401.3 🩺 內科專科考前版

401.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Selpercatinib + pralsetinib (RET-specific) for MEN2 MTC + RET fusion thyroid CA
    • Belzutifan (HIF-2α inhibitor, FDA 2021) for VHL-related RCC + pheo + pancreatic NET
    • ¹⁷⁷Lu-DOTATATE PRRT for SSTR+ NET in MEN1 + VHL
    • Crinecerfont (CRF1 antagonist, FDA 2024) for classic CAH (relevant to APS-1 if 21-OH def is part)
    • NGS panel standard for all suspected hereditary endocrine
    • ATA + CTAOH prophylactic thyroidectomy guideline by RET codon
  • Taiwan: 健保 RET genetic test 條件; MEN1 panel 條件; selpercatinib 條件 (高貎); belzutifan 自費 倚; PRRT 條件; cascade testing 健保 limited

401.3.0.2 🌟 Pearls (15)

401.3.0.2.1 MEN1
  1. Subtotal parathyroidectomy (3.5 glands) preferred over total + autotransplant in MEN1 (recurrence ~ 30% by 10 yr regardless)
  2. Gastrinoma in MEN1: often duodenal multifocal microscopic; 䞍 always resectable for cure; PPI mainstay; surgery for selective
  3. Insulinoma in MEN1: often multifocal; calcium stimulation test for localization
  4. Thymic carcinoid in MEN1 men: aggressive; CT chest screening
  5. Annual gut hormone panel: CgA, gastrin (off PPI 1 wk), insulin/C-peptide if hypo, glucagon, VIP, PP, somatostatin
401.3.0.2.2 MEN2
  1. RET codon-specific risk stratification (ATA 2015):
    • Highest (M918T): MEN2B; thyroidectomy by 1 yr
    • High (634, A883F): thyroidectomy by 5 yr
    • Moderate (609, 611, 618, 620, 768, 790, 791, 804, 891): calcitonin-guided, often 5-10 yr
  2. Stimulated calcitonin (calcium IV or pentagastrin) for early MTC detection
  3. MEN2A pheo bilateral 倚: cortical-sparing adrenalectomy (preserve cortex)
  4. MEN2B mucosal neuroma: lips, tongue, eyelids, cornea — recognizable phenotype
  5. MEN2B Marfanoid habitus distinct from Marfan (no aortic dissection, no ectopia lentis)
401.3.0.2.3 VHL + Others
  1. VHL surveillance: annual ophthalmology, brain/spine MRI q3-5 yr, abdominal MRI q1-2 yr (RCC + pancreas), pheo screen
  2. NF1 pheo: often unilateral, large; consider in NF1 with HTN
  3. Carney complex PPNAD: paradoxical Cushing’s with low-dose dex (cortisol increases)
  4. McCune-Albright GNAS mosaic: tissue-specific testing (not in blood); diagnose by phenotype + biopsy
  5. Familial isolated hyperparathyroidism (CDC73): increased risk parathyroid CA + jaw tumor; genetic testing for hereditary hyperPTH

401.3.0.3 📍 Taiwan + 健保

401.3.0.3.1 基因檢枬
  • MEN1, RET (MEN2), VHL, NF1, SDHA-D, CDKN1B (MEN4), CDC73, PRKAR1A 倚 panel
  • 健保條件: family Hx + clinical syndrome
  • 自費 panel for de novo / unclear
401.3.0.3.2 治療
  • 健保 cabergoline / bromocriptine (prolactinoma)
  • 健保 octreotide LAR / lanreotide depot for NET
  • 健保 SSA + everolimus + sunitinib for advanced PNET
  • 健保 ¹⁷⁷Lu-DOTATATE PRRT 條件 (SSTR+)
  • 健保 selpercatinib for MTC RET 條件
  • 健保 vandetanib + cabozantinib for advanced MTC 條件
  • Belzutifan 自費 (新, VHL specific)
401.3.0.3.3 Surveillance
  • 健保 imaging (CT, MRI, US)
  • 健保 EUS for pancreatic NET
  • 健保 DOTATATE PET (條件)
  • 健保 calcitonin, gut hormone panel (條件)
401.3.0.3.4 孞會 + 指匕
  • TES 內分泌孞會 + CTAOH 甲狀腺孞會 + Endocrine Society MEN Guideline 2012/2018
  • ATA 2015 MTC + thyroidectomy guideline
  • DAROC (盾關)
  • 國健眲 hereditary endocrine 蚈畫 (limited)

