Testing means earlier treatment
Thyroid cancer can be diagnosed by testing patients' blood for thyroglobulin (Tg), a protein produced in the thyroid gland.
Following a measurement survey, the variance in results from laboratory to laboratory across Europe was found to be unacceptably high. To rectify this situation, a reference material for calibrating Tg measurements was produced. In producing this material, over fifteen European laboratories had to work closely together to verify their procedures and eliminate errors.
Thyroid cancer and leukaemia are the two forms of cancer most likely to develop in many people after nuclear fall-outs. Thyroid cancer is often detected by measuring the levels of thyroglobulin (Tg), a protein produced by the thyroid gland, in the blood. This gland is located near the larynx in the throat and it secretes hormones to regulate growth and development. Thyroglobulin is crucial to the synthesis of these hormones.
Accurate and reliable measurement of Tg in blood serum allows patients with the disease to be closely monitored and their illness may be better controlled with radio-treatment. Although this measurement is not performed frequently, it is the most important measurement for following the development of the disease.
Measurements of Tg can also be used more prognostically to forecast the development of the cancer, especially following exposure to radiation. The levels of thyroglobulin in blood can be used to screen large populations who have been irradiated.
It is clearly very important for these measurements to be correct to ensure that the right diagnosis is made and so patients receive the correct treatment. Also, as people move around the European Community much more freely now, it is much more important for medical laboratories to be able to compare measurements that may not have been made in the same country, let alone the same institution.
Survey identifies huge variations in measurements
The most common method of measuring Tg levels is by using a specially manufactured kit, but several methods exist. A laboratory survey of thirty organisations assessed the variation between results obtained using different methods in different laboratories across Europe. A set of blood serum samples, with set levels of Tg, was distributed to each laboratory, who used their usual
technique to perform the measurements. The results were compared and discussed amongst the survey participants. The discrepancy between methods and the variation in results was found to be unacceptably high. In some cases, the laboratories found low levels of Tg impossible to even detect, while others obtained results showing more than double the true value. When the samples had slightly higher levels, the same types of problems arose; unbelievably, the results varied from 25% to nearly 600% of the true value.
With this sort of inaccuracy, it was clear that in order to use Tg measurements for effective diagnosis and monitoring, something drastic would have to be done.
Using skills across Europe to solve the problem
In 1987, with the support of the European Commission's Standards, Measurements and Testing programme, a project was initiated by the University Hospital in Copenhagen. It would go on to produce
a reference material to be used in the measurement of Tg levels in blood serum. Its main use is to calibrate measurement methods and to provide testing laboratories with a common reference point. This improves the quality of the results obtained.
Laboratories from nine European countries worked on the project, with input from medical chemists from Sweden and the United States. They first carried out a number of feasibility studies to check that the material they wanted to produce would be suitable as a reference material. The group considered methods of purifying the Tg serum. Pilot batches were prepared to test its homogeneity to ensure that the Tg in the final samples would not decompose.
Detailed procedure to develop the reference material
The final material was extracted from nine healthy French people's thyroid glands. Any abnormal glands were discarded. The tissues were pooled together and ground into a powder. As with any biomedical reference material, any tissues containing infectious diseases are also discarded after screening. The thyroglobulin samples were then purified and packaged in ampoules before being freeze dried. This prevents the samples' composition from changing. The purity was checked using several methods including electrophoresis. Here, the proteins are loaded onto a gel and an electric field is applied to separate them.
After in-depth homogeneity and stability tests were complete, the project team began to measure the precise levels of Tg in the material. This value would be relied upon by laboratories everywhere, so it was very important to get it right. The project partners worked closely to complete their own measurements accurately. Each of them would perform the measurement and then they compared results in technical meetings to see where minor improvements could be made to reduce the now small
variance in results.
Once this was achieved in 1993, the material became available to testing laboratories and manufacturers of Tg measurement kits around the world. Biomedical chemists can now compare their results with other institutions. The material allows their measurements to be traced to a reliable source.
Without the development of this reference material, accurate diagnosis and follow-up treatment would be difficult. Undoubtedly, many errors would be made and patients may not get the required treatment until it is too late.