Mild Thyrotoxicosis due to Seronegative Graves’ Disease or Disseminated Thyroid Autonomy

Background/Objective Disseminated thyroid autonomy (DTA) and seronegative Graves’ disease are rare causes of hyperthyroidism with similar clinical presentations. This case report highlights the diagnostic challenges between these entities. Case Presentation A 35-year-old male presented with palpitations, diaphoresis, and a small goiter. His TSH was 0.249 mIU/L (reference: 0.45–4.5 mIU/L) and free T4 was 3.0 ng/dL (reference: 0.88–1.77 ng/dL). Thyroid peroxidase antibodies, TRAb, and TSI were repeatedly negative. Ultrasound showed a diffusely enlarged thyroid, and radioactive iodine uptake was 35% (reference: 10% to 35%) with thyroid scintigraphy revealing diffusely increased uptake, indicating a hyperfunctioning thyroid without nodules. Treatment with Methimazole 5 mg daily resolved symptoms within 6 months. Discussion Thyroid biopsy can help distinguish DTA from seronegative Graves disease. DTA is marked by nodular hyperplasia without lymphocytic infiltration, indicating a non-autoimmune nature, while seronegative Graves’ disease exhibits diffuse follicular hyperplasia with lymphocytic infiltration, just as typical Graves’ disease despite undetectable autoatibodies. The possibility of false-negative TRAb results complicates diagnosis, with up to 22% of patients initially diagnosed with DTA later testing TRAb-positive upon retesting. Some cases of DTA may involve TSH receptor gene mutations. Conclusion This case highlights the complexity of distinguishing DTA, seronegative Graves’ disease and typical Graves’ disease with initial false negative testing. A systematic approach with repeat testing and, when feasible, biopsy, is critical to distinguish these entities. Further studies with histologic analysis are needed to clarify outcomes and develop tailored managements, as these conditions have different remission rates and are driven by different mechanisms.