What is the best course of action for a patient with a growing and tender thyroid nodule, decreasing Thyroid-Stimulating Hormone (TSH) levels, and a history of goiter, with TSH levels still within the normal range?

Management of Growing, Tender Thyroid Nodule with Declining TSH

This patient requires urgent fine-needle aspiration biopsy (FNA) to exclude malignancy, as nodule growth and tenderness are concerning features that warrant immediate cytological evaluation regardless of TSH status. 1, 2

Immediate Diagnostic Workup

Priority Testing Sequence

Perform FNA biopsy immediately for any growing nodule, as growth is a red flag feature that increases malignancy risk, and tenderness may indicate rapid growth, hemorrhage into a nodule, or inflammatory changes. 1, 2

Measure TSH, free T4, and free T3 to determine if the declining TSH trend has progressed to subclinical or overt hyperthyroidism, as this will fundamentally alter the diagnostic approach. 1

If TSH is now suppressed (<0.1 mIU/L) or low-normal (0.1-0.45 mIU/L), obtain a thyroid radionuclide scan with I-123 or Tc-99m to determine if the growing nodule is hyperfunctioning ("hot"), as hot nodules have <1% malignancy risk and do not require FNA. 3, 4

Critical Decision Point: Hot vs Cold Nodule

If the nodule is "hot" (hyperfunctioning) on scan:

• FNA is not indicated regardless of size or growth, as malignancy risk is <1%. 3, 4
• The tenderness likely represents rapid autonomous growth causing capsular stretch. 4
• Management focuses on treating the developing hyperthyroidism with radioactive iodine ablation or surgery. 4, 5

If the nodule is "cold" or isofunctioning on scan, or if TSH remains normal:

• Proceed immediately with ultrasound-guided FNA, as growth in a cold nodule significantly increases malignancy concern. 1, 2
• The combination of growth + tenderness + cold nodule raises suspicion for papillary thyroid carcinoma (80% of thyroid cancers present as cold nodules). 6

Understanding the Declining TSH Pattern

Clinical Significance

A slowly declining TSH that remains within normal range suggests the nodule may be developing autonomous function, transitioning toward a toxic adenoma, which occurs when thyroid nodules gain the ability to produce thyroid hormone independent of TSH stimulation. 4, 5

This pattern is consistent with early autonomously functioning thyroid nodule (AFTN), where the nodule produces enough thyroid hormone to partially suppress TSH but not yet enough to cause overt hyperthyroidism. 5

The growth and tenderness may represent:

• Rapid expansion of an autonomously functioning adenoma (most likely if TSH now suppressed). 4
• Hemorrhage into a benign or malignant nodule causing acute expansion and pain. 2
• Rapid growth of thyroid cancer (papillary carcinoma can occasionally present with pain). 1, 6

Ultrasound Evaluation

High-resolution thyroid ultrasound must assess specific malignancy risk features:

• Hypoechogenicity, microcalcifications, irregular borders, taller-than-wide shape, and intranodular vascularity all increase malignancy risk. 1
• Multiple suspicious features together significantly increase specificity for malignancy, though no single feature is diagnostic. 1
• Document nodule size precisely to track growth velocity, as rapid growth (>20% increase in two dimensions or >50% volume increase) is concerning. 2

Evaluate cervical lymph nodes bilaterally, as suspicious lymphadenopathy (loss of fatty hilum, microcalcifications, cystic changes, hypervascularity) suggests metastatic thyroid cancer. 1, 2

FNA Technique and Interpretation

Ultrasound-guided FNA is mandatory (not palpation-guided), as it improves diagnostic accuracy and allows targeting of the most suspicious areas within the nodule. 1, 2

Cytology results should be reported using the Bethesda Classification System:

