What is the best course of action for a patient with a goiter and multiple nodules, including a large and tender nodule on the right lobe, who is experiencing palpitations and severe anxiety, despite having normal Thyroid-Stimulating Hormone (TSH), Triiodothyronine (T3), Thyroxine (T4), Thyroid Receptor Antibody (TRAB), and Thyroid Peroxidase (TPO) antibody levels?

Urgent Evaluation and Management of Multinodular Goiter with Tender Nodule and Anxiety Symptoms

Immediate Priority: Rule Out Subacute Thyroiditis

This patient most likely has subacute thyroiditis (De Quervain's thyroiditis) presenting with a tender thyroid nodule, palpitations, and anxiety despite normal thyroid function tests. The combination of a large, tender nodule with hyperadrenergic symptoms (palpitations, severe anxiety) in the setting of normal TSH, T3, T4, and negative antibodies is pathognomonic for the thyrotoxic phase of subacute thyroiditis 1, 2.

Key Diagnostic Features Supporting Subacute Thyroiditis:

• Tender thyroid nodule is the hallmark finding that distinguishes subacute thyroiditis from other causes of thyrotoxicosis 2, 3
• Normal TSH with symptoms occurs because thyroid hormone release from inflamed tissue causes transient thyrotoxicosis, but TSH may not yet be suppressed in early phases 2, 4
• Negative TRAB and TPO antibodies effectively rules out Graves' disease and Hashimoto's thyroiditis 1, 2
• Palpitations and severe anxiety are classic manifestations of excess thyroid hormone release, even when serum levels appear normal due to timing of testing 2, 5

Immediate Diagnostic Workup Required

Essential Next Steps:

• Obtain erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) - markedly elevated in subacute thyroiditis (ESR typically >50 mm/hr) 2, 3
• Repeat thyroid function tests (TSH, free T4, free T3) within 1-2 weeks, as levels fluctuate rapidly in thyroiditis and initial testing may have missed the peak 2, 4
• Thyroid ultrasound with Doppler to assess nodule characteristics and vascularity - subacute thyroiditis shows hypoechoic areas with decreased vascularity, unlike Graves' disease which shows hypervascularity 5, 4
• Radioactive iodine uptake scan (RAIU) if diagnosis remains uncertain - subacute thyroiditis shows very low uptake (<5%), distinguishing it from Graves' disease and toxic nodular goiter which show increased uptake 2, 3, 4

Critical Distinction from Other Causes:

The normal thyroid function tests do NOT exclude thyrotoxicosis in this clinical context 2, 4. Subacute thyroiditis causes episodic hormone release, and serum levels may normalize between episodes while symptoms persist 3, 4.

Immediate Symptomatic Management

First-Line Treatment for Symptom Control:

• Beta-blocker therapy (propranolol 20-40 mg three times daily or atenolol 25-50 mg daily) to control palpitations and anxiety immediately 2, 3
• NSAIDs (ibuprofen 600 mg three times daily or naproxen 500 mg twice daily) for thyroid pain and inflammation 2, 3
• Consider short course of prednisone (40 mg daily, tapered over 4-6 weeks) if pain is severe or NSAIDs are insufficient 2, 3

Do NOT Start Antithyroid Drugs:

Methimazole or propylthiouracil are contraindicated in subacute thyroiditis because the thyrotoxicosis results from hormone release from damaged tissue, not increased synthesis 2, 3. These medications would be ineffective and potentially harmful 3.

Fine Needle Aspiration Biopsy Considerations

FNAB should be performed on the tender nodule ONLY after confirming the diagnosis of subacute thyroiditis and ruling out malignancy. 1

Indications for FNAB in This Patient:

• If the nodule persists beyond 3-4 months after resolution of thyroiditis symptoms 1, 4
• If ultrasound shows suspicious features (microcalcifications, irregular margins, taller-than-wide shape) suggesting possible papillary thyroid carcinoma 1, 4
• If RAIU scan shows focal increased uptake in the tender nodule, suggesting toxic adenoma rather than thyroiditis 3, 6, 4

Defer FNAB Initially Because:

• Acute inflammation makes cytology interpretation unreliable and increases risk of non-diagnostic samples 1, 4
• Tenderness indicates active thyroiditis, which is a clinical diagnosis that does not require tissue confirmation 2, 3
• Most subacute thyroiditis resolves spontaneously within 3-6 months, making immediate biopsy unnecessary 2, 3

Expected Clinical Course and Follow-Up

Natural History of Subacute Thyroiditis:

• Thyrotoxic phase (current presentation): lasts 3-6 weeks, characterized by anxiety, palpitations, and tender goiter 2, 3
• Hypothyroid phase: follows in 30-40% of patients, lasting 2-6 months, may require temporary levothyroxine 2, 3
• Recovery phase: thyroid function normalizes in 90-95% of patients by 12 months 2, 3

Monitoring Protocol:

• Recheck TSH, free T4, and free T3 every 4-6 weeks until thyroid function stabilizes 2, 3
• Monitor for development of hypothyroidism (fatigue, weight gain, cold intolerance) requiring temporary thyroid hormone replacement 2, 3
• Repeat thyroid ultrasound at 3-6 months to document resolution of inflammation and assess for persistent nodules requiring further evaluation 1, 4

Alternative Diagnoses to Exclude

If Subacute Thyroiditis is Ruled Out:

Toxic multinodular goiter becomes the next most likely diagnosis if RAIU shows increased uptake in multiple nodules 3, 6. However, this typically occurs in older patients (>50 years) and causes overt hyperthyroidism with suppressed TSH, not normal thyroid function tests 3, 6.

Autonomously functioning thyroid nodule (toxic adenoma) is possible if the tender nodule shows increased uptake on RAIU scan 6, 4. Treatment options include radioactive iodine ablation or surgical excision for nodules >3 cm causing compressive symptoms 6.

Anxiety disorder with incidental goiter should be considered only after excluding all thyroid-related causes of symptoms 1. The presence of a tender nodule makes primary psychiatric illness unlikely 2, 3.

Critical Pitfalls to Avoid

• Do not dismiss symptoms because thyroid function tests are normal - subacute thyroiditis causes fluctuating hormone levels that may be missed on single testing 2, 4
• Do not start antithyroid drugs empirically without confirming increased thyroid hormone synthesis on RAIU scan 2, 3
• Do not perform FNAB on acutely tender nodules - wait for inflammation to resolve to avoid non-diagnostic samples and unnecessary patient discomfort 1, 4
• Do not assume permanent hypothyroidism if it develops during the recovery phase - most patients recover normal thyroid function and can discontinue levothyroxine after 6-12 months 2, 3
• Do not overlook the need for beta-blocker therapy - palpitations and anxiety significantly impair quality of life and increase cardiovascular risk, even with normal thyroid function tests 2, 3