399.3 🩺 內科專科考前版

399.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Osilodrostat (Isturisa, FDA 2020) for Cushing’s — oral 11β-hydroxylase inhibitor
    • Relacorilant (selective GR antagonist) — phase 3 (less SE than mifepristone, no abortion concern in women)
    • Crinecerfont (CRF1 antagonist, FDA 2024) for classic CAH — reduces ACTH-driven androgen
    • Mass spec (LC-MS/MS) for steroids 越䟆越暙準避 immunoassay cross-reactivity
    • AVS lateralization still gold; ¹¹C-metomidate PET emerging as non-invasive alternative
    • MACS (mild autonomous cortisol secretion) — formerly “subclinical Cushing’s” — recognized as cardiometabolic risk
    • ICI hypophysitis (ipilimumab > pembro/nivo) — secondary AI common
    • Newer ACC drugs: mitotane + EDP combo standard; immunotherapy in trials
  • Taiwan: 健保 hydrocortisone, prednisone, dexamethasone, fludrocortisone, spironolactone, eplerenone, ketoconazole/metyrapone (off-label, 條件), osilodrostat 條件; CTAOH/TES 指匕 + Endocrine Society + ATA 對照

399.3.0.2 🌟 Pearls (20)

399.3.0.2.1 Cushing’s
  1. Cyclic Cushing’s: episodic; multiple testing over time
  2. Pseudo-Cushing’s: depression, alcoholism, obesity, PCOS — overlap; dex-CRH test 助分蟚
  3. MACS: 1mg dex 1.8-5.0 ÎŒg/dL; cardiometabolic + bone risk; consider treatment in selected
  4. Late-night salivary: 23:00 collection; outpatient convenient
  5. Hair cortisol: long-term cortisol exposure measurement (research)
  6. Dexamethasone metabolism issues: phenytoin, rifampin → ↑ metabolism → false positive
  7. High dose dex 8 mg ON: 90% suppress in CD; 10% ectopic also (overlap)
  8. IPSS pearls: technical center matters; pre-CRH + post-CRH; central:peripheral > 2 (basal), > 3 (post-CRH); lateralization for surgery 䞍可靠
399.3.0.2.2 AI
  1. APS-1 (AIRE): triad of mucocutaneous candidiasis + hypoparathyroidism + Addison’s; juvenile onset
  2. APS-2 (Schmidt): Addison’s + Hashimoto + T1DM ± vitiligo + celiac; adult onset
  3. ALD: X-linked; VLCFA testing in any unexplained primary AI in young male
  4. Acute pituitary post-op cortisol: AM cortisol Day 2-3 — > 15 likely sufficient, < 5 deficient
  5. Cosyntropin 1 ÎŒg test: more sensitive than 250 ÎŒg but less validated; for partial AI
  6. CBG variability: pregnancy, OCP ↑ CBG → total cortisol ↑ but free unchanged
399.3.0.2.3 Aldosteronism
  1. AVS technical demands: cortisol-corrected aldosterone ratios; selectivity index > 5; lateralization > 4 (basal) or > 2 (post-cosyntropin)
  2. ¹¹C-metomidate PET: non-invasive AVS alternative (selected centers; 22E)
  3. Liddle syndrome: ENaC activating; mimics PA but suppressed renin AND aldo; treat amiloride
  4. Pseudohypoaldosteronism Type 1 (loss-of-function MR or ENaC): salt-wasting in infancy
399.3.0.2.4 CAH
  1. Crinecerfont (Crenessity, FDA 2024): CRF1R antagonist; reduces HC dose needed in classic CAH
  2. Modified-release HC (Plenadren, Chronocort): better mimics circadian; for AI + CAH

