Calcium is the most closely controlled substance in the blood. The biologic variation of total calcium is ~2 % and of the biologically active free (ionized, ionic) calcium only l070.('-~) Thus, the monitoring of calcium in blood requires analytic procedures of high precision and accuracy. For patients with asymptomatic primary hyperparathyroidism, calcium monitoring involves the measurement of total calcium and free calcium. This review first considers the measurement of total calcium and then free calcium.
MEASUREMENT OF TOTAL CALCIUM
Analytic approaches
NUMBER OF ANALYTIC PROCEDURES have been utilizedA to measure total calcium over the last 50 years. Because of the small biologic variation, the need for methods of high precision and accuracy has long been apparent, and this analyte was one of the first to be addressed by professional organizations in laboratory medicine and clinical chemistry with interest in improving the performance of clinical laboratories. These efforts are now coordinated by the National Reference System for the Clinical Laboratory (NRSCL), formerly called the National Reference System in Clinical Chemistry. The NRSCL is a component of the National Committee for Clinical Laboratory Standards (NCCLS), which is a nonprofit organization that involves government, professional organizations, and industry and is the leading standards-setting organization for clinical laboratories in the United States.The components involved in the development and application of a standardization system are shown in Fig. 1. The key to the system are steps I1 through V. For calcium, a definitive method based on isotope dilution mass spectroscopy was developed by workers at the National Institute of Standards and Technology (NIST, formerly the National Bureau of Standards).(41 A primary reference material of calcium carbonate is available (standard reference material, SRM 915, available from NIST) and a reference method based on atomic absorption spectroscopy has been developed and validated.") In addition, a secondary reference material consisting of lyophilized sera with an assigned calcium value is available (SRM 909, NIST).These activities, along with the evolution of more automated procedures, have had a dramatic effect on the agreement among clinical laboratories for the measurement of total calcium. This improvement is readily apparent when comparing the interlaboratory precision 01' total calcium measurements with the survey samples of the College of American Pathologists quality control survey program ( Table 1). These data show that the interlaboratory precision of total calcium measurements decreased from =6Vo in the early 1970s to 3.3% in 1990. The precision in an individual laboratory can be even better ihan 3.3%. In the clinical chemistry laboratory at Barnes Hospital, the precision of total calcium measurements over the last year has been I .8-2.1 OJo for one type of analyzer and 2.3-3.1 Yo for another analyzer.It is my opinion that the current state of the art of total calcium measurement i...