|Cushings Syndrome due to Ectopic ACTH
|Congenital Adrenal hyperplasia
|Primary hyperaldosteronism (Conn's syndrome)
|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
- 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
- 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
- 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
- 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
- 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.