A thyroidectomy specimen from a patient with diffuse goiter and exophthalmos shows diffusely hyperplastic follicles lined by tall columnar epithelium with crowded nuclei projecting into the lumen as papillae. The colloid is pale and scalloped at its edges. The pathogenesis involves:

• A A constitutively activating GNAS mutation
• B Autoantibodies that stimulate the TSH receptor ✓
• C Antibodies against the iodide symporter NIS
• D Germline RET activation causing C-cell hyperplasia

Explanation

Graves disease is caused by autoantibodies directed against the TSH receptor that mimic TSH and stimulate hormone synthesis and gland growth, producing the diffuse hyperplasia, tall columnar cells, papillary infoldings and scalloped marginal colloid seen here. Activating GNAS mutations cause toxic adenoma, which is focal and autonomous rather than diffuse and immune mediated. Antibodies to NIS and germline RET activation are not mechanisms of Graves disease.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.