Report on a common survey in clinical laboratories in Belgium and in The Netherlands: immunoassays.

A common survey for immunoassays was organized for Belgian and Dutch laboratories. We compared the different statistical approaches used in the two schemes; both approaches lead to comparable results. Differences in overall consensus values and overall precision are related to a different selection of kits in the two countries. When analyzing results from users of representative kits in both countries, we found a very good correlation in accuracy but detected also some significant differences in precision for some samples for cortisol and theophylline determinations. For some observed differences there is actually no acceptable explanation.

The immunofluorometric TSH assay as first-line test for suspected thyroid dysfunction.

In this study of 103 patients with suspected thyroid dysfunction, the diagnostic value of a single basal immunofluorometric (IFMA) TSH measurement was evaluated and compared with the classical TRH test with RIA-TSH measurements, plasma TT4 concentrations and FT4I. A single basal TSH determination accurately predicted the TRH-stimulated TSH response, making the TRH test redundant in most patients. Because undetectable basal TSH did not always exclude a small rise in TSH, the TRH test could still be indicated in patients receiving thyroxine suppression therapy for thyroid cancer. Basal TSH differentiated accurately between euthyroidism and thyroid dysfunction, especially at the decision values of 0.20 and 4.0 mU/l, as proposed in this study. For diagnosis of clinical and subclinical hypo- and hyperthyroidism, additional measurement of TT4 and/or FT4I is necessary. A 2-yr follow-up of patients with subclinical thyroid dysfunction did not show progression to clinical disease. In some of the patients with subclinical hypothyroidism, substitution therapy with thyroxine had been started after initial testing. Indications for treatment of subclinical thyroid dysfunction are discussed.

Analytical evaluation of four sensitive assays of thyrotropin, including effects of variations in patient sampling.

Four immunometric kits for thyrotropin with detection limits below 0.1 milli-int. unit/L were evaluated with respect to accuracy, precision, specificity, matrix effects, and high-dose "hook" effect. We also studied variations of values related to the patients' sex and age and time of the day and season when samples were collected. Correlation among the four methods was excellent, except for a few samples, and the interference in these samples could be abolished by adding mouse serum or "suppression medium." These phenomena can also be expected to occur in other immunometric assays involving monoclonal antibodies. With some modifications all tests are suitable for a clinical study of the usefulness of the thyrotropin assay as a primary test for thyroid function.

The need for a sufficient number of low level sera in comparisons of different serum vitamin B12 assays.

Eight radiochemical methods for the assay of vitamin B12 in serum were compared with the microbiological assay with Lactobacillus leichmannii ATCC 7830 using 198 individual sera of patients. There was a good agreement between the results of most samples with some kits and the microbiological assay. However, especially in the sera of vitamin B12-deficient patients large discrepancies between the results could occur. These variations were due to both the kits used and the performance of the assays in different laboratories. A sufficient number of non-pooled sera of vitamin B12-deficient patients should be included in investigations to validate radiochemical methods.

A comparative study of free thyroxine estimations.

Two commercial methods (Immophase, Corning and FT4, Lepetit) for the measurement of free thyroxine (FT4) in serum have been experimentally evaluated. Ease of handling and rapidity were satisfactory. Precision profiles showed intra-assay coefficients of variation not exceeding 5% over the entire measurement range (0-70 pmol/l) for both methods. Interassay coefficients of variation were below 8%. Assay results of both methods correlated well with those obtained with a symmetric dialysis method, with correlation coefficients of 0.95 for the Immophase and 0.93 for the Lepetit method and slopes not significantly different from unity. Comparison with this reference method did not give any indication of serious methodological error in either of the kits in spite of theoretical doubts with regard to one of them.

A three-compartment model for the transport and distribution of Hippuran.

It is generally believed that after an intravenous injection of Hippuran its concentration in the plasma can be described as the sum of two exponentials. However, by collecting samples during the first minute after injection of the tracer, a third exponential term was found with a half-life of less than one minute. To explain its presence it was assumed that the plasma shares its Hippuran with two peripheral compartments, the rate of transfer from one compartment to another being proportional to the amount in the first of them. The proportionality factors have been determined for 20 adults and averaged. Substituting these averages in the differential equations for the distribution process, the only variable remaining is the renal excretion rate a (the fraction of plasma cleared per minute by the kidneys). If this procedure, which appears to be justified by the experimental results, is correct the shape of the plasma curve will be determined exclusively by a. It is shown that the (small) third compartment has a minor influence on the shape of the renogram curves.

Comparison between determination of free thyroxine index and effective thyroxine ratio in human serum.

Four thyroid function indices were determined in the sera of 181 patients: total thyroxine (T-4), the triiodothyronine resin uptake (T-3 B.C.-index), the free thyroxine (T-4) index, and the effective thyroxine ratio (E.T.R.).A statistically significant correlation between the free T-4 index and E.T.R. could be established though this correlation seemed to be worse than could be expected from the literature. Two sets of correlation coefficients were shown: one obtained with the ordinarily used Pearson or product-moment correlation and one with the Spearman rank correlation. Because the assumptions and requirements for the proper use of the product-moment correlation statistics, such as a normal distribution of both variables, are seldom met, expecially not if a selected number of controls and patients is used for the correlation, it is advisable to use some kind of rank correlation statistics instead.The advantages and disadvantages of the E.T.R. and free T-4 index determination are described.