Hyperthyroidism is a disease characterized by abnormally high levels of thyroid hormone secretion. It is caused either by Graves’ disease (Basedow’s disease) or by overactive thyroid nodules. However, Graves’ disease is responsible for the majority of cases. In Japan, Graves’ disease is diagnosed using the “Guidelines for the diagnosis of thyroid disease, 2010,” published by the Japan Thyroid Association [1] . As recommended in the guidelines, the measurement of thyroid uptake of radionuclide is used in the diagnosis of Graves’ disease. In Japan, ¹²³I and 99m TcO 4 − are currently used for thyroid scintigraphy. ¹²³I is an iodine radionuclide that is incorporated as a component of thyroid hormone after being absorbed into the thyroid gland, in the same way as non-radioactive iodine. 99m TcO 4 − behaves in a similar way to iodine and is also absorbed into the thyroid gland [2] . However, unlike ¹²³I, it is not incorporated as a component of thyroid hormone [2] , and therefore, does not reflect the organification of iodine. Although 99m TcO 4 − does not reflect true iodine metabolism in the same way as ¹²³I, the use of 99m TcO 4 − does not require the same preparatory procedures as ¹²³I, such as dietary iodine restriction [2] . A further advantage of 99m TcO 4 − is that the patient can be scanned 30 minutes after administration, and the test can thus be completed shortly after administration, whereas imaging with ¹²³I is typically performed 24 hours after administration [2] . Thus, 99m TcO 4 − thyroid scintigraphy is more convenient. The reference value for uptake of 99m TcO 4 − is set at 0.4% to 3% [2] . In addition to its use in diagnosis, the usefulness of 99m TcO 4 − uptake as a predictor of responsiveness to drug treatments [3] and of responsiveness to ¹²³I treatment [4] [5] has also been reported. 99m TcO 4 − thyroid scintigraphy is, thus, useful when diagnosing, as well as, when treating thyroid disease. There are reports of 99m TcO 4 − uptake correlating with free T3, free T4, and TSH receptor antibody [6] .

Free T4 value is an indicator for initial methimazole (MMI) dose, and in patients with free T4 ≥ 7 ng/mL, 30 mg/day of MMI is recommended [7] . However, the association between free T4 value and activity of Graves’ disease remains unclear. The aim of this study was to further investigate the correlation between blood test results and uptake of 99m TcO 4 − on thyroid scintigraphy in primary hyperthyroidism.

Thyroid scintigraphy in Japan can currently be performed using 99m TcO 4 − and ¹²³I or ¹³¹I. A correlation coefficient of 0.88 has previously been reported for test values 20 minutes after 99m TcO 4 − and 24 hours after ¹³¹I administration, indicating a strong positive correlation between the two [8] . Recently, the potential of 99m TcO 4 − in predicting ¹³¹I uptake in ¹³¹I therapy has also been reported [9] . In a study of the correlations between 99m TcO 4 − uptake and free T3, free T4, and TSH receptor antibody, the correlation coefficient was 0.593 (p < 0.01) with free T3, 0.334 (p < 0.01) with free T4, and 0.414 (p < 0.01) with TSH receptor antibody [7] . In a study using SPECT-CT, the correlation coefficient in 17 patients with Graves’ disease was 0.492 (but p > 0.05) for uptake and free T3 and 0.564 (p < 0.01) for uptake and free T4 [10] . In this study, the correlation coefficients were 0.60 (p < 0.01) between free T4 (all case), 0.39 (p < 0.01) between free T4 (under 7 ng/mL), 0.12 (p = 0.70) between free T4 (above 7 ng/mL), and 99m TcO 4 − thyroid scintigraphy uptake. Free T4 value is an indicator for determining MMI dose. For patients with free T4 < 7 ng/mL, 15 mg/day of MMI is recommended, and for those with free T4 ≥ 7 ng/mL, 30 mg/day MMI is recommended [6] . However, in this study, there were no significant value between 99m TcO 4 − uptake and free T4 in T4 ≥ 7 ng/mL group. Moreover, there were statically significant collation between 99m TcO 4 − uptake and free T4 in T4 < 7 ng/mL group, but the correlation coefficients were small. From these results, we think that T4 value is not necessary reflect the disease activity, and there is a problem about uniform MMI dose setting for patients based on T4 value.

The present study has several limitations. It was a single-center study and thus included a limited number of patients. Recently, a study of standard uptake value (SUV) using SPECT-CT reported that SUVmax and SUV were elevated in Graves’ disease, but there were no correlations with free T3 or with free T4 [10] . It has been suggested that this could be because the accumulation of 99m TcO 4 − in tissues, such as in the salivary glands, affects the measurement of uptake on planar imaging that fails to accurately reflect thyroid function [10] . There is, however, a probability that it is not appropriate to evaluate Graves’ disease activity using free T4 value. It is therefore possible that studies with SPECT imaging would yield different results to those with planar imaging. There is a need to further investigate 99m TcO 4 − uptake under established imaging conditions in multi-center, prospective clinical studies with a larger number of patients.

In primary hyperthyroidism (Graves’ disease), there is a correlation between free T4 value and 99m TcO 4 − thyroid scintigraphy uptake, but, there is no correlation in patients with high free T4 level.

The authors declare no conflicts of interest regarding the publication of this paper.

Okada, Y., Matsushita, S. and Yamaguchi, K. (2021) Correlation between Thyroid Scintigraphy and Blood Test in Primary Hyperthyroidism. Open Journal of Endocrine and Metabolic Diseases, 11, 71-78. https://doi.org/10.4236/ojemd.2021.113006

WBC: White Blood Cells

RBC: Red Blood Cells

TP: Total Protein

ALB: Albumin

LDH: Lactate Dehydrogenase

LDL-C: Low-Density Lipoprotein Cholesterol

HDL-C: High-Density Lipoprotein Cholesterol

TG: Triglyceride

BS: Blood Sugar

HBA1c (NGSP): Hemoglovbin A1c

T3: Triodothyronine

T4: Thyroxine

ALP: Alkaline Phosphatase