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Thyroid function evaluation by different commercially available free thyroid hormone measurement kits in term pregnant women and their newborns

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Abstract

Evaluation of thyroid status by measurement of free thyroid hormone concentrations seems particularly helpful in conditions with altered serum binding proteins. In pregnancy, a condition of increased thyroxine binding globulin, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations have been reported to be normal, increased or decreased. In the present study we have measured serum total and free thyroid hormone concentrations in pregnant women, their newborns and nonpregnant women. Serum FT4 and FT3 concentrations have been measured with 10 different commercially available kits and the results obtained have been compared. Serum total thyroid hormone concentrations in pregnant women were significantly higher than in their newborns and in nonpregnant women. Maternal serum FT4 concentrations measured with the different kits were always significantly lower than values in nonpregnant women. Furthermore, with one kit, the mean maternal serum FT4 concentration was below the normal range and with many kits, a large number of maternal serum samples had serum FT4 concentrations below the normal range. With all kits, except two, neonatal serum FT4 concentrations were higher than values in their respective mothers and, in general, lower than values in nonpregnant women. Serum FT3 concentrations in nonpregnant women were in the normal range, except with one kit, in which the mean serum FT3 concentration was below the normal range. Serum FT3 concentrations in newborns resulted markedly lower than in parturient and in non pregnant women. With almost all kits, serum FT3 values were below the normal range in many maternal samples. With one kit, maternal serum FT3 concentrations resulted higher than in nonpregnant women, whereas with the other kits serum FT3 concentrations were lower. Despite the variability of serum FT4 and FT3 concentrasions, serum TSH concentrations in pregnant women and their newborns, resulted in the normal range. These findings suggest that many kits for the measurement of serum free thyroid hormone concentrations do not seem adequate to evaluate the real thyroid status of pregnant women and newborns. Therefore, in these physiological conditions the measurement by commercial kits of serum FT4 and FT3 concentrations do not offer a real advantage in respect to serum total thyroid hormone determination.

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References

  1. Rajatanavin R., Braverman L.E. Euthyroid hyperthyroxinemia. J. Endocrinol. Invest. 6: 493, 1983

    Article  PubMed  CAS  Google Scholar 

  2. Wartofsky L. Indicazioni diagnostiche per il dosaggio dell’ormone tiroideo libera in malattie tiroidee e non. Lig. Quarter. 3: 49, 1984.

    Google Scholar 

  3. Hay I.D., Klee G.G. Thyroid disfunction. Endocrinol. Metab. Clin. North Am. 17: 473, 1988.

    PubMed  CAS  Google Scholar 

  4. Schatz D.L., Palter H.C., Russell C.S. Effects of oral contraceptives and pregnancy on thyroid function. Can. Med. Ass. J. 99: 882, 1968.

    PubMed Central  PubMed  CAS  Google Scholar 

  5. Fisher D.A., Hobel C.J., Garza R., Pierce C.A. Thyroid function in the preterm fetus. Pediatrics 46: 208, 1970.

    PubMed  CAS  Google Scholar 

  6. Harada A., Hershman J.M., Reed A.W., Braunstein G.D., Dignam W.J., Derzko C., Friedman S., Jewelewic Z.R., Pekary A.E. Comparison of thyroid stimulators and thyroid hormone concentrations in the sera of pregnant women J. Clin. Endocrinol. Metab. 48: 793, 1979.

    Article  PubMed  CAS  Google Scholar 

  7. Yamamoto T., Amino N., Tanizawa O., Doi K., Ichihara K., Azukizawa M., Miyai K. Longitudinal study of serum thyroid hormones, chorionic gonadotrophin and thyrotrophin during and after normal pregnancy. Clin. Endocrinol. (Oxf) 10: 459, 1979.

