400.3 🩺 內科專科考前版

400.3.0.1 📌 䞀頁重點

  • 22E updates:
    • PPGL hereditary 40% (revised)
    • DOTATATE PET (Ga-68) > MIBG for many PPGL (especially SDHx, head/neck, metastatic) — 22E preferred functional
    • ¹⁷⁷Lu-DOTATATE PRRT for metastatic SSTR+ PPGL (newer therapy)
    • Belzutifan (HIF-2α inhibitor) for VHL-related PPGL (FDA 2021)
    • Sunitinib (FIRSTMAPPP trial) for metastatic
    • Doxazosin > phenoxybenzamine trend for pre-op (less reflex tachycardia + better tolerated)
    • Recommended genetic testing for all PPGL (Endocrine Society)
  • Taiwan: 健保 phenoxybenzamine, doxazosin, propranolol; CT/MRI; MIBG (條件); DOTATATE PET (條件); ¹³¹I-MIBG therapy 條件; sunitinib (條件); belzutifan 條件 (limited)

400.3.0.2 🌟 Pearls (15)

400.3.0.2.1 Diagnosis
  1. Plasma fractionated metanephrine + normetanephrine preferred over urine; use upper-decision-limit cutoffs (rather than upper reference limit) to ↑ specificity
  2. Sample technique critical: 30-min supine before draw; avoid coffee/exercise/stress
  3. Catecholamine excretion correlates with tumor size + biochemical phenotype (epi+ pheo small; NE-only often larger / extra-adrenal; dopamine-only often SDHx)
  4. Conversion: NE → metanephrine via COMT (in tumor cells, regardless of catecholamine release); so metanephrine 比 catecholamine 曎穩定 (reflects tumor mass, not episodic release)
  5. Clonidine suppression test: 0.3 mg PO → measure metanephrine 3 h post; PCC 侍 suppress
400.3.0.2.2 Imaging
  1. CT washout for pheo: similar to incidentaloma (< 60% absolute washout suggests not adenoma)
  2. DOTATATE PET-CT sensitivity > MIBG in many series, especially SDHx (~ 90% vs 50%)
  3. Multifocal screening: MRI head/neck/abdomen/pelvis if SDHx + (multiple PGL pattern)
  4. MIBG-avid pheo + DOTATATE-avid correlate with treatment options
400.3.0.2.3 Pre-op + Surgery
  1. Doxazosin alternative to phenoxybenzamine: similar BP control, less reflex tachycardia, better tolerated, shorter half-life (manageable side effects)
  2. PRESCRIPT trial (Aug 2020): phenoxybenzamine vs doxazosin similar outcome
  3. CCB (nicardipine, amlodipine) adjunct: for refractory HTN despite α
  4. Magnesium sulfate IV intra-op: useful adjunct for crisis
  5. Hand-assisted laparoscopic + transabdominal preferred over open for most
400.3.0.2.4 Metastatic / Hereditary
  1. CASTOR scoring + Modified Grading System for Adrenal Pheochromocytoma + Paraganglioma (GAPP) for malignancy prediction (better than histology alone)

400.3.0.3 📍 Taiwan + 健保

400.3.0.3.1 Drugs
  • 健保 phenoxybenzamine (Dibenyline; 條件)
  • 健保 doxazosin 充分
  • 健保 propranolol, atenolol
  • 健保 phentolamine IV (intra-op crisis)
  • 健保 sodium nitroprusside IV
  • 健保 nicardipine IV/PO
400.3.0.3.2 Imaging + Genetic
  • 健保 CT/MRI 充分
  • 健保 ¹²³I-MIBG (條件; 醫孞䞭心)
  • 健保 ¹³¹I-MIBG therapy 條件
  • 健保 ⁶⁞Ga-DOTATATE PET (條件 expanding)
  • 健保 倚基因 panel for PPGL (條件)
400.3.0.3.3 Treatment
  • 健保 laparoscopic adrenalectomy
  • 健保 ¹³¹I-MIBG therapy
  • 健保 sunitinib 條件 (advanced)
  • 健保 ¹⁷⁷Lu-DOTATATE PRRT (條件; 限制䞭心)
  • Belzutifan 自費 (新, VHL specific)
400.3.0.3.4 孞會 + 指匕
  • TES 內分泌孞會 + Endocrine Society Pheochromocytoma + Paraganglioma Guideline 2014 + 曎新

400.3.0.4 🎓 內專必懂 (15)

