calca-protein--human and Carcinoma--Medullary

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Humans; Hypercalcemia; Hypocalcemia; Immunoradiometric Assay; Inflammation; Kidney Failure, Chronic; Luminescent Measurements; Osteoporosis; Protein Precursors; Radioimmunoassay; Reference Values; Sepsis; Thyroid Neoplasms

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Humans; Male; Middle Aged; Protein Precursors; Thyroid Neoplasms; Thyroidectomy

Calcitonin (CT) is a sensitive marker for evaluation of medullary thyroid cancer (MTC). However, CT measurement can vary with assay- and nonassay-dependent factors, and procalcitonin (PCT) measurement has been proposed for evaluating questionable increases in CT.. We tested 2 fully automated CT assays (Immulite [IL] and Liaison [LIA]) and 1 nonautomated CT assay (IRMA, Medipan) and compared these results with PCT (Brahms Kryptor). We evaluated preanalytical conditions and PCT cross-reactivity in sera of 437 patients with clinical conditions associated with hypercalcitoninemia. Additionally, we determined the true "nil" CT concentration in 60 thyroidectomized patients and defined CT cutoff concentrations for pentagastrin stimulation testing in 13 chronic kidney disease (CKD) patients and 10 MTC patients.. Markedly decreased CT concentrations were found after storage of sera for >2 h at room temperature and >6 h at 4 °C. Cutoff concentrations for basal and stimulated CT were disease and assay dependent. Proton pump inhibitor therapy was the most frequent reason for increased CT. PCT concentrations were higher in patients with MTC than in patients with CKD without infections (P<0.001). Whereas IL and LIA demonstrated comparable analytical quality, the IRMA gave increased CT concentrations in nil sera and showed cross-reactivity with PCT in patients with concomitant bacterial infection.. IL, LIA, and IRMA detected increased CT concentrations in non-MTC patients and discriminated MTC from CKD patients in pentagastrin tests. PCT assessment may be helpful in the diagnostic work-up of increased CT concentrations in questionable clinical circumstances.

Topics: Automation; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Calibration; Carcinoma, Medullary; Case-Control Studies; Cohort Studies; Female; Humans; Immunoassay; Luminescent Measurements; Male; Pentagastrin; Protein Precursors; Protein Stability; Reference Standards; Sensitivity and Specificity; Sex Characteristics; Thyroid Neoplasms; Thyroidectomy

Procalcitonin has been well established as an important marker of sepsis and systemic infection. The authors evaluated the diagnostic and predictive value of calcitonin and its prohormone procalcitonin in medullary thyroid cancer.. The authors systematically explored the ability of calcitonin and procalcitonin to identify medullary thyroid cancer and predict the endpoints local recurrence and distant metastases, as well as the progression-free survival. Patients with C-cell hyperplasia; patients after thyroidectomy for differentiated thyroid cancer, goiter, or Graves disease; and healthy subjects served as controls. The study was performed in accordance with the Reporting Recommendations for Tumor Marker Prognostic Studies of the National Cancer Institute.. Sixty-nine medullary thyroid cancer patients and 96 controls were included (median observed interval: 10.9 years [range, 1.4-47.5 years]; 981.8 patient-years). The 1-year, 5-year, 10-year, and 20-year recurrence rates were 9%, 34%, 45%, and 56%, respectively. Calcitonin had a higher diagnostic accuracy for detecting medullary thyroid cancer than procalcitonin (area under the curve [AUC], 0.94; 95% confidence interval [95% CI], 0.90-0.99 vs AUC, 0.89; 95% CI, 0.83-0.95 [P = .038]). The procalcitonin:calcitonin ratio predicted disease progression (AUC, 0.63; 95% CI, 0.51-0.75 [P = .036]) and progression-free survival (hazards ratio, 1.49; 95% CI, 1.09-2.04 [P = .013]).. The results of the current study indicate a superior diagnostic accuracy of calcitonin and an independent predictive value of the procalcitonin:calcitonin ratio. These findings may lead to improved diagnostic and therapeutic strategies for medullary thyroid cancer patients.

Topics: Adult; Aged; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Disease Progression; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Protein Precursors; Thyroid Neoplasms; Treatment Outcome