401.3.0.4 🎓 內專必懂 (15)

  1. MEN1 (3P) + cascade testing
  2. MEN1 parathyroid surgery (subtotal vs total)
  3. MEN1 pancreatic NET management (gastrinoma, insulinoma, NF)
  4. MEN1 surveillance schedule + lifelong
  5. MEN2 RET codon-specific thyroidectomy timing
  6. MEN2 pre-op pheo rule out + cortical-sparing adrenalectomy
  7. MEN2B distinctive features (mucosal neuroma, Marfanoid, GI)
  8. MEN2 selpercatinib + pralsetinib (22E)
  9. MEN4 mild MEN1-like + CDKN1B
  10. VHL multi-organ surveillance + belzutifan
  11. NF1 features + pheo workup
  12. Carney complex PRKAR1A
  13. McCune-Albright GNAS mosaic + tissue testing
  14. Familial paraganglioma (SDHx) specifically SDHB
  15. Genetic counseling + cascade testing logistics

401.3.0.5 ⚙ MEN1 Surveillance Detailed (內專)

Annual (from 8 yr; some earlier per family):
- Ca + ionized Ca + iPTH
- Prolactin + IGF-1 ± dynamic (overnight dex if Cushing's symptom)
- Fasting glucose + HbA1c (insulinoma surveillance)
- Gastrin (off PPI 1 wk; PPI causes false high — controversial)
- CgA, glucagon, VIP, PP, somatostatin (gut hormone panel)

Q1-3 yr:
- MRI sella (q3-5 yr if normal)
- Abdominal MRI / EUS / DOTATATE PET (q1-2 yr)
- Adrenal CT/MRI (per findings)

Q1-2 yr:
- CT chest (thymic carcinoid in men, very aggressive)

As needed:
- Octreoscan / DOTATATE PET for symptomatic NET
- Functional imaging for new functional NET

Family:
- Cascade testing for first-degree relatives
- Pre-symptomatic surveillance (kids start ~ 5-8 yr)
- Genetic counseling for family planning

401.3.0.6 ⚙ MEN2 RET Codon-Based Management (ATA 2015)

Highest Risk (Level D — M918T = MEN2B):
- Prophylactic total thyroidectomy in 1st year of life (or as soon as identified)
- Pre-op pheo screen
- Lifelong pheo + parathyroid (no, since MEN2B no PT) + MTC surveillance

High Risk (Level C — 634, A883F = MEN2A):
- Prophylactic total thyroidectomy by age 5
- Pre-op pheo screen
- Lifelong pheo + parathyroid + MTC surveillance

Moderate Risk (Level B — most other MEN2A codons):
- Prophylactic thyroidectomy by 5 yr OR earlier if calcitonin rising
- Pre-op pheo screen
- Lifelong surveillance

Low Risk (Level A — rare codons):
- Calcitonin-guided thyroidectomy timing
- Annual calcitonin from age 5

Pheo screening:
- Annual plasma metanephrine + normetanephrine + DOTATATE PET if available
- Start age 8-11 (depending on codon)

401.3.0.8 ⚙ Genetic Counseling Process (內專)

Step 1 — Identify candidate:
- Personal Hx (multiple endocrine tumors, early-onset, syndromic features)
- Family Hx (multiple affected relatives)
- Specific tumor types (e.g., MTC + pheo)

Step 2 — Pre-test counseling:
- Mode of inheritance + risk
- Implications of positive vs negative
- Insurance, employment, psychosocial
- Informed consent

Step 3 — Test:
- Multi-gene panel (NGS) for unclear cases
- Single gene if specific syndrome suspected (e.g., MEN1, RET)

Step 4 — Post-test counseling:
- Result interpretation (positive, negative, VUS)
- Surveillance plan
- Family cascade

Step 5 — Cascade testing:
- First-degree relatives
- Pre-symptomatic surveillance
- Decision-making for prophylactic interventions

Step 6 — Long-term:
- Multidisciplinary care
- Reproductive options (PGD, prenatal testing)
- Support groups

⚠ AI 草皿。