Graves’ disease with normal or heterogeneous 99mTc uptake: insights into the atypical scintigraphy patterns

Abstract

Objective: Graves’ disease (GD), an autoimmune disorder causing hyperthyroidism, is often diagnosed using 99mTc scintigraphy. While increased thyroidal 99mTc uptake with homogenous distribution is typical, atypical patterns (normal or heterogeneous) occur. This study aimed to investigate the determinants of these atypical uptake patterns in GD. Subjects and methods: Retrospective records review identified 238 GD patients diagnosed between January 2022 and December 2024. Normal 99mTc uptake (0.4%-3%) and heterogeneous distribution patterns were defined based on scintigraphy. Relevant clinical and biochemical data were compared between typical and atypical pattern groups. Results: Normal 99mTc uptake was observed in 25/238 (10.5%). Compared to increased uptake, it was associated with lower FT4, T3 levels (p < 0.01) and TRAb levels (p = 0.01) with similar prevalence of heterogeneous distribution (p > 0.05). Compared to homogeneous uptake, heterogeneous uptake subgroup (n = 30/238, 12.6%) had similar TRAb/T3 levels (p > 0.05) with lower FT4 (p = 0.04); and were more likely to have goiter grade > 1 (p < 0.05). Age, gender, smoking and thyroid eye disease were not associated with either atypical uptake pattern. In regression analysis, lower TRAb was associated with normal uptake (OR 0.798, 95% CI 0.660-0.965, p = 0.02), and goitre grade > 1 was associated with heterogeneous uptake (OR 4.34, 95% CI 1.25-15.03, p = 0.01). Conclusion: Atypical 99mTc uptake patterns were observed in a notable subset of GD. Normal uptake subgroup may reflect a mild evolving disease stage with lower TRAb, while heterogeneous uptake was primarily linked to increased thyroid size. These findings highlight the importance of integrating clinical and biochemical data when interpreting thyroid scintigraphy in suspected GD.