PTH Assay Research Articles

7588 Coexistent Toxic Nodular Goiter And Primary Hyperparathyroidism (PHPT), A Combo With Diagnostic And Management Implications

Abstract Disclosure: D. Dave: None. A. Bhan: None. S.D. Rao: None. About 17-84% of patients with PHPT have concomitant thyroid disorders, but the prevalence of coexistent hyperthyroidism in PHPT varies 9-14 %. A vast majority had Graves’ disease with only 3 cases of toxic multinodular goiter (MNG) and PHPT reported in the literature as of 2022 ([1]). We present a rare case of coexistent toxic MNG and PHPT. Case Description: A 68y woman presented with recent 23 kg unintended weight loss and palpitations, but no other symptoms. Denied having kidney stones or fractures. On examination she had fine tremors of hands, MNG without exophthalmos. An ultrasound showed multinodular MNG with cystic lesions. A diagnosis of toxic MNG was made. Laboratory results were: TSH (<0.01 uIU/mL), free T4 1,68 ng/dL (normal: 0.61-1.44 ng/ml), high serum Ca (11.0 - 11.4 mg/dl) over 4y, but PTH was unavailable prior to the visit when it was 107 pg/ml and 89 pg/ml after 3 months of antithyroid therapy. Despite clinical and biochemical euthyroidism after 3 months, serum Ca and PTH levels remained high (11.4 mg/dl and 89 pg/ml respectively). Because she had pulmonary embolism a few years ago, we deferred parathyroidectomy until complete remission of hyperthyroidism. Discussion: Hypercalcemia is the biochemical hallmark of PHPT but can occur in 2-10% of patients with hyperthyroidism alone but only 1% of those will have coexistent PHPT. When these two conditions coexist, hypercalcemia is moderate to severe, and an occasional patient may present with hypercalcemic crisis (2). Prior to the availability of PTH assays, it was a challenge to diagnose coexistent PHPT. Hypercalcemia in hyperthyroidism responds to propranolol but not in PHPT, although the response is variable (3). With the availability of sensitive PTH assays, this maneuver is not necessary. In most cases, current PTH assays distinguish hypercalcemia of hyperthyroidism with suppressed PTH from coexistent PHPT in whom PTH level is non-suppressed or elevated. Monitoring serum Ca and PTH levels during therapy of hyperthyroidism would be useful as normalization of serum Ca and PTH has occasionally been reported (4). In our patient, serum Ca and PTH levels remained high with 3-months of methimazole and atenolol. The impact of both conditions on bone and mineral metabolism are profound, with fractures and kidney stones. Since kidney stones are uncommon in hyperthyroidism, presence of kidney stone in a hyperthyroid hypercalcemic patient should alert the possibility of PHPT. Similarly, significant decrease in bone density in such patient also raises the possibility of PHPT. Prompt diagnosis and appropriate treatment of both conditions is necessary to avoid irreversible complications.

A-048 Reference Interval and Clinical Performance Studies for Vitros® Immunodiagnostic Products Intact PTH II Assay to Aid in Diagnosis of Calcium and Parathyroid Disorders and Intraoperative Testing

Abstract Background Intact parathyroid hormone (iPTH) measurements aid in the differential diagnosis of hypercalcemia, hypocalcemia, and parathyroid disorders. The National Academy of Clinical Biochemistry has established guidelines for intraoperative PTH testing to monitor surgical success during parathyroidectomies. Studies were conducted to define the reference interval and clinical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay, using samples from healthy individuals and patients with conditions commonly requiring iPTH testing, including intraoperative cases. Methods The reference interval study was conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c in serum samples from 134 healthy individuals. For the clinical performance study, serum samples from individuals with hypoparathyroidism, primary hyperparathyroidism, chronic renal failure (secondary or tertiary hyperparathyroidism), hypercalcemia, hypercalcemia of malignancies, and hypocalcemia were tested. Intraoperative samples used were collected from parathyroidectomy patients in series at each surgical timepoint along with the standard plasma samples used to determine surgical success. Results The reference samples were composed of 134 serum donors that met all inclusion/exclusion criteria for healthy donors and had a normal test result on calcium, TSH, alkaline phosphatase, creatinine, and phosphate assays. The reference interval for iPTH was determined to be 14.2-75.2 pg/mL. The results in various disease states demonstrated the clinical performance of the Vitros iPTH II assay. Of 32 intraoperative sample series included in the study, three samples demonstrated no intraoperative decrease in iPTH due to surgical failures. Consistent with the goal of the parathyroidectomy procedure, at least a 50% decrease in iPTH was observed between the presurgical and post-excision samples in all other sample series. The clinical concordance with the Roche PTH assay used intraoperatively in these procedures was 100%. Conclusions Defining the reference interval for a normal healthy population and results from the intended use population demonstrated that the Vitros iPTH II assay can be used as an aid in the diagnosis of calcium and parathyroid disorders and intraoperative testing.

