic hypocalcemia. Conclusion: Postoperative ΔPTH and ΔPTH% have the potential to be predictors of symptomatic hypocalcemia following thyroidectomy and could facilitate a safe early discharge.

Critical Governance Issue of Parathyroid Hormone Assays and its Selection in the Management of Chronic Kidney Disease Mineral and Bone Disorders.

Measurement of circulating parathyroid hormone (PTH) levels is essential for optimal management of mineral and bone disorders (MBD) in chronic kidney disease (CKD) patients. There are two major types of PTH assays currently in use: intact parathyroid hormone (i-PTH) and whole PTH (w-PTH) assays. The i-PTH assay is the current standard, and considerable information regarding the management of CKD-MBD has been obtained with this method. However, several limitations have been found with the i-PTH assay. One limitation is that i-PTH assay also measures fragments other than full-length PTH (1-84). Another limitation is the existence of multiple readout methods of the i-PTH assay. The w-PTH assay is theoretically ideal because it exclusively detects full-length PTH (1-84). However, clinical data proving the advantages of w-PTH measurement are not sufficient. For uremic patients, Kidney Disease Improving Global Outcomes suggest that PTH levels should be maintained within approximately two to nine times the upper normal limit of the i-PTH assays. The most critical issue in the evaluation of PTH levels is the lack of definitive PTH assay method. Evidence-based recommendations on clinical management goals of PTH are warranted.

Levels of serum sclerostin, FGF-23, and intact parathyroid hormone in postmenopausal women treated with calcitriol.

OBJECTIVE: This study aimed to determine the effect of calcitriol on serum concentrations of fibroblast growth factor-23 (FGF-23), sclerostin, intact parathyroid hormone (PTH), and handgrip strength in postmenopausal women with low bone mass. METHODS: A randomized, double-blind controlled trial was carried out among 141 postmenopausal women with low bone mass. Participants were randomized into two groups: 75 participants received calcitriol 0.5 µg/day and 66 participants received a placebo for 12 weeks. RESULTS: After 12-week calcitriol treatment, significant decreases in serum intact PTH (P=0.035) and sclerostin (P=0.039), as well as significant increases in serum creatinine (P=0.027), uric acid (P=0.032), 24-hour urinary calcium (P=0.0026), and left handgrip strength (P=0.03), were observed, compared to placebo group. Level of serum sclerostin was weakly but significantly positively correlated with serum PTH (r=0.277; P=0.01) and negatively correlated with 24-hour urinary calcium (r=-0.221; P=0.04) and left handgrip strength (r=-0.338; P=0.03) after calcitriol treatment. Multiple regression analysis demonstrated that decrease in serum sclerostin was associated with decrease in PTH serum level after calcitriol treatment (OR, 7.90; 95% CI, 2.28-27.42; P=0.002). However, no significant change in FGF-23 level was observed after calcitriol treatment. CONCLUSION: Calcitriol treatment yields a considerable decrease in serum sclerostin and significant increase of handgrip strength, and the change in serum sclerostin is regulated by serum PTH and by muscle strength.

Comparison of Intact PTH and Bio-Intact PTH Assays Among Non-Dialysis Dependent Chronic Kidney Disease Patients.

BACKGROUND: The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. METHODS: Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. RESULTS: Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, P<0.0001). This finding was consistent among CKD stages 3 to 5. PTH concentrations by both assays (intact and bio-intact PTH) positively correlated with urea (r=0.523, r=0.504; P=0.002, respectively), phosphorus (r=0.532, r=0.521; P<0.0001, respectively) and negatively correlated with blood calcium (r=-0.435, r=-0.476; P<0.0001, respectively), 25(OH) vitamin D, (r=-0.319, r=-0.353; respectively, P<0.0001) and the estimated glomerular filtration rate (r=-0.717, r=-0.688; P<0.0001, respectively). CONCLUSIONS: Among patients with CKD stages 3 to 5 not on dialysis, the bio-intact PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders with bone histomorphometric findings are needed to determine whether bio-intact PTH assay results are better surrogate markers in these early stages of CKD.