  1. PPGL definition + 40% hereditary
  2. 8 倧遺傳症候矀 + 各 phenotype
  3. SDHB → metastatic risk highest
  4. Catecholamine profile by source (adrenal vs extra-adrenal vs SDHx)
  5. Plasma fractionated metanephrine 1st line + 取血技術
  6. Imaging algorithm: CT/MRI → MIBG / DOTATATE PET
  7. DOTATATE PET 22E preferred for SDHx + extra-adrenal + metastatic
  8. Pre-op α-blocker (10-14d) → β-blocker → high-Na → surgery
  9. β-blocker first 倧忌
  10. Intra-op crisis management (nitroprusside, phentolamine, MgSO4)
  11. Post-op hypotension + hypoglycemia
  12. Bilateral pheo or hereditary: cortical-sparing adrenalectomy considered
  13. Metastatic management: MIBG therapy, PRRT, sunitinib, CVD chemo, belzutifan (VHL)
  14. Genetic testing for all + family cascade
  15. 22E new: doxazosin trend, DOTATATE > MIBG, belzutifan VHL, PRESCRIPT trial

400.3.0.5 ⚙ Genetic Testing Decision (內專詳)

All PPGL → multi-gene panel:
- RET (MEN2)
- VHL
- NF1 (clinical or genetic)
- SDHA, SDHB, SDHC, SDHD, SDHAF2
- TMEM127, MAX, FH

Algorithm:
1. Family Hx + clinical features → targeted gene
2. Phenotype clue:
   - Pheo + MTC + parathyroid → MEN2A (RET)
   - Pheo + MTC + mucosal neuroma + Marfan → MEN2B (RET M918T)
   - Pheo + hemangioblastoma / RCC → VHL
   - Pheo + neurofibroma → NF1
   - Multiple PGL + metastatic → SDHB
   - Head/neck PGL + paternal inheritance → SDHD
3. No clinical clue → comprehensive panel
4. Cascade testing for family if positive

Implications:
- Surveillance interval (more frequent in SDHB)
- Other tumor screening (RCC, MTC, NET)
- Family planning
- Risk-reducing strategies

400.3.0.6 ⚙ Pre-op Detailed Protocol (內專)

Day -14:
- Start α-blocker (phenoxybenzamine 10 mg BID OR doxazosin 1-2 mg/d)
- Daily up-titrate based on BP + symptoms
- Goal: BP < 130/80 sitting, orthostatic acceptable, symptom-free

Day -10 to -7:
- Phenoxybenzamine target 30-40 mg BID OR doxazosin 8-16 mg/d
- Add high-Na diet (5 g extra/d)
- Start β-blocker if reflex tachycardia (HR > 100)
  - β-blocker 必 after α established (avoid unopposed α)
  - Propranolol 20 mg q6h or atenolol

Day -7 to -3:
- Continue all
- IV NS day before surgery (volume expansion)
- Avoid emetogenic / triggers

Day 0 (Surgery):
- Premedicate adequately (avoid morphine — releases catecholamine)
- Anesthesia: avoid ketamine, ephedrine, succinylcholine, pancuronium, halothane (sensitize)
  - Use: vecuronium, rocuronium, sevoflurane, isoflurane, fentanyl, midazolam
- Intra-op monitor: arterial line + CVP + ETCO2
- HTN crisis: nitroprusside infusion, phentolamine bolus, MgSO4
- Tachyarrhythmia: esmolol (short-acting β)
- Post tumor isolation: phenylephrine for hypotension expected

Day +1:
- ICU
- Hypotension common 12-24h → IV NS + phenylephrine if severe
- Hypoglycemia → D5/D10
- Continue HC if bilateral
- Plasma metanephrine 1 mo post

Surveillance:
- 1 mo, 6 mo, then annual plasma metanephrine
- More frequent if hereditary (esp. SDHB)
- Imaging if biochemical recurrence

400.3.0.7 ⚙ Metastatic / Refractory Treatment (內專)

Treatment options (sequential / combined):
1. **¹³¹I-MIBG therapy** for MIBG-avid
   - Symptom control + biochemical response
   - Can be repeated
2. **¹⁷⁷Lu-DOTATATE PRRT** for SSTR-expressing (newer, better tolerated)
   - Pheo + PGL with positive DOTATATE PET
3. **Sunitinib** (multikinase TKI)
   - FIRSTMAPPP trial
4. **CVD chemo** (cyclophosphamide + vincristine + dacarbazine)
   - 30-40% response
5. **Temozolomide** for SDHx
6. **Belzutifan (HIF-2α inhibitor)** for VHL-related (FDA 2021)
7. **Symptomatic α + β blocker continuation**
8. **External beam RT** for bone mets, palliation
9. **Bisphosphonate / denosumab** for bone mets

Multidisciplinary: endocrine + onco + nuclear medicine + interventional radiology

⚠ AI 草皿。