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Graves hyperthyroidism

Thursday 12 January 2006

autoimmune hyperthyroidism, Graves disease, diffuse toxic goiter; Primary thyroid hyperplasia



- Atypia in Graves’ Disease, usually therapy related

Digital case

- JRC:18921 : Primary hyperplasia (Graves’ disease) with moderate involution.


- hyperplastic thyroid follicles
- follicles with papillary infoldings
- diffuse follicular hyperplasia
- hypertrophy of follicular cells
- retention of lobular architecture
- prominent vascular congestion
- tall follicular cells
- epithelial papillae usually lacking fibrovascular cores
- round nuclei
- basally located nuclei
- rarely overlapping nuclei
- typically decreased colloid , when present shows peripheral scalloping
- variable patchy lymphoid infiltrate in the stroma
- nuclear clearing (15%
- florid papillary hyperplasia (13%, may resemble papillary thyroid carcinoma)
- nuclear grooves or pseudonuclear inclusions (8%)
- nuclear enlargement
- multinucleation
- nuclear pleomorphism or prominent nucleoli (7%)
- mitotic figures (6%)
- psammoma bodies (1%)
- hyperplastic follicles may extend into adjacent skeletal muscle (1%)
- rarely small clusters of normal thyroid follicles in adjacent lymph node sinuses (Hum Pathol 2008;39:1080)

NB :
- preoperative potassium iodide to suppress vascularity causes epithelial involution and colloid accumulation
- Gland may look normal after 3 weeks of treatment
- Preoperative PTU exaggerates the hyperplasia and hypertrophy
- Radioactive iodine initially causes dissolution of some follicles, vascular changes, nuclear atypia and stromal fibrosis. Late changes are follicular atrophy, fibrosis, nodularity and oncocytic changes
- Periorbital tissue: lymphoplasmacytic infiltrate present in periorbital soft tissue and extraorbital skeletal muscles
- Skin hyperkeratosis: deposition of acid mucopolysaccharides in dermis

- possible follicular cell atypia in Graves disease, usually therapy-related

Differential diagnosis

- papillary thyroid carcinoma

  • enlarged overlapping nuclei
  • nuclear grooves
  • nuclear inclusions


- Locus 2q33: CTLA4
- Locus 4q12: GC
- Locus 6p11: AITD1 (MIM.608173)
- Locus 5q31-q33: AITD2 (MIM.608174)
- Locus 8q24: AITD3 (MIM.608175)
- Locus 10q: AITD4 (MIM.608176)
- Locus 18q21: AITD5 (MIM.601941)
- Locus 12q12-q14: VDR
- Locus 14q31: GRD1
- Locus 20q13.11: GRD2
- Locus Xp11: GRDX
- Locus Xq21.33-q22: GRD3

See also

- thyroid diseases

  • thyroid dysimmune diseases


- Brent GA. Clinical practice. Graves’ disease. N Engl J Med. 2008 Jun 12;358(24):2594-605. PMID: 18550875