Thyroid gland
Hyperplasia / goiter
Graves disease

Author: Shahidul Islam, M.D., Ph.D. (see Authors page)

Revised: 13 December 2016, last major update March 2009

Copyright: (c) 2003-2016,, Inc.

PubMed search: graves disease [title] thyroid

Cite this page: Graves disease. website. Accessed December 13th, 2016.
Definition / General
  • Autoimmune disorder with thyrotoxicosis, diffuse goiter, infiltrative ophthalmopathy and occasionally infiltrative dermopathy / pretibial myxedema (scaly thickening and induration of shin, seen late in disease in 5% - 10%)
  • Also thyroid acropachy - extremity swelling, clubbing of fingers and toes due to periosteal new bone formation, cardiac hypertrophy
  • Cause unknown
  • #1 cause of hyperthyroidism in children
  • Also called diffuse toxic goiter, autoimmune hyperthyroidism, Basedow's disease (in Europe)
  • Ophthalmopathy:
    • Increased volume of retro-orbital connective tissue and extraocular muscles, due to edema and accumulation of proteoglycans and hyaluronic acid, pushes eyeball forward
    • Sympathetic overstimulation causes wide eyed, staring gaze
    • Is associated with high titers of anti TSH antibodies
  • Autoantibodies:
    • Long acting thyroid stimulator (LATS): IgG that stimulates thyroid function similar to but slower than TSH (i.e. long acting)
    • Specific for Graves disease
    • Thyroid stimulating immunoglobulins (TSI) other than LATS also stimulate TSH receptor
    • TSI negative in 43% of children with Graves’ disease (J Pediatr Endocrinol Metab 2008;21:1085)
    • TSH binding inhibitor immunoglobulins prevent TSH from binding normally, have either a stimulatory or inhibitory effect
    • Antibody production is probably due to primary T cell autoimmunity (specific immunoglobulin variable gene families produce antigen receptors that bind to thyroid tissue)
    • Also antibodies to thyroid peroxidase (microsomal antigen) and thyroglobulin, which are also present in Hashimoto’s thyroiditis
  • Affects 2% of women in US, 0.3% of men
  • 85% of patients are women, usually ages 20 - 40 years; men are usually older
  • 60% concordance in identical twins; associated with HLA-B8 and HLA-DR3
  • Increased T3 / T4, increased uptake of radioactive iodine, decreased TSH
Case Reports
Clinical Images
Images hosted on other servers:

Rodney Dangerfield

Marty Feldman

Gross Description
  • Diffusely enlarged thyroid gland up to 150g, red and succulent cut surface resembles pancreas
  • Prominent vascularity
Gross Images
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Markedly enlarged gland

Micro Description
  • Diffuse hyperplasia and hypertrophy of follicular cells with retention of lobular architecture and prominent vascular congestion
  • Tall follicular cells with papillae usually lacking fibrovascular cores
  • Nuclei are round, often polarized, rarely overlap, colloid is pale with scalloped margins (colloid doesn’t fill the lumen, and scalloping is a fixation artifact), lymphoid follicles represent autoimmune phenomena, mostly T cells; also oncocytes, fibrosis
  • Nuclear clearing (15%), florid papillary hyperplasia (13%, may resemble papillary thyroid carcinoma), nuclear grooves or pseudonuclear inclusions (8%), nuclear enlargement, multinucleation, 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)
  • Note: 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 and nuclear changes
    • 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
Micro Images
Scroll to see all images.

Images hosted on PathOut server:

Courtesy of Andrey Bychkov, M.D., Ph.D.

Active tall epithelium with light vaculoated cytoplasm

Small nodule of atypical cells with bizarre nuclei

eosinophilic cells
with prominent
bizarre nuclei

Compensatory nodular hyperplasia

Prominent nuclear atypia / pleomorphism

Images from AFIP:

Diffuse hyperplasia with well developed papillae

Follicular cells lining papillae are tall and columnar

Hyperplastic small follicles

Images contributed by Dr. Mark R. Wick:

Various images

Images hosted on other servers:

Prominent infoldings of hyperplastic epithelium

Epithelium is tall columnar, colloid shows scalloping

No nuclear changes of papillary thyroid carcinoma

Various images

Numerous plasma cells

Follicles with pale colloid

Irregular follicles,
epithelium and
sparse colloid

Colloid has scalloped margins

Lobulated parenchyma with irregular follicles

Follicles with tall epithelium and sparse colloid

Figure 2B - mild atypia

Skin: pretibial myxedema

Virtual Slides
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Hyperplastic follicles are lined by tall columnar cells

Cytology Description
  • Follicular cells in clusters and sheets
  • Cells are tall with finely granular cytoplasm, marginal vacuoles and basal nuclei
  • Malignant cells in cases with papillary thyroid carcinoma have prominent nuclear elongation, pale powdery chromatin, intranuclear grooves and small eccentric nucleoli (Diagn Cytopathol 2004;31:64)
Positive Stains
Negative Stains
Electron Microscopy Description
  • Prominent rough endoplasmic reticulum and Golgi, well developed nucleoli in enlarged nuclei

"Histopathology Thyroid—Graves Disease"
by John R. Minarcik, M.D.

"Histopathology Thyroid—Graves Disease 2"
by John R. Minarcik, M.D.
Differential Diagnosis
Additional References