419.3 🩺 內科專科考前版

419.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Glucagon nasal (Baqsimi 3 mg) + glucagon SC autoinjector (Gvoke HypoPen) — easier for non-medical caregiver
    • Dasiglucagon — stable liquid analog (no reconstitution); approved for severe hypo
    • GLP-1 receptor PET imaging for insulinoma — most sensitive (22E)
    • CGM with alarms for hypoglycemia unawareness — gold standard prevention
    • AID (closed-loop pump) can prevent + treat hypo in T1DM
    • Diazoxide for insulinoma medical bridge; pasireotide LAR for SSTR+ NET
    • Selpercatinib / dabrafenib for refractory metastatic insulinoma with mutations (RET, BRAF)
  • Taiwan: 健保 glucagon kit 條件; 健保 octreotide 條件; 健保 diazoxide; 健保 GLP-1 PET 自費 (新, 限制䞭心); CGM 條件 (T1DM)

419.3.0.2 🌟 Pearls (15)

419.3.0.2.1 Diagnosis
  1. Plasma glucose < 55 (vs old < 50) for Whipple’s confirmation
  2. POC glucose meter < 70 in suspicious patient → confirm with venous serum
  3. Insulin assay: must rule out insulin Ab interference (gives false high or low)
  4. C-peptide / proinsulin / β-OHB all sampled at same time as low glucose
  5. Sulfonylurea screen panel: glipizide, glimepiride, glyburide, repaglinide, nateglinide
  6. Insulin / C-peptide ratio: > 1 (in pmol) suggests exogenous; useful adjunct
  7. GLP-1 receptor PET: highest sensitivity for insulinoma (vs DOTATATE which captures other NET)
419.3.0.2.2 Insulinoma
  1. MEN1 (10% of insulinoma): multiple, sometimes malignant; calcium stim test for localization in MEN1
  2. Insulinoma surgery: enucleation if peripheral + small; partial pancreatectomy if large or central
  3. Diazoxide medical bridge: 50-300 mg/d; works by suppressing β-cell K-ATP channel; SE: edema, hypertrichosis (kids), GI
419.3.0.2.3 Drug
  1. Sulfonylurea + alcohol = especially severe + prolonged hypo
  2. Glyburide vs glimepiride / glipizide: glyburide accumulates in CKD; should avoid in 老人 + CKD
  3. Levofloxacin > moxifloxacin for hypoglycemia (gatifloxacin withdrawn for this)
419.3.0.2.4 Special
  1. Post-bariatric hypoglycemia: insulin response > glucagon response → reactive; acarbose + low GI + protein priority + (off-label exenatide for severe)
  2. Autoimmune insulin syndrome (Hirata): HLA-DR4 in Asians; SH-drug related (methimazole MOST); resolves with drug discontinuation usually

419.3.0.3 📍 Taiwan + 健保

419.3.0.3.1 Drugs
  • 健保 D50, D10
  • 健保 glucagon emergency kit 條件 (T1DM, brittle T2DM)
  • Glucagon nasal (Baqsimi) 自費 倚 / 郚分 健保
  • Dasiglucagon (Zegalogue) 自費
  • 健保 octreotide for SU overdose 條件
  • 健保 diazoxide 條件 (insulinoma + congenital hyperinsulinism)
  • 健保 octreotide for insulinoma SSTR+ 條件
  • 健保 acarbose 充分
419.3.0.3.2 Workup + Imaging
  • 健保 72-h fasting test (條件; medical center)
  • 健保 insulin, C-peptide, proinsulin, β-OHB, sulfonylurea panel
  • 健保 EUS for pancreatic NET
  • 健保 DOTATATE PET 條件
  • GLP-1 receptor PET 自費 (新, 限制䞭心)
419.3.0.3.3 CGM + AID
  • 健保 CGM for T1DM 條件 (幎霡, brittle, hypo unaware)
  • 健保 AID (hybrid closed-loop) 限制 (条件)
419.3.0.3.4 孞會 + 指匕
  • DAROC (糖尿病孞會)
  • CTAOH (盾關)
  • ADA 2026 + Endocrine Society Hypoglycemia 2009

419.3.0.4 🎓 內專必懂 (15)

  1. Whipple’s triad + plasma glucose < 55 cutoff
  2. ADA Levels 1-3
  3. Adrenergic vs neuroglycopenic symptoms
  4. DM hypo causes + insulin/SU + risks
  5. Hypoglycemia unawareness + restoration
  6. 72-h fasting test protocol + interpretation
  7. Insulinoma diagnosis + treatment
  8. Insulinoma + MEN1 (10%)
  9. NICTH (IGF-2 ratio)
  10. Hirata syndrome (Asian, HLA-DR4, SH-drug)
  11. Post-bariatric hypoglycemia management
  12. SU overdose with octreotide
  13. Glucagon nasal + autoinjector (22E)
  14. GLP-1 receptor PET for insulinoma (22E)
  15. CGM + AID for hypo prevention