Differences between 2nd and 3rd generation seric parathormone determination methods on mortality in haemodialysis patients. / Diferencias entre los métodos de determinación de 2.ª y 3.ª generación de la parathormona sérica sobre la mortalidad en el paciente en hemodiálisis.

Parathormone plays a key role in controlling mineral metabolism. PTH is considered a uremic toxin causing cardiovascular damage and cardiovascular mortality in dialysis patients. There are two different assays to measure PTH called 2nd generation or intact PTH (iPTH) and 3rd generation or bioPTH (PTHbio). OBJECTIVE: To evaluate the differences in mortality of dialysis patients between both assays to measure PTH, as well as the possible prognostic role of the PTHbio/iPTH ratio. METHODS: 145 haemodialysis patients were included with 2-year monitoring including baseline laboratory test and annually thereafter. RESULTS: 21 patients died in the first year and 28 in the second. No correlation was found between PTH, PTHbio and PTHbio/iPTH ratio with mortality. Both PTH have a perfect correlation between them and correlate similarly with other molecules of the mineral metabolism. The extreme baseline values of PTH are those of higher mortality. In survival by iPTH intervals (according to guidelines and COSMOS study), a J curve is observed. When iPTH increases, the ratio decreases, possibly when increasing fragments no. 1-84. There is no greater prognostic approximation on mortality with PTHbio than PTHi. There was also no difference in mortality when progression ratio PTHbio/PTHi was analysed. CONCLUSIONS: We didn't find any advantages to using bioPTH vs. PTHi as a marker of mortality. BioPTH limits of normality must be reevaluated because its relationship with iPTH is not consistent. Not knowing these limits affects its prognostic value.

Early intact PTH (iPTH) is an early predictor of postoperative hypocalcemia for a safer and earlier hospital discharge: an analysis on 260 total thyroidectomies.

BACKGROUND: Hypocalcemia is the most frequent complication after thyroidectomy. Serum calcium levels are reliable only 48-72 hours postoperatively. Early intact PTH (iPTH) has been proposed as early predictor of postoperative hypocalcemia. Our aim is to assess the ability of iPTH in predicting postoperative hypocalcemia. METHODS: Two hundred and sixty patients underwent thyroidectomy with postoperative iPTH evaluation. The iPTH samplings were early performed after thyroidectomy. The calcium levels were dosed postoperatively. Age, sex, clinical diagnosis, obesity, comorbidities, previous neck surgery, preoperative therapy, type of surgery, dissectors used, lymphadenectomy, post-operative complications, reoperation and histological diagnosis were considered. The primary end-point was the postoperative hospital stay. The secondary end-points were serum calcium and iPTH. Three iPTH cut-offs were tested to assess which was the best value (10.0, 15.0, and 20.0 pg/mL). RESULTS: The iPTH cut-off value of 10.0 pg/mL was the most accurate and specific for hypocalcemia. Comparing the iPTH value with the different values of calcium respectively 24 and 48 hours after surgery, a statistically stronger association with the serum calcium levels 48 hours postoperatively has been shown. iPTH ≥10 pg/mL 3-6 hours after surgery was strongly correlated to early discharge. CONCLUSIONS: The correlation of iPTH with hypocalcemia is significant since a few hours after surgery and the value of iPTH ≥10 pg/mL is able to select those patients for a safe and early discharge. The use of the iPTH might avoid unnecessary extensions of hospitalization.

Intact parathyroid hormone levels are associated with increased carotid intima media thickness in HIV infected patients.

