423.3 🩺 內科專科考前版

423.3.0.1 📌 䞀頁重點

  • 22E updates:
    • Palopegteriparatide (Yorvipath, FDA 2024) — long-acting rhPTH for chronic hypoparathyroidism
    • Encaleret (CaSR antagonist) for ADH (autosomal dominant hypocalcemia) — FDA submission
    • PHPT NIH 2022 update — modest changes to surgical indications
    • 4D-CT = best for re-operation HPT
    • Cinacalcet + etelcalcetide for severe 2°/3° HPT in CKD
    • Burosumab anti-FGF-23 for X-linked hypophosphatemia + tumor-induced osteomalacia
  • Taiwan: 健保 cinacalcet (條件); 健保 calcitriol; 健保 phosphate binders; 健保 zoledronic acid + denosumab; rhPTH (palopegteriparatide, Natpara historical) 自費 倚; encaleret 未䞊垂; burosumab 自費 (rare); CTAOH/TES + AAES + Endocrine Society 指匕

423.3.0.2 🌟 Pearls (15)

423.3.0.2.1 PHPT
  1. Sestamibi sensitivity ~ 80% adenoma; ~ 50% hyperplasia (less localizing)
  2. Neck US adenoma vs lymph node ddx: shape, vascularity (Doppler), location
  3. 4D-CT preferred for re-operation / atypical / negative imaging
  4. Intra-operative PTH (IOPTH) drop > 50% from baseline = success
  5. MEN1 4-gland hyperplasia: subtotal parathyroidectomy (3.5 glands) preferred over total + autotransplant
  6. Parathyroid carcinoma: very high Ca (> 14), very high PTH, palpable mass; CDC73 mutation; 倚 in HPT-jaw tumor syndrome
  7. Persistent vs recurrent HPT: persistent (Ca high postop within 6 mo) vs recurrent (Ca high after 6 mo of normal)
  8. Familial isolated HPT (FIHP): CDC73 — surveillance for parathyroid CA
  9. Normocalcemic primary HPT: high PTH + normal Ca; controversial entity; rule out 25-D def first
423.3.0.2.2 Hypoparathyroidism
  1. Palopegteriparatide (Yorvipath) — once-daily SC; replaces previous rhPTH 1-84 (Natpara, withdrawn 2019 due to manufacturing)
  2. DiGeorge (22q11.2 deletion): hypoparathyroid + thymic hypoplasia + cardiac + cleft palate + hypocalcemia
  3. APS-1 hypoparathyroidism: autoimmune; AIRE mutation
  4. ADH (CaSR-GoF) vs PHPT: low PTH despite high Ca? 䞍; ADH causes hypocalcemia with low/normal PTH
  5. Encaleret (CaSR antagonist) for ADH — opposite mechanism of cinacalcet (CaSR agonist)
423.3.0.2.3 Special
  1. CKD-MBD parathyroidectomy for severe 3° HPT (Ca > 11 + PTH > 800 + uncontrolled): subtotal vs total + autotransplant; lifelong mineral monitoring

423.3.0.3 📍 Taiwan + 健保

423.3.0.3.1 Drugs
  • 健保 calcium carbonate / citrate / acetate / lactate
  • 健保 calcitriol (Rocaltrol)
  • 健保 cholecalciferol (Vit D3) over-the-counter
  • 健保 cinacalcet (Mimpara) 條件 (2° HPT in HD; parathyroid CA)
  • 健保 etelcalcetide IV (HD only; 條件)
  • 健保 phosphate binders (calcium-based, sevelamer, lanthanum, iron-based)
  • 健保 zoledronic acid IV q1y 條件 (osteoporosis, malignancy hypercalcemia)
  • 健保 denosumab Q6 mo 條件 (osteoporosis; not approved for hypercalcemia of malignancy in some countries)
  • 健保 calcitonin (rare use)
  • Palopegteriparatide (Yorvipath) 自費 倚 (新, refractory hypoparathyroidism)
  • Burosumab (Crysvita) 自費 倚 (X-linked hypophosphatemia, TIO)
423.3.0.3.2 Surgery + Imaging
  • 健保 sestamibi scan
  • 健保 neck US (high-resolution)
  • 健保 4D-CT 條件 (re-op)
  • 健保 parathyroidectomy (open + minimally invasive)
  • 健保 IOPTH 條件
423.3.0.3.3 孞會 + 指匕
  • TES + Taiwan Osteoporosis Society + AAES (Am Assoc Endocrine Surgeons) + Endocrine Society
  • AAES PHPT Guideline 2017
  • AACE Hypoparathyroidism 2023
  • KDIGO CKD-MBD 2017
  • Endocrine Society Hypocalcemia 2014

423.3.0.4 🎓 內專必懂 (15)

  1. Hypercalcemia comprehensive diagnostic algorithm
  2. PHPT vs FHH distinction (urine Ca/Cr ratio)
  3. PHPT NIH 2014 surgical indications
  4. Parathyroid imaging (sestamibi + US + 4D-CT)
  5. IOPTH monitoring during surgery
  6. MEN-related HPT (MEN1 4-gland; MEN2A adenoma; CDC73 carcinoma)
  7. Hypercalcemia of malignancy: 3 mechanisms + treatment
  8. Acute hypercalcemia treatment cascade
  9. Hypocalcemia algorithm
  10. Hypoparathyroidism: surgical (#1), autoimmune, genetic, Mg, ADH
  11. Pseudohypoparathyroidism (PHP) types
  12. rhPTH (palopegteriparatide, 22E)
  13. CKD-MBD severe parathyroidectomy considerations
  14. CaSR-related disorders (FHH, ADH; cinacalcet vs encaleret)
  15. 22E new: palopegteriparatide, encaleret, burosumab, 4D-CT, NIH 2022 update

