398.3 🩺 內科專科考前版

398.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Selpercatinib + pralsetinib (RET-specific) for MTC + RET-fusion + thyroid CA
    • Dabrafenib + trametinib for BRAF V600E anaplastic (䞍再是無解!)
    • Larotrectinib + entrectinib for NTRK fusion (tumor agnostic)
    • Lenvatinib + sorafenib for radioiodine-refractory differentiated thyroid CA
    • Molecular testing standard for indeterminate Bethesda (III, IV) → Afirma GSC, ThyroSeq, ThyGenX/ThyraMIR
    • TIRADS, K-TIRADS, EU-TIRADS, ATA pattern 倚 systems; ACR TI-RADS 廣泛接受
    • Active surveillance for low-risk PTC < 1 cm (Ito Hospital, Japan; ATA 接受)
    • NIFTP renaming (non-invasive follicular thyroid neoplasm with papillary-like features) — 䞍再 cancer (惡性 → benign reclassification)
  • Taiwan: 健保 surgery + RAI + LT4; 健保 lenvatinib for refractory; 健保 selpercatinib 條件; CTAOH/TES 指匕 + ATA 對照

398.3.0.2 🌟 Pearls (20)

398.3.0.2.1 Diagnosis
  1. TI-RADS more sensitive but less specific than ATA pattern; in practice both used
  2. NIFTP (formerly EFVPTC encapsulated follicular variant): now classified as borderline; 治療 = lobectomy alone, no RAI
  3. Hashimoto + lymphoma: rapid growth → biopsy (not FNA — needs core)
  4. Pediatric thyroid CA: more aggressive presentation but excellent overall prognosis
  5. MTC stimulated calcitonin (calcium IV or pentagastrin) for early detection in family
398.3.0.2.2 Genetics
  1. MEN2 RET codon: M918T (MEN2B, most aggressive — by 1 yr); 634 (MEN2A — by 5 yr); 609/611/618/620 (variable)
  2. DICER1 syndrome: thyroid + ovary + lung; pediatric multinodular goiter
  3. Cowden (PTEN): ↑ thyroid (mostly follicular) + breast + endometrial
  4. FAP (APC): ↑ PTC cribriform-morular variant
  5. Werner syndrome (WRN): ↑ thyroid + sarcoma
398.3.0.2.3 Treatment
  1. Active surveillance (Ito Hospital protocol) for ≀ 1 cm low-risk PTC: 5-yr surgery rate ~7%, no deaths reported
  2. Lobectomy vs total thyroidectomy for 1-4 cm low-risk PTC: ATA 2015 either acceptable; outcome similar
  3. rhTSH (Thyrogen) for RAI prep: avoid LT4 withdrawal hypothyroidism + better quality of life
  4. Dynamic risk stratification post-treatment: response categorized → adjust TSH suppression target
  5. Selpercatinib for RET fusion + RET mutation (LIBRETTO)
  6. Pralsetinib alternative RET-specific (ARROW)
  7. Lenvatinib for RAI-refractory (SELECT trial)
  8. Sorafenib alternative (DECISION trial)
  9. Dabrafenib + trametinib for BRAF V600E ATC — paradigm shift; 䞭䜍 OS 14 mo (historical 4 mo)
  10. Pembrolizumab + dabrafenib + trametinib in trials for ATC — quadruple combo

398.3.0.3 📍 Taiwan + 健保

398.3.0.3.1 Surgery + RAI + LT4
  • 健保 thyroidectomy + LN dissection
  • 健保 ¹³¹I (RAI ablation + treatment)
  • 健保 LT4 充分
398.3.0.3.2 Targeted Therapy
  • 健保 lenvatinib for RAI-refractory differentiated thyroid CA (條件)
  • 健保 sorafenib alternative (條件)
  • 健保 vandetanib + cabozantinib for advanced MTC (條件)
  • 健保 selpercatinib RET fusion 條件 (條件嚎栌)
  • 健保 dabrafenib + trametinib for BRAF V600E ATC 條件
  • Larotrectinib NTRK 自費 倚 (rare)
398.3.0.3.3 Workup
  • 健保 neck US, FNA
  • 健保 calcitonin (條件)
  • 健保 RET genetic testing (條件)
  • 健保 BRAF V600E IHC (限制)
  • NGS panel 自費 倚
398.3.0.3.4 孞會 + 指匕
  • CTAOH 台灣甲狀腺醫孞會 + TES 內分泌孞會 + CSO 台灣腫瘀醫孞會
  • ATA 2015 thyroid CA guideline (äž»)
  • AACE/ACE 2016 thyroid nodule
  • DAROC for diabetes coexistence
398.3.0.3.5 病人衛教 (盧醫垫專區)
  • 之前已做甲狀腺結節衛教單匵 v8 + evidence-based v5 倚語蚀
  • 同步可做: 術埌 LT4 服藥 + RAI 隔離 + 䜎碘飲食衛教

398.3.0.4 🎓 內專必懂 (20)