    Article  CAS  Google Scholar 

  8. Sterling K., Hagedus A. Measurement of free thyroxine concentration in human serum. J. Clin. Invest. 41: 1031, 1962.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Ingbar S.H., Braverman L.E., Dawber N.A., Lee G.Y. A new method for measuring the free thyroid hormone in human serum and an analysis of the factors that influence its concentration. J. Clin. Invest. 44: 1679, 1965.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Anderson B.G. Free thyroxine in serum in relation to thyroid function JAMA 203: 135, 1968.

    Article  Google Scholar 

  11. Avruskin T.W., Mitsuma T., Shenkman L., Sau K., Hollander C.S. Measurement of free and total serum T3 and T4 in pregnant subjects and in neonates. Am. J. Med. Sci. 271: 309, 1976.

    Article  PubMed  CAS  Google Scholar 

  12. Oppenheimer J.H., Squef R., Sueks M.I., Hauer H. Binding of thyroxine by serum proteins evaluated by equilibrium dialysis and electrophoretic techniques. Alterations in non-thyroidal illness. J. Clin. Invest. 42: 1769, 1963.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Robin N.I., Refetoff S., Fang V., Selenkow H.A. Parameters of thyroid function in maternal and cord serum at term pregnancy. J. Clin. Endocriol. Metab. 29: 1276, 1969.

    Article  CAS  Google Scholar 

  14. Malkasian G.D., Mayberry W.E. Serum total and free thyroxine and thyrotropin in normal and pregnant women, neonates and women receiving progestogens. Am. J. Obst. Gynecol. 108: 1234, 1970.

    CAS  Google Scholar 

  15. Souma J.A., Niejadlik D.C., Cottrel S., Rankel S. Comparison of thyroid function in each trimester of pregnancy with the use of triiodothyronine uptake, thyroxine iodine, free thyroxine, and free thyroxine index. Am. J. Obst. Gynecol. 116: 905, 1973.

    CAS  Google Scholar 

  16. Osathanondh R., Tulchinsky D., Chopra I.J. Total and free thyroxine and triiodothyronine in normal and complicated pregnancy. J. Clin. Endocrinol. Metab. 42: 98, 1976.

    Article  PubMed  CAS  Google Scholar 

  17. Braverman L.E., Abreau C.M., Brock P., Kleinmann R., Fournier L., Odstrchel G., Schoemaker H.Y.P. Measurement of serum free thyroxine by RIA in various clinical states. J. Nucl. Med. 21: 233, 1980.

    PubMed  CAS  Google Scholar 

  18. Bachrach L.K., Burrow G.N. Thyroid function in pregnancy Fetal-maternal relationships. In: Delange F., Fisher D.A., Malvaux P. (Eds.), Pediatric Thyroidology. Basel, Karger 1985, p. 1.

    Google Scholar 

  19. Mendel C.M., Cavalieri R.R. Transport of thyroid hormone in health and disease: recent controversy surrounding the free hormone hypothesis. Thyroid Today 11: 1, 1988.

    Google Scholar 

  20. Larsen P.R. Thyroid-pituitary interaction. Feedback regulation of thyrotropin secretion by thyroid hormones. N. Engl. J. Med. 306: 23, 1982.

    Article  PubMed  CAS  Google Scholar 

  21. Larsen P.R., Alexander N.M., Chopra I.J., Hay I.D., Hershman J.M., Kaplan M.M., Mariash C.N., Nicoloff J.T., Oppenheimer J.H., Solomon D.H., Surks M.I. Revised nomenclature for tests of thyroid hormones and thyroid-related proteins in serum. J. Clin. Endocrinol. Metab. 64: 1089, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Ekins R. Validity of analog free thyroxine immunoassays. Clin. Chem. 33: 2137, 1987.

    PubMed  CAS  Google Scholar 

  23. Midgley J.E.M., Moon C.R., Wilkins T.A. Validity of analog free thyroxin immunoassays. Part. II. Clin. Chem. 33: 2145, 1987.