399.3.0.3 📍 Taiwan + 健保

399.3.0.3.1 Cushing’s Disease
  • 健保 hydrocortisone, prednisone, dexamethasone, methylprednisolone (replacement + suppression test)
  • TSS 健保
  • 健保 RT for refractory
  • 健保 ketoconazole, metyrapone (off-label, 條件)
  • 健保 osilodrostat (Isturisa) 條件 (高貎)
  • 健保 pasireotide LAR (條件)
  • 健保 cabergoline (off-label, 條件)
  • Mifepristone 健保 停 not approved 倚
399.3.0.3.2 AI
  • 健保 hydrocortisone, prednisone, dexamethasone
  • 健保 fludrocortisone
  • DHEA 健保條件 (限制)
399.3.0.3.3 PA
  • 健保 spironolactone, eplerenone
  • 健保 amiloride
  • AVS 健保條件 (限制䞭心)
  • ¹¹C-metomidate 自費 / 醫孞䞭心
399.3.0.3.4 CAH
  • 健保 hydrocortisone (children + adults)
  • 健保 fludrocortisone (salt-wasting)
  • Crinecerfont 自費 (新藥, 條件 expanding)
  • Newborn screening: 國健眲 since 2006 含 17-OHP
399.3.0.3.5 ACC
  • 健保 mitotane 條件
  • EDP regimen (etoposide + doxorubicin + cisplatin) 健保條件
399.3.0.3.6 孞會 + 指匕
  • TES 內分泌孞會 + CTAOH 甲狀腺孞會 + DAROC 糖尿病孞會
  • Endocrine Society Cushing’s Guideline 2015
  • Endocrine Society AI Guideline 2016
  • Endocrine Society PA Guideline 2016
  • ATA / AACE 對照

399.3.0.4 🎓 內專必懂 (20)

  1. Adrenal anatomy + 3 zones GFR
  2. Steroidogenesis pathway + key enzymes (CAH spectrum)
  3. HPA axis + RAAS + adrenal androgen axis
  4. Cushing’s syndrome 3 step diagnosis (screen / dependence / source)
  5. IPSS technique + interpretation
  6. Cushing’s medical therapy ladder
  7. MACS recognition + management
  8. Adrenal crisis emergent management
  9. Stress dose protocols
  10. Cosyntropin 250 vs 1 ÎŒg + acute post-op caveat
  11. Primary vs secondary AI distinguish (ACTH, hyperpig, hyperK)
  12. APS-1, APS-2, ALD pattern
  13. PA screen / confirm / lateralize (ARR + saline + AVS)
  14. AVS technical interpretation (cortisol-corrected, selectivity, lateralization)
  15. CAH 21-OH classic (salt-wasting + simple virilizing) vs non-classic
  16. CAH 11β-OH and 17α-OH: HTN-causing variants
  17. Adrenal incidentaloma workup (functional + imaging + decision)
  18. ACC management (mitotane + EDP, advanced)
  19. Pediatric vs adult CAH steroid choice (HC for kids)
  20. 22E new drugs: osilodrostat, relacorilant, crinecerfont, modified-release HC (Plenadren, Chronocort)

399.3.0.5 ⚙ Cushing’s Disease Treatment Ladder (內專詳)

1st Line: Trans-sphenoidal surgery (TSS) — 70-80% cure for microadenoma
   ↓ if 侍 cured / recurrence
2nd Line: Repeat TSS / RT (Gamma Knife)
   ↓
Medical therapy (any of):
- Steroidogenesis inhibitor:
  - Osilodrostat (LINC-3, LINC-4) — newer, oral, well-tolerated
  - Ketoconazole (off-label; LFT monitor)
  - Metyrapone (11β-hydroxylase blocker; salt-wasting concern)
  - Levoketoconazole (newer; less hepatotoxicity than ketoconazole)
  - Etomidate IV (acute crisis only)
- Pituitary-directed:
  - Pasireotide LAR (10-30 mg q4w; SC option; ↑ hyperglycemia 60%+)
  - Cabergoline (off-label; mild cases)
- GR antagonist:
  - Mifepristone (Korlym; for DM-related; no biochemical marker)
  - Relacorilant (selective GR; phase 3, less anti-progesterone effects)
   ↓
Bilateral adrenalectomy — last resort
- Permanent steroid replacement
- Risk of Nelson's syndrome (preventive RT considered)