Comparison of two parathyroid hormone (pth) assay methods in the monitoring of black african hemodialysis patients in the ivory coast (Maglumi® vs Vidas Biomerieux® Kits)

Parathyroid hormone (PTH) testing is recommended once or twice a year to prevent bone complications resulting from chronic kidney disease. However, its interpretation is subject to many factors, including the generation of the PTH test used. For this reason, it is recommended that each laboratory establish its own PTH Upper Limit of Normality (ULN). In order to guarantee optimal management of hemodialysis patients in the public sector in Côte d'Ivoire (West Africa), it proved important to compare the diagnosis of hyperparathyroidism made using two platforms used in the laboratory in charge of monitoring these patients: PTH VIDAS® (3rd Generation) and PTH MAGLUMI® (2nd Generation). This was a cross-sectional study of 65 haemodialysis patients in Abidjan. PTH determinations were performed simultaneously on VIDAS® and MAGLUMI® platforms. The results obtained were interpreted on the basis of PTH threshold values pre-established in the laboratory. 86.15% of patients had concordant diagnoses on both platforms, compared with 13.85% with discordant diagnoses. Statistical analysis of these results showed a non-statistically significant difference.: The limitation posed by differences in PTH concentration given by different platforms can be circumvented by using PTH ULN stablished for each platform for a given population. Conclusion: The diagnoses made by the two platforms are thus superimposable using their respective PTH ULN.

SAT206 A Case Of Parathyroid Carcinoma Presenting As A Parathyroid Adenoma

Abstract Disclosure: P. Subarajan: None. A. Boutsicaris: None. C.A. Poku: None. N. Lopez: None. Distinguishing between parathyroid adenoma (PA) and parathyroid cancer (PC) in patients with primary hyperparathyroidism (PHPT) can be difficult to determine before pathology results. Estimates vary between studies, but roughly 85% of cases of PHPT are PAs. We present a case of a PC that presented clinically as a PA. A 59 year old female presented to Endocrinology for hypercalcemia that was incidentally noted to be 13.8 and 12.8 on initial recheck. Endocrinology completed a secondary workup of the hypercalcemia which noted a PTH of 147 in the setting of a calcium (Ca) of 12.6. Lab review showed that her corrected Ca had been elevated over the preceding 2 years. She had a replete 25-OH vitamin D of 43 and a GFR of 29. A neck ultrasound revealed a 2.1 cm mass suspicious for a parathyroid mass. A sestamibi scan was consistent with increased focal uptake at the inferior pole of the right thyroid lobe. She had renal dysfunction, hypercalcemia and newly diagnosed osteoporosis which prompted referral to endocrine surgery. Intraoperatively, an enlarged right inferior parathyroid gland and a large mass encompassing the inferior thyroid pole extending into the anterior mediastinum with lymphadenopathy were noted. En Bloc resection was completed and final pathology was consistent with high grade parathyroid carcinoma infiltrating the adjacent thyroid gland. Genetic testing for HPT-JT was negative and ultrasound monitoring has remained negative. PC is rare and typically has a clinical presentation and course that sets it apart from PA. The PTH is typically 3-10 times above the upper limit of normal in PC and only 1-2 times above the upper limit of normal in PA. As a result of the variation in PTH, serum Ca is more elevated in PC than PA. PC patients typically present with a parathyrotoxicosis that is profound. A palpable neck mass can be present in 40-70% of individuals with PC. Our patient had an equivocal presentation that appeared more consistent with PA, which can be problematic when deciding on the optimal surgical approach. Amino-PTH is hypersecreted in PC and reacts with 3rd generation PTH assays, but not second generation assays. Clinically, using a third/second generation PTH assay ratio >1 can support a possible clinical suspicion of PC over PA. En Bloc resection is the surgical approach of choice for suspected PC. En Bloc resection may not always be done for a patient with a presentation and evaluation consistent with PA: data shows that only 12.5% of PC patients underwent En Bloc resection, as opposed to 78.6% who underwent parathyroidectomy alone. This puts patients at risk of requiring repeat surgical intervention and poses a higher risk for recurrence. It brings to question whether every PA should be addressed with an En Bloc resection to avoid this inherent risk. This case adds to the literature of PC presenting as PA and supports the argument for standard En Bloc resection in all cases. Presentation: Saturday, June 17, 2023

