Ratio of Serum Free Triiodothyronine to Free Thyroxine in Graves' Hyperthyroidism and Thyrotoxicosis Caused by Painless Thyroiditis

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Abstract
The serum T3 to T4 ratio is a useful indicator for differentiating destruction-induced thyrotoxicosis from Graves' thyrotoxicosis. However, the usefulness of the serum free T3 (FT 3) to free T4 (FT4) ratio is controversial. We therefore systematically evaluated the usefulness of this ratio, based on measurements made using two widely available commercial kits in two hospitals. Eighty-two untreated patients with thyrotoxicosis (48 patients with Graves' disease and 34 patients with painless thyroiditis) were examined in Kuma Hospital, and 218 patients (126 with Graves' disease and 92 with painless thyroiditis) and 66 normal controls were examined in Ito Hospital. The FT3 and FT4 values, as well as the FT3/FT4 ratios, were significantly higher in the patients with Graves' disease than in those with painless thyroiditis in both hospitals, but considerable overlap between the two disorders was observed. Receiver operating characteristic (ROC) curves for the FT3 and FT4 values and the FT3/FT4 ratios of patients with Graves' disease and those with painless thyroiditis seen in both hospitals were prepared, and the area under the curves (AUC), the cut-off points for discriminating Graves' disease from painless thyroiditis, the sensitivity, and the specificity were calculated. AUC and sensitivity of the FT3/FT4 ratio were smaller than those of FT3 and FT4 in both hospitals. The patients treated at Ito hospital were then divided into 4 groups according to their FT4 levels (A: ≤2.3, B: >2.3~≤3.9, C: 3.9~≤5.4, D: >5.4 ng/dl), and the AUC, cut-off points, sensitivity, and specificity of the FT3/FT4 ratios were calculated. The AUC and sensitivity of each group increased with the FT4 levels (AUC: 57.8%, 72.1%, 91.1%, and 93.4%, respectively; sensitivity: 62.6%, 50.0%, 77.8%, and 97.0%, respectively). The means ± SE of the FT3/FT4 ratio in the Graves' disease groups were 3.1 ± 0.22, 3.1 ± 0.09, 3.2 ± 0.06, and 3.1 ± 0.07, respectively, versus 2.9 ± 0.1, 2.6 ± 0.07, 2.5 ± 0.12, and 2.3 ± 0.15, respectively, in the painless thyroiditis groups. In the painless thyroiditis patients, the difference in the FT3/FT4 ratio between group A and group D was significant (p<0.05). Thus, the FT3/FT4 ratio in patients with Graves' disease likely remains unchanged as the FT4 level rises, whereas this ratio decreases as the FT4 level rises in patients with painless thyroiditis. In conclusion, the FT3/FT 4 ratios of patients with painless thyroiditis overlapped with those of patients with Graves' disease. However, this ratio was useful for differentiating between these two disorders when the FT4 values were high.

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