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.
Benign thyroid nodules (∼ 95% of cases)
- Thyroid adenomas
- Thyroid cysts
- Dominant nodules of multinodular goiters
Malignant thyroid nodules (∼ 5% of cases)
Red flags for thyroid cancer ; 
- Patient characteristics
- Palpatory findings
- Firm or hard nodule
- Fixed nodule
- Cervical lymphadenopathy
- All thyroid nodules (including thyroid incidentalomas) should be evaluated for malignancy. 
- Initial tests in all patients: TSH levels and thyroid ultrasound 
- Subsequent tests
- Additional tests
Initial evaluation 
- Serum TSH: may be normal, elevated, or low
- Indicated in patients with palpable nodules or if there is clinical suspicion of malignancy
- Assess each nodule individually for risk features.
|Sonographic evaluation of thyroid nodules |
|Overview||Risk pattern||Ultrasound findings|
|Sonographic signs of thyroid malignancy||High risk|
|Intermediate risk|| |
|Sonographic signs of benign thyroid nodules||Low risk|| |
|Very low risk|| |
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.
Thyroid scintigraphy 
- Indication: thyroid nodule(s) in a patient with low TSH
- Contraindications: pregnant and breastfeeding women
- Findings and interpretation
Malignancy is rare in hyperfunctioning (hot) nodules. 
Fine-needle aspiration cytology (FNAC) 
Indications for FNAC of thyroid nodules
- Solid hypoechoic nodules ≥ 1 cm with/without additional
- 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).
- 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 
|I: Nondiagnostic or unsatisfactory|
|III: Atypia or follicular lesion of undetermined significance|
|IV: Follicular neoplasm or suspicious for follicular neoplasm|| |
|V: Suspicious for malignancy|| |
- Follicular adenoma is the most common type of thyroid adenoma. 
- 10–15% of follicular neoplasms are malignant.
Clinical features 
- Often presents as a slow-growing solitary nodule
- Patients are typically euthyroid.
- In rare cases, patients can manifest with (∼ 1% of follicular adenomas develop into ). 
- Thyroid function tests: TSH is typically normal.
- Thyroid ultrasound: may show or appear benign
- Confirmatory test
- Third most common cause of hyperthyroidism
- Sex: ♀ > ♂ 
- Age: more common in individuals 30–50 years of age
- Gain-of-function mutations of TSH receptor gene; in a single precursor cell → autonomous functioning of the of a single nodule → focal hyperplasia of thyroid follicular cells → toxic adenoma
- The autonomous thyroid nodule overproduces thyroid hormones → hyperthyroidism → decrease in pituitary TSH secretion → suppression of hormone production in the rest of the gland
- Palpable, usually painless nodule in otherwise normal gland
For the initial workup, see “Diagnostic approach to thyroid nodules.”
- Thyroid function tests: : ↑ T3 and ↓ TSH
- Thyroid ultrasound: ; in some cases, increased perfusion
- Solitary, hot nodule
- Suppression of rest of the gland
- FNAC: Indicated not as a confirmatory test for toxic adenoma but to identify malignancy in suspicious nodules (see “Indications for FNAC of thyroid nodules”)
- Initial management: treatment of hyperthyroidism
- Definitive treatment options 
- 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
- Chronic iodine deficiency/thyroid dysfunction → decreased hormone production → increased hypothalamic TRH secretion → persistent TSH stimulation of the thyroid gland → hyperplasia of thyroid nodules, some more active than others → multinodular goiter (nontoxic MNG)
- Multiple somatic mutations of TSH receptor occur in long-standing goiters (> 60% of cases) → autonomous functioning of some nodules (toxic MNG) → hyperthyroidism (due to ↑ release of both T3 and T4)
Clinical features 
- Thyroid function tests: ↑ T3 and ↓ TSH
- Thyroid ultrasound: multiple nodules within the thyroid parenchyma; increased perfusion
- Thyroid scintigraphy 
- FNAC: not routinely required (see “Indications for FNAC of thyroid nodules”)
- Histopathology of resected tissue: patches of enlarged follicular cells distended with colloid and with flattened epithelium
Classification and etiology 
- 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. 
- Most commonly due to cystic degeneration of thyroid tissue or involution of an adenoma
- 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).
- Thyroid function tests: typically normal
- Cystic components appear anechoic.
- May be mixed with solid components
- FNAC: based on FNAC indications for thyroid nodules 
Special patient groups
Pregnant patients 
- RAIA is contraindicated during pregnancy and breastfeeding.
- If thyroid cancer is suspected or diagnosed during pregnancy: