This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, B. W. Articles by Weetman, A. P. Search for Related Content PubMed PubMed Citation Articles by Kim, B. W. Articles by Weetman, A. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LEVOTHYROXINE Medline Plus Health Information Thyroid Cancer

Overexpression of Type 2 Iodothyronine Deiodinase in Follicular Carcinoma as a Cause of Low Circulating Free Thyroxine Levels

University of Sheffield Clinical Sciences Centre (A.P.W.) and Departments of Surgery (B.J.H.) and Clinical Chemistry (A.P.), Northern General Hospital, Sheffield, S5 7AU, United Kingdom; Thyroid Division (B.W.K., J.W.H., P.R.L.), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Thyroid Unit (G.H.D.) and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02108

Address all correspondence and requests for reprints to: Prof. A. P. Weetman, University Clinical Sciences Centre, Northern General Hospital, Sheffield, S5 7AU, United Kingdom. E-mail: k.f.watson{at}sheffield ac.uk.

Thyroid function is normally undisturbed in patients with thyroid carcinoma. We have identified three patients with large or widely metastatic follicular thyroid carcinoma who had a persistently increased ratio of serum T₃ to T₄ in the absence of autonomous production of T₃ by the tumor. To investigate the possibility of tumor-mediated T₄ to T₃ conversion, we assayed types 1 and 2 iodothyronine selenodeiodinase (D1 and D2) activity in a 965-g follicular thyroid carcinoma resected from one of these patients. The V_max for D2 was 8-fold higher than in normal human thyroid tissue. Resection of this tumor, leaving the left thyroid lobe intact, normalized the serum T₃ to T₄ ratio. In two other patients, treatment with sufficient levothyroxine to suppress TSH was associated with a high normal T₃ and a subnormal free T₄ index. In one, concomitant administration of the D1 inhibitors, propylthiouracil and propranolol, did not decrease the elevated serum T₃ to T₄ ratio. These data illustrate that increased T₄ to T₃ conversion in follicular thyroid carcinomas, probably by D2, can cause a significant perturbation in peripheral thyroid hormone concentrations.

This work was supported by Grants DK36256 and DK07529 from the National Institutes of Health.

Abbreviations: CT, Computed tomography; D1, type 1 iodothyronine deiodinase; D2, type 2 iodothyronine deiodinase; D3, type 3 iodothyronine deiodinase; DTT, dithiothreitol; FT₄I, free T₄ index; PTU, propylthiouracil; Tg, thyroglobulin.

This article has been cited by other articles:

				F. S. Celi, G. Coppotelli, A. Chidakel, M. Kelly, B. A. Brillante, T. Shawker, N. Cherman, P. P. Feuillan, and M. T. Collins The Role of Type 1 and Type 2 5'-Deiodinase in the Pathophysiology of the 3,5,3'-Triiodothyronine Toxicosis of McCune-Albright Syndrome J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2383 - 2389. [Abstract] [Full Text] [PDF]

				A. Miyauchi, Y. Takamura, Y. Ito, A. Miya, K. Kobayashi, F. Matsuzuka, N. Amino, N. Toyoda, E. Nomura, and M. Nishikawa 3,5,3'-Triiodothyronine Thyrotoxicosis due to Increased Conversion of Administered Levothyroxine in Patients with Massive Metastatic Follicular Thyroid Carcinoma J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2239 - 2242. [Abstract] [Full Text] [PDF]

				P. Laurberg, H. Vestergaard, S. Nielsen, S. E. Christensen, T. Seefeldt, K. Helleberg, and K. M. Pedersen Sources of Circulating 3,5,3'-Triiodothyronine in Hyperthyroidism Estimated after Blocking of Type 1 and Type 2 Iodothyronine Deiodinases J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2149 - 2156. [Abstract] [Full Text] [PDF]

				C. S. Kim, H. Ying, M. C. Willingham, and S.-y. Cheng The pituitary tumor-transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer Carcinogenesis, May 1, 2007; 28(5): 932 - 939. [Abstract] [Full Text] [PDF]

				Y. Kanou, A. Hishinuma, K. Tsunekawa, K. Seki, Y. Mizuno, H. Fujisawa, T. Imai, Y. Miura, T. Nagasaka, C. Yamada, et al. Thyroglobulin Gene Mutations Producing Defective Intracellular Transport of Thyroglobulin Are Associated with Increased Thyroidal Type 2 Iodothyronine Deiodinase Activity J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1451 - 1457. [Abstract] [Full Text] [PDF]

				F. W. J. S. Wassen, W. Klootwijk, E. Kaptein, D. J. Duncker, T. J. Visser, and G. G. J. M. Kuiper Characteristics and Thyroid State-Dependent Regulation of Iodothyronine Deiodinases in Pigs Endocrinology, September 1, 2004; 145(9): 4251 - 4263. [Abstract] [Full Text] [PDF]