ObjectiveThe 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.DesignA prospective multicenter study.PatientsThree hundred and seventy-five clinically euthyroid subjects.MethodsWe used five different C_T immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies.ResultsScreening 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.ConclusionIn 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.