II. Epidemiology

  1. Incidence of new Thyroid Nodules U.S.
    1. Overall: 9 Million/year
    2. Palpable Nodules: 300,000/year
  2. Prevalence: Palpable Thyroid Nodules
    1. Women: 7-8% lifetime Prevalence
    2. Men: 2% lifetime Prevalence
  3. Prevalence: Non-palpable Thyroid Nodules (incidental)
    1. Neck Ultrasound: 40%
    2. Autopsy: 36-50%
  4. Thyroid Cancer
    1. Palpable Nodules: 5-10% Incidence of Thyroid Cancer
    2. Incidental Nodules on Ultrasound: 1.5 to 5% Incidence of Thyroid Cancer
  5. Hyperfunctioning Thyroid Nodules (Toxic Thyroid Adenoma, Plummer Disease)
    1. Account for 5% of cases ("hot Nodules")
    2. Autonomously produce Thyroid hormone
    3. Arises from mutation in TSH receptor or Gs alpha gene
    4. Rarely malignant
  6. References
    1. Dean (2008) Endocrinol Metab 22(6): 901-11 [PubMed]

III. Risk Factors: Thyroid Cancer (in Thyroid Nodules)

  1. Head and neck radiation history (especiall radiation exposure in childhood)
    1. Palpable Thyroid Nodule is malignant in 20-50% of previously irradiated Thyroid Glands
  2. Age <20 years old or over 70 years old
  3. Male gender
  4. Graves Disease
  5. Family History of Thyroid Cancer
  6. Multiple endocrine neoplasia (MEN) type 2A or 2B
    1. Associated with up to 25% risk of Thyroid Cancer

IV. Symptoms

  1. Typically asymptomatic
  2. Large Nodules may cause local compression
    1. Dysphagia
    2. Choking sensation
  3. Hyperfunctioning Thyroid Nodules or "Hot Nodules" (5% of Thyroid Nodules)
    1. Hyperthyroidism symptoms

V. Signs

  1. Discrete palpable Thyroid Nodules in lower anterior neck
    1. Nodules are not typically palpable if <1 cm
    2. Nodules are classified as small when 1-4 cm
    3. Usually solitary
  2. Usually cold Nodule on Thyroid scan
    1. Only 1% are active Nodules (Hyperthyroidism)

VI. Labs

  1. Thyroid Stimulating Hormone (TSH)
    1. TSH suppressed in 5% of Thyroid Nodules that are hyperfunctioning ("hot Nodules")
    2. Increased TSH has a higher risk of Thyroid malignancy
  2. Serum Calcitonin
    1. Increased with Medullary Thyroid Carcinoma (rare)
    2. Indicated only in Family History or clinical suspicion of Medullary Thyroid Carcinoma or MEN Type 2

VII. Imaging

  1. Thyroid Ultrasound
    1. Indicated in all palpable Thyroid Nodule evaluations
  2. Radioactive Iodine Uptake Scan
    1. Indicated only if suppressed TSH (hyperfunctioning Thyroid Nodule or "hot Nodule")