419.3.0.5 ⚙ 72-h Fasting Test Protocol (內專詳)

Day 0:
- Patient hospitalized
- Stop nonessential medications (insulin, SU, etc)
- Start fast: water + non-caloric beverage only
- Baseline labs: glucose, insulin, C-peptide, proinsulin, β-OHB, sulfonylurea panel, insulin Ab

Monitoring (q4-6 h initially, q1-2 h later):
- Plasma glucose
- Symptom assessment

Stop test if:
- Glucose < 55 mg/dL + symptoms (sample everything)
- 72 hours elapsed
- Severe symptoms

Sampling at low glucose:
- Plasma glucose
- Insulin
- C-peptide
- Proinsulin
- β-OHB
- Sulfonylurea panel (urine + plasma)
- Insulin antibodies (Hirata)
- Cortisol (rule out AI)

Interpretation:
| Glucose | Insulin | C-peptide | Proinsulin | β-OHB | Sulfonylurea |
|--------|---------|-----------|------------|-------|--------------|
| < 55 + ↑ insulin + ↑ C-peptide + ↑ proinsulin + ↓ β-OHB + sulfonylurea − = INSULINOMA |
| < 55 + ↑ insulin + ↓ C-peptide + ↓ proinsulin + ↓ β-OHB = EXOGENOUS INSULIN |
| < 55 + ↑ insulin + ↑ C-peptide + ↑ proinsulin + sulfonylurea + = SULFONYLUREA |
| < 55 + ↓ insulin + ↓ C-peptide + ↑ β-OHB = COUNTER-REG hormone deficiency (cortisol/GH) |
| < 55 + ↓ insulin + ↓ C-peptide + IGF-2:IGF-1 ↑ = NICTH (IGF-2) |

Post-test:
- Resume diet + meds
- Imaging if insulinoma confirmed
- MEN1 evaluation if multiple

419.3.0.6 ⚙ Insulinoma Treatment (內專)

Localization (after biochemical confirmation):
1. CT/MRI pancreas with contrast
2. EUS (most sensitive for small)
3. DOTATATE PET if SSTR+ NET considered
4. **GLP-1 receptor PET** (22E most sensitive)
5. Selective arterial calcium stimulation + hepatic venous sampling (rare; very small/multiple)
6. Intraoperative US

Surgery:
- Enucleation if peripheral + small (preferred for benign)
- Distal pancreatectomy if larger / central
- Total pancreatectomy if multiple (MEN1 multiple)
- Cure rate ~90-95% for sporadic single

Medical (bridge or refractory):
- Diazoxide 50-300 mg/d (suppresses β-cell K-ATP)
  - SE: edema (fluid retention), hypertrichosis, GI
- Octreotide LAR if SSTR+ (limited efficacy in pure insulinoma)
- Pasireotide LAR (broader SSTR coverage)
- Verapamil (calcium channel blocker; some response)
- Frequent meals + complex carb

Malignant / Metastatic (~10% of insulinoma):
- Liver-directed therapy (TACE, RFA)
- Systemic: everolimus (mTOR), sunitinib (multikinase TKI)
- ¹⁷⁷Lu-DOTATATE PRRT (SSTR+)
- CAPTEM (capecitabine + temozolomide)
- Selpercatinib for RET (rare)

419.3.0.7 ⚙ Hypoglycemia Unawareness (內專)

Mechanism:
- Chronic recurrent hypo → ↓ catecholamine threshold (HAAF: hypoglycemia-associated autonomic failure)
- Impaired counter-regulatory response

Diagnosis:
- Patient reports hypo episodes without warning symptoms
- CGM shows hypo without symptoms

Restoration Protocol:
1. Avoid hypoglycemia for 2-3 weeks (relax HbA1c target temporarily)
2. CGM with predictive low alarms
3. Frequent SMBG before activities
4. Family/partner education for severe events
5. Hypoglycemia recognition training (some centers)

Long-term:
- AID (hybrid closed-loop) reduces hypo significantly
- Pancreas / islet transplant for severe brittle T1DM with hypo unawareness
- DAFNE (Dose Adjustment for Normal Eating) education

Reversal:
- Awareness can return in 50-80% with strict avoidance
- May not completely reverse if long-standing autonomic neuropathy

⚠ AI 草皿。