Charbonne Gael, Hallak Fatima, Rivera Cruz Alma Elizabeth, McDonald Stephen Devitt
Kettering Health Main Campus, Department of Internal Medicine, Kettering, Ohio.
Kettering Health Miamisburg, Internal Medicine Clinic, Miamisburg, Ohio.
AACE Clin Case Rep. 2024 Dec 5;11(2):102-106. doi: 10.1016/j.aace.2024.12.002. eCollection 2025 Mar-Apr.
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.
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.
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.
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.
背景/目的：弥漫性甲状腺自主性（DTA）和血清学阴性的格雷夫斯病是甲状腺功能亢进症的罕见病因，临床表现相似。本病例报告强调了这些疾病之间的诊断挑战。
一名35岁男性出现心悸、多汗和小甲状腺肿。他的促甲状腺激素（TSH）为0.249 mIU/L（参考值：0.45 - 4.5 mIU/L），游离甲状腺素（FT4）为3.0 ng/dL（参考值：0.88 - 1.77 ng/dL）。甲状腺过氧化物酶抗体、促甲状腺激素受体抗体（TRAb）和甲状腺刺激免疫球蛋白（TSI）多次检测均为阴性。超声显示甲状腺弥漫性肿大，放射性碘摄取率为35%（参考值：10%至35%），甲状腺闪烁显像显示摄取弥漫性增加，表明甲状腺功能亢进且无结节。每日服用5毫克甲巯咪唑治疗6个月内症状缓解。
甲状腺活检有助于区分DTA和血清学阴性的格雷夫斯病。DTA的特征是结节性增生且无淋巴细胞浸润，表明其非自身免疫性质，而血清学阴性的格雷夫斯病表现为弥漫性滤泡增生伴淋巴细胞浸润，尽管自身抗体检测不到，但与典型格雷夫斯病相同。TRAb结果假阴性的可能性使诊断复杂化，高达22%最初被诊断为DTA的患者在复查时TRAb呈阳性。一些DTA病例可能涉及促甲状腺激素受体基因突变。
本病例突出了在初始检测为假阴性时区分DTA、血清学阴性的格雷夫斯病和典型格雷夫斯病的复杂性。采用重复检测并在可行时进行活检的系统方法对于区分这些疾病至关重要。需要进一步进行组织学分析研究以明确结果并制定针对性的管理方案，因为这些疾病的缓解率不同且由不同机制驱动。
