Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Aug;80(2):522–534. doi: 10.1172/JCI113101

Role of serum carrier proteins in the peripheral metabolism and tissue distribution of thyroid hormones in familial dysalbuminemic hyperthyroxinemia and congenital elevation of thyroxine-binding globulin.

R Bianchi, G Iervasi, A Pilo, F Vitek, M Ferdeghini, F Cazzuola, G Giraudi
PMCID: PMC442266  PMID: 3112186

Abstract

To investigate the role of thyroxine-binding globulin (TBG) and albumin in the availability of thyroid hormones to peripheral tissues, comprehensive kinetic studies of thyroxine (T4) and triiodothyronine (T3) were carried out in eight subjects with familial dysalbuminemic hyperthyroxinemia (FDH), in four subjects with inherited TBG excess, and in 15 normals. In high-TBG subjects, the reduction of T4 and T3 plasma clearance rates (by 51% and 54%, respectively) was associated with normal daily productions; T4 and T3 distribution volumes were significantly reduced. In FDH subjects T4 clearance was less reduced (by 31%) than in high TBG; consequently T4 production rate was significantly increased (by 42%); T4 and T3 distribution volumes and T3 clearance rate were unchanged. Increased T3 peripheral production in FDH (by 24%) indicates that T4 bound to abnormal albumin is more available to tissues than T4 carried by TBG, thus suggesting an important role of albumin in T4 availability to the periphery.

