Thyroid & parathyroid glands
Hyperplasia / goiter
Multinodular goiter

Topic Completed: 1 February 2018

Minor changes: 31 December 2020

Copyright: 2003-2021,, Inc.

PubMed search: simple goiter thyroid

Swati Satturwar, M.D.
F. Zahra Aly, M.D., Ph.D.
Page views in 2020: 34,263
Page views in 2021 to date: 2,168
Cite this page: Aly F, Satturwar S. Multinodular goiter. website. Accessed January 20th, 2021.
Definition / general
  • Most common disease of thyroid gland
  • Diffuse or nodular enlargement with distorted outer surface
  • Grossly visible in 10% of thyroid glands at autopsy but microscopic nodularity is present in 40%
  • May cause compression of trachea (Asian Cardiovasc Thorac Ann 2006;14:416), esophagus or blood vessels and may grow behind sternum or clavicle (plunging goiter)
  • 3 - 5% risk of thyroid cancer, predominantly follicular variant of papillary thyroid carcinoma (S Afr J Surg 2014;52:5)
Essential features
  • Majority asymptomatic and euthyroid
  • Asymmetric diffuse or nodular enlargement of thyroid gland with distorted outer surface
  • Iodine deficiency is most common cause worldwide; however in the U.S., most goiters are due to autoimmune thyroiditis (i.e. Hashimoto disease)
  • Serum thyroid stimulating hormone (TSH) concentration is inversely proportional to the size of the goiter
  • Size of the goiter increases in proportion to the duration of the goiter
  • Histologically multiple variably sized dilated follicles lined by flattened to hyperplastic epithelium, with or without degenerative changes
  • 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
    • Also called nodular hyperplasia
  • Nontoxic goiter: no hyperthyroidism present
  • 90% of those affected are women
  • Develops more frequently during adolescence and pregnancy
  • Involves entire gland
  • Increase in TSH secretion is the main cause in iodine deficiency related goiter and in autoimmune (Hashimoto) thyroiditis; in persons with normal TSH, oxidative damage to follicular cells and then damage to DNA leads to hyperplasia
  • In individuals with normal TSH, thyroid enlargement is caused by multiple growth factors including TSH
  • Genetic factors
    • DICER1 syndrome : germline mutations in DICER1 gene in familial and childhood multinodular goiter (J Clin Endocrinol Metab 2016;101:1, Head Neck 2013;35:E369); patients also at increased risk of Sertoli-Leydig cell tumor, cystic nephroma and pleuropulmonary blastoma
    • PTEN hamartoma tumor syndrome: autosomal dominant disorder with germline mutation of PTEN tumor suppressor gene manifesting as multiple carcinomas and hamartomas in variety of organs including thyroid, presenting with multinodular goiter (J Clin Endocrinol Metab 2011;96:34, Thyroid 2011;21:135)
  • Some nodules eventually become autonomous due to activating mutations in the TSH receptor or G proteins within the thyroid follicular cells
  • 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: iron deficiency anemia, glossitis, esophageal dysphasia related to webs, may have thyroid enlargement (Orphanet J Rare Dis 2006;1:36)
Clinical features
  • Thyroid enlargement (goiter)
  • Majority asymptomatic and euthyroid
  • Hypothyroidism due to decreased production of T3 and T4 hormones
  • Hyperthyroidism (due to autonomous transformation)
  • Compression of trachea and esophagus (uncommon since enlargement is mainly towards strap muscle and subcutaneous tissue); compression of recurrent laryngeal nerve with hoarseness, phrenic nerve paralysis and Horner syndrome
  • Subacute obstructive symptoms with or without pain due to secondary hemorrhage into a nodule
  • Exertional dyspnea when tracheal diameter is less than 8 mm with stridor or wheezing when the diameter is less than 5 mm
  • Clinical examination
  • Thyroid function tests: TSH, T3, T4
  • Thyroid peroxidase antibodies
  • Thyroid ultrasound
  • CT or MRI to evaluate extent of goiter
  • Fine needle aspiration is indicated if:
    • History of rapid growth
    • Pain or tenderness
    • Unusually firm areas in the nodule
    • Suspicious sonographic features
  • Usually normal T3 / T4, normal radioactive iodine uptake, thyroglobulin may be elevated
Radiology description
  • Upper limits of normal for thyroid gland volume:
    • Adult men: 25 mL
    • Adult women: 18 mL
    • 13 - 14 years: 8 - 10 mL
    • 3 - 4 years: 3 mL
    • Neonate: 0.8 - 1.5 mL
  • Ultrasound:
    • Wide variety of appearances which include:
      • Enlarged iso / hyper echoic gland with surrounding hypoechoic halo
      • Sponge-like / honeycomb pattern
      • Anechoic areas may contain colloid
      • Internal calcification
  • Nuclear medicine:
    • 99mTc pertechnetate or radioiodine (123I) demonstrate an enlarged gland, with heterogeneous uptake
Radiology images