AIM: Preliminary evidence suggests that intact parathyroid hormone (iPTH) and bone mineral abnormalities may contribute to the development of vascular disease and are associated with reduced survival in the general population. Whether iPTH is associated with subclinical atherosclerosis in HIV-infected individuals has not been elucidated. METHODS: Cross-sectional study of 470 consecutive HIV-infected patients in whom we measured carotid intima-media thickness (cIMT), and collected demographical, clinical and laboratory data. High-cIMT was defined as a mean IMT above the 75th percentile for the study cohort. Parametric, non-parametric tests and logistic regression analyses were used to compare patients' characteristics between low- and high-cIMT and to test the association between high-cIMT and log-transformed iPTH. RESULTS: Of the 470 patients, 130 had high-cIMT. High-cIMT subjects were older and more likely to be male and have a history of cardiovascular disease. Glucose, lipid and iPTH levels were lower among low-cIMT subjects (p < 0.05). Unadjusted and multivariable adjusted analyses demonstrated an independent association between high-cIMT and iPTH (fully adjusted OR: 1.74; 95%CI: 1.08-2.79; p = 0.021). Bootstrap and sensitivity analyses confirmed these findings. CONCLUSIONS: Elevated iPTH was associated with subclinical atherosclerosis in HIV-infected subjects. Of note this association was statistically significant even for iPTH values within the range of normality. The existence of a causal relationship between iPTH and atherosclerosis needs to be fully explored in future investigations.

A Case of Vitamin D Deficiency without Elevation of Serum Alkaline Phosphatase in a Carrier of Hypophosphatasia.

Elevated serum alkaline phosphatase (ALP) is a screening marker for the diagnosis of vitamin D deficiency, which may fail to be diagnosed if serum ALP is not elevated. Here, we describe a case of vitamin D deficiency without elevation of serum ALP. A 1-year-old Japanese girl was referred to our hospital for the evaluation of genu varum. Her serum intact PTH level was elevated, while her serum ALP level was normal. Furthermore, her serum 25-hydroxyvitamin D level was reduced, and her urine phosphoethanolamine (PEA) level was mildly elevated. ALPL gene analysis revealed she was a heterozygous carrier of hypophosphatasia (c.1559delT). Serum intact PTH and urine PEA evaluations were helpful for diagnosing vitamin D deficiency and hypophosphatasia carrier status, respectively. Therefore, the possibility of vitamin D deficiency without elevation of serum ALP should be considered.

The relationship between intact PTH and biointact PTH (1-84) with bone and mineral metabolism in pre-dialysis chronic kidney disease (CKD).

OBJECTIVES: Abnormalities in PTH are implicated in the pathogenesis of bone abnormalities in chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD). PTH concentrations are important in clinical decision and management. This emphasises the importance of providing an assay which measures biologically active PTH. We compared concentrations of intact PTH with biointact PTH (1-84) in CKD and end stage renal disease (ESRD) and investigated the relationship between the 2 PTH assays with bone and mineral laboratory parameters and bone mineral density (BMD) in CKD. DESIGN AND METHODS: We assessed 140 patients (61 in ESRD and 79 with CKD stages 1-4) in this cross-sectional study. We measured biointact PTH (1-84) as well as routine biochemical parameters on all subjects. In the CKD cohort, bone turnover markers; bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase (TRACP)-5b and bone mineral density (BMD) were also determined. RESULTS: In ESRD, intact PTH concentration was significantly higher compared to biointact PTH (1-84) (422 [443] v/s 266 [251] pg/mL, (p<0.001) with an average bias of 60%. In CKD, intact PTH concentration was also higher compared to biointact PTH (1-84) (79[55] v/s 68[49] pg/mL p<0.001) with an average bias of 18%. Only the biointact PTH (1-84) assay showed any significant correlation with serum calcium concentrations (r=-0.26, p<0.05) and phosphate (r=0.25, p<0.05) in CKD. Following multilinear regression analysis and adjustment for all significant co-variables, only eGFR, BAP and 25 (OH)vitamin remained significantly associated with intact PTH and biointact PTH (1-84). The strength of association was stronger between BAP and biointact PTH (1-84) (biointact PTH (1-84): p=0.007, intact PTH: p=0.01). In adjusted analyses, only biointact PTH (1-84) was significantly associated with BMD at the fore-arm (FARM) (p=0.049). CONCLUSIONS: The study confirms the differences between intact PTH and biointact PTH (1-84) in ESRD. Whilst there may be similarities in the diagnostic ability of both intact and biointact PTH (1-84), our data suggest that biointact PTH (1-84) assay may better reflect bone metabolism and BMD in CKD. Further longitudinal studies are needed.