DIAGNOSIS OF ENDOCRINE DISEASE: IgG4-related thyroid autoimmune disease

Abstract

IgG4-related disease (IgG4-RD) is fibro-inflammatory, immune-mediated, systemic disease recognized as a defined clinical condition only in 2001. The prevalence of IgG4-RD is 6/100 000, but it is likely to be underestimated due to insufficient awareness of the disease. The diagnostic approach is complex because of the heterogeneity of clinical presentation and because of rather variable diagnostic criteria. Indeed, high concentrations of IgG4 in tissue and serum are not a reliable diagnostic marker. The spectrum of IgG4-RD also includes well-known thyroid diseases including Riedel’s thyroiditis, Hashimoto’s thyroiditis and its fibrotic variant, Graves’ disease and Graves’ orbitopathy. Results from clinical studies indicate that a small subset of patients with the above-mentioned thyroid conditions present some features suggestive for IgG4-RD. However, according to more recent views, the use of the term thyroid disease with an elevation of IgG4 rather than IgG4-related thyroid diseases would appear more appropriate. Nevertheless, the occurrence of high IgG4 levels in patients with thyroid disease is relevant due to peculiarities of their clinical course.

IgG4‐positive plasma cells in Hashimoto thyroiditis: IgG4‐related disease or inflammation‐related IgG4‐positivity?

“…Despite the persisting uncertainty whether HT is IgG4‐RD, HT with the IgG4‐positive plasma cells progress more rapidly into the thyroid tissue destruction and hypothyroidism clinically, so the earlier intervention can be hypothetically warranted in the diagnosed cases (24). The timely diagnosis of IgG4 positivity in HT has additional implication as FVHT may mimic malignancy and tissue and/or serum IgG4 may support inflammatory disease (17, 24), but the higher prevalence of malignancy in HT is acknowledged.…”

“…Nevertheless, the presence of IgG4‐positive plasma cells without accompanying histopathology can lead to overdiagnostics as IgG4‐positive cells were described in a wide range of inflammatory and lymphoproliferative disorders (10‐15). In addition, a raised serum IgG4 level is neither necessary nor adequate for the diagnosis (16, 17).…”

“…In the thyroid gland, Riedel thyroiditis (RT) has been proven both by morphology and IgG4 immunohistochemistry to be part of IgG4‐RD spectrum (18, 19). Despite difficulties in distinguishing between RT and FVHT, there is an extrathyroidal extension of fibrosis, an obliterative phlebitis and a lack of oncocytic metaplasia in RT as diagnostic differentiation hallmarks (17, 18).…”

An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report

“…Conversely, cases of biopsy-proven concomitant IgG4-RKD with both AAV and anti-GBM disease have been reported [ 10 , 11 ]. Graves’ disease with elevated IgG4 has been analysed in several studies, though no patients have previously been reported to have extra-thyroid involvement [ 12 ]. We advised our patient to undergo cross-sectional imaging to check for evidence of IgG4-RD affecting other organs, but he declined further investigation.…”

Proposal of diagnostic criteria for IgG4-related thyroid disease

“…Two patients had swelling in the salivary and pituitary glands, typical of systemic lesions observed in patients with IgG4-RD. Hashimoto's thyroiditis with elevated serum IgG4 levels is therefore suspected to include IgG4-RD and IgG4 thyroiditis [24,25].…”