Spurious intraoperative PTH results observed with 2nd, but not with 3rd generation PTH assays.

We report here an interference that has been observed with 2nd generation PTH assays (PTH2), but not with 3rd generation PTH ones (PTH3), during PTH monitoring occurring in a surgical intervention for the resection of a parathyroid adenoma. The patient was cured and calcium levels returned to normal the next day, but PTH did not decrease with PTH2 whereas it decreased by 50% with PTH3 assays during the intervention. The reason is probably a PTH fragment released by the parathyroid gland during surgery. This fragment possesses the C-terminal part of the peptide but lacks the first amino-acids and may thus be considered as a member of the non-(1-84) PTH fragments family. It has also a longer half-life than 1-84 PTH. To avoid reporting spurious results to the surgeons, we thus recommend using PTH3 assays for monitoring of intra-operative PTH.

Parathormone stability in hemodialyzed patients and healthy subjects: comparison on non-centrifuged EDTA and serum samples with second- and third-generation assays.

BACKGROUND: Parathyroid hormone (PTH) stability is important. Many studies have shown divergent results between EDTA and serum, which are mainly linked to differences in protocols or cut-offs used to determine whether or not PTH remained stable. No studies have yet compared PTH stability as measured by second- and third-generation assays on the same samples in hemodialyzed patients and healthy subjects. METHODS: Five pairs of samples (EDTA and gel tubes) were obtained in 10 hemodialyzed patients before a dialysis session and in 10 healthy subjects. One pair was centrifuged and run directly to define the "T0". Two pairs were kept at +4°C and two pairs were kept at +25°C. They were centrifuged after 4 and 18 h. Supernatant was kept at -80°C for 1 week. All samples were measured in a single batch, on Roche Cobas and DiaSorin XL second- and third-generation PTH assays. We used three different approaches to evaluate PTH stability: Wilcoxon test, an Acceptable Change Limit (ACL) according to ISO Guide 5725-6 and a Total Change Limit (TCL) derived from the sum of biological and technical variability according to WHO. RESULTS: PTH decreased in all samples. Stability of PTH was mainly dependent on the way it was evaluated. Percentages of decrease were systematically lower in EDTA vs. serum. Wilcoxon and ACL showed that PTH was no more stable after 4 h at +4°C in EDTA or serum gel tubes. None of the subjects presented a PTH decrease higher than the TCL with EDTA plasma. In serum gel tubes, PTH was unstable only when kept at 25°C for 18 h. CONCLUSIONS: PTH seems more stable in EDTA than in serum gel tubes but only when samples have to stay unprocessed for a long period (18 h) at room temperature (25°C), which can happen when samples are delivered from external care centers. For all the other conditions, using serum gel tubes is recommended since calcium measurement, which is necessary for a good PTH results interpretation, can be achieved on the same tube.

A Randomized, Double-Blind, Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency.

Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status.

The third/second generation PTH assay ratio as a marker for parathyroid carcinoma: evaluation using an automated platform.

BACKGROUND: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by second-generation PTH assays, the normal 3rd/2nd generation PTH ratio (<1) is inverted in PCa (ie, >1). OBJECTIVE: The objective of the investigation was to study the utility and advantages of automated 3rd/2nd generation PTH ratio measurements using the Liaison XL platform over existing manual techniques. SETTING: The study was conducted at a tertiary-referral academic center. DESIGN: This was a retrospective laboratory study. SUBJECTS: Eleven patients with advanced PCa (mean age 56.0 y). The controls were patients with primary-hyperparathyroidism (n = 144; mean age 53.8 y), renal transplantation (n = 41; mean age 50.6 y), hemodialysis (n = 80; mean age 65.2 y), and healthy elderly subjects (n = 40; mean age 72.6 y). RESULTS: The median (interquartile range) 3rd/2nd generation PTH ratio was 1.16 (1.10-1.38) in the PCa group, which was significantly higher than the control groups: hemodialysis: 0.74 (0.71-0.75); renal transplant: 0.77 (0.73-0.79); primary hyperparathyroidism: 0.76 (0.74-0.78); healthy elderly: 0.80 (0.74-0.83). An inverted 3rd/2nd-generation PTH ratio (>1) was seen in 9 of 11 PCa patients (81.8%) and in 7 of 305 controls (2.3%): 3 of 80 hemodialysis (3.8%), and 4 of 144 primary-hyperparathyroidism patients (2.8%). Of four PCa patients who had a normal PTH ratio with the manual method, two had an inverted 3rd/2nd-generation PTH ratio with the automated method. CONCLUSIONS: Study of the 3rd/2nd-generation PTH ratio in large patient populations should be feasible using a mainstream automated platform like the Liaison XL. The current study confirms the utility of the inverted 3rd/2nd-generation PTH ratio as a marker of PCa (sensitivity: 81.8%; specificity: 97.3%).