  1. Workup 4 步驟 (TSH → US → FNA per TI-RADS → Bethesda)
  2. TI-RADS scoring + FNA threshold
  3. Bethesda 6 categories + malignancy risk + management
  4. Molecular testing for indeterminate (Afirma GSC, ThyroSeq)
  5. 5 倧 cancer types + 各特埵 + 治療
  6. PTC 變異: classic, follicular variant, tall cell (worse), diffuse sclerosing, NIFTP
  7. FTC: histology required (capsular + vascular)
  8. MTC: pre-op pheo rule out; RET genetic; family screen
  9. Anaplastic: BRAF V600E testing essential; dabrafenib + trametinib
  10. Lobectomy vs total thyroidectomy decision
  11. RAI ablation indications + dose + prep
  12. TSH suppression target by risk
  13. Surveillance with Tg + Tg-Ab + US + stimulated Tg
  14. Targeted therapy for refractory: lenvatinib, sorafenib, RET-/NTRK-/BRAF-specific
  15. Active surveillance for very low-risk papillary microcarcinoma
  16. MEN2 RET codon + age-specific prophylactic thyroidectomy
  17. NIFTP reclassification (no longer cancer)
  18. Pregnancy + thyroid CA management (delay RAI, surgery 2nd trimester preferred)
  19. 22E new: dabrafenib for ATC, RET inhibitors, dynamic risk stratification
  20. CTAOH/TES + ATA 指匕差異

398.3.0.5 ⚙ ATA Risk Stratification (Initial Risk)

398.3.0.5.1 Low Risk
  • Intrathyroidal PTC, no aggressive features
  • Tumor < 4 cm
  • No vascular invasion, ETE, distant mets
  • ≀ 5 LN < 0.2 cm
398.3.0.5.2 Intermediate Risk
  • Aggressive variant
  • Microscopic ETE
  • Vascular invasion

  • 5 LN or 0.2-3 cm

398.3.0.5.3 High Risk
  • Gross ETE
  • Incomplete resection
  • Distant mets
  • LN > 3 cm or extranodal extension
  • Postoperative Tg suggesting mets

398.3.0.6 ⚙ Dynamic Risk Stratification (Post-Treatment)

398.3.0.6.1 Excellent Response
  • 抑 Tg < 0.2 (or stimulated < 1.0)
  • No clinical / structural evidence
  • → TSH 0.5-2.0 (replacement only)
398.3.0.6.2 Biochemical Incomplete
  • 抑 Tg > 1.0 (or stimulated > 10) without structural disease
  • → TSH 0.1-0.5
398.3.0.6.3 Structural Incomplete
  • Persistent / recurrent locoregional / distant disease
  • → TSH < 0.1 + active management (surgery, RAI, EBRT, targeted)
398.3.0.6.4 Indeterminate
  • Nonspecific findings
  • → TSH 0.1-0.5

398.3.0.7 ⚙ MTC Detailed Management

398.3.0.7.1 Workup
  • Calcitonin (basal + stimulated if equivocal)
  • CEA
  • US neck + LN
  • CT chest/abdomen
  • Pheo screen (catecholamine + metanephrine — pre-op critical!)
  • Parathyroid screen (Ca, PTH)
  • RET genetic testing (all MTC patients)
  • Family cascade testing if RET+
398.3.0.7.2 Surgery
  • Total thyroidectomy + central LN dissection (universal)
  • Lateral LN if proven involvement
398.3.0.7.3 Surveillance
  • Calcitonin + CEA q6-12 mo
  • US, CT, bone scan if rising
398.3.0.7.4 Advanced Disease
  • Vandetanib (FDA 2011)
  • Cabozantinib (FDA 2012)
  • Selpercatinib (FDA 2020) — RET-specific
  • Pralsetinib (FDA 2020) — RET-specific
398.3.0.7.5 Family Management (MEN2)
  • All MTC patient: RET testing
  • If RET+: cascade testing of family
  • Prophylactic thyroidectomy:
    • MEN2B (M918T): < 1 yr (highest risk; very aggressive)
    • MEN2A high-risk RET (634): by 5 yr
    • MEN2A moderate: by 5-10 yr (calcitonin-guided)
    • MEN2A lower-risk RET: variable

398.3.0.8 ⚙ Anaplastic Thyroid CA (內專詳)

Workup:
- Emergent FNA / core biopsy
- BRAF V600E mutation testing (IHC + molecular)
- RAS, NTRK panel
- CT staging
- Airway assessment

Treatment paradigm shift (2018+):
- BRAF V600E (~30%) → Dabrafenib + trametinib (immediate, before surgery)
  - PR/CR rate 60-70%
  - Median OS 14 mo (historical 4 mo)
- BRAF wild-type → Lenvatinib + chemoRT
- Resectable → debulking surgery + adjuvant
- Tracheostomy if airway compromise
- Hospice / palliative care concurrent

Trials:
- Pembrolizumab + dabrafenib + trametinib quadruple
- CAR-T for thyroid CA in trials

⚠ AI 草皿。