SAT567 Collision Tumor Of The Thyroid With Papillary Thyroid Carcinoma And Metastatic Renal Clear Cell Carcinoma With Concomitant Parathyroid Adenoma

Abstract Disclosure: C.M. Mirano: None. R.C. Mirasol: None. INTRODUCTION Collision tumors of the thyroid are rare diseases that have two or more histologically and morphologically distinct tumors that occur simultaneously within the thyroid. There are only a few reported cases of collision tumors involving a metastasis from a distant tumor and a papillary thyroid cancer. In addition, the coexistence of Primary Hyperparathyroidism (PHPT) with nonmedullary thyroid cancers is unusual with an incidence range between 2 to 24%. Here, we describe an unusual case of a patient with Papillary Thyroid Carcinoma and Metastatic Renal Clear Cell Carcinoma complicated with a Parathyroid Adenoma. CASE The patient is a 65 year-old female, known Renal Clear Cell Carcinoma Stage IV who underwent left nephrectomy, distal pancreatectomy splenectomy, and adjuvant chemotherapy. She then developed subclinical hyperthyroidism with bilateral thyroid nodules on ultrasound 13 years post nephrectomy. Thyroid Scintigraphy showed hypofunctioning nodules on both lobes. Biopsy of the thyroid nodules was done on showing a Metastatic Renal Cell Carcinoma. Laboratory tests also showed hypercalcemia and an elevated iPTH. SPECT-CT images showed uptake in the left thyroid suggestive of a parathyroid adenoma. She underwent four gland exploration with parathyroidectomy. Intraoperatively, pre-excision PTH assay extracted peripherally was 386.10 pg/mL. The right superior, right inferior, and left superior parathyroid gland were normal in size. The left inferior parathyroid gland was found to be enlarged measuring 2.5 x 2.0 cm, intrathyroidal in location and was encapsulated. The left inferior parathyroid was dissected and sent for histopathology. 10 minutes post excision PTH levels declined by 57%. After which, total thyroidectomy was done with note of a 2.5 x 2 cm firm mass at the right thyroid lobe slightly adherent to strap muscles. The left thyroid lobe had no palpable nodules, Histopathology of the thyroid isthmus showed one focus of follicular cells exhibiting nuclear changes consistent with papillary thyroid carcinoma. Microsections of the right thyroid lobe show a malignant neoplasm composed of atypical cells arranged in sheets that have enlarged, hyperchromatic to vesicular, pleomorphic, prominent nucleoli, irregular nuclear border, and clear cytoplasm consistent with metastatic clear cell carcinoma. Histopathology of the Left inferior parathyroid gland revealed findings consistent with Parathyroid Adenoma. She was discharged stable with normal calcium levels. CONCLUSION Collision tumors are rare and an adequate histologic assessment of these tumors are important for decisions regarding management. Differentials with patients with nodular goiter should always include metastatic disease in the background of an underlying carcinoma. It is equally important to be aware of concomitant PHPT and thyroid diseases in the management of patients with hypercalcemia. Presentation: Saturday, June 17, 2023

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 < 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 < 0.0001, respectively), phosphorus (r = 0.423, r = 0.427; P < 0.0001, respectively) and negatively correlated with blood calcium (r = −0.355, r = −0.421; P < 0.0001, respectively), protein (r = −0.289, r = −0.305; respectively, P < 0.0001) and the estimated glomerular filtration rate (r = −0.468, r = −0.485; P < 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.

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.

