Endocrinol Metab.  2022 Apr;37(2):312-322. 10.3803/EnM.2021.1318.

Immunoglobulin G4-Related Thyroid Disease: A Single-Center Experience and Literature Review

• Jin M
• Kim B
• Jang A
• Jeon MJ
• Choi YJ
• Lee YM
• Song DE
• Kim WG

• KMID: 2529223
• DOI: http://doi.org/10.3803/EnM.2021.1318

Abstract

Background
Immunoglobulin G4 (IgG4)-related disease is an entity that can involve the thyroid gland. The spectrum of IgG4-related thyroid disease (IgG4-RTD) includes Hashimoto thyroiditis (HT) and its fibrotic variant, Riedel thyroiditis, as well as Graves’ disease. The early diagnosis of IgG4-RTD is important because it is a medically treatable disease, and a delay in the diagnosis might result in unnecessary surgery. We present a case series of IgG4-RTD with a review of the literature.
Methods
We retrospectively reviewed the clinical presentation and the radiological and pathological findings of patients diagnosed with IgG4-RTD between 2017 and 2021 at a tertiary medical center in Korea. We also conducted a literature review of IgG4-RTD.
Results
Five patients were diagnosed with IgG4-RTD during the study period. The patients’ age ranged from 31 to 76 years, and three patients were men. Most patients visited the clinic for a neck mass, and hypoechogenic nodular lesions were observed on neck ultrasonography. Three patients had IgG4 HT, and two patients had IgG4 Riedel thyroiditis. All patients developed hypothyroidism that necessitated L-thyroxine replacement. The diagnosis of IgG4-RTD was confirmed after a pathological examination of the surgical specimen in the first two cases. However, the early diagnosis was possible after a core needle biopsy in three clinically suspected patients.
Conclusion
The diagnosis of IgG4-RTD requires clinical suspicion combined with serology and histological analyses using IgG4 immunostaining. The early diagnosis of IgG4-RTD is difficult; thus, biopsy with IgG4 immunostaining and serum IgG4 measurements will help diagnose patients suspected of having IgG4-RTD.

Keyword

Immunoglobulin G4; Thyroid diseases; Hashimoto disease; Riedel thyroiditis; Graves disease

Figure

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  Fig. 1. Initial thyroid ultrasonography showing heterogeneously decreased parenchymal echogenicity without a focal nodular lesion: transverse view (A), longitudinal view (B). Neck computed tomography showing diffuse enlarged and heterogeneous attenuation of the bilateral thyroid glands: transverse view (C), coronal view (D). Core needle biopsy showing dense interlobar stromal fibrosis and atrophy of thyroid follicles (E, F: H&E stain, ×100). Gross pathology of an enlarged thyroid gland with a weight of 135 g (G). Surgical pathology showing dense lymphoplasmacytic infiltration (H, I: H&E stain, ×200). Immunoglobulin G4 (IgG4) immunohistochemistry revealing diffuse infiltration of IgG4-positive plasma cells (J: IgG4 stain, ×200).

• 

  Fig. 2. Thyroid ultrasonography (US) shows a solid, irregular-shaped hypoechoic mass: transverse view (A), longitudinal view (B). Core needle biopsy (CNB) revealing interfollicular fibrosis (C: H&E stain, ×100), dense lymphoplasmacytic infiltration (D: H&E stain, ×200), and immunoglobulin G4 (IgG4)-positive plasma cells increased up to 63/high power fields (E: IgG4 stain, ×200). Thyroid US showing an irregular-shaped hypoechoic nodule with macrocalcification: transverse view (F), longitudinal view (G). Dense interlobar stromal fibrosis and atrophy of thyroid follicles are identified on CNB (H: H&E stain, ×100). In addition, there is substantial IgG4-positive plasma cell infiltration with the destruction of thyroid follicles in the CNB specimen (I: H&E stain, ×200; J: IgG4 stain, ×200). Thyroid US showing a solid, irregular-shaped hypoechoic lesion: transverse view (K), longitudinal view (L). CNB reveals a dense sclerotic inflammatory lesion (M: H&E stain, ×100; N: H&E stain, ×200) with IgG4-positive plasma cells (O: IgG4 stain, ×200).

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