What is the typical treatment approach for a patient with well-differentiated thyroid cancer?

Treatment of Well-Differentiated Thyroid Cancer

The standard treatment for well-differentiated thyroid cancer consists of total or near-total thyroidectomy followed by radioactive iodine (¹³¹I) ablation in most cases, with subsequent lifelong TSH-suppressive levothyroxine therapy. 1

Initial Surgical Management

Total or near-total thyroidectomy is the mandatory first-line treatment for differentiated thyroid cancer (DTC) when the diagnosis is made preoperatively and the nodule is ≥1 cm, or regardless of size if there is metastatic, multifocal, or familial disease. 1, 2

Pre-operative Assessment

• Perform comprehensive neck ultrasound to assess lymph node chain status before any surgical intervention. 1
• Compartment-oriented lymph node dissection should be performed when lymph node metastases are suspected preoperatively or confirmed intraoperatively. 1, 2

Exception for Very Low-Risk Disease

Less extensive surgery (lobectomy alone) may be acceptable only for unifocal DTC discovered incidentally at final histology after surgery for benign disorders, provided the tumor meets all of these criteria: 1, 2

• Small size (<1 cm)
• Intrathyroidal (no extrathyroidal extension)
• Favorable histological type (classical papillary, follicular variant of papillary, or minimally invasive follicular)
• No lymph node metastases

Surgical Outcomes

In expert hands, surgical complications including laryngeal nerve palsy and hypoparathyroidism occur in <1-2% of cases. 1

Radioactive Iodine (¹³¹I) Ablation Therapy

Surgery is routinely followed by ¹³¹I administration aimed at ablating remnant thyroid tissue and potential microscopic residual tumor, which decreases locoregional recurrence risk and facilitates long-term surveillance. 1

Indications Based on Risk Stratification

High-risk patients: ¹³¹I ablation is strongly recommended. 1, 2

Low-risk patients: ¹³¹I ablation is recommended. 1, 2

Very low-risk patients: No indication for ¹³¹I ablation (unifocal T1 tumors <1 cm with favorable histology, no extrathyroidal extension, and no lymph node metastases). 1, 2

Preparation Methods

Recombinant human TSH (rhTSH) is the preferred preparation method for radioiodine ablation, administered while the patient continues levothyroxine therapy. 1, 2 This approach:

• Achieves ablation success rates equivalent to levothyroxine withdrawal 1
• Maintains quality of life by avoiding hypothyroid symptoms 1
• Prevents negative cardiovascular, hepatic, renal, and neurological effects of acute hypothyroidism 3

Dosing

For ablation in patients without metastatic disease: A dose of 1850 MBq (50 mCi) is as effective as 3700 MBq (100 mCi) when using rhTSH preparation, even in the presence of lymph node metastases, and reduces whole-body radiation exposure. 1

For treatment of known metastatic disease: Higher doses of 100-200 mCi are used. 4

Post-Treatment TSH-Suppressive Therapy

All patients require lifelong levothyroxine therapy with two distinct goals: 5, 3

1. Thyroid hormone replacement (restoring euthyroidism)
2. TSH suppression to reduce growth and progression of any residual thyroid cancer cells 3, 6

TSH Target Levels

Initial suppressive phase: Maintain TSH below normal range in high-risk and intermediate-risk patients. 2

After achieving remission: Patients in complete remission (undetectable stimulated thyroglobulin <1.0 ng/mL and negative neck ultrasound) may be shifted from suppressive to replacement therapy, targeting TSH within the normal range. 1, 2

Long-Term Surveillance Strategy

Initial Follow-Up (2-3 months post-treatment)

• Check thyroid function tests (FT3, FT4, TSH) to verify adequacy of levothyroxine suppressive therapy. 1

First Assessment (6-12 months post-treatment)

Perform comprehensive evaluation to determine disease status: 1, 2

• Physical examination
• Neck ultrasound
• rhTSH-stimulated serum thyroglobulin measurement (with anti-thyroglobulin antibody assessment)
• Diagnostic whole body scan (WBS) may be omitted in low-risk patients with undetectable stimulated thyroglobulin and normal neck ultrasound 1

Patients Achieving Complete Remission

Approximately 80% of patients will demonstrate: 1

• Normal neck ultrasound
• Undetectable stimulated serum thyroglobulin (<1.0 ng/mL)
• Absence of serum thyroglobulin antibodies

These patients have a recurrence rate <1% at 10 years and require: 1, 2

• Annual physical examination
• Serum thyroglobulin measurement on replacement levothyroxine
• Annual neck ultrasound
• Indefinite monitoring (recurrences can occur even 20 years after initial treatment) 1, 2

Patients with Persistent Disease

Continue more intensive surveillance with stimulated thyroglobulin testing and consider additional diagnostic imaging or therapeutic interventions. 1

Management of Recurrent or Metastatic Disease

For locoregional recurrence: Surgical resection combined with therapeutic doses of ¹³¹I is the preferred approach. 2

When complete surgical excision is impossible or radioiodine uptake is absent: External beam radiotherapy should be used. 2

For radioiodine-refractory progressive disease: Systemic therapy with multi-kinase inhibitors (lenvatinib or sorafenib) should be considered, with molecular testing for targetable mutations (BRAF V600E, TERT promoter, RAS) to guide selection of newer targeted therapies. 2, 7

Critical Pitfalls to Avoid

Do not use oral levothyroxine to treat myxedema coma—this requires intravenous thyroid hormone replacement. 5

Do not initiate levothyroxine in patients with uncorrected adrenal insufficiency—treat with replacement glucocorticoids first to prevent acute adrenal crisis. 5

Do not rely on undetectable basal thyroglobulin alone during TSH suppression—persistent disease can exist despite undetectable thyroglobulin on suppressive therapy; stimulated thyroglobulin measurement is essential. 3

In elderly patients and those with cardiovascular disease: Initiate levothyroxine at less than full replacement dose due to increased risk of cardiac adverse reactions including atrial fibrillation. 5

Monitor diabetic patients closely after starting levothyroxine, as therapy may worsen glycemic control and require increased antidiabetic medication or insulin. 5

Avoid thyroid hormone over-replacement, which increases bone resorption and decreases bone mineral density—use the lowest effective dose. 5