D&E - Adrenal Axis Flashcards
Describe the adrenal axis.
- Hypothalamus secretes CRH.
- Cortisol stimulates anterior pituitary to release ACTH.
- ACTH stimulates the adrenal glands to release cortisol.
What are the actions of cortisol within the body?
- increased alertness
- inhibits the immune system
- inhibits bone formation
- raised blood glucose
- increases metabolism
What is adrenal insufficiency?
The condition in which the adrenal glands do not produce enough steroid hormones, cortisol and aldosterone.
What is Addison’s disease?
Adrenal insufficiency when the adrenal glands have been damaged, resulting in reduce cortisol and aldosterone secretion.
What are the causes of secondary adrenal insufficiency?
Inadequate ACTH release from the pituitary:
- pituitary adenomas
- surgery to the pituitary
- trauma
What is tertiary adrenal insufficiency?
Inadequate CRH release by the thalamus, usually a result of taking long-term oral steroids.
When exogenous steroids are suddenly withdrawn, the hypothalamus is not able to adequately replace with endogenous steroids.
This is why long-term steroids must be tapered slowly, to allow the adrenal axis to regain normal function.
Presentation of adrenal insufficiency.
- fatigue
- muscle weakness
- muscle cramps
- dizziness and fainting
- thirst and craving salt
- weight loss
- abdominal pain
- depression
- reduced libido
What are the signs of adrenal insufficiency, and why do these occur?
Bronze hyperpigmentation of the skin due to excess ACTH. ACTH stimulates melanocytes to produce melanin.
Hypotension.
What are the biochemical findings in adrenal insufficiency?
- hyponatraemia
- hyperkalaemia
- hypercalcaemia
- hypoglycaemia
- raised creatinine and urea (urea > creatinine = dehydration)
Which autoantibodies are associated with Addison’s disease?
- adrenal cortex antibodies
- 21-hydroxylase antibodies
What is the diagnostic test for pituitary insufficiency?
Short Synacthen test / ACTH stimulation test.
A dose of synthetic ACTH (Synacthen) is given in the morning, with blood cortisol checked before and after (30m, 60m) the dose.
The cortisol level should at least double in a healthy individual.
How is adrenal insufficiency managed?
- hydrocortisone to replace cortisol
- fludrocortisone to replace aldosterone
Patients are given a steroid card, ID tag and emergency letter to alert emergency services that they depend on steroids for life.
How are steroid doses altered during acute illness, for patients with adrenal insufficiency?
Doses are doubled during acute illness, to match the normal steroid response to illness.
What is Addisonian crisis?
An acute presentation of severe adrenal insuffieincy, where the absence of steroid hormones leads to life threatening emergency.
Presentation of Addisonian crisis?
- reduced consciousness
- hypotension
- hypoglycaemia
- hyponatraemia
- hypokalaemia
What are the triggers for Addisonian crisis?
- infection
- trauma
- acute illness
How should Addisonian crisis be managed?
- ABCDE approach to initial assessment
- IM hydrocortisone
- IV fluids
- correct hypoglycaemia (e.g. IV dextrose)
- careful monitoring of electrolytes and fluid balance
Define:
a) Cushing’s syndrome
b) Cushing’s disease
a) prolonged elevated levels of cortisol within the body.
b) prolonged elevated levels of cortisol within the body, secondary to an ACTH-secreting pituitary adenoma, stimulating excess cortisol release from the adrenal glands.
Causes of Cushing’s syndrome.
CAPE
Cushing’s disease (pituitary adenoma ACTH releasing).
Adrenal adenoma (adrenal tumour secreting excess cortisol).
Paraneoplastic syndromes
Exogenous steroids (most common)
Presentation of Cushing’s syndrome.
- anxiety
- depression
- insomnia
- round face
- central obesity
- abdominal striae
- hirsutism
- easy bruising
- hyperpigmentation of skin
What are the metabolic effects of Cushing’s syndrome?
- hypertension
- cardiac hypertrophy
- T2DM
- dyslipidaemia
- osteoporosis
Which paraneoplastic syndromes may cause Cushing’s syndrome?
Small cell lung cancer commonly causes ectopic ACTH release, stimulating excessive cortisol release from the adrenal glands.
How is Cushing’s syndrome diagnosed?
Dexamethasone suppression test to diagnose Cushing’s syndrome caused by a problem inside the body.
What is the normal physiological response to the dexamethasone suppression test?
Dexamethasone induces negative feedback upon the hypothalamus, reducing CRH output.
It also induces negative feedback on the anterior pituitary, reducing ACTH output.
Low CRH and ACTH output causes a low cortisol output by the adrenal glands.
A lack of cortisol suppression in response to dexamethasone suggests Cushing’s syndrome.
