Makindo Medical Notes

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

Bilateral inferior petrosal sinus sampling (BIPSS) following corticotropin-releasing hormone (CRH) stimulation is the current gold standard technique in the diagnosis of Cushing's disease.

About

• Harvey Cushing was a Boston neurosurgeon who pioneered operative surgery of the pituitary gland.
• Cushing’s disease refers specifically to the ACTH-secreting pituitary tumour that causes Cushing's syndrome, named in his honor.

Aetiology

• Caused by a pituitary tumour that secretes excess ACTH, leading to bilateral adrenal hyperplasia.
• Loss of normal circadian rhythm of cortisol secretion, which usually peaks in the morning.
• Microadenomas: Tumors < 1 cm; Mesoadenomas: Tumors = 1 cm; Macroadenomas: Tumors > 1 cm.
• Aryl hydrocarbon receptor Interacting Protein (AIP) mutations have been reported in familial pituitary adenomas.
• Rarely part of Multiple Endocrine Neoplasia (MEN) Type 1, associated with menin gene mutations.

Anatomy and Relations

Note the internal carotid artery (ICA) in relation to the pituitary gland.

Clinical Presentation

• Tumor mass effects: Headache, bitemporal hemianopia (visual field defects).
• Excess cortisol: Obesity, hypertension, moon face, buffalo hump, striae, easy bruising, diabetes, osteoporosis, and reduced immunity.
• Damage to pituitary: Hypopituitarism leading to menstrual abnormalities, loss of secondary sexual characteristics, infertility, etc.

When Cortisol Excess is Suspected

• Consider the Overnight Dexamethasone Suppression Test or diurnal salivary cortisol studies.
• Dexamethasone 1 mg is given orally between 11 pm and midnight.
• Serum cortisol is tested at 9 am the following morning. A value < 50 nmol/L is highly sensitive and specific to exclude Cushing's disease.
• If cortisol is elevated, measure ACTH to differentiate between adrenal and pituitary sources of excess cortisol.

Investigations

• Blood tests: FBC, U&E, LFTs, Ca.
• 24-hour urine free cortisol (UFC) is elevated.
• Salivary cortisol is elevated.
• Blood ACTH: Elevated in pituitary disease; low ACTH suggests an adrenal tumour.
• Dexamethasone Suppression Tests:
  • Low dose (1 mg): No change in plasma cortisol indicates Cushing's disease.
  • High dose (8 mg): Cortisol levels may drop by more than 50% in patients with Cushing's disease.
• MRI of the Pituitary: Can identify a pituitary tumour, though it detects only 70% of Cushing's-related tumours as many are too small.
• BIPSS: Bilateral inferior petrosal sinus sampling following CRH stimulation is the gold standard for confirming a pituitary source of ACTH.

Management

• Surgery: Transsphenoidal hypophysectomy is the primary surgical treatment for pituitary tumours. In larger tumours, a transfrontal approach may be required.
• Bilateral adrenalectomy: May be necessary if the tumour source is unlocatable or there is recurrence post-surgery. A possible complication is Nelson's syndrome (increased skin pigmentation due to elevated ACTH from the pituitary), treated with pituitary radiation.

References

• Research paper