Adrenal Gland Conditions

a) Adrenal medulla conditions

 

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 conditions

 

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

 

Symptoms:

– Muscle weakness and breakdown

– Osteoporosis

– Immune suppression

– Hypertension

– Hyperglycaemia (diabetes) + weight gain

 

Signs:

– 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:

 

Primary hyperaldosteronism:

This is a condition where there is excess production independent of the renin-angiotensin, causing increased sodium and water retention.

– It is characterized 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 is due to activation of renin-angiotensin system and it is 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

 

Primary insufficiency (increased ACTH):

This is 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.

 

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

 

Symptoms:

– 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

 

Treatment:

– 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