IgG4-related disease of the thyroid glands [Review]

Abstract

Abstract. Recent reports on Hashimoto's thyroiditis (HT) with increased numbers of IgG4-positive plasma cells suggest that this type of HT may have a close relationship to IgG4-related disease (IgG4-RD). This unique subgroup of HT is termed as IgG4 thyroiditis and reveals distinct clinical, serological, and sonographic features from the non-IgG4 thyroiditis group. On the basis of immunostaining for IgG4, HT was divided into an IgG4 thyroiditis group and a non-IgG4 thyroiditis group. Clinically, IgG4 thyroiditis was associated with younger age group, lower female-male ratio, higher levels of thyroid autoantibodies, diffuse low echogenicity, more rapid progress requiring surgical treatment and more subclinical hypothyroidism. Serum IgG4 concentrations elevated in IgG4 thyroiditis and decreased significantly after a thyroidectomy. Histopathologically, IgG4 thyroiditis showed a higher grade of stromal fibrosis, lymphoplasmacytic infiltration, and follicular cell degeneration than non-IgG4 thyroiditis. IgG4 thyroiditis may represent IgG4-RD of thyroid gland, because it shares common histopathological characteristics with IgG4-RD in other organs. The identification of IgG4-RD of the thyroid gland opens new insights not only for patient's treatment with HT but also for the development of new therapeutic approaches for this rapidly progressive destructive subtype of HT. This article mainly focuses on reviewing the unique histopathological, clinical, and serological features of IgG4 thyroiditis group of HT. The etiology and genetic changes of HT are also discussed.

IgG4-related Hashimoto’s thyroiditis – A new variant of a well known disease

“…However, as these patients usually present with a rapidly progressing neck swelling, surgery is often the first choice for treatment. Before surgical intervention serum IgG4 is often elevated but, after total thyroidectomy, levels usually exhibit a significant reduction and return to normal, indicating that the major origin of IgG4 is the thyroid gland (16). In our case, serum IgG4 was not performed preoperatively but a normal level one month after total thyroidec-tomy may suggest that it is decreasing and no other organ is involved besides the thyroid gland.…”

“…Therefore, in a patient with confirmed IgG4-related HT and no additional signs and symptoms, we consider that it is not mandatory to discard general IgG4-related disease. In addition, obliterative phlebitis is not present in any subtype of HT (16,24). Based on these features, our case is better defined as IgG4-related HT than as RT.…”

“…The same group in 2010 demonstrated that the IgG4 thyroiditis group was associated with male gender, rapid progress requiring surgery, more subclinical hypothyroidism, higher levels of thyroid autoantibodies and more diffuse low echogenicity on US, when compared with the non-IgG4 thyroiditis group (15). In 2012 these authors studied 105 patients with HT and, using the same cut-off, 28 cases (27%) were classified as IgG4 thyroiditis (16).…”

IgG4 Related Disease of the Head and Neck

“…Some groups now believe that a significant proportion of cases of fibrosing Hashimoto's thyroiditis, and a minority of cases with classic Hashimoto's thyroiditis belong to the spectrum of IgG4 related disease [3,4,[23][24][25][26]. However, unlike most other manifestations of the disease, both forms of thyroiditis (now termed IgG4 related thyroiditis) remain confined to the thyroid, and systemic manifestations have not been recognized [3,4,23,24]. Nonetheless, a significant proportion of patients with autoimmune pancreatitis and IgG4 related disease show evidence of hypothyroidism, thus arguing for an association between this thyroid disease and IgG4 related disease [27].…”

“…In a series of elegant papers, Kakudo identified a variant of Hashimoto's thyroiditis (IgG4 related thyroiditis) that showed elevated numbers of IgG4 positive plasma cellsdefined as greater than 20 IgG4 positive plasma cells per HPF, and an IgG4 to IgG ratio of greater than 30 % [3,23]. There were significant differences between patients with IgG4 positive thyroiditis and IgG4 negative thyroiditis.…”