Full text

PDF
522

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BEIERWALTES W. H., ROBBINS J. Familial increase in the thyroxine-binding sites in serum alpha globulin. J Clin Invest. 1959 Oct;38:1683–1688. doi: 10.1172/JCI103946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bianchi R., Mariani G., Molea N., Vitek F., Cazzuola F., Carpi A., Mazzuca N., Toni M. G. Peripheral metabolism of thyroid hormones in man. I. Direct measurement of the conversion rate of thyroxine to 3,5,3'-triiodothyronine (T3) and determination of the peripheral and thyroidal production of T3. J Clin Endocrinol Metab. 1983 Jun;56(6):1152–1163. doi: 10.1210/jcem-56-6-1152. [DOI] [PubMed] [Google Scholar]
  3. Bianchi R., Molea N., Cazzuola F., Fusani L., Mariani G. Preparation of radioiodothyronines for tracer turnover studies in man. J Nucl Med Allied Sci. 1981 Jul-Sep;25(3):133–139. [PubMed] [Google Scholar]
  4. Bianchi R., Pilo A., Mariani G., Molea N., Cazzuola F., Ferdeghini M., Bertelli P. Comparison of plasma and urinary methods for the direct measurement of the thyroxine to 3,5,3' - triiodothyronine conversion rate in man. J Clin Endocrinol Metab. 1984 Jun;58(6):993–1002. doi: 10.1210/jcem-58-6-993. [DOI] [PubMed] [Google Scholar]
  5. Bianchi R., Zucchelli G. C., Giannessi D., Pilo A., Mariani G., Carpi A., Toni M. G. Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma. J Clin Endocrinol Metab. 1978 Feb;46(2):203–214. doi: 10.1210/jcem-46-2-203. [DOI] [PubMed] [Google Scholar]
  6. Borst G. C., Eil C., Burman K. D. Euthyroid hyperthyroxinemia. Ann Intern Med. 1983 Mar;98(3):366–378. doi: 10.7326/0003-4819-98-3-366. [DOI] [PubMed] [Google Scholar]
  7. Burr W. A., Ramsden D. B., Hoffenberg R. Hereditary abnormalities of thyroxine-binding globulin concentration. A study of 19 kindreds with inherited increase or decrease of thyroxine-binding globulin. Q J Med. 1980;49(195):295–313. [PubMed] [Google Scholar]
  8. Cavalieri R. R., Steinberg M., Searle G. L. The distribution kinetics of triiodothyronine: studies of euthyroid subjects with decreased plasma thyroxine-binding globulin and patients with Graves' disease. J Clin Invest. 1970 Jun;49(6):1041–1050. doi: 10.1172/JCI106320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cefalu W. T., Pardridge W. M., Premachandra B. N. Hepatic bioavailability of thyroxine and testosterone in familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1985 Oct;61(4):783–786. doi: 10.1210/jcem-61-4-783. [DOI] [PubMed] [Google Scholar]
  10. Clerico A., Zucchelli G. C., Fusani L., Giannessi D., Mariani G., Bianchi R. A simplified method of measuring free tri-iodothyronine in serum by combined equilibrium dialysis and gel sephadex extraction. J Nucl Biol Med. 1976 Oct-Dec;20(4):176–178. [PubMed] [Google Scholar]
  11. Davis P. J., Gregerman R. I. Separation of thyroxine(T4)-binding proteins of human serum in polyacrylamide gel at pH 7.4. I. Effect of pH on distrubution of tracer quantities of T4. J Clin Endocrinol Metab. 1970 Feb;30(2):237–245. doi: 10.1210/jcem-30-2-237. [DOI] [PubMed] [Google Scholar]
  12. DiStefano J. J., 3rd, Jang M., Malone T. K., Broutman M. Comprehensive kinetics of triiodothyronine production, distribution, and metabolism in blood and tissue pools of the rat using optimized blood-sampling protocols. Endocrinology. 1982 Jan;110(1):198–213. doi: 10.1210/endo-110-1-198. [DOI] [PubMed] [Google Scholar]
  13. DiStefano J. J., 3rd, Malone T. K., Jang M. Comprehensive kinetics of thyroxine distribution and metabolism in blood and tissue pools of the rat from only six blood samples: dominance of large, slowly exchanging tissue pools. Endocrinology. 1982 Jul;111(1):108–117. doi: 10.1210/endo-111-1-108. [DOI] [PubMed] [Google Scholar]
  14. Dunn J. F., Nisula B. C., Rodbard D. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab. 1981 Jul;53(1):58–68. doi: 10.1210/jcem-53-1-58. [DOI] [PubMed] [Google Scholar]
  15. Gurpide E., Mann J. Interpretation of isotopic data obtained from blood-borne compounds. J Clin Endocrinol Metab. 1970 Jun;30(6):707–718. doi: 10.1210/jcem-30-6-707. [DOI] [PubMed] [Google Scholar]
  16. Gärtner R., Henze R., Horn K., Pickardt C. R., Scriba P. C. Thyroxine-binding globulin: investigation of microheterogeneity. J Clin Endocrinol Metab. 1981 Apr;52(4):657–664. doi: 10.1210/jcem-52-4-657. [DOI] [PubMed] [Google Scholar]
  17. Hays M. T., McGuire R. A. Distribution of subcutaneous thyroxine, triiodothyronine, and albumin in man: comparison with intravenous administration using a kinetic model. J Clin Endocrinol Metab. 1980 Nov;51(5):1112–1117. doi: 10.1210/jcem-51-5-1112. [DOI] [PubMed] [Google Scholar]
  18. Hennemann G., Docter R., Dolman A. Relationship between total thyroxine and absolute free thyroxine and the influence of absolute free thyroxine on thyroxine disposal in humans. J Clin Endocrinol Metab. 1971 Jul;33(1):63–67. doi: 10.1210/jcem-33-1-63. [DOI] [PubMed] [Google Scholar]
  19. Hennemann G., Docter R., Krenning E. P., Bos G., Otten M., Visser T. J. Raised total thyroxine and free thyroxine index but normal free thyroxine. A serum abnormality due to inherited increased affinity of iodothyronines for serum binding protein. Lancet. 1979 Mar 24;1(8117):639–642. doi: 10.1016/s0140-6736(79)91080-8. [DOI] [PubMed] [Google Scholar]
