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Thyroid nodules

Last updated: March 29, 2021

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Thyroid nodules are abnormal growths within the thyroid gland. They are present in approximately 50% of the general population but only palpable in 5–10% of the population. They are more common in women, especially in iodine-deficient regions, and their incidence increases with age. Thyroid nodules are the clinical manifestation of various underlying thyroid diseases. The majority of them are benign (∼ 95%), with colloid cysts, follicular adenomas, and Hashimoto thyroiditis being the most common causes. Approximately 5% of thyroid nodules are malignant, with papillary carcinoma being the most common form of malignant disease. A thyroid incidentaloma is a nodule that is discovered during imaging for an unrelated cause and should be evaluated in the same way as other nodules. The initial evaluation of all thyroid nodules includes a TSH assay and thyroid ultrasound. Sonographic signs of thyroid cancer should be further evaluated with fine-needle aspiration cytology (FNAC). Identification of a follicular neoplasm on FNAC necessitates further diagnostic evaluation with either molecular testing or surgical excision and histopathology because cytology cannot reliably distinguish between a follicular adenoma and a follicular carcinoma. A radioiodine uptake scan (thyroid scintigraphy) is used to evaluate nodules in patients with low TSH levels. Based on their iodine uptake on radioiodine scans, thyroid nodules can be categorized as autonomous/hot (increased uptake) or nonfunctional/cold (decreased uptake). The most common hot nodules are toxic adenomas and dominant nodules of toxic multinodular goiters. With a 5–15% risk of malignancy, cold nodules are clinically significant. Treatment depends on the underlying etiology and includes, e.g., surgery (thyroidectomy) for malignant and autonomous nodules, aspiration for thyroid cysts, and observation for small, benign nodules.

  • Sex: > (4:1)
  • Incidence: increases with age [1]
  • Geographic distribution: most common in inland regions without iodine fortification programs, where iodine content in food and water is low

References:[2]

Epidemiological data refers to the US, unless otherwise specified.

Benign thyroid nodules (∼ 95% of cases)

Malignant thyroid nodules (∼ 5% of cases)

In addition to red flags for thyroid cancer, a solid nodule on thyroid ultrasound or a cold nodule on thyroid scintigraphy should raise suspicion for thyroid cancer.

Approach [3][6][7]

Initial evaluation [3][6][9]

Sonographic evaluation of thyroid nodules [6]
Overview Risk pattern Ultrasound findings
Sonographic signs of thyroid malignancy High risk
  • Solid hypoechoic nodule or solid hypoechoic component with at least one of the following:
    • Irregular margins
    • Taller-than-wide shape
    • Microcalcifications
    • Rim calcifications with extruding tissue
    • Extrathyroidal extension
Intermediate risk
  • Solid hypoechoic nodule without high-risk features
Sonographic signs of benign thyroid nodules Low risk
  • Isoechoic or hyperechoic solid nodule
  • Cystic nodule with eccentric solid component
Very low risk
  • Partially cystic nodule
  • Spongiform nodule
Benign
  • Cystic nodules (anechoic) without solid component

Thyroid ultrasound is not a screening test for the general population. It is indicated as initial test for patients with palpable thyroid nodules or clinical suspicion for thyroid malignancy. [3]

Solid, hypoechoic nodules with irregular margins, microcalcifications, taller-than-wide shape, extrathyroidal growth, and/or cervical lymphadenopathy should raise suspicion for malignancy and require further evaluation with FNAC.