• Benign (Bethesda II): Follow with repeat ultrasound in 12-24 months to ensure stability. 2
• Malignant (Bethesda VI): Refer immediately for total thyroidectomy with central neck dissection. 1, 2
• Indeterminate (Bethesda III-V): Consider molecular testing (BRAF, RAS, RET/PTC, PAX8/PPARγ mutations) to better discriminate benign from malignant, as 97% of mutation-positive nodules are malignant. 1

Management Algorithm Based on Findings

If Hyperfunctioning Nodule Confirmed

Treat the developing hyperthyroidism:

• Radioactive iodine (I-131) ablation is first-line for most patients with toxic adenoma, achieving cure in 75-90% with single dose. 4, 5
• Surgery (thyroid lobectomy) is alternative for patients who decline radioiodine, have very large nodules (>4 cm), or have compressive symptoms. 5
• Monitor thyroid function every 6-8 weeks after treatment until stable, then annually. 1

If Cold Nodule with Benign Cytology

The combination of growth + benign cytology requires careful follow-up:

• Repeat FNA in 6-12 months to ensure the initial benign result was not a sampling error, as false-negative rates for FNA are 1-3%. 2
• Repeat ultrasound every 6-12 months for at least 2 years to document stability. 2, 5
• Consider surgery if continued growth despite benign cytology, as persistent growth raises concern for false-negative FNA or transformation. 2

If Malignant or Suspicious Cytology

Refer immediately to endocrine surgeon for:

• Total thyroidectomy for nodules ≥1 cm with papillary thyroid carcinoma. 1
• Central neck dissection if lymph nodes are clinically involved or if primary tumor has high-risk features. 1
• Post-operative radioactive iodine ablation for tumors >1 cm, with TSH suppression therapy targeting TSH 0.1-0.5 mIU/L for intermediate-risk patients or <0.1 mIU/L for high-risk patients. 1, 6

Special Considerations for This Patient

Addressing the Tenderness

Tenderness in a thyroid nodule is uncommon and warrants specific consideration:

• Acute hemorrhage into nodule causes sudden pain and rapid enlargement; ultrasound shows complex cystic and solid components. 2
• Subacute thyroiditis causes tender thyroid but typically affects the entire gland diffusely, not a single nodule. 1
• Rapidly growing malignancy occasionally presents with pain due to capsular invasion or hemorrhage. 1

If hemorrhage is suspected on ultrasound, FNA can be both diagnostic and therapeutic by decompressing the nodule, though cytology may be limited by blood contamination. 2

Monitoring the TSH Trend

Recheck TSH, free T4, and free T3 now to determine current thyroid status, as the declining trend may have progressed to overt suppression. 1

If TSH is now suppressed but patient remains asymptomatic:

• This represents subclinical hyperthyroidism from the nodule. 5
• Radionuclide scan becomes essential to confirm autonomous function before deciding on FNA. 3, 4
• Even if nodule is hot, treat the hyperthyroidism to prevent cardiovascular complications (atrial fibrillation risk increases 2.8-fold with TSH suppression). 7

If TSH remains normal despite the declining trend:

• The nodule may have partial autonomy insufficient to suppress TSH. 5
• Proceed directly to FNA without radionuclide scan, as normal TSH makes a hot nodule unlikely. 1

Critical Pitfalls to Avoid

Never assume a growing nodule is benign without cytological confirmation, as growth is one of the most concerning features for malignancy, occurring in up to 15% of thyroid nodules that prove to be cancer. 2, 5

Do not delay FNA waiting for TSH to normalize or decline further, as the growth and tenderness demand immediate evaluation regardless of thyroid function status. 1, 2

Avoid ordering radionuclide scan if TSH is normal, as this wastes time and resources; hot nodules are extremely rare with normal TSH, and the scan will not change management if TSH is not suppressed. 1, 3

Do not rely on a single benign FNA result if the nodule continues to grow, as false-negative rates exist and repeat FNA is mandatory to exclude sampling error. 2

Never start levothyroxine suppression therapy for a growing nodule, as this outdated practice is ineffective for preventing growth and may mask autonomous function by artificially suppressing TSH. 8, 5