Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease

Abstract

Objective: Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD.

Materials and methods: A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of ^99mTc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated.

Results: GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006).

Conclusion: A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients.

Keywords: Computed tomography; Euthyroidism; Graves' disease; Methimazole; Single-photon emission computed tomography.

Fig. 1. Acquisition of thyroidal 3-dimensional VOI from multiple 2-dimensional ROIs.

On transaxial CT images, ROIs were manually drawn along contour of thyroid. CT = computed tomography, ROI = region-of-interest, SPECT = single-photon emission computed tomography, VOI = volume-of-interest

Fig. 2. Kaplan-Meier curve difference for achieving euthyroidism using %uptake cutoff of 5.0%.

Patients with rapid responses (n = 18) had lower mean %uptake (2.6 ± 1.2%) than those with slow responses (n = 18, 11.3 ± 6.5%). Time to euthyroidism differed significantly between two groups (p = 0.006, log-rank test).

Fig. 3. Representative images.

(Good response) 46-year-old female Graves' disease patient showed mildly increased %uptake (2.6%). Notably, euthyroid patients had mean %uptake of 0.8 ± 0.5% as determined via same SPECT/CT protocol (11). Patient's initial MMI dose was 30 mg per day, and she achieved euthyroidism 130 days after initial MMI administration. Values of other variables investigated were SUVmax (98.48), SUVmean (30.03), functional thyroid mass (2330 g), T3 (400 ng/dL), free T4 (5.54 ng/dL), TSH (0.01 µIU/mL), TSHR-Ab (2.13 IU/L), and thyroid volume (77.6 mL). (Poor response) this 38-year-old female Graves' disease patient showed markedly increased %uptake of 12.66%. Initial MMI dose was 30 mg per day, but she had not achieved euthyroidism by last follow-up time-point of 167 days post-MMI administration. Values of other variables investigated were SUVmax (362.43), SUVmean (149.06), functional thyroid mass (6827 g), T3 (461 ng/dL), free T4 (17.74 ng/dL), TSH (0.05 µIU/mL), TSHR-Ab (33.14 IU/L), and thyroid volume (45.8 mL). Upper row: planar scintigraphy, middle row: SPECT (coronal and transaxial images), bottom row: SPECT/CT (coronal and transaxial images). MMI = methimazole, SPECT/CT = single-photon emission computed tomography/computed tomography, SUV = standardized uptake value, TSH = thyroid-stimulating hormone, TSHR-Ab = thyroid-stimulating hormone receptor antibody