Makindo Medical Notes

Related Subjects: |Adrenal Physiology |Addisons Disease |Phaeochromocytoma |Adrenal Adenomas |Adrenal Cancer |Cushing Syndrome |Cushing Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome

🩺 Adrenocortical carcinomas (ACC) are rare, aggressive malignancies of the adrenal cortex. They may be functional (secreting cortisol, androgens, or both) or non-functional, and often present late with mass effect or metastatic disease.

📍 About

• Incidence ~1 in 1,000,000 per year.
• Seen in children under 5 and adults in their 40s–50s.
• Highly aggressive with poor prognosis (5-year mortality 75–90%).
• Can be hormonally active:
  • 🌡️ Cortisol → Cushing’s syndrome.
  • ⚧ Androgens → virilisation/feminisation.
  • Rare: aldosterone secretion.

🧬 Genetic & Syndromic Associations

• Hereditary syndromes:
  • 🧪 Li-Fraumeni (TP53 mutations).
  • 👶 Beckwith–Wiedemann.
  • 🎭 Carney complex.
  • 🧩 Lynch syndrome.
  • MEN-1 (rare association).
• Key driver mutations: TP53, IGF2 overexpression.

⚠️ Symptoms

• Hormonal excess:
  • Weight gain, central obesity, striae (Cushing’s).
  • Hypertension, diabetes, muscle weakness.
  • Virilisation (hirsutism, voice deepening) or feminisation.
• Mass effect: abdominal pain, palpable mass, early satiety.
• Systemic: weight loss, fatigue, anorexia.

🔬 Investigations

• 🧪 Hormonal screen (always exclude functioning tumour):
  • Urinary free cortisol / dexamethasone suppression.
  • Cortisol, aldosterone, androgens, oestrogens.
  • Plasma metanephrines (exclude phaeochromocytoma).
• 📊 Bloods: FBC (anaemia), U&E, CRP.
• 📸 Imaging:
  • CT: mass >6 cm, heterogeneous, necrosis/calcification, local invasion or metastases (lung, liver, lymph nodes).
  • MRI: heterogeneous T2 hyperintensity; poor signal drop on chemical shift.
  • FDG PET: FDG-avid lesions highly suspicious (distinguish from benign adenoma).
• 🧬 Adrenal vein sampling may be considered if hormonal lateralisation is unclear.
• Biopsy: usually avoided unless diagnosis uncertain — risk of tumour spillage.

🧫 Pathology

• Large (>5–6 cm), irregular margins, invasion of capsule or adjacent structures.
• Cut surface: brown–orange–yellow (lipid content varies).
• Necrosis and haemorrhage common.
• Invasion of capsule, vessels, or soft tissue is hallmark of malignancy.

📊 Staging (ENSAT)

• Stage I: ≤5 cm, localised.
• Stage II: >5 cm, localised.
• Stage III: local invasion, regional lymph nodes, or tumour thrombus.
• Stage IV: distant metastases.

⚖️ Differentials

• Adrenal adenoma.
• Phaeochromocytoma.
• Adrenal pseudocyst.

💊 Management

• 📋 MDT discussion essential (endocrinology, oncology, surgery).
• 🗡️ Surgical resection = only curative option (R0 resection crucial).
• 💊 Adrenolytic therapy: Mitotane (mainstay systemic drug; both cytotoxic + adrenolytic).
• Adjuncts:
  • Chemotherapy (etoposide, doxorubicin, cisplatin + mitotane).
  • Radiotherapy (limited role, palliative or local recurrence).
  • Drugs to control cortisol excess: ketoconazole, metyrapone, mifepristone.
• 🧪 For hormone-secreting tumours: spironolactone/eplerenone (aldosterone), insulin/antihypertensives as supportive measures.

📉 Prognosis is poor. Average survival ~14.5 months; 5-year survival ~20–30% if metastatic. Outcome depends on stage, completeness of surgical resection, and tumour biology.

📚 Teaching Pearls

• Always biochemically screen for hormonal excess in an adrenal mass before biopsy/surgery.
• Size >6 cm and heterogeneous imaging = red flag for ACC vs adenoma.
• Mitotane is unique to adrenal oncology — cytotoxic + suppresses steroid synthesis.
• Think genetic syndromes (Li-Fraumeni, Beckwith-Wiedemann) in young patients with adrenal masses.

🔗 References

• Adrenal cancer review
• Adrenal adenoma collection