What is the best course of action for a middle-aged adult patient presenting with a thyroid goiter, tender thyroid nodules, palpitations, and night sweats, despite having normal Thyroid-Stimulating Hormone (TSH) and Thyroxine (T4) levels?

Urgent Evaluation for Subacute Thyroiditis with Immediate Thyroid Ultrasound and Fine-Needle Aspiration

The patient requires immediate thyroid ultrasound to evaluate the tender nodule for malignancy risk, followed by fine-needle aspiration biopsy of any suspicious nodules, as the combination of a large tender nodule with palpitations and night sweats despite normal TSH/T4 suggests either subacute thyroiditis with transient thyrotoxicosis or autonomous nodular function. 1

Initial Diagnostic Workup

Confirm Thyroid Function Status

• Repeat TSH with free T4 and free T3 measurements immediately, as normal TSH with hyperthyroid symptoms suggests either subclinical hyperthyroidism or autonomous nodular function 1, 2
• The palpitations and night sweats indicate possible thyrotoxicosis that may not be reflected in "normal" TSH values if tested during a euthyroid phase 3
• Low TSH levels are frequently encountered in multinodular goiter (29% of clinically euthyroid patients), and when low with normal free T3, the patient is at risk of developing overt hyperthyroidism 3

Imaging and Tissue Diagnosis

• Thyroid ultrasound is the mandatory first imaging study to characterize the tender nodule for malignancy risk using ACR TI-RADS criteria and evaluate nodule size, echogenicity, and vascularity 1
• Fine-needle aspiration biopsy should be performed on the large tender nodule and any other suspicious nodules identified on ultrasound, as approximately 5% of thyroid nodules harbor malignancy 2, 4
• The tenderness of the nodule raises concern for subacute thyroiditis, hemorrhage into a nodule, or rapid nodule growth—all requiring cytologic evaluation 2

Differential Diagnosis Algorithm

Most Likely: Subacute Thyroiditis with Transient Thyrotoxicosis

• The tender nodule with palpitations and night sweats despite "normal" TSH/T4 strongly suggests subacute thyroiditis in the thyrotoxic phase 3
• Subacute thyroiditis causes transient TSH suppression with normal or elevated free T3/T4, followed by a hypothyroid phase 3
• This diagnosis would explain the discordance between symptoms and reportedly normal thyroid function tests 3

Alternative: Autonomous Functioning Nodule(s)

• Toxic multinodular goiter or a single autonomous "hot" nodule can cause hyperthyroid symptoms with initially normal or low-normal TSH 3
• Thyroid scintigraphy with I-123 or Tc-99m should be performed if TSH is low or low-normal to identify autonomous function 1, 3
• Low TSH with normal free T3 in multinodular goiter indicates risk of progression to overt hyperthyroidism 3

Must Exclude: Thyroid Malignancy

• The large size and tenderness of the nodule mandate FNA to exclude malignancy, as 5% of nodules are malignant 2, 4
• Rapidly growing or hemorrhagic nodules can present with tenderness and compressive symptoms 2

Immediate Management Steps

Symptom Control

• If repeat testing confirms hyperthyroidism (low TSH with elevated free T4/T3), initiate beta-blocker therapy (propranolol 20-40mg TID or atenolol 25-50mg daily) immediately to control palpitations and adrenergic symptoms 2
• Beta-blockers provide rapid symptomatic relief while awaiting definitive diagnosis and treatment 2

Definitive Treatment Based on Etiology

If Subacute Thyroiditis:

• Self-limited condition requiring only symptomatic treatment with NSAIDs for pain and beta-blockers for hyperthyroid symptoms 3
• Monitor thyroid function every 4-6 weeks, as patients typically progress through thyrotoxic, euthyroid, and hypothyroid phases before recovery 3
• Avoid radioactive iodine or antithyroid drugs, as these are ineffective in thyroiditis 3

If Toxic Multinodular Goiter or Autonomous Nodule:

• Radioactive iodine (RAI) therapy is effective for toxic multinodular goiter, particularly in elderly patients or those with surgical contraindications 5, 4
• Pretreatment with recombinant human TSH (0.45mg IM) 24 hours before RAI increases uptake and efficacy, achieving 57.8% goiter volume reduction at 12 months 5
• Surgical thyroidectomy is preferred for large goiters with compressive symptoms (dysphagia, choking, airway obstruction) or when rapid resolution is needed 2, 4

If Malignant Cytology:

• Immediate surgical referral for thyroidectomy 2, 4

Critical Pitfalls to Avoid

• Never assume "normal" TSH/T4 excludes thyroid dysfunction when hyperthyroid symptoms are present—always measure free T3, as T3 toxicosis can occur with normal T4 3, 6
• Do not delay FNA of a large tender nodule based on normal thyroid function tests, as malignancy risk is independent of functional status 2, 4
• Avoid radioactive iodine scanning in euthyroid patients with multinodular goiter, as it does not determine malignancy risk and has low positive predictive value 1
• Do not initiate levothyroxine suppression therapy in patients with multinodular goiter and normal or suppressed TSH, as this risks iatrogenic hyperthyroidism with cardiac and bone complications 4
• Never miss concurrent Graves' disease in patients with goiter and hyperthyroid symptoms—measure thyroid-stimulating immunoglobulins (TSI) if TSH is suppressed with elevated free hormones 6