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Pheochromocytoma
This is an adrenaline producing tumour of the chromaffin cells.
It follows rule of 10’s – 10% bilateral, 10% familial, 10% malignant and 10% located outside adrenal gland in the bladder wall or organ of Zuckerandl by aortic bifurcation.
It is associated with the conditions like MEN 2A/B and neurofibromatosis type 1.
It is also seen in von Hippel-Lindau disease, an autosomal dominant hereditary condition characterised by tumours arising in multiple organs.
Symptoms
Triad of episodic headache, sweating and tachycardia (palpitations)
Hypertension, which may be resistant to treatment
Key tests
Blood tests show increased plasma metanephrine levels
Increased urinary metanephrines and vanillylmandelic acid levels
Abdominal CT/MRI scans are used to locate tumour
Management
Surgical excision to remove tumour is the definitive treatment
Medical management is used before surgery to control blood pressure.
1st line is alpha-blocker phenoxybenzamine, 2nd line is labetalol (if heart disease or tachycardia)
Hypercortisolism (Cushing’s syndrome)
A condition associated with excessive cortisol levels and loss of the negative feedback mechanism of the HPA axis and circadian rhythm of cortisol secretion.
A pseudo-Cushing’s syndrome can also be seen in chronic alcohol abuse or severe depression.
The insulin stress test is used to diagnose distinguish these from Cushing’s syndrome.
ACTH-independent causes
These cause low levels of ACTH due to negative feedback and adrenal atrophy.
Exogenous steroids – most common cause which leads to bilateral adrenal atrophy
Primary adrenal adenoma/hyperplasia/carcinoma – this leads to atrophy of uninvolved adrenal gland
ACTH-dependent causes
These lead to high levels of ACTH which results in adrenal hyperplasia.
Cushing’s disease – this is a condition where there is excess cortisol due to an ACTH secreting pituitary adenoma, which leads to bilateral adrenal hyperplasia
Ectopic ACTH production – this is a paraneoplastic syndrome which is associated with some cancers such as small cell carcinoma of the lung and renal cell carcinoma
Symptoms
Muscle weakness and breakdown
Osteoporosis
Immune suppression
Hypertension
Hyperglycaemia (diabetes) and weight gain
Signs
Abdominal striae- thinning of skin
Poor wound healing
Central obesity, buffalo hump
Moon faced shape
Key tests
First you want to confirm the diagnosis, then you can do tests to localise the lesion.
i) Blood tests – raised 9am morning cortisol
ii) Overnight dexamethasone test:
This involves giving dexamethasone at 11pm and measuring morning cortisol levels.
Normally cortisol is suppressed, but no suppression is seen in Cushing’s syndrome.
24 hour urinary free cortisol can also be tested for.
iii) Once you have diagnosed Cushing’s syndrome, try to locate the source.
Measure plasma ACTH. If this is high, it suggests a pituitary or ectopic source.
The 48 hour high-dose dexamethasone suppression test is used to help distinguish between pituitary tumour and ectopic ACTH tumour.
High dose dexamethasone suppresses pituitary ACTH, but not ACTH from ectopic.
iv) Imaging can then be used to locate the tumour.
If pituitary Cushing’s disease suspected, pituitary MRI scan is beneficial.
If an ectopic source suspected, a CT chest, abdomen and pelvis can be used
Management
This involves treating underlying cause, e.g., weaning steroids, removal of tumour
Hyperaldosteronism
This refers to excess aldosterone production which leads to symptoms.
There are two main types of hyperaldosteronism, depending on the cause:
Primary hyperaldosteronism
This refers to excess production of aldosterone independent of the renin-angiotensin system, which leads to increased sodium and water retention.
It is characterised by high aldosterone and low renin (as high BP inhibits renin).
Causes
Conn syndrome – aldosterone producing adenoma (most common)
Sporadic adrenal hyperplasia
Secondary hyperaldosteronism
This refers to high levels of aldosterone which occurs secondary to the activation of the renin-angiotensin system.
It is characterised by high aldosterone and high renin levels.
Causes
Poor renal perfusion e.g. renal artery stenosis, heart failure, diuretics
Symptoms
Hypertension which is resistant to treatment
Signs of hypokalaemia, e.g., weakness, cramps, arrythmias
Key tests
Measure aldosterone: renin ratio to differentiate between primary and secondary
Imaging CT/MRI abdomen can be used to locate tumour
Adrenal vein sampling
Management
For Conn’s syndrome – laparoscopic surgery to remove adenoma
For adrenal hyperplasia – K+ sparing diuretics, e.g., spironolactone/amiloride
Adrenal insufficiency
This is the failure of the adrenal gland to produce cortisol and aldosterone
Primary insufficiency (increased ACTH)
This is called Addison’s disease and it is due to an intrinsic failure of the adrenal gland.
The most common cause worldwide is TB.
The most common cause in the UK is autoimmune destruction of the adrenal gland.
It is also seen in Waterhouse-Friderichsen syndrome, haemorrhagic necrosis of adrenal glands classically seen in young children with Neisseria miningitidis infection.
Secondary insufficiency (decreased ACTH)
This refers to low cortisol secretion due to a factor extrinsic to the adrenal glands.
The most common reason is due to long term steroid therapy which leads to adrenal suppression.
It can also occur due to pituitary trauma/tumours/surgery.
Symptoms
Lack of cortisol – hypotension, muscle weakness
Lack of aldosterone – dehydration, hypovolemia, hyponatremia, hyperkalaemia
Metabolic acidosis
Hyperpigmentation due to raised melanocyte stimulating hormone levels
Key tests
The ACTH stimulation test (short Synacthen test) is gold standard.
This involves measuring serum cortisol levels before and 30 minutes after giving tetracosactide/synacthen (ACTH analogue)
If cortisol does not increase, it shows that patient has primary adrenal insufficiency
Management
Replace steroids – hydrocortisone
Replace aldosterone – fludrocortisone
In illness, double hydrocortisone dose, but keep fludrocortisone constant!
Addisonian crisis
This is a life-threatening deficiency of glucocorticoids and mineralocorticoids.
It can be seen in patients who forget to take their steroids or those who stop taking them suddenly, but also in times of increased stress due to infection.
It can cause severe hypotension, tachycardia and reduced consciousness.
It causes hyperkalaemia, hyponatraemia, hypoglycaemia and metabolic acidosis.
IV hydrocortisone should be given ASAP (fludrocortisone not required immediately)
Symptoms
Shock (increased HR, vasoconstriction, hypotension, weak/confused/coma)
Increased K+, decreased Na+, decreased glucose, metabolic acidosis
Management
If crisis is suspected, treat before biochemical results come
Give hydrocortisone 100mg IM or IV (fludrocortisone not required immediately!!!
Fluids – 1 litre saline over 30-60mins (with dextrose is hypoglycaemia)
Change to oral steroids after 72 hours
