Thyroid gland
Hyperplasia / goiter
Simple goiter and nontoxic multinodular goiter

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

Revised: 24 February 2017, last major update March 2009

Copyright: (c) 2003-2017,, Inc.

PubMed search: simple goiter thyroid

Cite this page: Simple goiter and nontoxic multinodular goiter. website. Accessed December 16th, 2017.
Definition / general
  • Goiter: enlargement of thyroid gland for any reason; usually euthyroid, but may be hypo- or hyperthyroid
  • Goiter is visible in 10% of thyroid glands at autopsy, but microscopic nodularity is present in 40%
  • Most common disease of thyroid gland
  • May put pressure on trachea (Asian Cardiovasc Thorac Ann 2006;14:416) or esophagus, or grow behind sternum or clavicle ("plunging goiter")
  • Also called nodular hyperplasia
  • Nontoxic: no hyperthyroidism present
  • Physiology: low T3 / T4 (various mechanisms) means negative feedback loop is inactive, causes increased TSH, which causes follicular hypertrophy and hyperplasia (goiter) with minimal colloid, later follicular atrophy with massive storage of colloid
  • Simple goiter: also called diffuse nontoxic goiter or colloid goiter
    • Thyroid gland usually 40 g or more
    • Eventually converts into multinodular goiter
  • Multinodular goiter: irregular enlargement of thyroid gland due to repeated episodes of hyperplasia and involution (degeneration) of simple goiter
    • Thyroid gland often 100 g or more, may resemble a neoplasm, particularly if a single firm dominant nodule is present
    • Nodules are clonal or polyclonal, and are due to heterogeneous responses of follicular epithelium to TSH
    • Exophthalmos of Graves disease is not present
  • Colloid goiter: descriptive but not a diagnostic term; means massive storage of colloid within follicles often with flattened epithelium
  • 90% of those affected are women, develops more frequently during adolescence and pregnancy
  • Causes of simple goiter or nontoxic multinodular goiter:
    • Endemic goiter: see topic
    • Sporadic goiter: usually teen / young women
      • Caused by goitrogens, hereditary or unknown
      • Usually euthyroid
    • Drug induced goiter: sulfonamides and phenylbutazone inhibit organification of iodine
      • Iodine containing drugs such as amiodarone interfere with thyroglobulin proteolysis
      • Iodine or lithium interfere with thyroglobulin breakdown and release of T3 / T4
    • Goitrogens: cassava, cabbage, cauliflower, brussels sprouts and turnips interfere with T3 / T4 synthesis
      • Cassava contains a thiocyanate which inhibits iodide transport within the thyroid
    • Hereditary: see dyshormonogenetic goiter
    • Plummer syndrome: hyperfunctioning thyroid nodule within a goiter, without ophthalmopathy or dermopathy of Graves disease
    • Plummer-Vinson (Paterson-Kelly) syndrome is different: iron deficiency anemia, glossitis, esophageal dysphasia related to webs, may have thyroid enlargement (Orphanet J Rare Dis 2006;1:36)
Clinical features
  • Usually normal T3 / T4, normal radioactive iodine uptake, thyroglobulin may be elevated
Radiology images

Images hosted on PathOut server:

Intramediastinal, contributed by Dr. Mark R. Wick

Case reports
  • Thyroxine (reduces TSH and size of diffuse simple goiters, less effective for multinodular goiter), radioactive iodine (safe and effective but may cause hypothyroidism), total thyroidectomy eliminates recurrences except for rare cases due to growth in embryonic remnants outside thyroid gland (World J Surg 2007;31:593), near total thyroidectomy reduces hypoparathyroidism (Langenbecks Arch Surg 2006;391:567)
Gross description
  • Simple goiters are usually firm with amber cut surface
  • Multinodular goiters are asymmetric, large, up to 2 kg, cystic and hemorrhagic with brown gelatinous colloid nodules with focal calcification and variable size, capsule usually intact and surface is bumpy
Gross images

Images hosted on PathOut server:

Contributed by Dr. Mark R. Wick

AFIP Images:

Various images

Images hosted on other servers:

Colloid cyst

Colloid goiter

Nodular goiter

Retrosternal goiter

Microscopic (histologic) description
  • Simple goiter: only one nodule grossly
    • Diffuse enlargement of follicles but with varying size, lined by flattened epithelium with involutional changes
    • Smaller follicles have more columnar epithelium
    • Also asymmetric papillary projections of crowded columnar cells
  • Multinodular goiter: multiple nodules grossly
    • Dilated follicles of varying sizes with flattened to hyperplastic epithelium
    • Degenerative changes of scarring, hemorrhage and hemosiderin laden macrophages, calcifications, cysts, cholesterol clefts
    • May have papillary projections and Sanderson polsters
    • May have granulomatous reaction to colloid, oncocytic cells, osseous metaplasia, chronic thyroiditis, highly atypical nuclei if exposed to radioactive substances
    • Rarely vascular invasion at periphery of nodule
Microscopic (histologic) images

Scroll to see all images.

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D.:

Aggregate of small follicles at one pole of large colloid nodule

Contributed by Dr. Rajeshwari K. Muthusamy:

62 year old woman with adipose metaplasia

Contributed by Dr. Mark R. Wick:


Colloid, PAS stain

AFIP Images:

No capsule identified

Sanderson polster

With hypercellular focus

With adipose metaplasia of stroma

Papillary area

Clear cell change

Focal squamous metaplasia

Images hosted on other servers:

Follicles irregularly enlarged

Colloid goiter

Colloid goiter with cholesterol clefts

Squamous metaplasia (CK 5 / 6+) in capsule

Virtual slides

Images hosted on other servers:

Struma colloides nodosa

Cystic adenomatous nodule

Cytology description
  • Abundant cracked to watery colloid, flat sheets of uniform follicular cells, macrophages, oncocytic cells
Cytology images

Images hosted on other servers:

Watery colloid and focal dense colloid

Large amounts of background colloid


Differential diagnosis
  • Dyshormonogenetic goiter: increased cellularity is usually diffuse
  • Follicular carcinoma: has vascular or capsular invasion, although multinodular goiter may have vascular invasion at periphery of nodule
  • Toxic goiter: clinical hyperthyroidism
  • DD of dominant nodule in nodular goiter vs. adenoma: adenoma is usually single, totally surrounded by capsule, dissimilar from remaining parenchyma, compresses adjacent tissue, composed of follicles smaller than normal gland, monoclonal