Abstract
Previous studies have suggested that there is an overproduction of triiodothyronine (T3) relative to thyroxine (T4) in patients with thyrotoxicosis associated with Graves' disease. To evaluate whether or not an increased ratio of T3 to T4 in thyroidal secretion could be contributing to this relative T3 hyperproduction, T3, T4, and iodine were measured in thyroglobulin (Tg) from controls and patients with Graves' disease who had been treated either with propranolol only or with antithyroid drugs plus iodide before surgery. To avoid possible artifacts associated with pulse labeling and chromatography, T3 and T4 were determined by radioimmunoassay of Pronase hydrolysates of purified Tg. Results of analyses of Tg from six control patients and seven with Graves' disease, not receiving thiourea drugs or iodide, showed that the iodine content of Graves' disease Tg was not different from normal. Both contained 3.4 residues of T4/molecule Tg, but there was 0.39±0.08 (mean±SD) residue of T3/molecule Tg in Graves' Tg as opposed to 0.23±0.07 residue T3 molecule Tg in controls matched for iodine content (P < 0.01). This difference resulted in a significantly lower T4/T3 molar ratio (9±2) in Graves' Tg as opposed to control (15±2, P < 0.001). In Tg from patients with treated Graves' disease, iodine, T3, and T4 were reduced, but the reduction in the latter was more substantial, resulting in a T4/T3 molar ratio of 3.4±1. Fractionation of Tg from all groups by RbCl density gradient ultracentrifugation indicated that at physiological levels of Tg iodination, the molar ratio of T3/Tg was consistently higher in Graves' disease. The specific mechanism for this difference is not known, but it is not due to iodine deficiency. If T3 and T4 are secreted in this altered ratio in patients with Graves' disease, the magnitude of the difference could explain the relative T3 hyperproduction which is characteristic of this state.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abrams G. M., Larsen P. R. Triiodothyronine and thyroxine in the serum and thyroid glands of iodine-deficient rats. J Clin Invest. 1973 Oct;52(10):2522–2531. doi: 10.1172/JCI107443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Abuid J., Larsen P. R. Triiodothyronine and thyroxine in hyperthyroidism. Comparison of the acute changes during therapy with antithyroid agents. J Clin Invest. 1974 Jul;54(1):201–208. doi: 10.1172/JCI107744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Azizi F., Vagenakis A. G., Bush J. E., Braverman L. E. Effect of propranolol on various aspects of thyroid function in the rat. Metabolism. 1974 Jun;23(6):525–529. doi: 10.1016/0026-0495(74)90080-8. [DOI] [PubMed] [Google Scholar]
- Bilstad J. M., Edelhoch H., Lippoldt R., Rall J. E., Salvatore G. Isolation and characterization of discrete fragments of 27 S thyroid iodoprotein. Arch Biochem Biophys. 1972 Jul;151(1):341–350. doi: 10.1016/0003-9861(72)90505-x. [DOI] [PubMed] [Google Scholar]
- Chopra I. J., Fisher D. A., Solomon D. H., Beall G. N. Thyroxine and triiodothyronine in the human thyroid. J Clin Endocrinol Metab. 1973 Feb;36(2):311–316. doi: 10.1210/jcem-36-2-311. [DOI] [PubMed] [Google Scholar]
- Dunn J. T., Ray S. C. Changes in the structure of thyroglobulin following the administration of thyroid-stimulating hormone. J Biol Chem. 1975 Aug 10;250(15):5801–5807. [PubMed] [Google Scholar]
- Dussault J. H., Lam R., Fisher D. A. The measurement of serum triiodothyronine by double column chromatography. J Lab Clin Med. 1971 Jun;77(6):1039–1050. [PubMed] [Google Scholar]
- Greer M. A., Allen C. F., Torresani J., Roques M., Lissitzky S. TSH stimulation of iodothyronine formation in prelabeled thyroglobulin of hypophysectomized rats. Endocrinology. 1974 May;94(5):1224–1231. doi: 10.1210/endo-94-5-1224. [DOI] [PubMed] [Google Scholar]
