What are the differential diagnoses for a patient with a nontoxic goiter?

Differential Diagnoses for Nontoxic Goiter

The differential diagnosis for nontoxic goiter includes multinodular goiter (most common), simple diffuse goiter, Hashimoto's thyroiditis, colloid goiter, hyperplastic/adenomatoid nodules, follicular neoplasms (adenoma), and rarely, well-differentiated thyroid carcinoma or anaplastic thyroid carcinoma presenting with pre-existing goiter. 1, 2

Primary Differential Categories

Benign Etiologies (Most Common)

Multinodular Nontoxic Goiter

• The most frequent presentation in clinical practice, particularly in women in their fifth and sixth decades 3
• Develops over many years with multiple nodules of variable size and activity 2
• Associated with iodine deficiency (affects 500-600 million people worldwide), iron deficiency, selenium deficiency, female sex, and advancing age 3
• Presents with heterogeneous uptake on scintigraphy if performed 2

Simple Diffuse Goiter

• Uniform thyroid enlargement without discrete nodules 4
• Often represents early phase of goitrogenesis that may progress to nodular disease over time 5
• Typically associated with iodine deficiency or goitrogenic substances 4

Hashimoto's Thyroiditis

• Classified as benign on FNA cytology 1
• May present with diffuse or nodular enlargement 1
• Diagnosed primarily through clinical presentation and thyroid function tests, with imaging reserved for atypical presentations 2

Colloid Goiter/Hyperplastic Nodules

• Benign cytologic findings on FNA 1
• Represent accumulation of colloid within follicles causing glandular enlargement 1

Neoplastic Etiologies Requiring Exclusion

Follicular or Hürthle Cell Neoplasm

• Cannot be definitively classified as benign or malignant on FNA alone 1
• Requires surgical excision for definitive diagnosis 1
• Important to identify as these require different management than simple goiter 5

Well-Differentiated Thyroid Carcinoma

• Papillary or follicular carcinoma may present within a goiter 1
• FNA is highly sensitive for papillary carcinoma but can yield false-negative results 1
• Ultrasound should identify suspicious nodules requiring biopsy even in the setting of goiter 2

Anaplastic Thyroid Carcinoma

• More than 80% of ATC patients have a history of pre-existing goiter 1
• Presents with rapidly enlarging neck mass, dyspnea, dysphagia, neck pain, or hoarseness 1
• Approximately 50% have prior or coexisting differentiated carcinoma 1
• Requires core or surgical biopsy if FNA is suspicious or non-definitive 1

Critical Diagnostic Approach

Initial Evaluation Algorithm

• Measure serum TSH first—this is the single most important test to guide the diagnostic pathway 2, 6
• If TSH is normal (euthyroid), proceed with thyroid ultrasound as first-line imaging 2
• Ultrasound provides superior morphological evaluation and identifies suspicious nodules requiring FNA 2, 6
• FNA should be performed on prominent palpable nodules or those with suspicious ultrasound features 7, 6

When to Consider Additional Testing

• Thyroid autoantibodies (anti-TPO) measured by 74% of clinicians to evaluate for Hashimoto's thyroiditis 6
• Radionuclide uptake scan is NOT indicated in euthyroid patients with goiter unless evaluating for substernal extension 2
• CT imaging is superior to ultrasound for evaluating substernal extension and tracheal compression when obstructive symptoms are present 8

Common Pitfalls to Avoid

• Do not skip TSH measurement before imaging—proceeding directly to uptake scan in euthyroid patients wastes resources and has low diagnostic value 2
• Do not rely on radionuclide scanning to determine malignancy—it has low positive predictive value and does not help decide which nodules to biopsy 2
• Do not assume all goiters are benign—false-negative FNA results occur, and worrisome clinical findings (rapid growth, compressive symptoms, history of radiation) should override reassuring cytology 1, 7
• Do not miss coexisting malignancy—ultrasound must be performed to identify suspicious nodules even in the setting of obvious benign multinodular goiter 2

Special Considerations for Specific Presentations

Compressive Symptoms (dyspnea, dysphagia, orthopnea)

• Ultrasound confirms thyroid origin and characterizes morphology 2, 8
• CT scan is preferred over MRI to evaluate substernal extension and degree of tracheal compression 8
• These symptoms are indications for surgical treatment 7

Rapid Growth

• Increases suspicion for malignancy, particularly anaplastic transformation 1, 7
• Core or surgical biopsy may be needed if FNA is non-diagnostic 1
• Surgical excision is preferred treatment 7