What are the recommended diagnostic evaluation and first‑line management guidelines for an adult with a clinically palpable, enlarged, active thyroid gland (goiter) presenting with compressive symptoms or thyroid dysfunction?

Management of Active and Enlarged Thyroid Gland (Goiter)

Begin with serum TSH measurement as the mandatory first step, followed immediately by thyroid ultrasound to characterize morphology and assess for nodules; if TSH is suppressed (< 0.4 mIU/L), proceed to radioiodine uptake scan to differentiate the cause of thyrotoxicosis. 1, 2

Initial Diagnostic Evaluation

Biochemical Testing

• Measure TSH first in all patients with suspected goiter, as it has 98% sensitivity and 92% specificity for detecting thyroid dysfunction 2
• If TSH is abnormal, obtain free T4 (FT4) and free T3 (FT3) to complete the functional assessment 2
• TSH < 0.1 mU/L indicates significant hyperthyroidism; TSH 0.1-0.45 mU/L requires repeat testing with FT4 and FT3 within 4 weeks 2
• TSH > 6.5 mU/L indicates hypothyroidism 2

Imaging Algorithm Based on TSH Results

For Normal or Elevated TSH (Euthyroid or Hypothyroid):

• Ultrasound is the sole imaging modality needed to confirm thyroid origin, measure size, characterize nodules, and assess malignancy risk using ACR TI-RADS criteria 1, 3
• Do NOT perform radioiodine uptake scan in euthyroid patients, as it has low diagnostic value and does not help determine malignancy or guide biopsy decisions 1, 3

For Suppressed TSH (< 0.4 mU/L with Thyrotoxicosis):

• Perform ultrasound first to evaluate thyroid morphology, detect nodules, and identify suspicious features requiring biopsy 1
• Follow with radioiodine uptake scan (preferably I-123) to differentiate toxic multinodular goiter, toxic adenoma, Graves' disease, or destructive thyroiditis 1, 4
• This sequence prevents missing coexisting thyroid nodules that may require malignancy evaluation 1

Additional Imaging for Compressive Symptoms

• If dyspnea, orthopnea, dysphagia, or dysphonia are present, obtain chest CT scan to evaluate tracheal compression, substernal extension, and retropharyngeal involvement 3
• CT is superior to ultrasound for assessing substernal goiter and degree of airway compromise 3

First-Line Management by Clinical Scenario

Nontoxic Multinodular Goiter (Normal TSH)

Small, Asymptomatic Goiter:

• Annual observation with TSH measurement and thyroid palpation is sufficient 5
• Do NOT use levothyroxine suppression therapy, as it is often unsuccessful and risks iatrogenic hyperthyroidism 5, 6

Large Goiter with Compressive Symptoms:

• Total thyroidectomy is the preferred treatment for symptomatic goiters causing dyspnea, dysphagia, or cosmetic concerns 5, 6, 7
• Surgery should be performed by experienced surgeons, especially for substernal goiters, to avoid respiratory compromise 7

Toxic Multinodular Goiter (Suppressed TSH with Hyperthyroidism)

Primary Treatment Options:

• Surgery (total thyroidectomy) or radioiodine (¹³¹I) are both recommended first-line treatments 5, 4
• Surgery achieves euthyroid state more rapidly, particularly for large goiters with large autonomously functioning nodules 5
• Radioiodine is preferred for older patients or those with significant comorbidities, though it may require higher doses for large goiters 5, 6
• Antithyroid drugs (methimazole, propylthiouracil) can be used for initial control but have 50% recurrence rates after 12-18 months 4

Predictors of Recurrence with Antithyroid Drugs:

• Age < 40 years, FT4 ≥ 40 pmol/L, TSH-binding inhibitory immunoglobulins > 6 U/L, and goiter size ≥ WHO grade 2 increase recurrence risk 4

Nodule Evaluation and Biopsy

• Use ACR TI-RADS criteria from ultrasound to select nodules for fine-needle aspiration biopsy (FNAB) 3, 8
• Biopsy should only be performed after ultrasound characterization, not as an initial diagnostic step 3
• In toxic goiter with suppressed TSH, radioiodine scan identifies "hot" nodules that do not require biopsy, as they are rarely malignant 1

Critical Pitfalls to Avoid

• Never proceed directly to radioiodine uptake scan without checking TSH first, as this wastes resources and exposes euthyroid patients to unnecessary radiation 1
• Never skip ultrasound in hyperthyroid patients, as this may miss coexisting nodules requiring malignancy evaluation 1
• Never use levothyroxine suppression in patients with already suppressed TSH, as this will worsen thyrotoxicosis 5
• Never delay surgical evaluation for large substernal goiters with respiratory symptoms, as sudden growth can critically compromise the airway 7