Subsequent evaluation

Thyroid scintigraphy [3][10]

Malignancy is rare in hyperfunctioning (hot) nodules. [11]

Fine-needle aspiration cytology (FNAC) [3][6]

  • Indications for FNAC of thyroid nodules
    • Solid hypoechoic nodules ≥ 1 cm with/without additional sonographic signs of thyroid cancer
    • Consider for solid hypoechoic nodules < 1 cm if any of the following are present:
    • Partly cystic, isoechoic, and hyperechoic nodules ≥ 1.5 cm (low-risk pattern)
    • Consider in spongiform or partly cystic nodule ≥ 2 cm (very low-risk pattern).
  • Procedure
    • Thyroid cells are obtained using a fine (e.g., 25-gauge) needle, and then observed under a microscope. [3]
    • Multiple nodules may require FNAC depending on their sonographic appearance.
  • Findings: categorized according to the Bethesda system for thyroid cytopathology

If thyroid scintigraphy is performed, sonographic features of thyroid nodules should be used to determine which cold nodules require FNAC. Cold nodules with a benign appearance on thyroid ultrasound do not routinely require FNAC.

Bethesda system for thyroid cytopathology [13]

Diagnostic category

Management [6]
I: Nondiagnostic or unsatisfactory
II: Benign
  • No further immediate diagnostic tests required
  • Repeat FNAC or sonography within 1– 2 years depending on sonographic features.
    • After two benign findings, no further follow-up is needed.
    • If there is an increase in size or the size is > 4 cm: Consider surgical removal for symptom relief.
III: Atypia or follicular lesion of undetermined significance
  • Consider any of the following:
IV: Follicular neoplasm or suspicious for follicular neoplasm
V: Suspicious for malignancy
VI: Malignant

Epidemiology

Clinical features [9]

Diagnostics [6]

Follicular adenoma is a histopathological diagnosis. Cytology alone cannot distinguish between adenoma and carcinoma. For the initial workup, see “Diagnostic approach to thyroid nodules”.

Treatment [9]

Epidemiology

  • Third most common cause of hyperthyroidism
  • Sex: > [15]
  • Age: more common in individuals 30–50 years of age

Pathophysiology

Clinical features

Diagnostics [16]

For the initial workup, see “Diagnostic approach to thyroid nodules.”

Treatment [10]

Epidemiology [16]

  • Sex: >
  • Age: often > 60 years
  • Second most common cause of hyperthyroidism
  • Develops in 10% of patients with a long-standing nodular goiter
  • More prevalent in iodine-deficient regions

Pathophysiology

Clinical features [16]

Diagnostics [16]

For the initial workup of a nodular goiter, see “Diagnostic approach to thyroid nodules.”

Treatment [10][17]

Classification and etiology [7]

  • Simple cysts are exclusively fluid-filled nodules lined by benign epithelial cells.
  • Complex cysts are partly solid and partly cystic and carry a 5–10% risk of malignancy. [19]
  • Most commonly due to cystic degeneration of thyroid tissue or involution of an adenoma

Clinical features

  • Palpable thyroid nodule
  • Hemorrhage into a cyst → pain and rapid enlargement of the nodule
  • A large cyst or extensive hemorrhage can cause compression symptoms (e.g., hoarseness, dysphagia).

Diagnostics [6]

The initial workup is the same as that for other thyroid nodules (see “Diagnostic approach to thyroid nodules”).

  • Thyroid function tests: typically normal
  • Thyroid ultrasound
    • Cystic components appear anechoic.
    • May be mixed with solid components
  • FNAC: based on FNAC indications for thyroid nodules [6][20]
    • Purely cystic nodule: diagnostic FNAC not recommended
    • Partly cystic nodule
      • Low risk pattern (eccentric solid component): FNAC if size is ≥ 1.5 cm
      • Very low risk pattern: Consider FNAC if size is ≥ 2 cm.

Treatment [6]

  • Benign cysts
    • Asymptomatic cysts: observation
    • Large or symptomatic cysts (or patient preference)
      • Aspiration with/without ethanol ablation [21]
      • Surgery may be considered if aspiration is not effective.
  • Malignant cysts: See “Thyroid cancer.”

Pregnant patients [3]

Management of thyroid nodules in pregnancy is similar to those in nonpregnant patients, except for the following points.

Children [3]

  • Management is similar to that of thyroid nodules in adults.
  • Thyroid nodules in children are more frequently malignant.
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  6. Multinodular Goiter.
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