a) Adrenal medulla
• Pheochromocytoma – This is an adrenaline producing tumour of the chromaffin cells
– Follows rule of 10s – 10% are bilateral, 10% familial, 10% malignant and 10% located outside adrenal medulla in the bladder wall or organ of Zuckerandl by aortic bifurcation.
– Most are unilateral on the right
– Associated with MEN 2A/B, Neurofibromatosis type 1
– Also linked to von Hippel-Lindau disease – an autosomal dominant hereditary condition associated with tumors arising in multiple organs
Symptoms: Triad of episodic headache, sweating and tachycardia (palpitations), with hypertension
Diagnosis – Increased plasma Metanephrine level
– Increased 24-hr urine Metanephrines + Vanillylmandelic acid
– Abdominal CT/MRI scan to locate tumour
Management – First stabilise the patient with medical therapy:
-1st line is alpha-blocker phenoxybenzamine, 2nd line is labetalol (if heart disease or tachycardia)
– Surgical excision to remove tumour is the definitive treatment
b) Adrenal cortex
• Hypercortisolism (Cushing’s syndrome)
This is a clinical state produced by chronic cortisol excess and loss of the normal feedback mechanism of the HPA axis and circadian rhythm of cortisol secretion (normally highest in morning).
ACTH-independent causes: (gives low ACTH –> adrenal atrophy)
– Exogenous steroids – most common cause, gives bilateral adrenal atrophy, steroids suppress ACTH
– Primary adrenal adenoma/hyperplasia or carcinoma – leads to atrophy of uninvolved adrenal gland
ACTH-dependent causes: (gives high ACTH –> adrenal hyperplasia)
– Cushing’s disease – bilateral adrenal hyperplasia from an ACTH secreting pituitary adenoma
– Ectopic ACTH production – from small cell carcinoma of lung giving bilateral adrenal hyperplasia.
Pseudo-Cushing’s: (mimics symptoms and obscures test results)
– Chronic alcohol abuse or severe depression
– Insulin stress test is used to diagnose these and distinguish from Cushing’s disease
– Muscle weakness and breakdown
– Immune suppression
– Hyperglycemia (diabetes) + weight gain
– Abdominal striae- thinning of skin
– Poor wound healing
– Central obesity, buffalo hump
– Moon faced shape
Diagnosis – First you want to confirm the diagnosis, then you can do tests to localise the lesion.
– 1st line: Overnight dexamethasone test –> give dexamethasone at 11pm + measure cortisol at 8am
– Normally cortisol is suppressed, but no suppression seen in Cushing’s syndrome.
– 2nd line: 24hr urinary free cortisol.
Once you have diagnosed Cushing’s syndrome want to locate the cause.
– Measure plasma ACTH –> if high it indicates pituitary or ectopic source.
– If ACTH-dependent –> do 48hr high-dose dexamethasone suppression test
– Will distinguish between pituitary tumour and ectopic ACTH tumour
– Dexamethasone would supress pituitary ACTH, but not ACTH from ectopic source.
– If pituitary Cushing’s disease –> pituitary MRI If ectopic source –> CT chest/abdo/pelvis
Treatment – Stop steroids if iatrogenic, surgical removal if tumour
Complications: Nelson Syndrome – in Cushing’s treated with bilateral adrenalectomy, loss of -ve feedback gives raised ACTH causing enlargement of pituitary adenoma + pigmentation of skin
• Hyperaldosteronism – This refers to excess aldosterone production existing in two types:
o Primary hyperaldosteronism – excess production independent of the renin-angiotensin, causing increased sodium and water retention.
– Characterized by high aldosterone and low renin (as high BP inhibits renin)
Causes: Conn syndrome – aldosterone producing adenoma (most common)
– Sporadic adrenal hyperplasia
o Secondary hyperaldosteronism – due to activation of renin-angiotensin system
– Characterized by high aldosterone and high renin
Causes: Poor renal perfusion e.g. renal artery stenosis, heart failure, diuretics
Symptoms – Often asymptomatic but gives signs of hypokalaemia –> weakness, cramps, alkalosis
– Increased Na expands blood volume –> hypertension
Diagnosis: Measure Aldosterone: Renin Ratio –> then CT abdomen + adrenal vein sampling
Treatment – Conn’s syndrome –> laparoscopic surgery to remove adenoma
– Hyperplasia –> K+ sparing diuretics e.g. spironolactone/amiloride
• Adrenal insufficiency – This is the failure of the adrenal gland to produce cortisol and aldosterone
o Primary insufficiency (increased ACTH) – called Addison’s disease and is due to failure of gland itself
– TB is the most common cause worldwide
– Also due to autoimmune destruction (most common cause in UK) gives chronic insufficiency
– Waterhouse-Friderichsen syndrome –> haemorrhagic necrosis of adrenal glands classically in young children with N miningitidis infection.
o Secondary insufficiency (decreased ACTH) – This is caused by a factor extrinsic to the adrenal glands
– Most common cause is iatrogenic due to long term steroid therapy and adrenal suppression
– Also due to pituitary disease leading to lack of ACTH
– Lack of cortisol –> hypotension, muscle weakness
– Lack of aldosterone –> dehydration, hypovolemia, hyponatremia, hyperkalaemia
– Metabolic acidosis
– increased ACTH –> causes hyperpigmentation due to increase melanocyte stimulating hormone
Diagnosis – 1st line ACTH stimulation test (Short Synacthen test)
– Measure cortisol before + 30 minutes after giving Tetracosactide/Synacthen (ACTH analogue)
– If cortisol does not increase, shows that patient has primary adrenal insufficiency
2nd line – Measure 9am serum cortisol, if lower than 100nM, then highly suggestive of Addison’s
– Replace steroids – hydrocortisone
– Replace aldosterone – fludrocortisone
In illness, double hydrocortisone dose, but keep fludrocortisone constant!
• Addisonian crisis
Causes: Failure to take steroid tablets, increased stress due to infection
Symptoms: Shock (increased HR, vasoconstriction, hypotension, weak/confused/coma)
– increased K+, decreased Na+, decreased glucose, metabolic acidosis
Treatment – if crisis is suspected, treat before biochemical results come i) Give hydrocortisone 100mg IM or IV (fludrocortisone not required immediately!!!)
ii) Fluids – 1 litre saline over 30-60mins (with dextrose is hypoglycaemia)
iii) Change to oral steroids after 72 hours