What test would be used to:
a) exclude Cushing’s syndrome?
b) confirm suspected Cushing’s syndrome?
c) determine the cause of Cushing’s syndrome?
a) low-dose overnight test
b) low-dose 48-hour test
c) high-dose 48-hour test
Describe the low-dose overnight, dexamethasone suppression test.
1mg dexamethasone is given at 10pm, and cortisol is checked at 9am the following morning.
A normal result is that the cortisol level is suppressed.
If cortisol is not suppressed, Cushing’s syndrome cannot be excluded.
Describe the low dose 48-hour, dexamethasone suppression test.
0.5mg dexamethasone is taken QDS, starting at 9AM on day 1.
Cortisol is checked on day 1 (before the first dose) and day 3 (after the last dose).
A normal result is that the cortisol level on day 3 is suppressed.
If cortisol is not suppressed, this indicates Cushing’s syndrome.
Describe the high dose 48-hour, dexamethasone suppression test.
2mg dexamethasone is taken QDS, starting at 9AM on day 1.
Cortisol is checked on day 1 (before the first dose) and day 3 (after the last dose).
The higher dose is enough to suppress the cortisol in Cushing’s syndrome caused by a pituitary adenoma (Cushing’s disease), but not when it is caused by an adrenal adenoma or ectopic ACTH.
Besides dexamethasone suppression testing, how else can Cushing’s syndrome be investigated?
FBC (elevated WCC)
U&Es (hypokalaemia if adrenal adenoma is also secreting aldosterone).
MRI brain (pituitary adenoma)
CT chest (small cell lung cancer)
Treatment of Cushing’s disease?
Transphenoidal removal of pituitary adenoma.
Treatment of Cushing’s syndrome secondary to adrenal tumour?
Laparoscopic removal of adrenal tumour.
What is a phaeochromocytoma?
A tumour of the Chromaffin cells of the adrenal glands that secretes excessive adrenaline.
Give the genetic associations of phaeochromocytomas.
- MEN 2
- neurofibromatosis 2
- Von Hippel-Lindau disease
Presentation of phaeochromocytoma.
- anxiety
- sweating
- headache
- tremor
- palpitations
- hypertension
- tachycardia
Symptoms are usually intermittent, as adrenaline is secreted in bursts in phaeochromocytomas.
What are the complications of untreated phaechromocytomas?
- hypertensive crisis
- encephalopathy
- hyperglycaemia
- pulmonary oedema
- cardiac arrhythmias
- death
How is phaechromocytoma diagnosed?
- plasma free metanephrines*
- 24-hour urine catecholamines
CT or MRI to look for tumour.
*breakdown product of adrenaline
Why is serum catcholamine or serum adrenaline not useful in diagnosing phaeochromocytomas?
Catecholamines and adrenaline have a very short half life in the blood.
What is the management of phaeochromocytomas?
Alpha blockers (phenoxybenzamine or doxazosin) initiated at diagnosis.
Beta blockers when established on alpha blockers.
Only definitive management is surgical removal of the tumour.
What is hyperaldosteronism?
Excess levels of aldosterone.
Conn’s syndrome is an adrenal adenoma that produces too much aldosterone.
What are the actions of aldosterone?
- increase sodium reabsorption from the distal tubule
- increase potassium secretion from the distal tubule
- increase hydrogen secretion from the collecting ducts
What is primary hyperaldosteronism?
Adrenal glands are directly responsible for producing too much aldosterone.
Serum renin will be low as the high blood pressure suppresses it.
What are the causes of primary hyperaldosteronism?
Bilateral adrenal hyperplasia
Adrenal adenoma secreting aldosterone (Conn’s syndrome)
Familial hyperaldosteronism
What is secondary hyperaldosteronism?
Excessive renin release stimulating the release of excessive aldosterone, due to disproportionately lower blood pressure in the kidneys.
What are the causes of secondary hyperaldosteronism?
Disproportionately lower blood pressure in the kidneys causes excessive renin release:
- renal artery stenosis
- heart failure
- liver cirrhosis and ascites
How is hyperaldosteronism screened for?
Aldosterone-to-renin ratio (ARR):
High aldosterone and low renin indicates primary hyperaldosteronism.
High aldosterone and high renin indicates secondary hyperaldosteronism.
How is hyperaldosteronism investigated?
- ACR
- blood pressure (hypertension)
- U&Es (hypokalaemia; hypernatraemia)
- VBG (metabolic alkalosis)
To find the underlying cause:
- CT / MRI for adrenal tumour
- renal artery imaging
- adrenal vein sampling
How is hyperaldosteronism managed?
Aldosterone antagonists to medically manage:
- eplerenone
- spironolactone
Surgical management includes removal of adrenal adenomas (Conn’s syndrome) and percutaneous renal artery angioplasty to treat renal artery stenosis.
