To whom should I refer a patient with multiple thyroid nodules, including some that are suspicious, for further evaluation and management?

Referral for Multiple Thyroid Nodules with Suspicious Features

For a patient with multiple thyroid nodules including suspicious ones, refer directly to an endocrinologist first for comprehensive evaluation, risk stratification, and ultrasound-guided fine-needle aspiration (FNA) biopsy. 1 If FNA confirms malignancy or suspicious cytology (Bethesda V/VI), immediate referral to an experienced endocrine surgeon is then required for total or near-total thyroidectomy. 1

Initial Referral Pathway: Endocrinology

Start with endocrinology referral because this specialist will coordinate the diagnostic workup and determine which nodules require biopsy based on ultrasound risk stratification. 1, 2 The endocrinologist will:

• Perform high-resolution thyroid ultrasound to characterize all nodules and assess cervical lymph nodes 1, 3
• Measure TSH to determine if any nodules are autonomously functioning 1
• Conduct ultrasound-guided FNA on the most suspicious nodule(s) based on size and sonographic features 1, 2
• Measure serum calcitonin to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone 1

Which Nodules Get Biopsied

The endocrinologist will prioritize FNA based on this algorithm 1:

• Any nodule ≥1 cm with ≥2 suspicious ultrasound features (solid composition, marked hypoechogenicity, microcalcifications, irregular/microlobulated margins, absence of peripheral halo, central hypervascularity) 1
• Any nodule ≥4 cm regardless of ultrasound appearance due to increased false-negative rate 1
• Nodules <1 cm only if suspicious features PLUS high-risk clinical factors (history of head/neck irradiation, family history of thyroid cancer, suspicious cervical lymphadenopathy, age <15 years) 1

When to Refer Directly to Surgery

Bypass endocrinology and refer directly to an endocrine surgeon only in these specific circumstances 1:

• FNA already performed showing malignant or suspicious cytology (Bethesda V/VI) requiring total or near-total thyroidectomy for nodules ≥1 cm 1
• Follicular neoplasia (Bethesda IV) with normal TSH and "cold" appearance on thyroid scan requiring surgical excision for definitive diagnosis 1
• Confirmed metastatic, multifocal, or familial differentiated thyroid carcinoma regardless of nodule size 1

Surgical Referral Considerations

When referring to surgery, ensure the surgeon is experienced in thyroid surgery, particularly if the patient has 4:

• Germline RET proto-oncogene mutation (medullary thyroid carcinoma or MEN syndromes) requiring specialized surgical approach 4
• Very young age (<5 years) requiring pediatric thyroid surgery expertise 4
• Suspected parathyroid involvement (hyperparathyroid-jaw tumor syndrome) where biopsy is discouraged due to risk of seeding carcinomatous cells 4

Critical Pitfalls to Avoid

Do not refer to surgery without cytological confirmation unless there are compelling clinical circumstances, as proceeding directly to thyroidectomy without tissue diagnosis may result in inappropriate surgical extent. 1 The exception is when a patient refuses FNA despite confirmed need, or has contraindications to the procedure. 4

Do not assume all nodules in a multinodular gland require biopsy. The endocrinologist will use TIRADS classification to determine which specific nodules warrant FNA based on their individual risk profiles. 1, 2 Typically, the largest nodule with the most suspicious features is biopsied first. 1

Do not delay referral for nodules with high-risk features. Microcalcifications are highly specific for papillary thyroid carcinoma (specificity 93.6%, positive likelihood ratio 42.0), and their presence warrants urgent evaluation even in nodules <1 cm if combined with other risk factors. 5

Special Clinical Scenarios

If Patient Has Compressive Symptoms

Refer to endocrinology first for evaluation, but expedite surgical consultation if symptoms are severe (dysphagia, dyspnea, vocal cord paralysis). 1 Surgery may be indicated even for benign nodules causing significant compression. 1

If Patient Has Suppressed TSH

The endocrinologist should order a radioiodine uptake scan to determine if nodules are "hot" (autonomously functioning). 1 If hot, medical management with radioactive iodine may be preferred over surgery, and FNA is not indicated. 1 If cold with suppressed TSH, proceed with FNA as the nodule remains at risk for malignancy. 1

If Patient Has Family History of Thyroid Cancer

This lowers the threshold for FNA even in smaller nodules (<1 cm), particularly if there is family history of medullary thyroid carcinoma or familial syndromes (MEN 2A, MEN 2B, familial MTC). 4, 1 Consider genetic counseling and screening for RET proto-oncogene mutations. 4