Makindo Medical Notes

🧪 Bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation is the gold standard to confirm a pituitary source of ACTH in suspected Cushing’s disease.

📖 About

• Harvey Cushing, a Boston neurosurgeon, pioneered pituitary surgery.
• Cushing’s disease = ACTH-secreting pituitary adenoma causing cortisol excess. (Cushing’s syndrome is the broader clinical state of cortisol excess, regardless of cause.)

🧬 Aetiology

• ACTH-secreting pituitary tumour → bilateral adrenal hyperplasia + loss of normal circadian cortisol rhythm.
• Microadenomas <1 cm; Mesoadenomas = 1 cm; Macroadenomas >1 cm.
• AIP mutations can underlie familial pituitary adenomas.
• Rarely associated with MEN1 (menin gene).

🧠 Anatomy & Relations

⚠️ Pituitary closely related to the internal carotid artery (ICA) and optic chiasm.

🩺 Clinical Presentation

• Mass effect: Headache, bitemporal hemianopia.
• Cortisol excess: Truncal obesity, moon face, buffalo hump, purple striae, easy bruising, hypertension, diabetes, osteoporosis, immunosuppression.
• Pituitary damage: Hypopituitarism → menstrual irregularities, infertility, reduced secondary sexual characteristics.

🔍 When Cortisol Excess is Suspected

• Overnight dexamethasone suppression test:   • Give dexamethasone 1 mg at 11 pm → serum cortisol at 9 am.   • Cortisol < 50 nmol/L = suppression (rules out Cushing’s).   • Failure to suppress = abnormal.
• ACTH measurement differentiates adrenal vs pituitary cause.
• Salivary cortisol (late night) and 24-hr urinary free cortisol are also useful.

🔬 Investigations

• Bloods: FBC, U&E, LFTs, Ca (to assess comorbidity/complications).
• 24-hour UFC: Elevated in Cushing’s.
• ACTH levels: High/normal = pituitary cause; low = adrenal source.
• Dexamethasone suppression tests:
  • Low dose (1 mg): No suppression → possible Cushing’s.
  • High dose (8 mg): ≥50% cortisol fall suggests pituitary source.
• MRI pituitary: Identifies adenoma in ~70% (many are too small).
• BIPSS: Gold standard for differentiating pituitary from ectopic ACTH.

🎯 Management

• First-line: Transsphenoidal hypophysectomy (removal of pituitary tumour).
• Radiotherapy: Consider if surgery is incomplete or contraindicated.
• Bilateral adrenalectomy: Option for refractory disease → risk of Nelson’s syndrome (skin pigmentation, aggressive pituitary tumour growth).
• Medical therapy (bridge/adjunct): Metyrapone, ketoconazole, or mitotane to block cortisol synthesis.

📚 References

• Research paper