Skip to main content

Advertisement

Log in

Thyroxine uptake by human hepatoma cells from serum of patients submitted to long-term thyroxine suppressive therapy

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The significance of thyroxine (T4) uptake from serum in the assessment of thyroid status was evaluated, using human hepatoma (Hep G2) cells, in 30 euthyroid subjects, 6 hypothyroid and 19 hyperthyroid patients, and in 23 athyreotic cancer patients under T4 suppressive therapy. Cellular thyroxine (CT4) was determined according to Sarne and Refetoff, J. Clin. Endocrinol. Metab. 61: 1046, 1985. CT4 averaged 9.9 ± 2.8 pg/well (mean ± SD, range 5.7–15.3) in euthyroid subjects, 1.5 ± 1.0 pg/well (range 0.05–4.2) in hypothyroid patients, 40.5 ± 18.8 pg/well (range 18.3 ± 104.7) in hyperthyroid patients, and 23.7 ± 7.2 pg/well (range 14.2–40.2) in T4-treated patients. In eu-, hypo- and hyperthyroid patients, a significant correlation was observed between CT4 and free T4 index (FT4I), free T4 (FT4) or Sex Hormone Binding Globulin (SHBG) values. In T4-treated patients, CT4 values were correlated with FT4I values, but not with FT4 or SHBG levels. All T4-treated patients with elevated SHBG levels had elevated FT4, FT4I and CT4 values. In contrast, of the 16 T4-treated subjects with normal serum SHBG concentrations, all but one had normal FT3, 3 (19%) had elevated FT4, 10 (62%) elevated FT4I and 13 (81%) elevated CT4, but all (100%) had undetectable TSH levels. Thus, considering serum SHBG concentrations as a parameter of hepatic tissue response to thyroid hormone, CT4 values, at least in T4-treated patients, do not accurately reflect the liver responsiveness to thyroid hormone action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kahn A. Serum thyroxine levels in patients receiving L-thyroxine suppression or replacement therapy. Can. Med. Assoc. J. 109: 279, 1973.

    PubMed Central  PubMed  CAS  Google Scholar 

  2. Murchison L.E., Chesters M.I., Bewsher P.D. Serum thyroid hormone levels in patients on thyroxine replacement therapy. Horm. Metab. Res. 8: 324, 1976.

    Article  PubMed  CAS  Google Scholar 

  3. Sawin C.T., Hershman J.M., Chopra I.J. The comparative effect of T4 and T3 on the TSH response in young adult males. J. Clin. Endocrinol. Metab. 44: 273, 1977.

    Article  PubMed  CAS  Google Scholar 

  4. Schimmel M., Utiger R.D. Thyroidal and peripheral production of thyroid hormones. Review of recent findings and their clinical implications. Ann. Intern. Med. 87: 760, 1977.

    Article  PubMed  CAS  Google Scholar 

  5. Krugman L.G., Hershman J.M. TRH test as an index of suppression compared with the thyroid radioiodine uptake in euthyroid goitrous patients treated with thyroxine. J. Clin. Endocrinol. Metab. 47: 78, 1978.

    Article  PubMed  CAS  Google Scholar 

  6. Johansen K., Hansen J., Perrild H., Skorsted L., Kampman J.P. The effect of suppressive therapy of nontoxic goiter on serum levels of thyroxine, 3,5,3′-triiodothyronine and 3, 3′, 5′-triiodothyronine. Acta Med. Scand. (Suppl.) 624: 25, 1979.

    CAS  Google Scholar 

  7. Lamberg B.-A., Rantanen M., Saarinen P., Liewendahl K., Sivula A. Suppression of TSH response to TRH by thyroxine therapy in differentiatedthyroid carcinoma patients. Acta Endocrinol. (Copenh.) 91: 248, 1979.

    CAS  Google Scholar 

  8. Ingbar J.C., Borges M., Iflah S., Kleinmann R.E., Braverman L.E., Ingbar S.H. Elevated serum thyroxine concentrations in patients receiving “replacement” dose of levothyroxine. J. Endocrinol. Invest. 5: 77, 1982.

    Article  PubMed  CAS  Google Scholar 

  9. Salmon D., Rendell M., Williams J., Smith C., Ross D.A., Wand J.M., Howard J.E. “Chemical hyperthyroidism”. Serum triiodothyronine levels in clinically euthyroid individuals treated with levothyroxine. Arch. Intern. Med. 142: 571, 1982.

    Article  PubMed  CAS  Google Scholar 

  10. Jennings P.E., O’Malley B.P., Griffin K.E., Northover B., Rosenthal F.D. Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case of “tissue thyrotoxicosis”. Br. Med. J. 289: 1645, 1984.

    Article  CAS  Google Scholar 

  11. Pearce C.J., Himsworth R.L. Total and free thyroid hormone concentrations in patients receiving maintenance replacement therapy with thyroxine. Br. Med. J. 288: 693, 1984.

    Article  CAS  Google Scholar 

  12. Pinchera A., Martino E., Pacchiarotti A., Bartalena L., Breccia M., Aghini-Lombardi F. Validity of serum free thyroid hormones in the assessment of the adequacy of L-thyroxine suppressive therapy. Nuc Compact 16: 387, 1985.

    Google Scholar 

  13. Rendell M., Salmon D. “Chemical hyperthyroidism”: the significance of elevated thyroxine levels in L-thyroxine treated individuals. Clin. Endocrinol. (Oxf.) 22: 693, 1985.

