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 Cushingwas 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