What is the next step in managing a female patient with a goiter (enlargement of the thyroid gland) and multiple nodules, including a large and tender right nodule, who presents with constipation, palpitations, nocturnal sweating, and tachycardia, despite having normal thyroid panel and antibody (TRAB and TPO) tests?

Thyroid Ultrasound with Selective Fine-Needle Aspiration

Despite normal thyroid function tests, this patient requires thyroid ultrasound immediately to characterize the nodules and identify which require fine-needle aspiration biopsy, as approximately 5% of nodules harbor malignancy and the large, tender right nodule warrants specific evaluation. 1, 2

Diagnostic Algorithm

Step 1: Thyroid Ultrasound (Immediate Next Step)

• Ultrasound is the mandatory first-line imaging to characterize nodule morphology and stratify malignancy risk using standardized criteria 1, 3
• The American College of Radiology specifically recommends ultrasound as the preferred initial imaging modality for multinodular goiter, even when TSH is normal 1
• Ultrasound will evaluate the number, size, and sonographic features of all nodules to determine which require biopsy 1, 2

Step 2: Identify Suspicious Features on Ultrasound

Look specifically for these high-risk characteristics that mandate FNA:

• Hypoechogenicity 1, 3
• Microcalcifications 1, 3
• Irregular borders 1, 3
• Absence of peripheral halo 1
• Solid aspect 1, 3
• Intranodular blood flow 1, 3
• Taller-than-wide shape 1, 3

Step 3: Fine-Needle Aspiration Biopsy

• FNA should be performed on any nodule >1 cm with suspicious ultrasound features 1
• The large, tender right nodule specifically requires evaluation given its size and clinical presentation 1
• Approximately 5% of nodules may harbor cancer, making selective biopsy essential 1, 2

Addressing the Clinical Presentation

The Paradox of Symptoms with Normal Labs

This patient presents with symptoms suggesting thyroid dysfunction (palpitations, nocturnal sweating, tachycardia) alongside constipation, yet has normal thyroid panels. This clinical picture requires consideration of:

• The symptoms may be unrelated to thyroid pathology and could represent other conditions (cardiac arrhythmia, anxiety, menopause-related symptoms) 2
• The tender nodule could indicate subacute thyroiditis or hemorrhage into a nodule, which can cause transient symptoms 2
• Subclinical hyperthyroidism can occasionally present with subtle symptoms before TSH becomes fully suppressed 4

Why Radionuclide Scanning is NOT Indicated

• The American College of Radiology explicitly advises against radionuclide scanning in euthyroid patients to determine malignancy risk or guide biopsy decisions 1, 3, 5
• Radionuclide scanning has low positive predictive value for malignancy in this setting 3, 5
• Most nodules are "cold" on scanning, and most cold nodules are benign, making the test unhelpful 1
• Scanning is only indicated when TSH is suppressed (thyrotoxicosis), which is not the case here 5

Additional Considerations if Obstructive Symptoms Develop

If the patient develops dysphagia, dysphonia, stridor, or worsening dyspnea:

• CT neck without contrast becomes superior to ultrasound for evaluating substernal extension, retropharyngeal extension, and degree of tracheal compression 1, 3
• This would be indicated before surgical planning if obstructive symptoms emerge 3

Critical Pitfalls to Avoid

• Do not skip ultrasound evaluation - it is essential for identifying which nodules require FNA in a multinodular goiter 1
• Do not order radionuclide scanning as initial imaging - it is not recommended for euthyroid goiter evaluation 1, 3
• Do not order FDG-PET/CT as initial imaging for goiter evaluation 1
• Do not assume all nodules are benign simply because thyroid function is normal - malignancy risk exists independent of thyroid hormone levels 2, 6

Follow-up Based on FNA Results

• Malignant cytology: Refer for surgery 2
• Suspicious/indeterminate cytology: Generally advise surgery unless autonomous function can be confirmed by scintigraphy 2
• Benign cytology with large symptomatic goiter: Consider surgery for symptom relief if pressure symptoms develop 2
• Benign cytology, asymptomatic: Periodic follow-up with neck palpation and ultrasound examination 2