🧪 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

🧾 Case Examples – Cushing’s Disease

Case 1 – Young Woman with Classic Features 👩 A 29-year-old woman presents with weight gain, acne, and irregular periods. Exam: round “moon face,” truncal obesity, thin limbs, purple striae. 🧪 Cortisol not suppressed on low-dose dexamethasone; ACTH high; MRI: 5 mm pituitary adenoma. 👉 Diagnosis: Pituitary Cushing’s disease. 👉 Management: Transsphenoidal pituitary surgery (first-line).

Case 2 – Resistant Hypertension & Diabetes 👨 A 46-year-old man has poorly controlled hypertension and new-onset diabetes. Exam: proximal muscle weakness, easy bruising, facial plethora. 🧪 High-dose dexamethasone suppresses cortisol (pituitary source). 👉 Diagnosis: Pituitary-dependent Cushing’s disease. 👉 Management: Pituitary resection; ketoconazole/metyrapone if not surgical candidate.

Case 3 – Chronic Disease with Osteoporosis 🦴 A 55-year-old woman with years of fatigue and depression presents with vertebral fractures. Exam: buffalo hump, thin fragile skin, poor wound healing. 🧪 Inferior petrosal sinus sampling confirms pituitary ACTH source. 👉 Diagnosis: Longstanding untreated Cushing’s disease. 👉 Management: Pituitary surgery, bone protection (bisphosphonates, vitamin D).

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Cushing disease