A 15-year experience: intraoperative parathyroid hormone assay for the management of primary hyperparathyroidism in a UK endocrine surgical unit.

This study aims to evaluate the outcomes of first-time parathyroidectomy for primary hyperparathyroidism using intraoperative PTH (IOPTH) assay in the light of the UK National Institute for Health and Care Excellence (NICE) guidelines for the management of primary hyperparathyroidism. This is a retrospective cohort analysis of a prospectively maintained database of endocrine surgery in a tertiary centre. Preoperative radiological localisation (concordance and accuracy), intraoperative PTH parameters and adjusted serum calcium at minimum 6-month follow-up were analysed. The accuracy of IOPTH to predict post-operative normocalcaemia and the number needed to treat (NNT) within the cohort when IOPTH was utilised were determined. Differences between groups were evaluated with Chi-squared and Fisher's exact test. Between January 2004 and September 2018, 849 patients (75.4% women), median age 64 years (IQR 54-72), were analysed. The median preoperative adjusted serum calcium was 2.80mmol/l (IQR 2.78-2.90), and the median preoperative PTH was 14.20pmol/l (IQR 10.70-20.25). The overall first-time cure (normocalcaemia) rate was 96.4%. The sensitivity, specificity, positive predictive value and negative predictive values of IOPTH were 96.8%, 83.2%, 97.6% and 78.8%, respectively, with an accuracy of 95.1%. For patients with concordant scans (48.3%), a targeted approach without IOPTH would have achieved a cure rate of 94.1% compared with 98.0% using IOPTH (p<0.01) CONCLUSION: The use of IOPTH assay significantly improved the rate of normocalcaemia at 6 months. The low NNT to benefit from IOPTH, particularly those patients with a single positive scan, and the inevitable reduction in the potential costs incurred from failure and reoperation justify its utilisation.

Evolution of the Diagnosis and Treatment of Primary Hyperparathyroidism.

This study aims to present the evolution of our center's approach to treating primary hyperparathyroidism (PHPT) from diagnosis to intraoperative interventions. We have also evaluated the intraoperative localization benefits of indocyanine green fluorescence angiography. This retrospective single-center study involved 296 patients who underwent parathyroidectomy for PHPT between January 2010 and December 2022. The preoperative diagnostic procedure included neck ultrasonography in all patients, [99mTc]Tc-MIBI scintigraphy in 278 patients, and, in 20 doubtful cases, [18F] fluorocholine positron emission tomography (PET) computed tomography (CT) was performed. Intraoperative PTH was measured in all cases. Indocyanine green has been administered intravenously since 2020 to guide surgical navigation using a fluorescence imaging system. The development of high precision diagnostic tools that can localize an abnormal parathyroid gland in combination with intra-operative PTH assay (ioPTH) enables the surgical treatment of PHPT patients with focused approaches and excellent results that are stackable with bilateral neck exploration (98% of surgical success). Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly and with minimal risk, especially when pre-operative localization has failed. When everything else fails, it is only an experienced surgeon who can resolve the situation.

Determination of parathyroid hormone: from radioimmunoassay to LCMS/MS.

Parathyroid hormone (PTH) determination is of paramount importance for the exploration of diseases related with calcium metabolism and for the follow-up of patients suffering from bone and mineral disorders associated with chronic kidney diseases (CKD-MBD). Unfortunately, the biologically active form of PTH, i.e. 1-84PTH, circulates in the blood stream with many fragments and post-translationally modified forms, which decreases the specificity of immunoassays. The assays used to measure PTH, either from 2nd or 3rd generation, are not standardised, which may lead to interpretation errors and clinical consequences. Reference ranges for PTH have neither been always correctly established and the stability of the peptide is also a matter of concern. Fortunately, these last years, newer techniques using mass spectrometry (either high resolution or triple quadripole) coupled with liquid chromatography have been developed, which will help to standardise the different assays. Indeed, PTH assays standardisation is one of the task of the IFCC Committee for Bone Metabolism. Such standardisation will allow a better consistency in the interpretation of the results and will promote studies aiming at the establishment of correct reference ranges.

