How should a patient with diffuse multinodular goitre and an American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) 3 (probably benign) thyroid ultrasound be initially managed?

Management of Diffuse Multinodular Goiter with TIRADS 3 Nodules

For a patient with diffuse multinodular goiter containing TIRADS 3 (probably benign) nodules, measure serum TSH first, then perform ultrasound-guided fine-needle aspiration (FNA) only on nodules ≥2.5 cm or those with additional high-risk clinical features, while observing smaller nodules with annual surveillance ultrasound. 1, 2

Initial Diagnostic Pathway

Measure TSH before any further decisions, as this determines the entire management algorithm and urgency of intervention. 1 The presence of thyrotoxicosis versus euthyroid status fundamentally changes whether you proceed with radionuclide scanning or move directly to nodule characterization. 3

Key Clinical Context to Document

• History of head and neck irradiation increases malignancy risk approximately 7-fold and lowers the FNA threshold even for TIRADS 3 nodules 1, 4
• Family history of thyroid cancer, particularly medullary carcinoma or familial syndromes 1, 4
• Compressive symptoms including dysphagia, dyspnea, choking sensation, or voice changes 2, 5
• Rapid nodule growth (≥3 mm increase in any dimension) is one of the strongest predictors of malignancy 4

Management Algorithm Based on TSH Results

If TSH is Suppressed (Toxic Multinodular Goiter)

Proceed to radionuclide uptake and scan to identify hyperfunctioning versus isofunctioning/hypofunctioning nodules. 3 Compare the scan to ultrasound findings to target hypofunctioning or isofunctioning nodules for FNA, as these carry higher malignancy risk. 3 Treatment options include radioactive iodine or surgery, with surgery providing more rapid resolution for large goiters with autonomously functioning nodules. 6

If TSH is Normal or Elevated (Nontoxic Multinodular Goiter)

Do not order radionuclide scanning in euthyroid patients, as it has low positive predictive value for malignancy and does not add value for risk assessment. 1, 4 Ultrasound features should guide all management decisions. 4

FNA Decision Algorithm for TIRADS 3 Nodules

TIRADS 3 nodules carry a baseline malignancy risk of approximately 5-13%. 7, 8 The ACR guidelines recommend different size thresholds based on TIRADS category:

Proceed with FNA if:

• Nodule ≥2.5 cm (standard threshold for TIRADS 3) 2, 8
• Any size nodule with ≥2 additional suspicious features on ultrasound: marked hypoechogenicity, microcalcifications, irregular margins, absence of peripheral halo, or central hypervascularity 2, 4
• Nodule ≥1 cm with high-risk clinical factors: history of radiation, family history of thyroid cancer, age <15 years, suspicious cervical lymphadenopathy 1, 4
• Compressive symptoms clearly attributable to specific nodules 2, 5
• Documented growth ≥3 mm in any dimension during surveillance 4

Observation is appropriate for:

• TIRADS 3 nodules <2.5 cm without high-risk clinical features or additional suspicious ultrasound characteristics 2, 8
• Asymptomatic patients with stable nodule size and normal TSH 6, 5

Surveillance Protocol for Observed Nodules

Perform repeat ultrasound at 12-24 months to assess for interval growth or development of suspicious features. 2, 4 Annual clinical evaluation with TSH measurement and thyroid palpation is sufficient for stable nodules. 6, 5

Do not use CT or MRI for routine surveillance, as ultrasound provides superior resolution for nodule characterization. 4 Reserve CT for evaluating substernal extension or tracheal compression when surgery is being considered. 2

Management Based on FNA Results

Bethesda II (Benign)

Continue surveillance with repeat ultrasound at 12-24 months, as malignancy risk is only 1-3%. 2, 4 However, a reassuring FNA should not override worrisome clinical findings, as false-negative results occur in 11-33% of cases. 4

Bethesda III/IV (Indeterminate)

Consider molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations to refine malignancy risk, as 97% of mutation-positive nodules are malignant. 2, 4 If molecular testing is unavailable or indeterminate, surgery is generally recommended for definitive diagnosis. 2, 5

Bethesda V/VI (Suspicious or Malignant)

Refer immediately for total or near-total thyroidectomy with pre-operative assessment of cervical lymph node compartments. 2, 4

Critical Pitfalls to Avoid

• Do not skip ultrasound evaluation even if planning specialist referral, as it provides essential information guiding urgency and type of intervention 1
• Do not proceed directly to radionuclide scanning in euthyroid patients with multinodular goiter 1
• Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function 4
• Do not use levothyroxine suppression therapy in patients with suppressed TSH levels, as this risks toxic symptoms without proven benefit for nodule size reduction 6
• Do not perform FNA on all nodules in a multinodular goiter—select the largest nodule, those with suspicious features, or hypofunctioning nodules on scan 3, 2

When to Refer for Surgery

Immediate surgical referral is indicated for:

• Malignant or suspicious cytology (Bethesda V/VI) 2, 4
• Large goiters with compressive symptoms (dysphagia, dyspnea, airway obstruction) 2, 5
• Substernal extension with tracheal compression 2
• Toxic multinodular goiter in patients preferring definitive treatment over radioiodine 6, 5

Endocrinology consultation is recommended for managing indeterminate cytology, applying TIRADS criteria for nodule selection, and coordinating surveillance protocols. 1