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Clinical Chemistry 44: 2550-2551, 1998;
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(Clinical Chemistry. 1998;44:2550-2551.)
© 1998 American Association for Clinical Chemistry, Inc.

Technical Briefs

Furosemide Interference in Newer Free Thyroxine Assays

Robert C. Hawkins

Department of Pathology and Laboratory Medicine, Tan Tock Seng Hospital, Moulmein Road, Singapore 308433

Furosemide is a commonly used diuretic available in both oral and intravenous formulations. Furosemide is a known inhibitor of thyroid hormone binding in serum (1), and high-dose treatment with furosemide can lower total thyroxine and increase its free fraction in vivo (2). The difficulty in assessing thyroid status in severe illness is well known (3), and this difficulty can be complicated by treatment with drugs such as furosemide. The following study was undertaken after investigation of a patient in the coronary care unit with a thyroid-stimulating hormone (TSH) concentration within the health-related reference interval coupled with a free thyroxine of >77 pmol/L on the Abbott AxSYM immunoassay analyzer (reference interval, 9–24 pmol/L). In a subsequent sample, the free thyroxine was 16.2 pmol/L. The error was attributed to contamination of the sample by intravenous furosemide. I investigated the effects of furosemide on the measurement of free thyroxine and TSH, using three different assay systems: the AxSYM from Abbott Laboratories, the ACS:180 from Chiron, and the Vitros from Ortho Clinical Diagnostics.

An intravenous formulation of furosemide (28.5 mmol/L) from Hoechst Laboratories was diluted with serum from a pool of euthyroid individuals to produce eight samples with dilution factors ranging from 100 to 6000. The serum pools and all diluted samples were analyzed for both free thyroxine and TSH, using the Abbott AxSYM, the Chiron ACS:180, and the Ortho Vitros. The Abbott AxSYM uses microparticle enzyme immunoassay technology, whereas the Chiron ACS:180 and the Ortho Vitros use chemiluminescent assay systems. The sample volume:total volume ratios for the free thyroxine assays were as follows: Vitros, 0.20; AxSYM, 0.11; and ACS:180, 0.04. All results were compared with those from the serum pool and displayed as the percentage of change in analyte concentration.

The relative effects of furosemide contamination on free thyroxine in serum are shown in Fig. 1 . The Ortho Vitros assay was most affected, whereas the ACS:180 assay showed the least interference from the presence of furosemide. Assay sensitivity to furosemide increased with increasing sample volume:total volume ratios. I found no significant change in measured TSH concentration with any furosemide dilution in any assay (data not shown).



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  		Figure 1. Change in free thyroxine measurement (%) vs furosemide concentration (µmol/L).

{diamondsuit}, Vitros; {square}, AxSYM; {bullet}, ACS:180.

The interference of furosemide with free thyroxine assays should further discourage sampling for thyroid tests from intravenous sites where furosemide has been administered, because contamination of the sample by even small volumes of furosemide significantly affected thyroxine results. The differences in sensitivity to furosemide interference among assays appear to reflect the serum dilution used in each method. This concern may apply to interference from other drugs (e.g., salicylates and fenclofenac) as well as to other assays (e.g., free triiodothyronine).

This study does not address the in vivo effect of furosemide administration on thyroxine measurement. Because oral furosemide may influence measurement of the free thyroxine index (4), the time interval between doses of oral furosemide and blood sampling should be considered in result interpretation. Both the Vitros and AxSYM assays use sample volume:total volume ratios greater than the ratio (0.09) used by the assay in that study (4). Thus, it is likely that the in vivo effect from oral furosemide will be even greater in the Vitros and AxSYM assay systems. Furosemide concentrations of 6.6–73.0 µmol/L reported with routine therapeutic doses of furosemide (5) fall within the range of furosemide concentrations examined here. Clinicians thus may need greater awareness to potential interference from drugs such as furosemide when interpreting results from newer free thyroxine assays that use large sample volume:total volume ratios. TSH measurement may be a more useful test for assessing thyroid function in such cases.


Footnotes

fax 65-253-6507, e-mail Robert_Hawkins{at}notes.ttsh.gov.sg


References

  1. Stockigt J, Lim C-F, Barlow J, Wynne K, Mohr V, Topliss D, et al. Interaction of frusemide with serum thyroxine-binding sites: in-vivo and in-vitro studies and comparison with other inhibitors. J Clin Endocrinol Metab 1985;60:1025-1031. [Abstract]
  2. Stockigt J, Lim C-F, Barlow J, Stevens V, Topless D, Winnie K. High concentrations of furosemide inhibit serum binding of thyroxine. J Clin Endocrinol Metab 1984;59:62-66. [Abstract]
  3. Surks M, Chopra I, Mariash C, Nicoloff J, Solomon D. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA 1990;263:1529-1532. [Abstract]
  4. Newnham H, Hamblin P, Long F, Lim C-F, Topliss D, Stockigt J. Effect of oral frusemide on diagnostic indices of thyroid function. Clin Endocrinol 1987;26:423-431. [Medline] [Order article via Infotrieve]
  5. Cutler R, Forrey A, Christopher T, Kimpel B. Pharmacokinetics of furosemide in normal subjects and functionally anephric patients. Clin Pharmacol Ther 1974;15:588-596. [ISI][Medline] [Order article via Infotrieve]



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Intermethod Discordant Free Thyroxine Measurements in Bone Marrow-transplanted Patients
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N. D. Christofides and R. C. Hawkins
Furosemide Interference in Newer Free Thyroxine Assays • Dr. Hawkins responds:
Clin. Chem., August 1, 1999; 45(8): 1315 - 1315.
[Full Text] [PDF]

This Article
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Right arrow Endocrinology and Metabolism

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