Adrenal Medullary Disorders

Adrenal Medulla Overview - Catecholamine Factory

• Origin: Neural crest cells (neuroectoderm).
• Cells: Chromaffin cells (modified postganglionic sympathetic neurons).
• Hormones: Synthesizes and secretes catecholamines:
  • Epinephrine (Adrenaline) - ~80%
  • Norepinephrine (Noradrenaline) - ~20%
  • Dopamine (trace amounts)
• Regulation: Stimulated by acetylcholine from preganglionic sympathetic fibers.

⭐ The enzyme Phenylethanolamine N-methyltransferase (PNMT), crucial for converting norepinephrine to epinephrine, is induced by cortisol from the adrenal cortex. This highlights the cortico-medullary interaction.

Pheochromocytoma - Adrenaline Rush Hour

• Neuroendocrine tumor of chromaffin cells (adrenal medulla; or extra-adrenal paraganglia e.g., organ of Zuckerkandl). Secretes catecholamines (mainly Norepinephrine, Epinephrine).
• Clinical: Episodic "PHE" triad - Palpitations, Headache, Episodic sweating. Severe, paroxysmal hypertension is characteristic.
• 📌 Rule of 10s (classic): 10% extra-adrenal, 10% bilateral, 10% malignant, 10% pediatric, 10% familial. (Note: familial incidence now considered higher, ~25% or more with genetic testing).
• Diagnosis:
  • Biochemical: ↑ Plasma free metanephrines (most sensitive test) OR ↑ 24-hr urinary fractionated metanephrines & catecholamines. Vanillylmandelic acid (VMA) is less specific.
  • Imaging: CT/MRI of abdomen/pelvis to localize tumor. MIBG (¹²³I-metaiodobenzylguanidine) scan for extra-adrenal sites or suspected metastases.
• Associated Syndromes: Multiple Endocrine Neoplasia (MEN) 2A & 2B, Von Hippel-Lindau (VHL) disease, Neurofibromatosis type 1 (NF1), Succinate Dehydrogenase (SDHx) gene mutations.
• Management:
  • Pre-operative: α-adrenergic blockade (e.g., phenoxybenzamine) for 10-14 days to control blood pressure and allow for volume expansion, followed by β-blockers (e.g., propranolol) if tachycardia develops (ONLY after adequate α-blockade).
  • Definitive: Surgical resection of the tumor.

⭐ Pre-operative α-adrenergic blockade (e.g., phenoxybenzamine) is essential to prevent life-threatening hypertensive crisis during surgery due to catecholamine release on tumor manipulation.

Paraganglioma - Pheo's Wild Cousin

• Extra-adrenal neuroendocrine tumors from paraganglia (neural crest).
• Locations:
  • Sympathetic chain (abdomen - organ of Zuckerkandl, thorax): Catecholamine-secreting.
  • Head/Neck (carotid body, glomus): Often non-secretory; mass effects, CN palsies.
• Symptoms (if secreting): Episodic HTN, palpitations, headache, sweating.
• Diagnosis: ↑ metanephrines (plasma/urine); CT/MRI, MIBG scan.
• Genetics: High hereditary link (e.g., SDHx, VHL, RET mutations).

⭐ ~30-40% of paragangliomas/pheochromocytomas are hereditary.

Neuroblastoma - Kiddo's Neural Crest Crisis

• Most common extracranial solid childhood tumor; median age 18-24 months.
• Origin: Neural crest cells (adrenal medulla/sympathetic ganglia).
• Key Gene: N-MYC amplification (poor prognosis).
• Presentation: Abdominal mass (most common), pain, fever.
  • Opsoclonus-myoclonus syndrome ("dancing eyes-feet").
  • Blueberry muffin rash (skin mets).
• Diagnosis: ↑ urine VMA/HVA; biopsy shows small, round, blue cells, Homer-Wright pseudorosettes.
• Favorable Prognosis: Age < 18 months, no N-MYC amp, Stage 4S (infants <1yr, specific mets).

⭐ Spontaneous regression is a unique feature, especially in infants or Stage 4S disease.

High‑Yield Points - ⚡ Biggest Takeaways

• Pheochromocytoma: Most common adult adrenal medullary tumor; presents with episodic headaches, sweating, tachycardia.
• Diagnose pheochromocytoma via ↑ plasma/urinary metanephrines and catecholamines (VMA).
• Strong association with MEN 2A/2B, VHL, NF1 syndromes.
• Pre-operative management: alpha-blockers (e.g., phenoxybenzamine), then beta-blockers before surgery.
• Neuroblastoma: Commonest extracranial solid childhood tumor; features ↑ urinary HVA/VMA.
• Neuroblastoma: Homer-Wright pseudorosettes on histology; N-myc amplification signifies poor prognosis.
• Pheochromocytoma Rule of 10s: ~10% malignant, bilateral, extra-adrenal_._