IMMULITE® Free T4 Analog Assay Revisited
Complementary Role to IMMULITE® Third
Generation TSH Assay

This article is a condensed version of a DPC technical report titled "IMMULITE Free T4 Analog Assay Revisited: Complementary Role to IMMULITE Third Generation TSH for Assessing Thyroid Status in an Ambulatory Patient Population." For a copy of the technical report, contact your local DPC representative or, in the US, call 800.372.1782 and request catalog number ZB179‚A.

Introduction
The National Academy of Clinical Biochemistry has recommended the complementary use of TSH and free (or total) T4 for the differential diagnosis and management of hypo- and hyperthyroidism.^1,2 Certain considerations and controversies, however, surround the choice of free T4 assays.^3,4 Study Objectives The present study was undertaken to evaluate the clinical utility of the IMMULITE Free T4 assay, as an adjunct to the IMMULITE Third Generation TSH assay, for the differential diagnosis of hypo- and hyperthyroidism among ambulatory patients at a large outpatient clinic. IMMULITE Free T4 results were evaluated in the context of diagnosed thyroid status and matching IMMULITE Third Generation TSH results. Given that direct equilibrium dialysis has come to be regarded as the "gold standard,"^5,6 IMMULITE free T4 results were also evaluated relative to matching free T4 results obtained with the Nichols Institute equilibrium dialysis kit.

Patients were grouped into one of five categories based on review of their medical records: euthyroid, untreated hypothyroid, untreated hyperthyroid, hypothyroid on thyroid replacement or suppressive therapies, and hyperthyroid undergoing treatment. This study did not include hospitalized patients because of the generally recognized confounding effects of severe nonthyroidal illness and its associated medications on the interpretation of thyroid function tests.^2,7

Results and Conclusions
Both the IMMULITE and Nichols free T4 results tended to be concordant with matching TSH results among euthyroid and untreated hypo- and hyperthyroid patients. Both sets of free T4 results, however, exhibited a high frequency of discordance with matching TSH results among patients undergoing thyroid treatment regimens. During initiation of treatment and subsequent changes in thyroxine dosages, discordance between free T4 and TSH results is expected. Reestablishment of euthyroid TSH concentrations may be delayed in some patients. Free T4 is the more reliable indicator of thyroid status during this period.²

Discordance between matched Nichols dialysis and IMMULITE free T4 results can for the most part be explained by the high bias of the Nichols assay relative to other commercial free T4 assays. Overestimation of free T4 appears to be a contributing factor underlying incidences of discordant free T4 results among treated hypothyroid and hyperthyroid patients.

In a TSH-centered strategy, the IMMULITE analyzer, with its combination of third generation TSH and free T4 assays, constitutes a powerful, fully automated laboratory tool for the differential diagnosis and management of thyroid disease in an ambulatory patient population. When used with a clear understanding of limitations, the IMMULITE Free T4 analog assay is clinically useful for thyroid function assessment and for monitoring thyroid therapy in patients.

Euthyroid Patients (n=57)
Free T4 (ng/dL)

*FT4 = 0.74

Hypothyroid Patients on
Replacement or Suppressive Therapies (n = 68)
Free T4 (ng/dL)

*FT4 = 0.98 , 0.94

Untreated Hypothyroid Patients (n = 23)
Free T4 (ng/dL)

*FT4 = 0.98 , 0.94

Untreated Patients Undergoing Treatment (n = 7)
Free T4 (ng/dL)

Untreated Hyperthyroid Patients (n = 13)
Free T4 (ng/dL)

*FT4 = 2.5

References

1. Sawin CT, ed. Standards of laboratory practice: Laboratory support for the diagnosis & monitoring of thyroid disease. National Academy of Clinical Biochemistry, 1996.

2. Demers LM. Thyroid disease: setting a standard for collaboration and cost containment. Clin Lab News 1998;24:22-3.

3. Csako, G. Free hormone measurements. In: Diamandis EP, Christopolous TK, editors. Immunoassay. New York: Academic Press, 1996: 423-81.

4. Nelson JC, Wilcox RB. Analytical performance of free and total thyroxine assays. Clin Chem 1996;42:146-54.

5. Spencer, CA. Clinical evaluation of free T4 techniques. J Endocrinol Invest 1986;9 (Suppl 4): 57-66.

6. Ekins R. Measurement of free hormones in blood. Endocr Rev 1990;11:5-46.

7. Stockigt JR. Guidelines for diagnosis and monitoring of thyroid disease: nonthyroidal illness. Clin Chem 1996;42:188-92.