  20. Hershman J. M., Nademanee K., Sugawara M., Pekary A. E., Ross R., Singh B. N., DiStefano J. J., 3rd Thyroxine and triiodothyronine kinetics in cardiac patients taking amiodarone. Acta Endocrinol (Copenh) 1986 Feb;111(2):193–199. doi: 10.1530/acta.0.1110193. [DOI] [PubMed] [Google Scholar]
  21. Ingbar S. H. CLINICAL AND PHYSIOLOGICAL OBSERVATIONS IN A PATIENT WITH AN IDIOPATHIC DECREASE IN THE THYROXINE-BINDING GLOBULIN OF PLASMA. J Clin Invest. 1961 Nov;40(11):2053–2063. doi: 10.1172/JCI104431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kaptein E. M., Grieb D. A., Spencer C. A., Wheeler W. S., Nicoloff J. T. Thyroxine metabolism in the low thyroxine state of critical nonthyroidal illnesses. J Clin Endocrinol Metab. 1981 Oct;53(4):764–771. doi: 10.1210/jcem-53-4-764. [DOI] [PubMed] [Google Scholar]
  23. Lalloz M. R., Byfield P. G., Himsworth R. L. Hyperthyroxinaemia: abnormal binding of T4 by an inherited albumin variant. Clin Endocrinol (Oxf) 1983 Jan;18(1):11–24. doi: 10.1111/j.1365-2265.1983.tb03181.x. [DOI] [PubMed] [Google Scholar]
  24. Lee W. N., Golden M. P., Van Herle A. J., Lippe B. M., Kaplan S. A. Inherited abnormal thyroid hormone-binding protein causing selective increase of total serum thyroxine. J Clin Endocrinol Metab. 1979 Aug;49(2):292–299. doi: 10.1210/jcem-49-2-292. [DOI] [PubMed] [Google Scholar]
  25. Mendel C. M., Cavalieri R. R. Thyroxine distribution and metabolism in familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1984 Sep;59(3):499–504. doi: 10.1210/jcem-59-3-499. [DOI] [PubMed] [Google Scholar]
  26. Nicoloff J. T., Low J. C., Dussault J. H., Fisher D. A. Simultaneous measurement of thyroxine and triiodothyronine peripheral turnover kinetics in man. J Clin Invest. 1972 Mar;51(3):473–483. doi: 10.1172/JCI106835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oppenheimer J. H., Bernstein G., Hasen J. Estimation of rapidly exchangeable cellular thyroxine from the plasma disappearance curves of simultaneously administered thyroxine-131-I and albumin-125-I. J Clin Invest. 1967 May;46(5):762–777. doi: 10.1172/JCI105577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Oppenheimer J. H., Schwartz H. L., Surks M. I. Letter: (to the editor). Erratum: revised calculations of common parameters of iodothyronine metabolism and distribution by noncompartmental analysis. J Clin Endocrinol Metab. 1975 Dec;41(06):1172–1173. doi: 10.1210/jcem-41-6-1172. [DOI] [PubMed] [Google Scholar]
  29. Pardridge W. M., Landaw E. M. Tracer kinetic model of blood-brain barrier transport of plasma protein-bound ligands. Empiric testing of the free hormone hypothesis. J Clin Invest. 1984 Sep;74(3):745–752. doi: 10.1172/JCI111490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pardridge W. M., Mietus L. J. Influx of thyroid hormones into rat liver in vivo. Differential availability of thyroxine and triiodothyronine bound by plasma proteins. J Clin Invest. 1980 Aug;66(2):367–374. doi: 10.1172/JCI109865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Refetoff S., Fang V. S., Marshall J. S., Robin N. I. Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess. J Clin Invest. 1976 Feb;57(2):485–495. doi: 10.1172/JCI108301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ruiz M., Rajatanavin R., Young R. A., Taylor C., Brown R., Braverman L. E., Ingbar S. H. Familial dysalbuminemic hyperthyroxinemia: a syndrome that can be confused with thyrotoxicosis. N Engl J Med. 1982 Mar 18;306(11):635–639. doi: 10.1056/NEJM198203183061103. [DOI] [PubMed] [Google Scholar]
  33. Sakurada T., Yamaguchi T., Yoshida K., Yamamoto M., Onodera S. Kinetics of thyroxine and triiodothyronine in a case of thyroxine-binding globulin deficiency with hypothyroidism. Tohoku J Exp Med. 1974 Feb;112(2):133–140. doi: 10.1620/tjem.112.133. [DOI] [PubMed] [Google Scholar]
  34. Sterling K., Brenner M. A. Free thyroxine in human serum: simplified measurement with the aid of magnesium precipitation. J Clin Invest. 1966 Jan;45(1):153–163. doi: 10.1172/JCI105320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stockigt J. R., Topliss D. J., Barlow J. W., White E. L., Hurley D. M., Taft P. Familial euthyroid thyroxine excess: an appropriate response to abnormal thyroxine binding associated with albumin. J Clin Endocrinol Metab. 1981 Aug;53(2):353–359. doi: 10.1210/jcem-53-2-353. [DOI] [PubMed] [Google Scholar]
  36. Sutherland R. L., Simpson-Morgan M. W. The thyroxine-binding properties of serum proteins. A competitive binding technique employing sephadex G-25. J Endocrinol. 1975 Jun;65(3):319–332. doi: 10.1677/joe.0.0650319. [DOI] [PubMed] [Google Scholar]
  37. TAIT J. F. REVIEW: THE USE OF ISOTOPIC STEROIDS FOR THE MEASUREMENT OF PRODUCTION RATES IN VIVO. J Clin Endocrinol Metab. 1963 Dec;23:1285–1297. doi: 10.1210/jcem-23-12-1285. [DOI] [PubMed] [Google Scholar]
  38. Travis J., Bowen J., Tewksbury D., Johnson D., Pannell R. Isolation of albumin from whole human plasma and fractionation of albumin-depleted plasma. Biochem J. 1976 Aug 1;157(2):301–306. doi: 10.1042/bj1570301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yamamoto T., Doi K., Ichihara K., Miyai K. Reevaluation of measurement of serum free thyroxine by equilibrium dialysis based on computational analysis of the interaction between thyroxine and its binding proteins. J Clin Endocrinol Metab. 1980 May;50(5):882–888. doi: 10.1210/jcem-50-5-882. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES