fT3 index/TSH index ratio and free thyroid hormone index in the differential diagnosis of thyrotoxicosis

Year 2022, Volume: 5 Issue: 2, 586 - 591, 15.03.2022

Davut Sakız , Murat Çalapkulu , Muhammed Erkam Sencar , Bekir Ucan , İlknur Öztürk Ünsal , Mustafa Özbek , Erman Çakal

https://doi.org/10.32322/jhsm.1058324

Cited By: 1

Abstract

Aim: Common causes of thyrotoxicosis are hyperthyroidism and destructive thyroiditis. Hyperthyroidism is a condition characterized by high serum thyroid hormone levels as a result of over-synthesis of thyroid hormones, the most common causes of which are Graves' disease (GD) and toxic nodular goiter (TNG). Subacute thyroiditis (SAT) causes thyrotoxicosis due to the circulating thyroid hormones of destructive thyroiditis. Differential diagnosis is important because GD, TNG and SAT treatment approaches are different. The aim of this study was to analyze whether it is possible to make a differential diagnosis for these conditions by examining free thyroid hormones, fT3/fT4 ratio, fT3 index/TSH index (fT3I/TSHI) ratio and Free Thyroid Hormone Index (FTHI).
Material and Method: This retrospective study included 150 patients who were diagnosed with GD, TNG and SAT. The fT3 index (fT3I) was calculated as the ratio between the fT3 value and the fT3 upper limit of normal value (fT3I=fT3/4 pg/ml). The fT4 index (fT4I) was calculated as the ratio between the fT4 value and the fT4 upper limit of normal value (fT4I=fT4/1.23 mg/dl). The TSH index (TSHI) was calculated as the ratio between TSH value and the TSH lower limit of normal limit (TSHI=TSH/0.38 mIU/L). The FTHI index was calculated using the formula of (fT3 level/fT3 upper limit of normal) / (fT4 level/fT4 upper limit of normal).
Results: The fT3, fT3/fT4 ratio and FTHI were found to be higher in hyperthyroid patients compared to subacute thyroiditis patients. fT4 and fT3I/TSHI levels were similar in hyperthyroid patients and SAT patients (p=0.49, p=0.11, respectively ). The cut-off level of FTHI for hyperthyroidism was determined as 0.97 with sensitivity of 75% and specificity of 76.3% (AUC=0.833, p< 0.001). When hyperthyroidic patients were divided into two groups as GD and TNG, no significant difference was found in fT3/fT4 ratio (p:0.99). The fT3 (p<0.001) and fT4 (p<0.001) values were found to be higher, and TSH values were found to be lower (p=0.001) in GD. The fT3I/TSHI ratio was found to be higher in Graves' patients (p<0.001). The cut off level for Graves’ disease was determined as sT3I/TSHI>324.58.
Conclusion: FTHI is useful in differentiating hyperthyroid conditions such as GD and TNG from SAT. FTHI is insufficient in the differential diagnosis of Graves disease and TNG. The fT3I/TSHI ratio is higher in Graves' disease than in TNG and SAT. The combination of FTHI and sT3I/TSHI methods can increase diagnostic accuracy.

Keywords

Hyperthyroidism, Free T4, T3/T4 ratio, Graves Disease, Toxic Nodular Guatr, Subacute Thyroiditis

Supporting Institution

None

References

• Sharma A, Stan MN. Thyrotoxicosis: diagnosis and management. Mayo Clin Proc 2019; 94: 1048-64.
• Kravets I. Hyperthyroidism: diagnosis and treatment. Am Fam Physician 2016; 93: 363-70.
• Sarkar SD. Benign thyroid disease: what is the role of nuclear medicine? Semin Nucl Med 2006; 36: 185-93.
• Pearce EN, Farwell AP, Braverman LE. Thyroiditis. New Engl J Med 2003; 348: 2646-55.
• De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet 2016; 388: 906-18.
• Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines Of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27: 315-89.
• Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016; 26: 1343-421.
• Sencar ME, Çalapkulu M, Sakiz D, et al. Frequency of thyroid antibodies at the diagnosis of subacute thyroiditis. Turkish J Endocrinol Metab 2020; 24: 144-8.
• Barbesino G, Tomer Y. Clinical review: clinical utility of tsh receptor antibodies. J Clin Endocrinol Metab 2013; 98: 2247.
• Yoshimura Noh J, Momotani N, Fukada S, Ito K, Miyauchi A, Amino N. Ratio of serum free triiodothyronine to free thyroxine in graves’ hyperthyroidism and thyrotoxicosis caused by painless thyroiditis. Endocr J 2005; 52: 537-42.
• Izumi Y, Hidaka Y, Tada H, et al. Simple and practical parameters for differentiation between destruction-induced thyrotoxicosis and Graves’ thyrotoxicosis. Clin Endocrinol (Oxf) 2002; 57: 51-8.
• Shıgemasa C, Abe K, Tanıguchı S-I, et al. Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves’ disease despite similar serum total T4 levels. J Clin Endocrinol Metab 1987; 65: 359-63.
• Tura Bahadır Ç, Yılmaz M, Kılıçkan E. Free triiodothyronine to free thyroxine ratio in the differential diagnosis of thyrotoxicosis and hyperthyroidism: a retrospective study. Int J Clin Pract 2021; 75: E14003.
• Narkar R, Mishra I, Baliarsinha A, Choudhury A. Rapid differential diagnosis of thyrotoxicosis using T3/T4 ratio, Ft3/Ft4 ratio and color doppler of thyroid gland. Indian J Endocrinol Metab 2021; 25: 193.
• Sriphrapradang C, Bhasipol A. Differentiating Graves’ disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine. Ann Med Surg 2016; 10: 69-72.
• Wu Z, Zhu Y, Zhang M, et al. Serum ratio of free triiodothyronine to thyroid-stimulating hormone: a novel index for distinguishing Graves’ disease from autoimmune thyroiditis. Front Endocrinol (Lausanne) 2021; 11: 1-7.
• Sümbül HE, Acıbucu F. Graves’ disease and thyroiditis can be differentiated using only free thyroid hormone levels. Eur Res J 2019; 6: 314-8.
• Yanagisawa T, Sato K, Kato Y, Shimizu S, Takano K. rapid differential diagnosis of Graves’ disease and painless thyroiditis using total T3/T4 ratio, TSH, and total alkaline phosphatase activity. Endocr J 2005; 52: 29-36.
• Gilbert J. Thyrotoxicosis – investigation and management. Clin Med (Northfield Il) 2017; 17: 274-7.
• Chen X, Zhou Y, Zhou M, Yin Q, Wang S. Diagnostic values of free triiodothyronine and free thyroxine and the ratio of free triiodothyronine to free thyroxine in thyrotoxicosis. Int J Endocrinol 2018; 2018: 1-8.