USEFULNESS OF FREE THYROXINE TO FREE TRIIODOTHYRONINE RATIO FOR DIAGNOSTICS OF VARIOUS TYPES OF HYPERTHYROIDISM
Background: Different types of hyperthyroidism are treated differently. The correct diagnosis enables the adequate treatment. Clinical experiences suggest that free thyroxine (fT4) to free triiodothyronine (fT3) ratio is different for different types of hyperthyroidism. Considering the paucity of literature data on the topic our aim was to evaluate the role of the serum fT4 to fT3 (fT4/fT3)ratio in diagnostics of various types of hyperthyroidism.
Methods: In retrospective clinical study we included 440 consecutive subjects, examined between February and August 2010, 350 females and 90 males aged between 15 and 97 years, among them 225 healthy subjects (HS), 80 patients with Graves' disease (GD), 48 with toxic adenoma (TA), 61 patients with hyperthyroid Hashimoto’s thyroiditis (HHT), 17 with subacute thyroiditis (ST), and 9 patients with iodine-induced hyperthyroidism (IIH). Thyrotropin (TSH), fT4, fT3 and thyroid autoantibodies were measured. The fT4/fT3 ratio was calculated.
Results: The fT4/fT3 ratio was significantly different for various disorders causing hyperthyroidism (p<0.001). Compared with the fT4/fT3 ratio in HS (2.86±0.52), the ratio was significantly higher in HHT and ST (3.27±0.72 and 3.31±0.54, respectively, p<0.001 for both). In GD, the fT4/fT3 ratio was the lowest (2.55±0.58) and in IIH the highest (5.13±1.97). Both ratios significantly differed from the ratio in HS (p<0.001 for both) and in other hyperthyroid patients (p<0.001 for both). In patients with TA, the fT4/fT3 ratio was similar as in HS (2.85±0.71) (p=0.085).
Conclusion: The fT4/fT3 ratio is different in various types of hyperthyroidism and therefore represents a useful tool in the diagnostic procedure.
Panicker V, Cluett C, Shields B, Murray A, Parnell KS, Perry JR, et al. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab. 2008; 93: 3075-81.
Maia AL, Kim BW, Huang SA, Harney JW, Larsen PR. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest. 2005; 115: 2524-33.
Mortoglou A, Candiloros H. The serum triiodothyronine to thyroxine (T3/T4) ratio in various thyroid disorders and after Levothyroxine replacement therapy. Hormones. 2004; 3: 120-6.
Cooper DS, 2003 Hyperthyroidism. Lancet 9: 459-468.
Noh YJ, Momotani N, Fukada S, Ito K, Miyauchi A, Amino N. Ratio of serum free thiiodothyronine to free thyroxine in Graves’ hyperthyroidism and thyrotoxicosis caused by painless thyroiditis. Endocr J. 2005; 52: 537-42.
Ito M, Toyoda N, Nomura E, Takamura Y, Amino N, Iwasaka T, et al. Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with 3,5,3'-triiodothyronine-predominant Graves’ disease. Eur J Endocrinol. 2011; 164: 95-100.
Sesmilo G, Simó O, Choque L, Casamitjana R, Puig-Domingo M, Halperin I. Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism. Endocrinol Nutr. 2011; 58: 9-15.
Zaletel K, Gaberšček S, Pirnat E, Krhin B, Hojker S. Ten-year follow-up of thyroid epidemiology in Slovenia after increase in salt iodization. Croat Med J. 2011; 52: 615-21.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87: 489-99.
Quintero OL, Amador-Patarroyo MJ, Montoya-Ortiz G, Rojas-Villarraga A, Anaya JM. Autoimmune disease and gender: plausible mechanism for the female predominance of autoimmunity. J Autoimmun. 2011; 38: J109-19.
Essebag V, Reynolds MR, Hadjis T, Lemery R, Olshansky B, Buxton AE, et al. Sex differences in the relationship between amiodarone use and the need for permanent pacing in patients with atrial fibrillation. Arch Intern Med. 2007; 167: 1648-53.
Roten L, Rimoldi SF, Schwick N, Sakata T, Heimgartner C, Fuhrer J, et al. Gender differences in patients referred for atrial fibrilattion management to a tertiary center. Pacing Clin Electrophysiol. 2009; 32: 622-6.
Hamburger JI. Evolution of toxicity in solitary nontoxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab. 1980; 50: 1089-93.
Tsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. Can J Cardiol. 2009; 25: 421-4.
Hosoi Y, Murakami M, Mizuma H, Ogiwara T, Imamura M, Mori M. Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells. J Clin Endocrinol Metab. 1999; 84: 3293-300.
Nishikawa M, Toyoda N, Yonemoto T, Ogawa Y, Tabata S, Sakaguchi N, et al. Quantitative measurement for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease. Biochem Biophys Res Commun. 1998; 29: 642-6.
Woeber KA. Triiodothyronine production in Graves’ hyperthyroidism. Thyroid. 2006; 16: 687-90.
Leisner B. In-vivo Bestimmung des thyreoidalen Jodgehalts bei funktioneller Autonomie. Acta Med Austriaca. 1990; 17 Suppl I: 33-5.
Zimmermann MB. Iodine deficiency. Endocr Rev. 2009; 30: 376-408.
Amino N, Yabu Y, Miki T, Morimoto S, Kumahara Y, mori H, et al. Serum ratio of triiodothyronine to thyroxine, and thyroxine-binding globulin and calcitonin concentrations in Graves' disease and destruction-induced thyrotoxicosis. J Clin Endocrinol Metab. 1981; 53: 113-6.
Martino E, Bartalena L, Bogazzi F, Braverman LE. The effect of amiodarone on the thyroid. Endocrine Rev. 2001; 22: 240-54.
Eskes SA, Wiersinga WM. Amiodarone and thyroid. Best Pract Res Clin Endocrinol Metab. 2009; 23: 735-51.
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