    PubMed  CAS  Google Scholar 

  24. Emerson C.H., Braverman L.E., De Vito J.J. Serum thyrotropin concentrations are more tightly correlated with serum triiodothyronine concentrations than serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats. Endocriology 124: 2415, 1989.

    Article  CAS  Google Scholar 

  25. Fisher D.A., Klein A.H. Thyroid development and disorders of thyroid function in the newborn. N. Engl. J.Med. 304: 702, 1981.

    Article  PubMed  CAS  Google Scholar 

  26. Dussault J.H. Neonatal screening for congenital hypothyroidism. In: Delange F., Fisher D.A., Malvaux P. (Eds.), Pediatric Thyrodology. Basel, Karger 1985, p. 106.

    Google Scholar 

  27. Emrich D., Herrmann J., Joseph K., Jungst D., Mahlstedt H., Panitz N., Pfannenstiel P. New test principle of measurement of free thyroxine (FT4) in serum. The result of a multi-centre trial. Nuc. Compact 12: 56, 1981.

    CAS  Google Scholar 

  28. Midgley J.E.M., Wilkins T.A. The direct estimation of free hormones by a simple equilibrium radioimmunoassay. Amersham International Ltd., Amersham, Bucks, 1981.

    Google Scholar 

  29. Amino N., Nishi K., Miyai K., Tanizawa O. Interpretation of free thyroxine radioimmunoassay data. Lancet 1: 1300, 1982 (letter).

    Article  PubMed  CAS  Google Scholar 

  30. Franklyn J., Sheppard M.C., Ramsden D.B. Serum free thyroxine and free triiodothyronine concentrations in pregnancy. Br. Med. J. 287: 394, 1983.

    Article  CAS  Google Scholar 

  31. Franklyn J., Sheppard M.C., Ramsden D.B., Hoffenberg R. Free triiodothyronine and free thyroxin in sera of pregnant women and subjects with congenital increased or decreased thyroxin-binding globulin. Clin. Chem. 29: 1527, 1983.

    PubMed  CAS  Google Scholar 

  32. Wang Y.S., Pekary A.E., England M.L., Hershman J.M. Comparison of a new ultrafiltration method for serum free T4 and free T3 with two RIA kits in eight groups of patients. J. Endocrinol. Invest. 8: 495, 1985.

    Article  PubMed  CAS  Google Scholar 

  33. Meinhold H., Wenzel K.W. Measurement of serum FT4 in pregnancy and binding protein abnormalities by different methods. Nuc. Compact 16: 365, 1985.

    CAS  Google Scholar 

  34. Ratcliffe W.A., Stewart M.F. Diagnostic performance of two new analog assays for free thyroxin. Clin. Chem. 32: 2124, 1986.

    PubMed  CAS  Google Scholar 

  35. Witherspoon L.R., El Shami A.S., Shuler S.E., Neely H., Sonnemaker R., Gilbert S.S., Alyea K. Chemically blocked analog assays for free thyronines. II. Use of equilibrium dialysis to optimize the displacement by chemical blockers of T4 analog and T3 analog from albumin while avoiding displacement of T4 and T3 from thyroxine-binding globulin. Clin. Chem. 34: 17, 1988.

    PubMed  CAS  Google Scholar 

  36. Hopton M.R., Ashwell K., Scott I.V., Harrop J.S. Serum free thyroxine concentration and free thyroid hormone indices in normal pregnancy. Clin. Endocrinol. (Oxf) 18: 431, 1983.

    Article  CAS  Google Scholar 

  37. Waud J.M., Chan D.W., Drew H.M., Oropeza M.J., Sucupira M.S., Scheinin B., Garrison G.M., Mayo M., Taylor E., Stem J., Graham D., Coyle J.T., Niebyl J., Wagner H.N. Clinical evaluation of two direct procedures for free thyroxin, and of free thyroxin index determined non isotopically and by measuring thyroxin-binding globulin. Clin. Chem. 29: 1908, 1983.

