What are the recommended diagnostic tests and treatment options for a patient presenting with a nodular goiter, considering potential underlying causes and complications, including hyperthyroidism and malignancy?

Diagnostic Testing for Nodular Goiter

Start with thyroid ultrasound and serum TSH measurement as your initial diagnostic workup for all patients with nodular goiter. 1, 2

Initial Diagnostic Algorithm

Step 1: Thyroid Function Assessment

• Measure serum TSH to determine functional status (euthyroid vs. hyperthyroid) 1, 3
• This single test reliably identifies whether the goiter is toxic (hyperthyroid) or nontoxic 3, 4

Step 2: Imaging Evaluation

Primary imaging modality:

• Thyroid ultrasound is the first-line and most appropriate imaging study for nodular goiter evaluation 1, 2
• Ultrasound is significantly more sensitive than CT for detecting thyroid nodules and characterizing their features 1
• Document each nodule's size, location, composition, echogenicity, margins, calcifications, and shape 1

When to add CT imaging:

• Add CT without IV contrast when substernal extension is suspected, as ultrasound has limitations evaluating the inferior border and mediastinal involvement 1, 2
• CT is superior for assessing tracheal compression and extent of disease below the thoracic inlet 1, 2
• For symptomatic patients with compression symptoms (dysphagia, choking, airway obstruction), obtain CT before surgery to evaluate substernal extension 1

Step 3: Risk Stratification and Biopsy Selection

Apply ACR TI-RADS criteria:

• Characterize each nodule for malignancy risk using the ACR TI-RADS scoring system 1
• Higher TI-RADS scores require biopsy at smaller size thresholds 1
• Select specific nodules for fine-needle aspiration biopsy (FNAB) based on size and suspicious ultrasound features, not simply because multiple nodules are present 1, 3

Common pitfall to avoid: Do not biopsy all nodules in a multinodular goiter—this leads to unnecessary procedures. Instead, target only those meeting TI-RADS criteria for biopsy based on suspicious features and size thresholds. 1

Step 4: Additional Testing for Hyperthyroid Goiters

If TSH is suppressed (toxic nodular goiter):

• Three equivalent first-line options exist: thyroid ultrasound (already obtained), I-123 radionuclide uptake and scan, or I-131 radionuclide uptake with Tc-99m pertechnetate scan 2
• Radionuclide uptake confirms thyroid tissue composition and identifies hypofunctioning or isofunctioning nodules that require biopsy despite hyperthyroidism 2, 5
• This distinguishes autonomous nodules from those requiring FNAB evaluation 3

Management Based on Test Results

For Malignant or Suspicious Cytology

• Refer for surgery immediately if FNAB shows malignant cytology 3
• For indeterminate/suspicious cytology, surgery is generally advised unless scintigraphy confirms autonomous function of the nodule 3

For Toxic Multinodular Goiter

• Treat hyperthyroidism first with antithyroid medications:
  • Methimazole is preferred for most patients 6
  • Propylthiouracil is reserved for patients intolerant of methimazole or in first trimester pregnancy 7
• Definitive treatment options after achieving euthyroid state:
  • Surgery provides rapid resolution and is preferred for large goiters with bulky nodules 3, 8
  • Radioactive iodine (I-131) is safe and effective, particularly for patients who are poor surgical candidates 3, 5

For Nontoxic Multinodular Goiter with Benign Cytology

Symptomatic patients (compression symptoms):

• Surgery is the preferred treatment for large goiters causing dysphagia, choking, or airway obstruction 3, 8
• Obtain CT scan preoperatively to evaluate substernal extension and tracheal compression 1

Asymptomatic patients with benign nodules:

• Observe with periodic follow-up rather than intervening 3
• Annual evaluation with neck palpation, serum TSH, and ultrasound examination 3, 8
• Levothyroxine suppression therapy is controversial and often unsuccessful; avoid in patients with already suppressed TSH to prevent iatrogenic hyperthyroidism 8

Critical Imaging Pitfalls to Avoid

• Do not rely on CT or MRI alone to differentiate benign from malignant nodules—these modalities have limited utility for this purpose 2
• Do not use imaging alone to predict malignancy—cytology via FNAB is required for definitive assessment 2
• Ultrasound may miss central compartment and retropharyngeal lymph node metastases where CT has higher sensitivity 1
• For goiters with significant caudal spread, ultrasound cannot adequately assess mediastinal structure involvement 1