Levothyroxine-induced serum free thyroxine response following radioactive iodine administration in patients thyroidectomized for differentiated thyroid cancer: A randomized controlled trial.

PURPOSE: Patients undergoing thyroidectomy for differentiated thyroid cancer (DTC) may require 131-radioactive iodine (RAI) administration for remnant ablation or disease treatment. After ingestion, RAI resides within the gastrointestinal tract potentially leading to mucosal damage and abnormalities in the absorption of levothyroxine (LT4). The aim of this study was to evaluate whether serum FT4 peak, induced by a LT4 challenge, changes according to the LT4 formulation (solid or liquid) in both RAI and non-RAI-treated DTC patients. METHODS: This was a monocentric controlled clinical trial, with a parallel two-groups (1:1) randomization of sequence of LT4 formulation. Patients received 200 mcg LT4 orally administered at 08:00 h, in both solid and liquid formulation, at one-week interval, at baseline and after 1, 3, and 6 months from RAI administration. At each time-point, circulating FT4 was evaluated both before LT4 assumption as well as after 1 and 3 h. FT4 increments were evaluated as area under the curve response (AUC). Analogous protocol with the same time-intervals was followed for non-RAI patients. RESULTS: The trial included 29 consecutive DTC patients, nineteen of whom were submitted to RAI. In RAI subjects, we observed an overall significant reduction in serum FT4 increments with the most relevant decrease at the 1-month time-point, (FT4 AUC: 4.46 ± 0.72 (M ± SD) vs 4.07 ± 0.63 in baseline vs 1-month, P = 0.001) without any difference between the two LT4 formulations. No difference in serum FT4 AUC was found in non-RAI subjects. CONCLUSION: LT4-induced serum FT4 responses are reduced following RAI administration in thyroidectomized DTC patients.

Comparison of Procalcitonin Assays on KRYPTOR and LIAISON® XL Analyzers.

Our laboratory performs procalcitonin (PCT) assays on a Brahms KRYPTOR analyzer with the Brahms PCT sensitive Kryptor kit. In this study, we wanted to compare the assays obtained in this way with the ones performed on the LIAISON® XL. From January to May 2017, 171 samples were analyzed, of which 65 from female patients (age: 22-98 years) and 106 from male patients (age: 16-97 years). The PCT determination was performed using the LIAISON® XL and KRYPTOR analyzers, by chemiluminescence (Chemiluminescence immunoassay-CLIA) (LIAISON® BRAHMS PCT® II GEN) and immunofluorescence (Brahms PCT sensitive Kryptor) assay, respectively. For the LIAISON® BRAHMS PCT® II GEN, 52% of the results were placed between 0.0 and 0.5 ng/mL, 18% between 0.5 and 2.0 ng/mL, and 30% between 2.0 and 100 ng/mL; the mean was 4.09 ng/mL, the median 0.456 ng/mL, the maximum value 97.2 ng/mL, and the minimum value 0.02 ng/mL. For the Brahms PCT sensitive Kryptor, 55% of the results were positioned between 0.0 and 0.5 ng/mL, 21% between 0.5 and 2.0 ng/mL, and 24% between 2.0 and 100 ng/mL; the mean was 3.72 ng/mL, the median 0.39 ng/mL, the maximum value 103 ng/mL, and the minimum value 0.01 ng/mL. The mean of the results obtained with the two methods showed no significant differences (3.717 for Kryptor and 4.094 for LIAISON®). PCT assay with Brahms reagents, both on the Kryptor and LIAISON®XL platforms, offers excellent performance in terms of sensitivity and specificity.

Assessment of Access hsTnI 99th percentiles upper reference limits following IFCC recommendations.

BACKGROUND: The detection of an increase and/or decrease of cardiac troponin (cTnI) values, with at least one value above the 99th percentile of the upper reference limit (URL) have a central role in acute myocardial infarction (AMI) diagnosis. The employment of sex specific 99th percentile URLs and High-sensitivity (Hs) assays are recommended. We assessed sex specific 99th percentile URL for Access Hs-cTnI and AccuTnI3+ (Beckman Coulter) using European donor reference population following recent International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations. METHODS: 300 males and 300 females plasma samples were collected. Both chemiluminescent immunoenzymatic assays were performed on UniCel DxI 800 platform (Beckman Coulter). RESULTS: For Access hsTnI, the observed sex-specific 99th percentile URLs were 5.5 (90% CI: 4.4-7.6) for females and 13.9 ng/L (90% CI: 7.4-17.4) for males. For AccuTnI+3 we could not establish them because the assay couldn't report detectable values of troponin for most of the analyzed samples. CONCLUSION: The sex-specific 99th percentile URLs established for Access hsTnI assay were significantly lower than those declared by the manufacturer caused by the different choice of population selection, age groups and sample types: for those reasons, we maintain the 99th URLs provided by manufacturer.

Analytical Evaluation of Free Testosterone and Cortisol Immunoassays in Saliva as a Reliable Alternative to Serum in Sports Medicine.

BACKGROUND: This study was aimed to investigate whether measurement of free testosterone and cortisol in saliva is a reliable alternative to their assessment in serum for monitoring physical fitness in professional athletes. METHODS: We studied 25 members of the soccer team Parma F.C., playing in Italian major football league. Blood and saliva samples were collected at fasting, before a regular training session. Cortisol, total and free testosterone, as well as the ratio between free testosterone and cortisol, were assessed in paired serum and saliva samples, and their results were compared. RESULTS: An excellent correlation was found between serum and saliva cortisol (r = 0.751; P < 0.001). A significant correlation was also observed between free testosterone in serum and saliva (r = 0.590; P = 0.002), whereas no significant correlation was found between total testosterone in serum and saliva (r = 0.181; P = 0.387). A significant correlation was found for the free testosterone to cortisol ratio in serum and saliva (r = 0.43; P = 0.031). All athletes (25/25; 100%) declared that they would feel more comfortable to have saliva rather than blood serially collected. CONCLUSIONS: The results of this study suggest that measurement of free testosterone and cortisol in saliva may be seen as a reliable alternative to their assessment in serum.

Circulating concentrations of free thyroxine after an oral intake of liquid LT4 taken either during fasting conditions or at breakfast.

BACKGROUND AND AIM OF THE WORK: Liquid levothyroxine (LT4) given at breakfast normalizes TSH in hypothyroid patients. However, a few studies are available on circulating free thyroxine (FT4) concentrations after liquid vs solid LT4 preparations. METHODS: During an "ad interim" analysis on serum FT4 after 200 mcg liquid LT4 consumption while fasting in thyroidectomized thyroid cancer patients, we found that seven subjects fortuitously took liquid LT4 at breakfast. As established in the original protocol, serum FT4 was measured both at baseline as well as at 3 and 4 hours after solid or liquid LT4 consumption. We compared serum profile of FT4 in these subjects with those obtained in other subjects participating in the same study who took liquid LT4 (n. 7 subjects) or solid LT4 (n. 7 subjects) while fasting. The percentage increase of circulating FT4 was calculated at the above reported peak-times over the baseline values. RESULTS: Circulating FT4 increased of about 40% in each group of subjects at both the 3rd and the 4th hour with no difference between these two time points in either group. The maximum FT4 % increase, irrespective of the time point, was 44.62 ± 3.05 (Mean ± SE), 44.84 ± 5.43, and 43.83 ± 1.30 after fasting solid, fasting liquid, and breakfast liquid LT4 consumption, respectively, with no differences among the three groups. CONCLUSIONS: Circulating FT4 obtained after 3 and 4 hours from the ingestion of 200 mcg liquid LT4 is not influenced by meal and is comparable with that observed after solid LT4 preparations ingested while fasting.

Analytical assessment of the novel Maglumi squamous cell carcinoma antigen (SCCA) immunoluminometric assay.

BACKGROUND: The demand for routine measurement of squamous cell carcinoma antigen (SCCA) is rapidly increasing in clinical laboratories, due to the central role that this biomarker plays in staging and monitoring patients with various forms of squamous cell carcinomas (SCCs). METHODS: The present analytical evaluation of Maglumi SCCA was aimed to assess the imprecision, linearity and comparability against a widely used technique. RESULTS: The intra- and inter-assay imprecision was comprised between 2.6-4.2% and between 5.0-7.3%, respectively. The linearity of the test was excellent in the range of SCC values comprised between 1.0 and 18.0 ng/mL (r=0.998; P<0.001). A highly significant correlation was observed between Maglumi SCCA and BRAHMS Kryptor SCC in the range of values comprised between 0.44 and 15.18 ng/mL (r=0.960; P<0.001). The mean bias was 0.79 ng/mL (95% CI, 0.61-0.97) and the diagnostic agreement at the respective diagnostic cut-offs was 95%. CONCLUSIONS: The results of this study confirm that Maglumi SCCA may be regarded as a suitable alternative to Kryptor SCC for routine and fully-automated assessment of SCCA in clinical laboratories.

