Thyroid Nodules

Thyroid nodules are discrete, focal abnormalities within the thyroid gland. They are an extremely common clinical and incidental imaging finding, and the great majority prove benign on appropriate evaluation.

The essential task in every case is systematic risk stratification to identify the small proportion harbouring malignancy. It combines clinical assessment, ultrasound characterisation and, where indicated, fine needle aspiration cytology.

This approach avoids both missing a significant malignancy and unnecessary invasive investigation or surgery for the many benign nodules. Prevalence on sensitive imaging in the general population is very high.

Epidemiology and risk stratification principles

• Thyroid nodules are identified on ultrasound in a substantial proportion of the adult population. Prevalence increases with age and is significantly higher on ultrasound than on clinical palpation alone.
• This reflects the high sensitivity of modern imaging for small, clinically insignificant nodules, the great majority of which never need intervention.
• Risk factors raising concern for malignancy in a nodule are a history of head or neck irradiation (particularly radiotherapy in childhood), and a family history of thyroid cancer or a hereditary cancer syndrome (including multiple endocrine neoplasia type two).
• Rapid nodule growth is a further risk factor.
• Concerning examination findings are a firm, fixed nodule, associated cervical lymphadenopathy and vocal cord palsy.

• The great majority of thyroid nodules are asymptomatic. They are discovered incidentally on examination for an unrelated reason or, increasingly commonly, on imaging (ultrasound, computed tomography or positron emission tomography) for an unrelated indication.
• Larger nodules may produce a visible or palpable neck swelling. Uncommonly they cause compressive symptoms, including dysphagia or, with significant retrosternal extension, tightness or breathlessness. These symptoms more typically reflect a larger multinodular goitre than an isolated solitary nodule.
• Clinical features raising concern for malignancy are rapid growth, a firm or hard, irregular, fixed nodule on palpation, associated cervical lymphadenopathy, and a relevant personal or family history of risk factors.
• Hoarseness raises the same concern, as it can reflect recurrent laryngeal nerve involvement from local malignant infiltration.
• The great majority of patients with thyroid nodules, including those confirmed to harbour malignancy, are clinically and biochemically euthyroid.
• Normal thyroid function testing therefore gives no reassurance about whether a nodule is benign or malignant. It should not replace structured, nodule specific risk assessment.

• Thyroid stimulating hormone measurement is an appropriate initial step and guides the diagnostic pathway. A normal value does not itself reassure about malignancy risk.
• A suppressed thyroid stimulating hormone suggests a functioning, hyperfunctioning nodule, which carries a very low likelihood of malignancy. Radioactive iodine uptake scanning rather than fine needle aspiration cytology is then the more appropriate next step.
• Thyroid ultrasound is the essential, central investigation for any thyroid nodule. It characterises nodule size and sonographic features associated with malignancy risk: marked hypoechogenicity, irregular or infiltrative margins, microcalcifications, a taller than wide shape, and evidence of extrathyroidal extension.
• Structured risk stratification systems (such as the Thyroid Imaging Reporting and Data System, or equivalent systems) place nodules in defined risk categories. The combination of sonographic features and nodule size then guides the decision on fine needle aspiration biopsy.
• Fine needle aspiration cytology, under ultrasound guidance, is indicated for nodules meeting the size and sonographic risk criteria of the risk stratification system used.
• Cytology is reported with a standardised system (such as the Bethesda system). Categories run from benign, through several categories of indeterminate significance, to malignant or suspicious for malignancy, and guide management.
• Molecular testing on aspirate material is increasingly used for cytologically indeterminate nodules to refine malignancy risk. Where it suggests a sufficiently low residual risk, continued surveillance can replace diagnostic surgery.
• Radioactive iodine uptake scanning is reserved for a nodule with a suppressed thyroid stimulating hormone. It confirms autonomous hyperfunction (a hot nodule), which has very low malignancy risk and generally does not need fine needle aspiration cytology.
• A cold, non functioning nodule instead needs ultrasound based risk assessment and, where indicated, cytological evaluation.

• Benign cytology occurs in the great majority of biopsied nodules. It is managed with clinical and, where indicated by nodule characteristics, periodic ultrasound surveillance rather than surgical excision. The false negative rate is very low, though not absent.
• Surveillance interval and duration are guided by the initial nodule characteristics and risk profile.
• Indeterminate cytology needs individualised management according to the subcategory, molecular testing results where available, and overall clinical risk.
• Lower risk indeterminate categories are managed with repeat fine needle aspiration or continued surveillance. Higher risk categories, or those where molecular testing supports a higher residual malignancy risk, go to diagnostic surgical excision (typically diagnostic lobectomy).
• Malignant or suspicious for malignancy cytology warrants surgical referral for definitive management. The extent of surgery (lobectomy versus total thyroidectomy) is individualised to tumour characteristics, size and other clinical factors.
• Autonomously functioning (hot) nodules have a suppressed thyroid stimulating hormone and are confirmed on radioactive iodine uptake scanning. Management depends on the presence and severity of clinical hyperthyroidism and follows principles similar to toxic adenoma, addressed under hyperthyroidism.
• Options for hot nodules are radioactive iodine ablation, surgical excision or, for smaller asymptomatic nodules without significant biochemical hyperthyroidism, continued observation.
• Nodules causing significant compressive symptoms may warrant surgical consideration on those symptoms alone, whatever their cytological risk category, given the potential for progressive local compression as the nodule or goitre grows.
• Regular clinical follow up, with periodic reassessment and, where appropriate to initial risk, repeat ultrasound over subsequent years, underpins risk stratified management.
• The priority is not to miss a significant malignancy, balanced against the harms of overinvestigation and overtreatment of the very common, generally benign thyroid nodule.