Effect of underfilling of tubes with EDTA on PTH assay measured by Cobas analyzer

Effect of underfilling of tubes with EDTA on PTH assay measured by Cobas analyzer

New, simple, fast, whole blood Intraoperative PTH assay – Laboratory and Clinical validation

Abstract Introduction IOPTH monitoring is a reliable method of predicting cure during the surgery for Primary Hyperparathyroidism (PHPT) but current methods are slow and require presence of laboratory staff. NBCL Connect is the first Analyser which can be used by theatre staff and measures whole blood PTH in 5 minutes. Aim Laboratory and Clinical validation of new IOPTH assay in patients undergoing surgery for PHPT. Methods Intra and inter assay variability using BioRad Liquichek Specialty Immunoassay, internal quality controls and serum and whole blood PTH concentrations in patients cured by parathyroidectomy for PHPT measured on NBCL and “gold standard” Future Diagnostics (FD) and Roche platforms. Pearson coefficient was used for linear correlation between measurements. Results Preliminary precision data confirms good analytical performance of NBCL Analyser which is similar to that of FD platform. Further precision, accuracy, linearity and sensitivity studies are ongoing. Plasma PTH concentration from 4 patients (5 samples each, total 20) measured on NBCL and FD platforms showed good correlation (R 0.90, slope 0.644, IC – 0.68) Whole blood PTH concentration in 2 patients (5 samples each, total 10) measured on NBCL, FD and Roche platforms showed good correlation. 50% reduction in circulating PTH, main (Miami) criteria confirming biochemical cure, were similar for all 3 platforms Conclusions NBCL Connect Analyser assay showed good laboratory and clinical performance able to predict biochemical cure in patients undergoing surgery for PHPT. Our preliminary data suggests that this straightforward to operate and fast system is a promising technology which can be used widely during parathyroid surgery.

A RARE CASE OF MAXILLARY BROWN TUMOUR AS PRIMARY PRESENTATION OF THE PARATHYROID CARCINOMA.

Background: Brown tumours are expansile osteolytic lesions of bone, occurring in Hyperparathyroidism. Brown tumours occur most commonly in ribs, clavicle, long bones and pelvis and are uncommon in other facial bones except mandible. Other facial bones are rarely affected. Brown tumors are due to the direct effect of the parathyroid hormone. Brown tumors occur more with primary hyperparathyroidism than secondary. However, they are reported more in secondary hyperparathyroidism. In primary hyperparathyroidism, a parathyroid adenoma is a cause in 81% while other causes include hyperplasia in 15% and parathyroid carcinoma only in 4%. We present a case report of maxillary Brown tumor due to parathyroid carcinoma in an elderly male patient. Case Report: A 67-year-old male presented with right maxillary swelling increasing in size for the last few months associated with ipsilateral nasal block and right eye epiphora. The contrast CT scan of paranasal sinuses and neck revealed a large expansile right maxillary tumor aggressively eroding maxillary wall with extension into the orbital oor, ethmoid, sphenoid sinuses, nasal cavity, and oral cavity with the erosion of hard palate and soft tissue extension to subcutaneous Plane. A three cm sized soft tissue density lesion was also noted posterior to the right thyroid lobe in CT sections of the neck. Blood prole was normal except extremely high serum parathormone and calcium as well as mildly elevated serum creatinine (S. PTH 3437 pg./ml. S. Ca. 19 mg%. S. Creatinine 1.77mg%.) Ultrasonography of the abdomen also revealed calcication in the renal medulla. Right lower parathyroidectomy was done with the frozen section as well as the Intraoperative Rapid PTH assay. The PTH level was reduced by 90 percent of the original value. The nal histopathology was suggestive of parathyroid carcinoma. Summary: The patient was under regular surveillance, as the maxillary tumor was under remittance after the resection of parathyroid carcinoma. Parathyroid carcinoma is a very rare tumor and involvement of maxillary bone due to primary hyperparathyroidism due to parathyroid carcinoma is also uncommon.

O62: INTRA-OPERATIVE ADJUNCTS IN MINIMALLY INVASIVE RADIO-GUIDED PARATHYROIDECTOMY AT A SPECIALIST ENDOCRINE SURGERY CENTRE

Abstract Introduction Primary Hyperparathyroidism (PH) is common cause of hypercalcaemia (0.3% of the population). Minimally invasive radio-guided parathyroidectomy (MIRP) has been made possible due to advancements in pre-operative imaging i.e. sestamibi scans allowing localisation of areas of parathyroid hyperactivity. Method Due to the disagreement in the literature regarding which intra operative adjunct is best used in MIRP surgery to decrease recurrence, the rationale for this study is to examine and compare the performance of these adjuncts in consecutive patients i.e. 1. Intra operative PTH assay (IOPTHA) 2. Tc-99m radio-guidance using a gamma probe and the 20% rule 3. Frozen section analysis. Result 45 MIRP procedures were carried out between 01/07/2018 and 30/10/2019. 77.8% were females; mean age was 62 years (range 30 - 79). Final pathology showed that in 43 of the cases parathyroid tissue was correctly removed; thyroid tissue was identified for the other 2 cases. 20% rule was positive in 43 out of the 45 cases and negative in 2 (sensitivity 100%, specificity 100%). A drop in IOPTHA greater than 50% was found in 41 out of the 45 cases but not in 4 (sensitivity 93.9%, specificity 100%). Frozen section was 100% concordant with final pathology (45/45). AUC analysis showed no significant difference in the performance of these tests (p = 0.15) but was around 1 for 20% rule and Frozen section. Conclusion When radio-guidance and frozen sections are added to IOPTHA, the success rate of parathyroidectomy is markedly improved. Using them together will greatly reduce recurrent hyperparathyroidism. Take-home message When radio-guidance and frozen sections are added to Intra-operative PTH assays in Minimally Invasive Radio-Guided Parathyroidectomy, the success rate of parathyroidectomy is markedly improved. Using them together as in our study will greatly reduce the incidence of recurrent hyperparathyroidism and thus recurrent surgery.

Parathyroid hormone measurement in chronic kidney disease: Impact of inter-method variability on mineral bone disease assessment

BackgroundParathyroid hormone (PTH) is measured routinely as part of Chronic Kidney Disease Bone and Mineral Disorders (CKD-MBD) assessment. Multiple PTH assays exist with known differences resulting in CKD-MBD guidelines recommending treatment based on assay-specific thresholds. The study objectives are to assess between manufacturer and within manufacturer variability of PTH assays and the impact of assay variability on the assessment of CKD-BMD using both vendor defined and empirically derived thresholds. MethodsData were collected from Ontario, Canada’s Proficiency Testing Program (24 challenge vials, 115–133 laboratories all using secondary generation PTH assays. Mean PTH and precision by the coefficient of analytical variation (CVa) were calculated. For each vial, whether the manufacturer’s mean value exceeded the vendor-defined and empirically-derived upper limit of normal (ULN) was recorded and the concordance between assays was determined. ResultsAcross all laboratories, the mean PTH range was 12.0 ± 3.9 pmol/L and the mean CVa was 30%. The percent of vials with a mean PTH exceeding manufacturer’s specific ULN varied substantially between manufacturers. Only 58% of vials had complete concordance as to whether mean PTH was above assay-specific ULNs. This increased to 83% using the empirically derived ULN. ConclusionsCKD-BMD assessment and management will depend on the PTH assay. The between-assay variability is reduced but not eliminated when empirically derived reference intervals are used. Improvements in PTH measurement are required in order to ensure consistent patient care.

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.

