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 . As recommended in the guidelines, the measurement of thyroid uptake of radionuclide is used in the diagnosis of Graves’ disease. In Japan, 123I and 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. behaves in a similar way to iodine and is also absorbed into the thyroid gland . However, unlike 123I, it is not incorporated as a component of thyroid hormone , and therefore, does not reflect the organification of iodine. Although does not reflect true iodine metabolism in the same way as 123I, the use of does not require the same preparatory procedures as 123I, such as dietary iodine restriction . A further advantage of 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 . Thus, thyroid scintigraphy is more convenient. The reference value for uptake of is set at 0.4% to 3% . In addition to its use in diagnosis, the usefulness of uptake as a predictor of responsiveness to drug treatments  and of responsiveness to 123I treatment   has also been reported. thyroid scintigraphy is, thus, useful when diagnosing, as well as, when treating thyroid disease. There are reports of uptake correlating with free T3, free T4, and TSH receptor antibody .
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 . 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 on thyroid scintigraphy in primary hyperthyroidism.
2.1. Study Design and Sample Selection
This was a single-center, retrospective, observational study.
The study involved patients diagnosed with primary hyperthyroidism (Graves’ disease) based on clinical findings, blood tests, thyroid ultrasound, and thyroid scintigraphy (uptake ≥3%) at St. Marianna University School of Medicine Hospital between 1 January 2010 and 31 December 2019.
2.2. Blood Tests
The following laboratory parameters were measured at time of diagnosis and the results examined: WBC count, RBC count, hemoglobin, platelet count, TP, ALB, LDH, ALP, Na, K, Cl, Ca, blood glucose, HbA1c, neutral lipids, LDL-C, HDL-C, free T3, free T4, TSH, TSH receptor antibody, anti-thyroglobulin antibody, and thyroglobulin.
2.3. Ultrasound Scans
The thyroid volume was visually evaluated, and blood flow measured using thyroid ultrasound, at the time of diagnosis. The results were later examined and compared.
2.4. Thyroid Scintigraphy
Uptake and area on planar thyroid scintigraphy images were taken 10 to 20 minutes after intravenous administration of at around 185 MBq (suitably adjusted using body weight × 3 MBq as a guide) and results examined. The scintillation cameras used were ECAM and GX7200 (Canon/Toshiba Medical Systems Corporation, Nasu, Japan).
2.5. Statistical Analysis
The correlations between uptake on thyroid scintigraphy and blood test results were evaluated. Correlation coefficients were assessed using Spearman’s rank correlation coefficient. We used EZR (Easy ZR), developed by Jichi Medical University, Saitma Medical center (Omiya Medical center) for statistical analysis, and the significance level was set at p < 0.05.
2.6. Ethical Considerations
This study was conducted with the approval of the Ethics Committee of St. Marianna University, School of Medicine (4779). The patients had the option to opt-out of the study using the “opt-out” facility on the hospital homepage and in the hospital.
Fifty-four consecutively arriving patients at the hospital were selected; 12 were men, 42 were women, and their mean age was 43.0 ± 14.0 years (Table 1).
3.2. Blood Test Results
· Blood counts
The WBC count (n = 51) is 6156 ± 3301/μL, the RBC count (n = 51) is 4.4 ± 0.6 × 106/μL, hemoglobin (n = 51) is 12.4 ± 1.8 g/dL, and the platelet count (n = 51) is 20.6 ± 5.6 × 104/μL (Table 1).
TP (n = 45) is 6.7 ± 0.6 g/dL, ALB (n = 37) is 3.8 ± 0.4 g/dL, LDH (n = 48) is 163 ± 28.1 IU/L, ALP (n = 48) is 385.6 ± 263 IU/L, Na (n = 51) is 140 ± 2.0 mEq/L, K (n = 51) is 4.1 ± 0.3 mEq/L, Cl (n = 51) is 105 ± 1.9 mEq/L, Ca (n = 26) is 8.9 ± 1.8 mg/dL, LDL-C (n = 38) is 66.0 ± 22 mg/dL, HDL-C (n = 38) is
Table 1. Patients’ demographic characteristics.
47.9 ± 16.0 mg/dL, TG (n = 37) is 81.0 ± 45.2 mg/dL, BS (n = 54) is 111.3 ± 18.7 mg/dL, and HbA1c (NGSP) (n = 24) is 6.0% ± 0.9% (Table 1).
Free T3 (n = 54) is 14.6 ± 6.8 pg/mL (reference value 2.39 - 4.06 pg/mL), free T4 (n = 53) is 5.0 ± 2.3 ng/mL (reference value 0.76 - 165 ng/mL), and TSH receptor antibody (n = 54) is 14.2 ± 17.5 IU/L (reference value ≤ 2 IU/L). Thyroglobulin (n = 20) is 198.0 ± 256.0 ng/mL (reference value 0 - 33.7 ng/mL). Thyroglobulin antibody (n = 34) is 393.0 ± 256 IU/mL (reference value ≤ 4.11 IU/mL). TSH (n = 54) is 0.01 ± 0.0 μIU/mL (reference value 0.541 - 4.261 μIU/mL) (Table 1).
3.3. Ultrasound Scans
Blood flow was evaluated in 50 patients. The superior thyroid artery showed increased blood flow in 42 patients and no increase in 8 patients.
Thyroid size was evaluated in 49 patients. The thyroid was enlarged in 39 patients and not enlarged in 10 patients (Table 1).
3.4. Thyroid Scintigraphy
The uptake on thyroid scintigraphy was 10.0% ± 7.1%. The uptake was 5.0% ± 3.6% in the right lobe and 5.2% ± 4.10% in the left lobe. The area is 43.8 ± 12.1 cm2 (Table 1).
3.5. Correlation Coefficients
The correlation coefficient for TSH receptor antibody and uptake on thyroid scintigraphy was 0.48 (p < 0.01). The correlation coefficient for free T3 and uptake on thyroid scintigraphy was 0.53 (p < 0.01). 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 thyroid scintigraphy uptake (Table 2).
There were no significant correlations with blood test results.
Table 2. The correlation coefficient between thyroid scintigraphy and blood test.
Thyroid scintigraphy in Japan can currently be performed using and 123I or 131I. A correlation coefficient of 0.88 has previously been reported for test values 20 minutes after and 24 hours after 131I administration, indicating a strong positive correlation between the two . Recently, the potential of in predicting 131I uptake in 131I therapy has also been reported . In a study of the correlations between 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 . 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 . 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 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 . However, in this study, there were no significant value between uptake and free T4 in T4 ≥ 7 ng/mL group. Moreover, there were statically significant collation between 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 . It has been suggested that this could be because the accumulation of in tissues, such as in the salivary glands, affects the measurement of uptake on planar imaging that fails to accurately reflect thyroid function . 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 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 thyroid scintigraphy uptake, but, there is no correlation in patients with high free T4 level.
WBC: White Blood Cells
RBC: Red Blood Cells
TP: Total Protein
LDH: Lactate Dehydrogenase
LDL-C: Low-Density Lipoprotein Cholesterol
HDL-C: High-Density Lipoprotein Cholesterol
BS: Blood Sugar
HBA1c (NGSP): Hemoglovbin A1c
ALP: Alkaline Phosphatase
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