Endocrine: Adrenals

Question 1

What does the adrenal medulla secrete?

Answer 1

Adrenaline/noradrenaline. This is important for the body’s short term response to stress (ie fight or flight) This is in response to the sympathetic nervous system.

Question 2

What does the adrenal cortex secrete?

Answer 2

This is more concerned with the body’s long term stress response. Stress causes the release of CRH from the hypothalamus which then causes the release of ACTh from the pituitary gland. This causes the release of cortisol and androgen.
Aldosterone is also released from here but is controlled by the RAAS system

Question 3

What effects does aldosterone have on the balance of sodium and pottassium?

Answer 3

More aldosterone causes pottassium excretion and sodium reabsorption.

Question 4

What are the three areas of the adrenal cortex and what do they secrete?

Answer 4

Zona Glomerulosa - aldosterone
Zona fasiculatis - 
cortisol 
Zona reticularis 
- adrenal androgens

Question 5

What can cause adrenal insufficiency?

Answer 5

Primary
- Addisons
- Congenital adrenal hyperplasia
- Adrenal TB/Malignancy
Secondary
- Iatrogenic (too much exogenous steroid leads to atrophy of the adrenals )
- Pituiatry and hypothalmic problems of CRH/ACTH secretion

Question 6

What autoantibodies are associated with addisons disease?

Answer 6

21 Hydroxylase antibodies (positive in 70% of people with addisons)

Question 7

What other conditions is addisons disease associated with?

Answer 7

Type 1 diabetes
Autoimmune thyroid disease
Pernicious anaemia

Question 8

What is the commonest cause of primary adrenal insufficiency?

Answer 8

Addisons disease

Question 9

What are the features of addisons disease?

Answer 9

Anorexia/weight loss 
Fatigue 
Dizziness and low blood pressure 
Abdominal pain, vomiting and diarrhoea 
Skin pigmentation

Question 10

What are the sodium and pottasium levels like in addisons disease?

Answer 10

Low sodium 
High pottassium (due to deficiency of mineralocorticoids)

Question 11

In addisons, are people hypo or hyper glycaemic?

Answer 11

Hypoglycaemic

Question 12

Why is the skin pigmented in addisons disese?

Answer 12

Increases ACTH causes skin pigmentation

Question 13

What test is done is you suspect addisons? What are the normal and abnormal results of this test?

Answer 13

Short synacthen test
- Measure the plasma cortisol levels before and 30 minutes and 60 minutes after an ACTH injection.
- Normal results would be:
Normal: Less than 170 per litre before ACTH and then over 580 after ACTH.
In patients with addisons there is no rise in cortisol after ACTH.

Question 14

What is Autoimmune polyendocrine/polyglandular syndrome type 1?

Answer 14

A condition whereby multiple endocrine glands fail due to autoimmunity. It is an autosomal recessive disorder located on chromosome 21. The three main components are 1. Hypoparathyroidism 2. Chronic mucocutaneous candida
3. Autoimmune adrenal insufficiency

Question 15

What are the renin and aldosterone levels like in addisons disease?

Answer 15

Renin is high but aldosterone is low

Question 16

What is maintenence treatment for addisons disease?

Answer 16

15 - 30mg of hydrocortisone daily in divided doses (trying to mimic diurnal variation - try not to give at night as can cause insomnia)
Fludricortisone (pottasium and blood pressure need to be carefully monitored)

Question 17

What advice should people with addisons disease who take steroids be given about sick day rules/exercise?

Answer 17

Double dose in febrile illness/injury or stress (IM if vomiting)
Add 5 - 10mg if strenous activity

Question 18

What signs and symptoms would make you suspicious of an addisonian crisis?

Answer 18

Confusion 
lethargy 
Fever
Hyperkalaemia 
Hypercalcaemia 
Hypoglycaemia 
Hyponatremia 
Hypotension 
Hypothyroid 
Sever vomiting and diarrhoea resulting in dehydration

Question 19

What is an adrenal crisis? What can cause/precipitate it?

Answer 19

Insufficient levels of cortisol due to untreated addisons, sudden cessation of steroids, bleeding into the adrenals (seen in meningitis causes by neisseria meningitidis), congenital adrenal hyperplasia

Question 20

What is the investigation and management of an adrenal crisis?