399.3.0.6 ⚙ Primary Aldosteronism Workflow (內專)

Step 1 — Screen (ARR):
- Plasma aldosterone (ng/dL) / plasma renin activity (ng/mL/hr)
- ARR > 30 + plasma aldo > 15 → suspicious
- Caveats:
  - Stop spironolactone, eplerenone 4-6 wk
  - K replacement to normal (䜎 K → false low aldo)
  - Stop ACE-i/ARB if possible (lower ratio)
  - Stop β-blocker (false elevate ratio)
  - Acceptable on alpha-blockers, calcium channel blockers (nondihydropyridine)

Step 2 — Confirm (suppression):
- Saline infusion: 2 L NS over 4 h → aldo > 10 ng/dL post = confirmed
- Captopril challenge: 25-50 mg → aldo 侍 suppress = confirmed
- Oral Na load (24-h urine aldo on high-Na diet)

Step 3 — Subtype (lateralize):
- CT/MRI adrenal:
  - 4-10 mm + > 35 yo → not reliable for unilateral source (CT misses microadenomas, false attributes hyperplasia)
  - Younger + clear adenoma → CT acceptable to skip AVS
- AVS = gold standard for lateralization:
  - Bilateral simultaneous catheterization
  - Cosyntropin stimulation often used
  - Selectivity index (cortisol catheter / peripheral) > 5
  - Lateralization index (corrected aldo dominant / non-dominant) > 4
- ¹¹C-metomidate PET: emerging non-invasive (research)

Step 4 — Treat:
- Lateralized → laparoscopic adrenalectomy
- Bilateral → MRA (spironolactone, eplerenone) ± amiloride

399.3.0.7 ⚙ Adrenal Crisis 詳现 (內專)

1. ABCs + 2 large-bore IV
2. **Hydrocortisone 100 mg IV STAT** + 50 mg q6h × 24 h
   - If severe shock: continuous infusion 200 mg/24 h
   - Don't wait for confirmatory test (high benefit, low risk)
   - HC has both glucocorticoid + mineralocorticoid (aldosterone replacement effect at high doses; less need for fludrocortisone acutely)
3. **Aggressive IV NS** (1-2 L fast)
4. **D5W or D10W if hypoglycemic** (concurrent reaction; IV dextrose mandatory if symptomatic)
5. **Treat trigger**:
   - Sepsis: broad-spectrum antibiotic + cultures
   - GI loss
   - Surgery / trauma
   - MI / PE
   - Sudden steroid withdrawal
6. **Monitor**:
   - Vitals q15 min
   - Glucose hourly initially
   - Electrolytes (Na, K) q4-6 h
   - Volume status
7. **Avoid**: BZD, opioid (worsens hypoventilation if comatose); hypotonic fluids early
8. **After 24-48 h stable**: taper to oral HC + fludrocortisone (in primary AI)
9. **Discharge teaching**:
   - Stress dose education
   - Medical alert bracelet
   - Emergency injection kit (HC 100 mg IM)
   - Triple dose for fever > 38, vomit, diarrhea, dental procedure

399.3.0.8 ⚙ MACS (Mild Autonomous Cortisol Secretion) (內專, 22E)

Definition: 
- 1-mg dex cortisol > 1.8 ÎŒg/dL
- No overt Cushing's (no moon face, striae)
- Adrenal incidentaloma usually
- ACTH suppressed or normal-low

Cardiometabolic associations:
- HTN, DM2, dyslipidemia, osteoporosis, CV mortality ↑

Management:
- Lifestyle (HTN/DM/lipid/bone management)
- If 1-mg dex cortisol > 5 → "overt" → surgery considered
- 1.8-5.0 + comorbidity → individualized; surgery in selected
- Adrenalectomy improves HTN, DM in some studies
- Post-op stress dose required (HPA suppressed)

⚠ AI 草皿。