P1414THE PREDICTORS OF PARATHYROID HORMONE VARIABILITY IN HEMODIALYSIS PATIENTS

Abstract Background and Aims KDIGO Clinical Practice Guidelines suggest in hemodialysis (HD) patients using a dialysate calcium concentration between 1,25 and 1,5 mmol/L and maintaining serum intact parathyroid hormone (sPTH) levels in the range of approximately 2 to 9 times the upper normal limit for the assay. The aim of the study was to evaluate the predictors of PTH variability in HD patients over a 12 months period. Method The multicenter restrospective study encompassed 398 patients (256M and 142F) with the average age 59,64±13,29 years and the average HD vintage 78,63±64,26 months. Over a 12 months (M0-M12) period: serum calcium (sCa), serum phosphorus (sPi), serum alkaline phosphatase (sAPh), oral calcium-carbonate daily dose, oral calcitriol weekly dose, and dialysate Ca concentration (dCa) were monitored monthly, and sPTH at 6 months. According to PTH assay reference level (18,4-80,1 pg/ml) 3 groups of patients were categorized: patients with low sPTH&amp;lt;160, with target range sPTH =160-721, and with high sPTH&amp;gt;721. For statistical analysis chi-square test, analysis of variance with repeated measures and logistic regression analysis were performed by softver SPSS. Results Over a 12 months period the number of patients with low sPTH significantly decreased, but the number of patients with target range sPTH and high sPTH increased (Chi square=269,45; p&amp;lt;0.001). On the basis of overall pattern of sPTH fluctuation over a 12 months period six subgroups of patients were observed: consistently low in 20,6% of patients, consistently within the target range in 22,1%, consistently high in 14,07%, low-amplitude fluctuation with low and target range sPTH levels (LAL) in 31,4%, low-amplitude fluctuation with target range and high sPTH levels (LAH) in 10,55%, and high-amplitude fluctuation (HA) subgroup with low, target range and high sPTH levels in 1,25%. In 35 patients constantly hemodialyzed over a 12 months period with dCa=1,25 mmol/L due to high sCa the significant increase of sPTH (M0=797±657 vs M12=1030±740 pg/ml; p=0.001) and no significant changes of sCa (M0=2,44± vs M12=2,34± mmol/L; n.s.), sPi (M0=1,81±0,49 vs M12=1,68±0,49 mmol/L; n.s.), Ca-carbonate daily dose (M0=1,88±1,54 vs M12=2,22±1,53 g/d; n.s.) and calcitriol weekly dose (M0=0,84±1,38 vs M12=1,1±1,41 ucg/w; n.s.) were observed. In 24 patients constantly hemodialyzed with dCa=1,75 mmol/L due to low sCa the significant decrease of sPTH (M0=518±582 vs M12=391±530 pg/ml; p=0.037) and no significant changes of sCa (M0=2,17±0,19 vs M12=2,18±0,17 mmol/L; n.s.), sPi (M0=1,3±0,34 vs M12=1,36±0,52 mmol/L; n.s.), Ca-carbonate daily dose (M0=2,53±1,58 vs M12=2,1±1,91 g/d; n.s.) and calcitriol weekly dose (M0=1,33±1,23 vs M12=1,42±1,69 ucg/w; n.s.) were observed. In 195 patients constantly hemodialyzed with dCa=1,5 mmol/L no significant changes of sPTH (M0=388±421 vs M12=434±459 pg/ml; n.s.), sCa (M0=2,29±0,18 vs M12=2,27±0,15 mmol/L; n.s.), sPi (M0=1,48±0,41 vs M12=1,52±0,41 mmol/L; n.s.), Ca-carbonate daily dose (M0=2,42±1,4 vs M12=2,57±1,2 g/d; n.s.) and calcitriol weekly dose (M0=0,47±0,72 vs M12=0,38±0,68 ucg/w; n.s.) were observed. By model of logistic regression analysis dCa=1,75 (OR=8,33), increased sCa (OR=7,7), and presence of diabetes mellitus (OR=2,44) were the most significant predictors of low sPTH&amp;lt;160 (Chi square=116,27; p&amp;lt;0.001), but the increased sCa (OR=6,88), dCa=1,25 (OR=5,08), and the increased sPi (OR=2,72) were the most significant predictors of high sPTH&amp;gt;721 (Chi square=72,475; p&amp;lt;0.001). Conclusion The prolonged use of dCa=1,25 in patients with high sCa led to significant sPTH increase likely due to net negative calcium balance, but prolonged use of dCa=1,75 in patients with low sCa led to significant sPTH decrease likely due to net positive calcium balance.

Comparison between Second- and Third-Generation PTH Assays during Minimally Invasive Parathyroidectomy (MIP).