- Inoue K., Taurog A. Digestion of 131I-labeled thyroid tissue with maximum recovery of 131I-iodothyronines. Endocrinology. 1967 Aug;81(2):319–332. doi: 10.1210/endo-81-2-319. [DOI] [PubMed] [Google Scholar]
- Lamas L., Dorris M. L., Taurog A. Evidence for a catalytic role for thyroid peroxidase in the conversion of diiodotyrosine to thyroxine. Endocrinology. 1972 Jun;90(6):1417–1426. doi: 10.1210/endo-90-6-1417. [DOI] [PubMed] [Google Scholar]
- Larsen P. R. Technical aspects of the estimation of triiodothyronine in human serum: evidence of conversion of thyroxine to triiodothyronine during assay. Metabolism. 1971 Jun;20(6):609–624. doi: 10.1016/0026-0495(71)90009-6. [DOI] [PubMed] [Google Scholar]
- Larsen P. R. Thyroidal triiodothyronine and thyroxine in Graves' disease: correlation with presurgical treatment, thyroid status, and iodine content. J Clin Endocrinol Metab. 1975 Dec;41(06):1098–1104. doi: 10.1210/jcem-41-6-1098. [DOI] [PubMed] [Google Scholar]
- Larsen P. R. Triiodothyronine: review of recent studies of its physiology and pathophysiology in man. Metabolism. 1972 Nov;21(11):1073–1092. doi: 10.1016/0026-0495(72)90038-8. [DOI] [PubMed] [Google Scholar]
- Larsen P. R., Yamashita K., Dekker A., Field J. B. Biochemical observations in functioning human thyroid adenomas. J Clin Endocrinol Metab. 1973 May;36(5):1009–1018. doi: 10.1210/jcem-36-5-1009. [DOI] [PubMed] [Google Scholar]
- Loewenstein J. E., Wollman S. H. Kinetics of equilibrium labeling of the rat thyroid gland with 125-I. Endocrinology. 1967 Nov;81(5):1063–1073. doi: 10.1210/endo-81-5-1063. [DOI] [PubMed] [Google Scholar]
- Lowenstein J. E., Wollman S. H. Distribution of organic 125-I and 127-I in the rat thyroid gland during equilibrium labeling as determined by autoradiography. Endocrinology. 1967 Nov;81(5):1074–1085. doi: 10.1210/endo-81-5-1074. [DOI] [PubMed] [Google Scholar]
- Nagataki S., Uchimura H., Masuyama Y., Nakao K., Ito K. Triiodothyronine and thyroxine in thyroid glands of euthyroid Japanese subjects. J Clin Endocrinol Metab. 1972 Jul;35(1):18–23. doi: 10.1210/jcem-35-1-18. [DOI] [PubMed] [Google Scholar]
- Riesco G., Taurog A., Larsen R., Krulich L. Acute and chronic responses to iodine deficiency in rats. Endocrinology. 1977 Feb;100(2):303–313. doi: 10.1210/endo-100-2-303. [DOI] [PubMed] [Google Scholar]
- Rolland M., Montfort M. F., Valenta L., Lissitzky S. Iodoamino acid composition of the thyroglobulin of normal and diseased thyroid glands. Comparison with in vitro iodinated thyroglobulin. Clin Chim Acta. 1972 Jun;39(1):95–108. doi: 10.1016/0009-8981(72)90304-x. [DOI] [PubMed] [Google Scholar]
- STUDER H., GREER M. A. A STUDY OF THE MECHANISMS INVOLVED IN THE PRODUCTION OF IODINE-DEFICIENCY GOITER. Acta Endocrinol (Copenh) 1965 Aug;49:610–628. doi: 10.1530/acta.0.0490610. [DOI] [PubMed] [Google Scholar]
- Schneider A. B., Edelhoch H. Equilibrium density centrifugation of thyroglobulin in RbCl. Effect of iodine. J Biol Chem. 1971 Nov;246(21):6592–6598. [PubMed] [Google Scholar]
- Sterling K., Refetoff S., Selenkow H. A. T3 thyrotoxicosis. Thyrotoxicosis due to elevated serum triiodothyronine levels. JAMA. 1970 Jul 27;213(4):571–575. doi: 10.1001/jama.213.4.571. [DOI] [PubMed] [Google Scholar]
- Valenta L. J. Thyroid peroxidase, thyroglobulin, cAMP and DNA in human thyroid. J Clin Endocrinol Metab. 1976 Aug;43(2):466–469. doi: 10.1210/jcem-43-2-466. [DOI] [PubMed] [Google Scholar]
- Wartofsky L., Dimond R. C., Noel G. L., Frantz A. G., Earll J. M. Failure of propranolol to alter thyroid iodine release, thyroxine turnover, or the TSH and PRL responses to thyrotropin-releasing hormone in patients with thyrotoxicosis. J Clin Endocrinol Metab. 1975 Sep;41(3):485–490. doi: 10.1210/jcem-41-3-485. [DOI] [PubMed] [Google Scholar]