Analytical evaluation of Diazyme procalcitonin (PCT) latex-enhanced immunoturbidimetric assay on Beckman Coulter AU5800.

BACKGROUND: This study was aimed to evaluate the analytical performance of the novel Diazyme procalcitonin (PCT) immunoturbidimetric assay on Beckman Coulter AU5800. METHODS: Diazyme PCT is a latex-enhanced immunoturbidimetric assay, developed for use on laboratory instrumentations with capability of reading absorbance at 600 nm. This analytical evaluation included the assessment of limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, carryover, and method comparison between Diazyme PCT and Kryptor PCT on 129 routine serum inpatient samples. RESULTS: The LOB, LOD, and functional sensitivity of Diazyme PCT were 0.16, 0.26, and 0.28 ng/mL, respectively. The intra- and inter-assay imprecision of Diazyme PCT was between 2.9% and 7.8%. The linearity was excellent in the range of PCT values between 0.16 and 56 ng/mL, and the carryover was negligible (0.02%). A highly significant agreement was found between Kryptor PCT and Diazyme PCT in a range of concentrations between 0.16 and 111 ng/mL (Diazyme PCT=1.10×Kryptor PCT-0.89; r=0.960; p<0.001). The mean bias was 0.48 ng/mL (95% CI, -0.58 to 1.54 ng/mL). The strength of agreement between Kryptor PCT and Diazyme PCT was between 85% and 96% at 0.50, 2.0, and 10 ng/mL cutoffs. CONCLUSIONS: Diazyme PCT appears to be a reliable assay for diagnosis and management of critical care patients susceptible to severe bacterial infections.

A novel algorithm for the prediction of prostate cancer in clinically suspected patients.

BACKGROUND: Prostate cancer (PCa) represents the most common solid tumor affecting men and its early detection remains the best approach to improve survival rates. The assessment of serum levels of PSA is currently used for PCa screening but the low specificity of the test results in a high number of false positives. Other forms of PSA may be detected in the bloodstream including PSA associated with immunoglobulin M (PSA-IgM) which, alone or combined with PSA, has shown diagnostic accuracy for PCa. OBJECTIVES: The aim of the study is to improve the diagnostic accuracy of PSA-IgM by developing a multivariable model which includes serum biomarkers and routine diagnostic parameters to obtain a predictive index useful in the post-screening clinical practice. PATIENTS AND METHODS: One hundred sixty male patients with clinical suspect of PCa underwent a trans-rectal ultrasound guided first prostate biopsy with a standardized sampling scheme. To generate the model, we assessed the presence of PSA and PSA-IgM complexes in sera of patients and the prostate volume of each patient. A novel predictive probability for PCa (iXip) was obtained combining non-overlapping biomarkers normalized with diagnostic parameters. RESULTS: The study population included 49 patients with PCa diagnosed at biopsy and 111 controls in which prostate biopsy showed the presence of benign prostatic hyperplasia, inflammation, atypical small acinar proliferation or high-grade prostatic intraepithelial neoplasia. The iXip values for patients with PCa (mean ± SD=0.467 ± 0.160) were significantly higher (p-value < 0.001) than control subjects (mean ± SD=0.314 ± 0.098) and the iXip AUC (0.787) was significantly greater (p-value < 0.001) than the AUCs of each biomarker. CONCLUSIONS: iXip shows a significant increase in diagnostic performance compared to PSA and PSA-IgM and its post-screening use may facilitate decision-making in recommending for biopsy clinically suspected patients.

Interference by heterophilic antibodies in immunoassays: wrong increase of myoglobin values.

Aim of this work is to illustrate how analytical interference in immunoassay may produce serious errors in clinical laboratory results. The sophisticated quality assurance schemes used in many laboratories do not identify erroneous results arising from aberrant samples. Recently attention has been focused on the incidence and implication of false-positive results arising from the presence of certain substances in a patient's serum that interfere with one or more steps in immunoassays. In this paper, we present the case of a 92 year-old woman whose plasma myoglobin concentrations falsely increased when measured using the Beckman Access assay. We demonstrated that heterophilic antibodies accounted for the falsely increased myoglobin values, and we suggest how to resolve such situations.