VIII. Evaluation

  1. Step 1: Identify palpable Nodule on exam
  2. Step 2: Obtain TSH
    1. TSH Low: Go to Step 3
    2. TSH Normal: Go to Step 4
  3. Step 3: Obtain Radioactive Thyroid Scan
    1. Hot Nodule
      1. Euthyroid
        1. Consider Subclinical Hyperthyroidism monitoring
      2. Hyperthyroidism
        1. Go to Hyperthyroidism Management
        2. Typically managed with Radioactive Iodine 131 Ablation
    2. Cold Nodule
      1. More likely to be malignant (5-15% of cases)
      2. Go to Step 4
  4. Step 4: Thyroid Ultrasound
    1. Benign appearing Nodule <1 cm with negative clinical history
      1. Observe and follow
      2. Repeat thyroid Ultrasound in 6 months
    2. Nodule >1 cm (or any size if Thyroid Cancer risk factors or suspicious findings)
      1. Cystic lesion
        1. Go to Step 5 (FNA) and sample the solid component of lesion under Ultrasound guidance
        2. Recurrent benign cystic Nodules may be excised or ablated with Alcohol injection if symptomatic
      2. Solid Lesion
        1. Go to Step 5 (FNA)
    3. Lesion with extracapsular invasion or associated Cervical Lymphadenopathy (Thyroid Nodule of any size)
      1. Go to Step 5 (FNA)
    4. Multiple Nodules >1 cm each
      1. Go to Step 5 (FNA) and sample up to 3 of the Nodules
    5. Thyroid Nodule >4 cm
      1. Higher risk of malignancy (as well as false negative FNA due to sampling error)
      2. Diagnostic lobectomy is preferred over FNA
  5. Step 5: Fine needle aspiration (FNA)
    1. Indications
      1. Thyroid Nodule >1-2 cm
      2. Thyroid Cancer risk factors (see above)
      3. Ultrasound with suspicious findings
        1. Hypoechogenicity
        2. Solid Nodule with microcalcifications
        3. Intranodular vascularity
    2. Consider Ultrasound guided FNA (improves diagnostic accuracy of biopsy)
      1. Small Nodules
      2. Cystic Nodules with a solid component
    3. Benign
      1. False Negative Rate: <10%
      2. Repeat thyroid Ultrasound in 6-18 months after initial Thyroid FNA
        1. Thyroid growth: Repeat Thyroid FNA
        2. No significant Thyroid Nodule growth: Repeat thyroid Ultrasound in 3-5 years
      3. Slow serial growth of benign Thyroid Nodules
        1. Unlikely to be malignant if initial FNA negative
        2. Alexander (2003) Ann Intern Med 138:315-8 [PubMed]
      4. Levothyroxine suppression for benign Nodules is not recommended
    4. Suspicious: Frozen section
      1. Thyroid Cancer risk: 40-45%
      2. Consider Thyroid lobectomy if still inconclusive
    5. Malignant
      1. False Positive Rate: 2%
      2. Thyroidectomy

IX. Evaluation: Thyroid Nodules in Pregnancy

  1. Start with TSH and thyroid Ultrasound (as in evaluation above)
    1. Thyroid FNA if indicated (as in evaluation above)
  2. Exception: Suppressed TSH (Hyperthyroidism)
    1. Postpone Thyroid Uptake Scan until after Pregnancy and Lactation
    2. Treat symptomatic Hyperthyroidism with antithyroid medication

X. Evaluation: Thyroid Nodules in Children and Adolescents

  1. Rare: 1-2% of children
  2. High risk of Thyroid Cancer: 27%
  3. Evaluation Strategy
    1. Nodule excision indications (without Thyroid FNA)
      1. Children (Thyroid FNA is unreliable)
      2. Family History of Thyroid Cancer or MEN type 2
    2. Thyroid FNA
      1. Adolescents without Nodule excision indications

XI. Differential Diagnosis

  1. Thyroid Carcinoma (5-10% in adults, 14-40% in children)
  2. Dominant follicle in Multinodular Goiter (23%)
  3. Thyroid cyst (simple or mixed)
  4. Thyroiditis
  5. Thyroid Adenoma
    1. Simple or colloid Macrofollicular Adenoma
      1. Most common type
      2. Follicles of normal size
    2. Embryonal (Trabecular) adenoma
      1. Mostly stroma and minimal follicles
    3. Fetal Microfollicular Adenoma
      1. Small follicles with minimal colloid
      2. Follicular cancer found in 5% of cases
    4. Hurthle Cell Adenoma (uncommon)

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Ontology: Thyroid Nodule (C0040137)

