Cushing disease

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

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

About

• Harvey Cushing was a Boston neurosurgeon who pioneered operative surgery of the pituitary
• It is the ACTH secreting pituitary tumour cause of Cushing's syndrome that is named after him

Aetiology

• Pituitary tumour secreting excess ACTH causes bilateral adrenal hyperplasia
• Loss of normal circadial rhythm usually peaks in am
• Microadenomas < 1 cm, Mesoadenoma = 1 cm, Macroadenomas > 1 cm
• AIP (Aryl hydrocarbon receptor Interacting Protein) mutations have been reported in familial pituitary adenomas:
• Rarely part of MEN Type 1, due to mutations of the menin gene.

Anatomy and relations: Note ICA

Clinical

• Tumour mass: headache, bitemporal hemianopia
• Excess Cortisol: Obesity, Hypertension, moon face, buffalo hump, striae, bruising, diabetes, osteoporosis, reduced immunity
• Damage to pituitary: hypo pituitary - menstrual abnormalities, loss of secondary sexual characteristics, infertility etc,

Cortisol Excess Suspected

• If Cortisol excess suspected then consider Overnight Dexamethasone suppression tests or diurnal salivary cortisol studies
• Dexamethasone 1 mg is given at night orally between 11 and 12 midnight
• Serum cortisol is tested at 9 am and a value < 50 nmol/L is highly sensitive and specific to exclude Cushing's disease
• If elevated then check ACTH to see if the excess is adrenal or pituitary origin

Investigations

• FBC, U&E, LFTs, Ca, Random cortisols can mislead and not useful
• 24-hour urine free cortisol (UFC) measurement is high
• Cortisol saliva testing high
• Blood ACTH is elevated (low suggests adrenal tumour producing cortisol)
• A low dose dexamethasone 1 mg test leads to no change in plasma cortisol
• A high dose dexamethasone 8mg test may be enough to more than halve morning cortisol (as occurs in normals).
• MRI Pituitary: enlarged pituitary mass which may extend above the gland. However MRI detects only 70% of pituitary tumours causing Cushing’s (many are too small).
• Bilateral inferior petrosal sinus sampling (BIPSS) following corticotropic-releasing hormone (CRH) stimulation is the current gold standard technique in the diagnosis of Cushing disease

Management

• Surgery to remove pituitary tumour: Transphenoidal hypophysectomy or for very large tumours transfrontal approach used
• Bilateral adrenalectomy if source unlocatable, or recurrence post-op. Complication is Nelson's syndrome with skin pigmentation due to high ACTH from an enlarging pituitary. Treat with pituitary radiation.

References

• Research paper