    PubMed  CAS  Google Scholar 

  38. Sheehan C.P., Christofides N.D. Evaluation of labeled antibody assay for free thyroxin. Program 64th Annual Meeting American Thyroid Association, San Francisco, September 6–9 1989, T90.

    Google Scholar 

  39. Kubasik N.P, Lundberg P.A., Brodows R.G., Hallauer G.D., Same D.G., Lindstedt G., Bengtsson C., Nystrom E. Free thyroxin by radioimmunoassay: evaluation of a new direct method involving a radiolabeled thyroxin analog. Clin. Chem. 29: 1781, 1983.

    PubMed  CAS  Google Scholar 

  40. Pacchiarotti A., Martino E., Bartalena L., Buratti L., Mammoli C., Stringini F., Fruzzetti F., Melis G.B., Pinchera A. Serum thyrotropin by ultrasensitive immunoradiometric assay and serum free thyroid hormones in pregnancy J. Endocrinol. Invest. 9: 185, 1986.

    Article  PubMed  CAS  Google Scholar 

  41. Hindle E.J., Haldon S. Discrepant serum FT4 values — a TBG dependency? Clin. Chem. 32: 2104, 1986 (letter).

    PubMed  CAS  Google Scholar 

  42. Amino N., Yamada T., Mitsuma T., Nogimori T., Tanizawa O., Kawashima M., Kurachi K., Miyai K. Increase in plasma thyrotropin-releasing hormone in normal human pregnancy. J. Clin. Endocrinol. Metab. 53: 1288, 1981.

    Article  PubMed  CAS  Google Scholar 

  43. Byfield PGH, Lalloz MRA, Pearce C.J., Himsworth R.L. Free thyroid hormone concentrations in subjects with various abnormalities of binding proteins: experience with Amerlex free-T4 and free-T3 assays. Clin. Endocrinol. (Oxf.) 19: 277,1983.

    Article  CAS  Google Scholar 

  44. Bayer M.F. Free thyroxine results are affected by albumin concentration and nonthyroidal illness. Clin. Chim. Acta 130: 391, 1983.

    Article  PubMed  CAS  Google Scholar 

  45. Howorth P.J.N., Maclagan N.F. Clinical application of serum-total-thyroxine estimation, resin uptake, and free-thyroxine index. Lancet 1: 224, 1969.

    Article  PubMed  CAS  Google Scholar 

  46. Sarin R.K., Anderson B.G. Serum thyroxine resin uptake of liothyronine 125I, and free thyroxine index. Arch. Intern. Med. 126: 631, 1970.

    Article  PubMed  CAS  Google Scholar 

  47. Witherspoon L.R., El Shami A.S., Shuler S.E., Neely H., Sonnemaker R., Gilbert S.S., Alyea K. Chemically blocked analog assays for free thyronines. I. The effect of chemical blockers on T4 analog and T4 binding by albumin and by thyroxin-binding globulin. Clin. Chem. 34: 9, 1988.

    PubMed  CAS  Google Scholar 

  48. Wilke T.J., Sheedy T.J., Hirning D.A. Performance characteristics and diagnostic value (vs other tests) of two radioimmunoassay kits for estimating free triiodothyronine in serum. Clin. Chem. 30: 216, 1984

    PubMed  CAS  Google Scholar 

  49. Forshaw K.M., van Heyningen C. Diagnostic value of a modified assay of free triiodothyronine in serum. Clin. Chem. 33: 2093, 1987.

    PubMed  CAS  Google Scholar 

  50. Csako G., Zweig M.H., Benson C., Ruddel M. On the albumin dependence of measurements of free thyroxin. I. Technical performance of seven methods. Clin. Chem. 32: 108, 1986.

    PubMed  CAS  Google Scholar 

  51. Konno N., Nakazato T., Hagiwara K., Taguchi H. A comparison of measurements of serum free T3 concentration by equilibrium dialysis, free T3 index, and T3: TBG ratio in thyroidal and non-thyroidal illnesses. Acta Endocrinol. (Copenh) 103: 501, 1983.