Calcitonin (CT) is the main medullary thyroid carcinoma (MTC) tumor marker. However, it has several limitations, including a concentration-dependent biphasic half-life, sensitivity to rapid in vitro degradation, and the presence of different isoforms/fragments. Procalcitonin (PCT), the prohormone of calcitonin, is free of these limitations but is currently used only as a sepsis marker.. The objective of the study was to determine whether PCT is suited as a MTC tumor marker by comparing the diagnostic performance of PCT with that of CT in MTC.. PCT and CT were measured in a total of 835 subjects, including normal volunteers (n = 197) and patients with active-MTC (n = 91), cured-MTC (n = 42), neuroendocrine tumors (n = 225), mastocytosis (n = 48), follicular cell-derived thyroid carcinoma (cured = 120, persistent/recurrent = 55), and benign thyroid disease (n = 57).. PCT levels were significantly higher in the active-MTC patients (mean 126.4 ng/ml) than the cured-MTC patients (mean <0.1 ng/ml). The overall concordance between the two markers was 95.7% (kappa = 0.81). Receiver-operating characteristic curve analysis showed no significant difference in diagnostic performance between CT and PCT. PCT's diagnostic sensitivity and specificity were 91 and 96%, respectively. The corresponding values for CT were 99 and 98%. Analyte stability studies showed that CT is very unstable in vitro with a decrease of 35-50% from the original value 24 h after the blood draw, whereas PCT levels did not significantly change during this time.. A strong correlation was observed between PCT and CT levels in patients with MCT. Given PCT's greater analytical stability, we conclude that it represents a promising complementary MTC tumor marker.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Female; Follow-Up Studies; Humans; Male; Middle Aged; Protein Precursors; Reference Values; Retrospective Studies; Thyroid Neoplasms

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Creatinine; Enzyme-Linked Immunosorbent Assay; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Thyroid Neoplasms

The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects.. A prospective multicenter study.. Three hundred and seventy-five clinically euthyroid subjects.. We used five different C(T) immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies.. Screening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no C(T) was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between C(T) levels and age or body mass index (BMI) (primarily in men). The distribution of C(T) levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest C(T) values were around twice as high in men than women, and were higher in smokers than non-smokers. Conclusion In clinical practice (and after having excluded the usual causes of raised C(T) levels), the interpretation of C(T) assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Calcium; Carcinoma, Medullary; Female; Gastrins; Humans; Immunoassay; Iodide Peroxidase; Male; Middle Aged; Prospective Studies; Protein Precursors; Reagent Kits, Diagnostic; Reference Values; Smoking; Thyroid Neoplasms; Thyrotropin; Urea

Procalcitonin (PCT) is a protein synthetized by the thyroid C cells, inside which it is cut into calcitonin (CT) and catacalcin. It remains undetectable in serum in normal conditions. Its level increases during inflammation and in small cell lung cancer. There have been studies suggesting that the PCT level increases in medullary thyroid carcinoma (MTC). So far there have been no reports that would assess the usefulness of PCT detection in MTC. Our aim was to evaluate the usefulness of serum PCT assays in patients with MTC. We investigated 24 patients at 17-78 years of age, all after total thyroidectomy due to MTC. All patients had serum CT concentrations measured by radioimmune assay. The upper limit of the CT level was 60 pg/ml. The serum PCT was evaluated with an immunochromatographic kit. The reaction was considered positive when the PCT level exceeded 0.5 ng/ml. In all cases the C-reactive protein (CRP) serum level was measured. The statistical analysis was performed with Statistica 5.1G. The CT levels in all patients varied from 0 to 1410, mean 603.8 pg/ml. In 8 patients the CT level was within normal range, in 6 patients it was marginally, and in 10 patients markedly elevated. The PCT test was considered positive in 16 patients. There was correlation among serum PCT and CT concentrations (Spearman test, p<0.0001). The PCT levels varied considerably among patients with normal, marginally and markedly elevated CT levels (Kruskal-Wallis test, p=0.0013). All patients had normal CRP values. Fisher's exact test revealed a correlation between serum PCT and CT increase (p=0.04). Further studies on a larger group of patients should be considered; thus, the PCT assay can be considered useful in cases of unclear CT concentration.

Topics: Adolescent; Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Female; Humans; Male; Middle Aged; Protein Precursors; Radioimmunoassay; Statistics as Topic; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

Raised plasma levels of procalcitonin (proCT) represent an early marker for septicaemia. They are related to disease severity and inversely to outcome and response to treatment. ProCT is presumably synthesised in tIssues other than the thyroid C-cells which are the source of calcitonin (CT) in normal physiology. This study compares proCT and its cleavage products in the serum of patients with septicaemia with those in medullary thyroid carcinoma (MTC).. Immunoreactive proCT and its cleavage products were extracted from the serum of patients with septicaemia or MTC using octadecylsilyl silica columns and characterised by reversed phase HPLC and Western blot analysis. ProCT, CT(1-32) and the flanking peptides PAS-57 and PDN-21 were recognised with antibodies specific for the individual peptides.. ProCT and a 10 kDa polypeptide were recognised with antibodies to PAS-57, CT(1-32) and PDN-21. An 8 kDa proCT fragment was detected with antibodies to CT and PDN-21. However, intact CT(1-32), PAS-57 and PDN-21, found in the serum of MTC patients, were undetectable. The results indicate partial cleavage of proCT in septicaemia different from that in MTC patients.. ProCT and 10 and 8 kDa proCT fragments were recognised in the circulation of septic patients. They were different from the known proCT-processing products PAS-57, CT(1-32) and PDN-21 identified in the serum of normal subjects and of MTC patients. Distinct cleavage of proCT may contribute to the symptoms of septicaemia.

Topics: Aged; Blotting, Western; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Sepsis; Thyroid Neoplasms