Schulter et al ETJ 2018.pdf (3.5 MB)
Noninflammatory Diffuse Follicular Hypertrophy/ Hyperplasia of Graves Disease: Morphometric Evaluation in an Experimental Mouse Model
journal contribution
posted on 2018-10-01, 17:41 authored by Schlüter Anke, Anja Eckstein, Brenzel A., Horstmann Mareike, Lang, Stephan, Berchner-Pfannschmidt Utta, Banga JP, Salvador J. Diaz-CanoSalvador J. Diaz-CanoObjectives: Experimental
models of Graves hyperthyroid disease accompanied by Graves
orbitopathy (GO) can be efficiently induced in susceptible inbred
strains of mice by immunization by electroporation of heterologous human
TSH receptor (TSHR) A-subunit plasmid. The interrelated pathological
findings in the thyroid glands of Graves disease (GD) that explain the
core changes classically include diffuse follicular hyperplasia and
multifocal mild lymphocytic infiltrate. However, the relative
contributions of different thyroid tissue components (colloid,
follicular cells, and stroma) have not been previously evaluated. In
this study, we characterize the thyroid gland of an experimental mouse
model of autoimmune GD. Our objective was to define the relative
contribution of the different thyroid tissue components to the pathology
of glands in the experimental model. Methods: Mice were immunized with
human TSHR A-subunit plasmid. Antibodies induced to human TSHR were
pathogenic in vivo due to their cross-reactivity to mouse TSHR. Results:
Autoimmune thyroid disease in the model was characterized by
histopathology of hyperplastic glands with large follicular cells.
Further examination of thyroid glands of immunized animals revealed a
significantly increased follicular area and follicle/stroma ratio,
morphometrically correlated with a noninflammatory follicular
hyperplasia/hypertrophy. The increased follicle/stroma ratio was the
most relevant morphometrically variable summarizing the pathological
changes for screening purposes. Conclusion: GD thyroid glands are
enlarged and characterized by a noninflammatory diffuse follicular cell
hyperplasia/hypertrophy and a significant increase in the follicles with
an increased follicle/stroma ratio. Overall, this mouse model is a
faithful model of an early hyperthyroid status of GD (diffuse glandular
involvement and follicular expansion).