Answer 20

1. Take bloods for cortisol and ACTH
2. IV hydrocortison succunate 100mg STAT
3. IV fluids
   Monitor blood glucose and look for underlying cause eg infection. Fludricortisone may be needed later on dependant on the underlying cause.

Question 21

What causes secondary adrenal insufficiency?

Answer 21

1. Exogenous steroid use.

2. Pituitary/hypothalamic tumours

Question 22

What are the causes of cushings syndrome?

Answer 22

ACTH dependant 
- Pituitary adenoma 
- Ectopic ACTHH 
- Ectopic CRH
ACTH independent 
- Adrenal adenoma 
- Adrenal carcinoma 
- Nodular hyperplasia 
- Exogenous steroids

Question 23

What is cushings syndrome?

Answer 23

The clinical syndrome of glucocorticoid excess and loss of normal feedback mechanisms.

Question 24

What is cushings disease?

Answer 24

Excess glucocorticoid due to a pituitary adenoma secreting ACTH and causing bilateral adrenal hyperplasia

Question 25

What kind of tumours commonly produce ACTH?

Answer 25

Small cell lung cancer (these patients will also be pigmented due to ACTH)

Question 26

How do you diagnose and classify cushings disease?

Answer 26

1. Establish cortisol excess
   - Overnight dexamethasone suppression test (can be done as an outpatient) and involves giving the patient 1mg dexamethasone at midnight and then test cortisol in the morning. If this is normal then there has been negative feedback from ACTH is response to the dexamethasone. In cushings syndrome this will be raised.
   - 24 urinary free cortisol
   If these 1st line tests are abnormal then the next test is the dexamethasone supression test. In this you give 0.5mg dexamethasone every 6 hours for 2 days. You then measure the cortisol levels before and after. In cushings there is a failure to suppress cortisol release.

Question 27

In normal individuals at what time of day are cortisol levels highest and lowest?

Answer 27

Lowest at midnight

Highest in the early morning ( a couple of hours before wakening)

Question 28

What tests are used to determine the cause of cushings syndrome?

Answer 28

Plasma ACTH - If low/undetectable then it is likely the cause is coming from the adrenal glands. Therefore a CT of the adrenals is needed. If there is no mass seen then adrenal vein sampling can be done.
If ACTH is detectable then the cause is pituitary or ectopic. These can be distinguished by the high dose dexamethasone supression test where you give 2mg of dexamethsone every 6 hours for 2 days. Partial or complete supression indicates cushings disease (pituitary adenoma) as there is still some feedback control. No supression indicates an ectopic cause.
If cushings disease is likely then an MRI of the pituitary is needed. If an ectopic is thought to be the cause then a CT chest, abdo, pelvis is needed.

Question 29

If you have a young person with resistant hypertension and hypokalaemia what diagnosis would you consider?

Answer 29

Primary aldosteronism

Question 30

What is primary hyperaldosteronism?

Answer 30

Excess production of aldosterone , independant of the RAAS. This causes sodium and water retention and decreases renin release. This causes symptoms of hypertension, hypokalaemia, and alkalosis. This is most often caused by an aldosterone producing adenoma (Conn’s syndrome) but can be caused by biltaeral hyperplasia or an andrenal carcinoma.

Question 31

How do you make a diagnosis of primary aldosteronism?

Answer 31

1. Confirm aldosterone excess
   - Measure aldosterone: renin ratio
   - In ratio raised then saline supression test. Failure of plasma aldosterone to supress by 50% with 2 litres of normal saline confirms that there is primary aldosteronism
2. Confirm subtype
   - Adrenal CT to look for adenoma
   - Adrenal vein sampling.

Question 32

How do you treat conns syndrome?

Answer 32

Unilateral laprascopic adrenalectomy - this cures hypokalaemia and hypertension

Question 33

How do you treat bilateral adrenal hyperplasia?

Answer 33

MR antagonists (spironolactone or eplerenone)

Question 34

What is a phaemochromocytoma?

Answer 34

Catecholamine producing tumours that arise from sympathetic paraganglia cells. they are collection of adrenalin secreting chromaffin cells and are mostly found in the adrenal medulla.

Question 35

What electrolyte abnormalities do you see in addisons disease?

Answer 35

Hyperkalaemia
Hyperuricaemia
Hypoglycaemia

Question 36

What test do you do to confirm a diagnosis of addisons disease?

Answer 36

Short Synacthen test