thyroid nodules

thyroid nodules

Extremely common clinical finding (up to 50% of adults on US). The goal is to identify the <5% that are malignant (Differentiated Thyroid Cancer) while avoiding over-treatment of benign disease.

initial workup

TSH determines next steps

1. serum TSH

• Low TSH: $\to$ Radionuclide Scan (${}^{123}$I or ${}^{99m}$Tc).
  • Hot Nodule: Hyperfunctioning. Malignancy risk <1%. Do NOT Biopsy. Treat as toxic multinodular goitre/adenoma.
  • Cold Nodule: Non-functioning. Malignancy risk 5–15%. Proceed to Ultrasound.
• Normal/High TSH: $\to$ Proceed directly to Ultrasound.

clinical pearl

A “Hot” nodule is virtually never malignant. If TSH is suppressed, you generally do not need an FNA, even if the US features look ugly (unless there is a discordant cold area).

ultrasound risk stratification (ATA 2015)

Decision to biopsy (FNA) is based on Size + Sonographic Pattern.

Pattern	US Features	Malignancy Risk	FNA Cutoff
High Suspicion	Solid hypoechoic + (Microcalcifications, Irregular margins, Taller-than-wide, or Extrathyroidal extension).	>70–90%	$\ge$ 1 cm
Intermediate	Solid hypoechoic (no high-risk features).	10–20%	$\ge$ 1 cm
Low Suspicion	Isoechoic or Hyperechoic solid; Partially cystic with eccentric solid areas.	5–10%	$\ge$ 1.5 cm
Very Low	Spongiform; Partially cystic (no eccentric solid areas).	<3%	$\ge$ 2 cm
Benign	Purely cystic.	<1%	No Biopsy

• Lymph Nodes: FNA any suspicious cervical lymph node (microcalcs, cystic change, loss of fatty hilum) regardless of size.

the bethesda system (cytopathology)

The result of the FNA dictates management.

Class	Diagnostic Category	Malignancy Risk	Management
I	Non-diagnostic	1–4%	Repeat FNA (w/ US guidance).
II	Benign	0–3%	Clinical Follow-up. (US in 12–24 mos).
III	AUS / FLUS (Atypia/Follicular Lesion of Undetermined Significance)	5–15%*	Repeat FNA or Molecular Testing.
IV	Follicular Neoplasm	15–30%*	Molecular Testing or Diagnostic Lobectomy.
V	Suspicious for Malignancy	60–75%	Surgery (Lobectomy or Total).
VI	Malignant	97–99%	Surgery (Total Thyroidectomy or Lobectomy).

*Risk estimates vary by centre and NIFTP reclassification.

indeterminate nodules (III & IV)

Bethesda III and IV are the “Grey Zone.”

• Do NOT do a frozen section for Follicular Neoplasm (IV). You cannot distinguish Adenoma vs Carcinoma on frozen section (requires capsular invasion).
• Shift towards Molecular Testing (e.g., ThyroSeq, Afirma) to rule out cancer and avoid diagnostic surgery. If molecular testing negative $\to$ observe.

special situations

incidentalomas

• CT/MRI: Incidental nodules found on cross-sectional imaging require US if age <35 or size >1cm.
• PET-Positive Nodules: Focal uptake on FDG-PET has a high malignancy risk (~35%).
  • Action: Ultrasound + FNA is mandatory if >1 cm.

cystic nodules

• Pure cysts are almost always benign.
• Recurrent cystic nodules (refilling after FNA) can be treated with Ethanol Ablation or Surgery if compressive.

molecular testing

Used for Indeterminate (Bethesda III/IV) cytology.

• Rule-Out Tests (High NPV): e.g., Afirma GSC. If negative, risk is similar to benign nodule $\to$ Observe.
• Rule-In Tests (High PPV): e.g., ThyroSeq v3. Identifies mutations (BRAF V600E, RET/PTC, RAS). If positive $\to$ Surgery (and guides extent).

when to operate?

1. Malignant (Bethesda VI) or Suspicious (V) cytology.
2. Indeterminate (III/IV) with suspicious molecular markers or patient preference.
3. Large nodules (>4 cm) regardless of cytology (high false negative rate of FNA).
4. Compressive symptoms (dysphagia, positional dyspnea).
5. Cosmetic concern.