Contributed by Mark R. Wick M.D.

Intrathoracic (ectopic) goiter

Case reports
  • Asymptomatic, euthyroid patients with benign multinodular goiters (< 80 mL): monitoring by annual neck exam, TSH level and thyroid ultrasound as required
  • For very large goiters (> 80 - 100 mL) or goiters that continue to grow: thyroidectomy
  • For patients who have nontoxic benign goiters that continue to grow but who are poor surgical candidates or prefer to avoid surgery: radioiodine therapy
Clinical images

Images hosted on other servers:

Large goiter

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
  • Capsule is usually intact and surface is bumpy
Gross images

Contributed by Swati Satturwar, M.B.B.S., Andrey Bychkov, M.D., Ph.D.

External surface

Cut surface

Nodular thyroid

AFIP images

Various images

Images hosted on other servers:

Colloid cyst

Colloid goiter

Nodular goiter

Retrosternal goiter

Microscopic (histologic) description
  • Variable sized dilated follicles with flattened hyperplastic epithelium
  • Nodules may be present but without thick capsule
  • Secondary changes may be seen, including foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia
  • Some of the cystically dilated follicles may show papillary projections (Sanderson polsters) that may mimic papillary carcinoma; however, they lack the nuclear features of papillary carcinoma
  • Cytologic atypia (in the form of highly atypical nuclei) if exposed to radioactive substances
Microscopic (histologic) images

Contributed by Swati Satturwar, M.B.B.S., Andrey Bychkov, M.D., Ph.D., Rajeshwari K. Muthusamy, M.D.

Dilated follicles


Degenerative changes

Reactive fibrosis

False angioinvasion

Aggregate of small follicles

62 year old woman with adipose metaplasia

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:

Cystic adenomatous nodule

Cytology description
  • Sparse to moderately cellular smears with abundant thin or thick colloid, flat sheets with evenly spaced follicular cells, pigment laden macrophages and oncocytic cells
  • Rare microfollicles
  • No cytologic features of papillary thyroid carcinoma (nuclear pseudo inclusion, nuclear elongation, nuclear overlap, finely dispersed chromatin)
Cytology images

Contributed by Ayana Suzuki, C.T.

Watery colloid

Cracking colloid

Follicular clusters

3D structures

Paravacuolar granules

Cyst fluid only

Images hosted on other servers:

Watery colloid and focal dense colloid

Large amounts of background colloid


Thyroid multinodular goiter

Histopathology thyroid: nodular goiter

Histopathology thyroid: colloid goiter

Differential diagnosis
  • Adenoma: usually single, totally surrounded by capsule, dissimilar from remaining parenchyma, compresses adjacent tissue and composed of follicles smaller than normal gland; can mimic monoclonal dominant nodule in nodular goiter
  • 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
  • Papillary carcinoma: distinct nuclear features seen in papillary carcinoma; lacks the Sanderson polsters found in goiters
  • Toxic goiter: clinical hyperthyroidism
Board review style question #1
Histological features of nodular goiter include all of the following except:

  1. Cysts, hemorrhage, granulomatous response, fibrosis, calcification or osseous metaplasia
  2. Nodules with distinct thick capsule
  3. Papillary projections of the epithelium
  4. Variable sized follicles with flattened hyperplastic epithelium
Board review style answer #1
B. Nodules may or may not be present in nodular goiter but generally lack a thick capsule. Prominent features are variable sized dilated follicles with flattened hyperplastic epithelium. Secondary changes include foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia. Some of the cystically dilated follicles may show papillary projections (Sanderson polsters). Cytologic atypia in the form of highly atypical nuclei occurs in patients exposed to radioactive substances.
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