    Article  CAS  Google Scholar 

  14. Bartalena L., Martino E., Pacchiarotti A., Grasso L., Aghini-Lombardi F., Buratti L., Bambini G., Breccia M., Pinchera A. Factors affecting suppression of endogenous thyrotropin secretion by thyroxine treatment: retrospective analysis in athyreotic and goitrous patients. J. Clin. Endocrinol. Metab. 64: 849, 1987.

    Article  PubMed  CAS  Google Scholar 

  15. Same D.H., Refetoff S. Measurement of thyroxine uptake from serum by cultured human hepatocytes as an index of thyroid status: reduced thyroxine uptake from serum of patients with nonthyroidal illness. J. Clin. Endocrinol. Metab. 61: 1046, 1985.

    Article  Google Scholar 

  16. Bartalena L., Tata J.R., Robbins J. Characterization of nascent and secreted thyroxine-binding globulin (TBG) in cultured human hepatoma (Hep G2) cells. J. Biol. Chem. 259: 13605, 1984.

    PubMed  CAS  Google Scholar 

  17. Romelli P.B., Pennisi F., Vancheri L. Measurement of free thyroid hormones in serum by column adsorption chromatography and radioimmunoassay. J. Endocrinol. Invest. 2: 25, 1979.

    Article  PubMed  CAS  Google Scholar 

  18. Galen R.S., Gambino S.L. Beyond normality: the predictive value and efficiency of medical diagnoses. John Wiley & Sons, New York, 1980.

    Google Scholar 

  19. Pinchera A., Martino E., Bartalena L., Aghini-Lombardi F., Bambini G. Radioimmunoassay utilization in the assessment of thyroid status. In: Albertini A., Ekins R.P., Galen R.S. (Eds.), Cost/benefit and predictive value of radioimmunoassay. Elsevier, Amsterdam, 1984, p. 151.

    Google Scholar 

  20. Martino E., Bambini G., Bartalena L., Mammoli C., Aghini-Lombardi F., Baschieri L., Pinchera A. Human serum thyrotrophin measurement by ultrasensitive immunoradiometric assay as a first-line test in the evaluation of thyroid function. Clin. Endocrinol. (Oxf.) 24: 141, 1986.

    Article  CAS  Google Scholar 

  21. Spencer C.A. Clinical evaluation of free T4 techniques. J. Endocrinol. Invest. 9 (Suppl. 4): 57, 1986.

    PubMed  Google Scholar 

  22. Bartalena L., Mariotti S., Pinchera A. Radioimmunoassay of thyroid hormones. In: Patrono C., Peskar B.A. (Eds.), Handbook of Experimental Pharmacology. Springer-Verlag, Berlin, 1987, vol. 82, p. 401.

    Google Scholar 

  23. Bartalena L., Martino E., Falcone M., Buratti L., Grasso L., Mammoli C., Pacchiarotti A., Aghini-Lombardi F., Balzano S., Pinchera A. Evaluation of the nocturnal serum thyrotropin (TSH) surge, as assessed by TSH ultrasensitive assay, in patients receiving long term L-thyroxine suppression therapy and in patients with various thyroid disorders. J. Clin. Endocrinol. Metab. 65: 1265, 1987.

    Article  PubMed  CAS  Google Scholar 

  24. Spencer C.A., Lai-Rosenfeld A.O., Guttler R.B., Lo Presti J., Marcus A.O., Nimalasuriya A., Eigen A., Doss R.C., Green B.J., Nicoloff J.T. Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay. J. Clin. Endocrinol. Metab. 63: 349, 1986.

    Article  PubMed  CAS  Google Scholar 

  25. Ross D.S., Neer R.M., Ridgway E.C. Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine. Am. J. Med. 82: 1167, 1987.

    Article  PubMed  CAS  Google Scholar 

  26. Rosner W., Aden D.P., Khan M.S. Hormonal influences on the secretion of steroid-binding proteins by a human hepatoma-derived cell line. J. Clin. Endocrinol. Metab. 59: 806, 1984.

    Article  PubMed  CAS  Google Scholar 

  27. Olivo J., Southren A.L., Gordon G.G., Tochimoto S. Studies of the protein binding of testosterone in disorders of thyroid function. J. Clin. Endocrinol. Metab. 31: 539, 1970.

    Article  PubMed  CAS  Google Scholar 

  28. De Nayer Ph., Lambot M.P., Desmons M.C., Rennotte B., Malvaux P., Beckers C. Sex hormone-binding protein in hyperthyroxinemic patients: a discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. J. Clin. Endocrinol. Metab. 62: 1309, 1986.

    Article  PubMed  Google Scholar 

  29. Same D.H., Weinberg M. Normal cellular uptake of thyroxine (T4) from serum of patients with familial dysalbuminemic hyperthyroxinemia (FDH) or elevated thyroxine-binding globulin (TBG): T4 bound to albumin is not preferentially transferred to tissue. In: Medeiros-Neto G., Gaitan E. (Eds.), Frontiers in Thyroidology. Plenum Press, New York, 1986, vol. 1, p. 551.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bartalena, L., Martino, E., Falcone, M. et al. Thyroxine uptake by human hepatoma cells from serum of patients submitted to long-term thyroxine suppressive therapy. J Endocrinol Invest 11, 629–635 (1988). https://doi.org/10.1007/BF03350199

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350199

Key-words

Navigation