    CAS  Google Scholar 

  52. Hirano T., Singh J., Srinivasan G., Pildes R. Post-natal thyroid function in low birth weight infants; a longitudinal assessment of free thyroxine and thyroid hormone binding globulin. Acta Endocrinol. (Copenh) 110: 56, 1985.

    CAS  Google Scholar 

  53. Pacchiarotti A., Bartalena L., Chiovato L., Falcone M., Buratti L., Ciampi M., Giusti L.F., Grasso L., Fenzi G.F., Martino E., Pinchera A. Free thyroxine values in dried blood spots on filter paper in newborns are related to both gestational age and birth body weight. J. Endocrinol. Invest. 11: 515, 1988.

    Article  PubMed  CAS  Google Scholar 

  54. Liewendahl K., Tikanoja S., Helenius T., Valimaki M. Discrepancies between serum free triiodothyronine and free thyroxin as measured by equilibrium dialysis and analog radioimmunoassay in nonthyroidal illnesses. Clin. Chem. 30: 760, 1984.

    PubMed  CAS  Google Scholar 

  55. Kaptein E.M., Macintyre S.S., Weiner J.M., Spencer C.A., Nicoloff J.T Free thyroxine estimates in nonthyroidal illness: comparison of eight methods. J. Clin. Endocrinol. Metab. 52: 1073, 1981.

    Article  PubMed  CAS  Google Scholar 

  56. Rajatanavin R., Fournier L., De Cosimo D., Abreau C., Braverman L.E. Elevated serum free thyroxine by thyroxine analog radioimmunoassays in euthyroid patients with familial dysalbuminemic hyperthyroxinemia. Ann. Int. Med. 97: 865, 1982.

    Article  PubMed  CAS  Google Scholar 

  57. Beck-Peccoz P., Romelli P.B., Cattaneo M.G., Faglia G., White E.L., Barlow J.W., Stockigt J.R. Evaluation of free thyroxine methods in the presence of iodothyronine-binding autoantibodies. J. Clin. Endocrinol. Metab. 58: 736, 1984.

    Article  PubMed  CAS  Google Scholar 

  58. Mardell R., Gamlen T.R. Artifactual reduction in circulating free thyroxine concentration by radioimmunoassay. Lancet 1: 973, 1982.

    Article  PubMed  CAS  Google Scholar 

  59. Rajatanavin R., Fournier L., Abreau C.M., Braverman L.E. Free thyroxine RIA concentration (GammaCoat) is spuriously elevated in blood collected in silicon- coated vacutainer tubes. J. Nucl. Med. 23: 751, 1982.

    Google Scholar 

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Authors and Affiliations

  1. Centro per lo Studio, Prevenzione, Diagnosi e Cura delle Tireopatie Cattedra di Endocrinologia Università di Parma, Via A. Gramsci 14, 43100, Parma, Italy

    E. Roti, E. Gardini, R. Minelli, L. Bianconi & M. Flisi

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  1. E. Roti
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  2. E. Gardini
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  3. R. Minelli
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  4. L. Bianconi
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  5. M. Flisi
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Additional information

This study was supported in part by grant 88.00.628.04 of Consiglio Nazionale delle Ricerche, Roma by grant “Patologia della Tiroide: Indagine dei Fattori Etiopatogenetici” of Ministero Pubblica Istruzione 40%, Roma, Italy.

Dr. Eliana Gardini is a recipient of a Fellowship from Associazione Volontaria Promozione Ricerca Tumori (A.VO.PRO.RI.T.), Parma, Italy.

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Roti, E., Gardini, E., Minelli, R. et al. Thyroid function evaluation by different commercially available free thyroid hormone measurement kits in term pregnant women and their newborns. J Endocrinol Invest 14, 1–9 (1991). https://doi.org/10.1007/BF03350244

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