Differentiating TRAb-positive painless thyroiditis from Graves' disease using biochemical and ultrasound findings

Endocr J. 2026 May 20. doi: 10.1507/endocrj.EJ26-0047. Online ahead of print.

Abstract

Differentiating painless thyroiditis (PT) from Graves' disease (GD) is important for appropriate management. This study evaluated whether thyroid-stimulating hormone (TSH) receptor antibody (TRAb)-positive PT can be differentiated from GD using biochemical and ultrasound findings. This retrospective study included 1,924 patients with thyrotoxicosis associated with PT or GD who visited Kuma Hospital between November 2020 and September 2023. TRAb titers and radioactive iodine uptake (RAIU) or technetium-99m pertechnetate (99mTc) uptake were measured in all patients. Patients were classified into TRAb-positive PT (n = 16), TRAb-negative PT (n = 222), and GD (n = 1,686). Serum alkaline phosphatase (ALP), TSH, free triiodothyronine (FT3)/free thyroxine (FT4) ratio, and thyroid blood flow were analyzed. No significant differences were observed between TRAb-positive and TRAb-negative PT in any single parameter. TRAb-positive PT significantly differed from GD in ALP (mean: 74.6 vs. 111.5 IU/L, p < 0.05), TSH (median: 0.037 vs. 0.007 μIU/mL, p < 0.001), FT3/FT4 ratio (mean: 2.54 vs. 3.30, p < 0.001), and blood flow (mean: 2.11% vs. 11.60%, p < 0.05). A scoring system assigned one point to each parameter-ALP above the upper limit, TSH below the detection limit, FT3/FT4 ratio >3.00, and blood flow >4.00%. None of the patients with TRAb-positive PT scored ≥3, compared with 65.7% of patients with GD. TRAb-positive PT can be differentiated from GD using combined biochemical and ultrasound markers. Our practical scoring system supports clinical decision-making when RAIU is not readily available or contraindicated and may help avoid unnecessary antithyroid therapy.

Keywords: Graves’ disease; Painless thyroiditis; Thyroid-stimulating hormone receptor antibody.