423.3.0.5 ⚙ PHPT Surgical Workflow (內專)

Step 1 — Confirm Diagnosis:
- Repeated Ca + iPTH (correct for albumin)
- 25-D level (correct deficiency first if < 30)
- 24h urine Ca + Cr (rule out FHH if Ca/Cr ratio < 0.01)
- Phosphate, eGFR
- DXA (hip + spine + forearm)
- VFA (vertebral fracture assessment)

Step 2 — Surgical Indication (NIH 2014):
- Symptomatic
- Ca > 1 mg/dL above upper limit
- 24h urine Ca > 400 mg/d
- Nephrolithiasis / nephrocalcinosis
- eGFR < 60
- T-score ≀ -2.5 (hip/spine/forearm)
- Vertebral fracture
- Age < 50

Step 3 — Pre-op Imaging:
- Sestamibi scan + neck US (1st)
- 4D-CT if discordant or re-op
- Confirm anatomy + variants

Step 4 — Surgery:
- Minimally invasive parathyroidectomy (MIP) for localized adenoma
- IOPTH monitoring (drop > 50% = success)
- Bilateral exploration if hyperplasia / unclear / MEN

Step 5 — Post-op:
- Ca + PTH q6-12h initially
- Vit D + Ca supplementation
- Hungry bone syndrome risk (severe pre-op disease)
- Calcium binders if hypocalcemia transient
- Permanent hypoparathyroid risk ~ 1-3%

Step 6 — Long-term:
- Re-check Ca + PTH 6 mo + 1 yr
- DXA q1-2 yr
- Address comorbidity (HTN, CV)
- Family genetic testing if MEN/CDC73 suspected

423.3.0.6 ⚙ Severe Hypoparathyroidism Management

Acute symptomatic:
- IV calcium gluconate 10% 1-2 g over 10-20 min + ECG
- Continuous infusion 1-2 mg/kg/hr if persistent
- Mg replacement if low
- Slow oral transition

Chronic (lifelong):
- Calcium 1-2 g/d in divided doses
- Active Vit D (calcitriol 0.5-2 ÎŒg/d in divided doses; or longer-acting alfacalcidol)
- Avoid calcium phosphate stones (target Ca-P product < 55)
- Phosphate-restricted diet
- Magnesium replacement
- Periodic 24h urine Ca (avoid hypercalciuria + nephrolithiasis)

Refractory / Difficult Cases:
- **Palopegteriparatide (Yorvipath, FDA 2024)**: long-acting PTH; once-daily SC
  - Indications: refractory + frequent hypocalcemia + nephrolithiasis + cognitive
  - Contraindications: increased bone turnover, prior radiation
- Previously: Natpara (rhPTH 1-84) — withdrawn 2019
- Teriparatide off-label (short-acting; multiple daily doses)

Long-term Surveillance:
- Annual: Ca, PTH, Mg, P, 25-D, creatinine, 24h urine Ca, DXA
- Renal US for nephrocalcinosis q3-5 yr
- CT brain for basal ganglia calcification (Fahr)
- Cataract surveillance
- Cognitive assessment

423.3.0.7 ⚙ FHH (Familial Hypocalciuric Hypercalcemia)

Genetics:
- CASR loss-of-function (most common)
- AP2S1 (rare)
- GNA11 (rare)
- AD inheritance

Diagnosis:
- High Ca + high or inappropriately normal PTH (looks like PHPT!)
- **24h urine Ca/Cr clearance ratio < 0.01** (KEY)
- Family Hx (first-degree relatives have high Ca)
- Genetic testing CaSR

Why distinguish from PHPT:
- FHH is benign; surgery does NOT correct hypercalcemia
- Surgery is unnecessary + leads to permanent hypocalcemia (no underlying defect)

Management:
- No surgery
- Family screening
- Education (benign condition)
- Symptomatic only

Caveat:
- Type 3 (GNA11): may have additional features
- Severe neonatal form (homozygous CASR LoF): NSHPT — neonatal severe hyperparathyroidism; very rare; emergency parathyroidectomy

423.3.0.8 ⚙ Parathyroid Carcinoma (内專)

Recognition:
- Very high Ca (> 14)
- Very high PTH (10-100x normal)
- Palpable neck mass
- Recurrent / metastatic
- Family Hx (CDC73)

Workup:
- Imaging: US + sestamibi + 4D-CT
- Genetic: CDC73 (HRPT2)

Surgery:
- En bloc resection: parathyroid + ipsilateral thyroid lobe
- Avoid capsular rupture (seeding)
- Lymph node dissection if visible

Long-term:
- Cinacalcet for symptomatic hypercalcemia control (palliative)
- Bisphosphonate / denosumab for bone
- Surveillance: Ca, PTH, imaging
- Family screening (CDC73)
- Recurrence common
- Metastases: lung, bone, liver — palliative

⚠ AI 草皿。