278.3 🏥 內科專科考前版

278.3.1 Mechanistic Deep Dive

278.3.1.1 Genetics of PA

  • KCNJ5 mutation (40% of APA) — affects K channel, causes Ca influx, autonomous aldosterone
  • CACNA1D, ATP1A1, ATP2B3, CTNNB1 — somatic mutations
  • Familial:
    • Type I (GRA): CYP11B1/2 chimeric gene → ACTH-driven aldosterone → glucocorticoid suppresses
    • Type II: unknown
    • Type III: KCNJ5 germline
    • Type IV: CACNA1H

278.3.1.2 Genetics of Pheo (2024 — Comprehensive Testing)

  • 40% germline mutations
  • MEN2 (RET): pheo + medullary thyroid + parathyroid
  • VHL: pheo + RCC + hemangioblastoma
  • NF1: pheo + neurofibromas, café-au-lait
  • SDHB/C/D/A/AF2: paragangliomas, often extra-adrenal, malignant risk (SDHB)
  • TMEM127, MAX, FH: less common
  • Cascade screening of relatives

278.3.2 Recent Trials & Updates

278.3.2.1 CORAL (2014)

  • N = 947 ARAS + HTN
  • Stent + OMT vs OMT alone
  • No difference in CV events
  • Subgroups (FMD, severe HTN, flash edema) excluded
  • Established OMT primary, stent for select

278.3.2.2 PATHWAY-2 (2015) — Confirmed PA Implication

  • Many “resistant HTN” patients respond to spironolactone → suggest PA-like physiology

278.3.2.3 ENDOCRINE SOCIETY PA Guideline (2024)

  • Lower screening threshold
  • ARR + plasma aldo > 10 in some patients
  • AVS only for surgical candidates
  • C-11 metomidate PET emerging

278.3.2.4 2024 Update on Pheo Genetics (ENDOCRINE SOCIETY)

  • ALL patients should have germline testing
  • Tailored surveillance based on mutation
  • Family screening cascade

278.3.2.5 Aprocitentan + PA

  • May benefit PA-related resistant HTN
  • Endothelin pathway also activated

278.3.3 High-Yield Specialist Points

278.3.3.1 Adrenal Vein Sampling (AVS) Technical

  • Bilateral catheterization
  • Cortisol + aldosterone in each adrenal vein + IVC
  • Cosyntropin stimulation increases reliability
  • Lateralization ratio > 4 (with cosyntropin) or > 2 (without)
  • Failure rate 5-30% (operator-dependent)
  • Refer to high-volume center

278.3.3.2 Pheo Crisis Management

  • α-blockade (phentolamine IV, phenoxybenzamine PO)
  • Nicardipine, nitroprusside for HTN
  • Volume resuscitation
  • Magnesium sulfate (catecholamine antagonist + α-blocker)
  • AVOID metoprolol/atenolol alone

278.3.3.3 OSA in Resistant HTN

  • 70%+ have OSA
  • CPAP modest BP effect (~ 2 mmHg)
  • Best in patients with elevated nocturnal BP
  • Address concomitant obesity

278.3.3.4 NEW: 11β-HSD2 Imaging

  • C-11 metomidate PET binds adrenal cortisol synthesis enzymes
  • Distinguishes APA from non-functioning adenoma
  • Less invasive than AVS
  • Emerging since 2021

278.3.3.5 Mineralocorticoid Excess Beyond PA

  • Apparent mineralocorticoid excess (AME):
    • 11β-HSD2 deficiency
    • Cortisol acts as mineralocorticoid
    • Licorice (glycyrrhizic acid) inhibits 11β-HSD2
  • Liddle syndrome:
    • SCNN1A/B/G gain-of-function → constitutive ENaC
    • Low renin + aldo, hypokalemia + HTN
    • Amiloride treatment (not MRA)
  • Geller syndrome:
    • MR mutation activated by progesterone → severe pregnancy HTN

278.3.3.6 Acromegaly Workup

  • IGF-1 (best screen)
  • OGTT growth hormone suppression
  • Pituitary MRI
  • Treatment: surgery, somatostatin analogs (octreotide), pegvisomant (GH receptor antagonist)

278.3.3.7 MRI Adrenal Characterization

  • T1, T2, in/out-of-phase
  • Pheo: T2 bright, no fat
  • Adenoma: chemical shift loss of signal
  • Carcinoma: T2 bright, necrosis

278.3.4 Pearls

  • Primary aldosteronism is the most common endocrine cause and very underdiagnosed
  • ARR is screening, not diagnostic — confirmatory testing required
  • AVS gold standard for lateralization before surgery
  • Pheo workup: plasma free metanephrines first; α-block before β-block
  • Genetic testing for ALL pheo patients (2024)
  • CORAL trial: OMT primary for ARAS; FMD → angioplasty
  • OSA + resistant HTN: very high prevalence; treat with CPAP
  • C-11 metomidate PET, lutetium-177 DOTATATE = emerging tools