Definition (NCI) A nodular lesion that develops in the thyroid gland. Causes include adenoma, thyroiditis, fluid-filled cyst, multinodular goiter, and carcinoma.
Definition (MSH) A small circumscribed mass in the THYROID GLAND that can be of neoplastic growth or non-neoplastic abnormality. It lacks a well-defined capsule or glandular architecture. Thyroid nodules are often benign but can be malignant. The growth of nodules can lead to a multinodular goiter (GOITER, NODULAR).
Concepts Neoplastic Process (T191)
MSH D016606
SnomedCT 190234009, 237495005, 76917005
English Nodule, Thyroid, Nodules, Thyroid, Thyroid Nodules, Thyroid Gland Nodule, Thyroid Nodule, Thyroid Nodule [Disease/Finding], thyroid nodule, Nodule(s);thyroid, thyroid nodules, Thyroid nodule, Thyroid nodule (disorder), Nodule of Thyroid Gland, Nodule of Thyroid, Nodule of the Thyroid Gland, Nodule of the Thyroid, thryoid nodules
Dutch schildkliernodus, Nodus, schildklier-, Schildkliernodus
German Schildddruesenknoetchen, Schilddrüsenknoten
Italian Nodulo della tiroide, Nodulo tiroideo
Portuguese Nódulo da tiroideia, Nódulo da Glândula Tireoide
Spanish Nódulo tiroideo, nódulo tiroideo (concepto no activo), nódulo tiroideo (trastorno), nódulo tiroideo, Nódulo Tiroideo
Japanese 甲状腺結節, コウジョウセンケッセツ
Swedish Knuta i sköldkörtel
Czech tyreoidální uzel, Thyreoidální uzel
Finnish Kilpirauhaskyhmy
Russian TIREOIDNYI UZEL, SHCHITOVIDNOI ZHELEZY UZEL, ТИРЕОИДНЫЙ УЗЕЛ, ЩИТОВИДНОЙ ЖЕЛЕЗЫ УЗЕЛ
Croatian TIREOIDNI ČVOR
Polish Guzki tarczycy
Hungarian Pajzsmirigy-csomó
Norwegian Skjoldkjertelknute, Tyreoideaknute
French Nodule thyroïdien, Nodule de la thyroïde

Ontology: Toxic thyroid adenoma (C0302840)

Concepts Disease or Syndrome (T047)
SnomedCT 449097000
Dutch schildklieradenoom toxisch
French Adénome toxique de la thyroïde
German toxisches Schilddruesenadenom
Italian Adenoma della tiroide tossico
Portuguese Adenoma da tiroideia tóxico
Spanish Adenoma tiroideo tóxico, adenoma folicular de glándula tiroides hiperfuncionante (trastorno), adenoma folicular de glándula tiroides hiperfuncionante, adenoma tiroideo tóxico
Japanese 中毒性甲状腺腺腫, チュウドクセイコウジョウセンセンシュ
English toxic thyroid adenoma (diagnosis), toxic thyroid adenoma, toxic adenoma, Toxic thyroid adenoma, Hyperfunctioning follicular adenoma of thyroid gland, Hyperfunctioning follicular adenoma of thyroid gland (disorder), Thyroid adenoma toxic
Czech Toxický adenom štítné žlázy
Hungarian Toxikus pajzsmirigy adenoma

Ontology: Mass of thyroid gland (C0349453)

Concepts Neoplastic Process (T191)
SnomedCT 237557003, 276378000
Italian Massa della tiroide
Japanese 甲状腺腫瘤, コウジョウセンシュリュウ
Czech Rezistence v oblasti štítné žlázy
English Mass of thyroid gland, Mass of thyroid gland (finding), Thyroid lump (disorder), Thyroid lump, thyroid mass on exam (physical finding), thyroid mass on exam, mass thyroid, thyroid lumps, Lump(s);thyroid, Mass;thyroid, lump thyroid, masses thyroid, lumps thyroid, thyroid mass, Thyroid lump (finding), Thyroid gland mass, Thyroid mass, thyroid lump
Spanish tumoración tiroidea (trastorno), tumoración tiroidea (hallazgo), masa tiroidea, tumoración tiroidea, Masa tiroidea
Hungarian Pajzsmirigy térfoglaló folyamata
Portuguese Massa tireoidiana
Dutch schildkliergezwel
French Masse thyroïdienne
German Schilddruesenmasse