Methods 112 patients (of which 72.3% females) underwent MIP by the same surgeon. Age, sex, body mass index (BMI), pre- and postoperative serum calcium, creatinine, 25(OH)D levels, PTH at baseline (PTH T0), and PTH at 10 minutes after adenoma resection (PTH T10) were recorded. Both PTH 2G and PTH 3G assays were assessed using the Diasorin assays. Results The mean age was 56.1 ± 14.7 years. Mean value of BMI, preoperative calcium, 25(OH)D, and CKD-EPI-eGFR were, respectively, 26.8 ± 4.8 kg/m2, 110.9 ± 7.9 mg/L, 19.3 ± 9.2 ng/mL, and 88.6 ± 25.6 mL/min/1.73 m2. PTH 2G and PTH 3G assays were well correlated at PTH T0 and PTH T10 (respectively, correlation coefficient 0.74 and 0.72 for intraclass correlation type 3). The median PTH fall was, respectively, of 79.9% and 82.5% for PTH 2G and PTH 3G. Multivariate analysis using the combined PTH 2G and PTH 3G as a dependent variable with 2 repeated measurements (at PTH 0 and PTH 10) showed a significant effect of preoperative calcium on IOPTH fall (p=0.001, effect size 0.13), while no significant effects were observed for sex, age, BMI, and 25(OH)D. Conclusion PTH 2G and PTH 3G assays resulted in a similar drop in IOPTH values. Elevated preoperative calcium levels are the only independent predictor of IOPTH decline. Further studies are needed to determine other factors that can influence PTH kinetics.

Parathormone Levels in a Middle-Eastern Healthy Population Using 2nd and 3rd Generation PTH Assays.

Background The purpose of the current study is to determine PTH reference values in vitamin-D-replete Lebanese adults using 2nd and 3rd generation PTH assays and to look at the factors that affect PTH variations. Methods Fasting PTH was measured using 2nd and 3rd generation Diasorin PTH assays in 339 vitamin-D-replete healthy subjects aged 18 to 63 years (230 men and 109 women) who have normal calcium levels and an eGFR ≥60 ml/mn. 25-OH vitamin D (25(OH)D) was measured using the Diasorin assay. Results For the 2nd PTH generation, median (IQR) levels were 48.9 (34.9–66.0) pg/ml, and its 2.5th–97.5th percentile values were 19.7–110.5 pg/ml for 25(OH)D values between 20 and 30 ng/ml, and 19.7–110.7 pg/ml for 25(OH)D values ≥30 ng/ml. For the 3rd PTH generation, the median (IQR) values were 23.9 (17.7–30.5) pg/ml, and its 2.5th–97.5th percentile values were, respectively, 9.2 and 50.2 pg/ml for 25(OH)D values between 20 and 30 ng/ml, and 8.4 and 45.4 pg/ml for 25(OH)D values ≥30 ng/ml. The median (IQR) serum 25(OH)D levels were 27.5 (23.8–32.7) ng/ml. 2nd and 3rd generation PTH values are strongly correlated (r = 0.96, p < 0.0001), but poorly concordant (Lin's concordance coefficient 0.365, 95% CI: 0.328–0.401) with observations beyond the 95% Bland–Altman limits of agreement. 2nd and 3rd generation PTH levels did not differ according to gender and were significantly correlated with age but not with 25(OH)D and serum calcium levels. Conclusion Lebanese adult healthy subjects have higher 2nd and 3rd generation PTH levels compared with the reference range provided by the manufacturer. The reference range was not influenced by changing the 25(OH)D cutoff. The clinical significance of the higher PTH levels in our population should be investigated.

"Intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism"

Introduction: Currently, parathyroidectomy represents the elective surgical treatment and the only one curative that relieves the patient of metabolic complications and improves the quality of life of the patient. Intraoperative confirmation of PTH is required to reflect the fact that the correct parathyroid gland has been extracted. Material and method: The study is retrospective. The period on which the data was gathered over a period of 2 years. The values of the PTH assay were obtained from blood drawn from the ipsilateral cephalic vein of the hyperproductive parathyroid gland: 1. at the moment of anesthesia induction; 2. at identification; 3. at 10 minutes after the extraction; 4. at 20 minutes after extraction. Results: We identified a number of 25 patients operated for primary hyperparathyroidism. Preoperative values of PTH were 380pg/mL with a maximum value of 821 pg/mL. PTH values decreased by 55% at 5 min, 68% at 10 minutes and 74% at 15 minutes. A marked reduction in PTH values occurred after the first 5 minutes while the interval between 10-15minutes associated a variation of only 8-10% decrease. Conclusion: Intraoperative PTH assay is a useful technique to predict the success of the intervention. The technique is standard although some issues have been raised and are still under discussion.