5: Adrenal gland disorders - physiology, Addison's, Cushing's, primary aldosteronism

Question 1

What are the two parts of the adrenal gland?

Answer 1

Adrenal cortex

Adrenal medulla

Question 2

What are the three zones of the adrenal cortex?

Answer 2

Zona glomerulosa

Zona fasciculata

Zona reticularis

Question 3

What hormone is produced in the zona glomerulosa of the adrenal cortex?

Answer 3

Mineralocorticoids

e.g aldosterone

Question 4

What hormones are produced in the zona fasciculata of the adrenal cortex?

Answer 4

Glucocorticoids

cortisol

Question 5

What hormones are produced in the zona reticularis of the adrenal cortex?

Answer 5

Androgens

Question 6

Which cells, found in the adrenal medulla, secrete catecholamines?

Answer 6

Chromaffin cells

Question 7

What is the precursor molecule for steroid hormones?

Answer 7

Cholesterol

Question 8

Which axis regulates cortisol and androgen production by the adrenal cortex?

Answer 8

Hypothalamic-pituitary-adrenal axis

Question 9

What regulates aldosterone secretion by the adrenal cortex?

Answer 9

Renin-angiotensin system

Which is regulated by blood pressure & renal perfusion

Question 10

Corticosteroids bind to which kind of receptor?

Answer 10

Nuclear receptor

to alter transcription of protein

Question 11

What are some

a) cardio
b) metabolic
c) bone and soft tissue

effects of cortisol?

Answer 11

a) Increased BP, cardiac output and renal perfusion

b) Increased blood glucose level, increased lipolysis and proteolysis, central redistribution of fat

c) Reduced serum calcium (inc. rate of onset of osteoporosis), reduced rate of wound healing

Question 12

Cortisol (accelerates / dampens down) the immune response.

Answer 12

dampens down immune response

Question 13

Which physiological processes are corticosteroids used to suppress?

Give examples of specific diseases.

Answer 13

Immune response

so allergic diseases like asthma, eczema and anaphylaxis

Inflammation

so inflammatory diseases like RA, UC and Crohn’s disease

Question 14

In which diseases are exogenous corticosteroids used as a replacement for a deficiency in the body?

Answer 14

Adrenal insufficiency

e.g Addison’s disease (autoimmune reaction resulting in deficiency of cortisol), non-functioning adrenal tumours, non-functioning pituitary tumours

Question 15

Aldosterone is a (glucocorticoid / mineralocorticoid) produced by the adrenal cortex.

What is its function?

Answer 15

mineralocorticoid

Stimulates Na⁺ reabsorption in the distal tubules and collecting ducts, therefore controlling sodium homeostasis and blood pressure via RAAS

Question 16

What is the commonest cause of primary adrenal insufficiency?

Answer 16

Addison’s disease

Also consider Congenital adrenal hyperplasia

Question 17

Apart from Addison’s disease, what else can cause primary adrenal insufficiency?

Answer 17

Congenital adrenal hyperplasia

TB

Malignancy

Question 18

Adrenal insufficiency caused by a problem with the gland itself is (primary / secondary).

Answer 18

primary

Question 19

Addison’s disease is an ___ disease.

Answer 19

autoimmune

Question 20

What is destroyed by autoimmune reaction in Addison’s disease?

Answer 20

Adrenal cortex

Question 21

70% of people with Addison’s disease are positive for what?

Answer 21

Autoantibodies

Question 22

People with Addison’s disease are more likely to have other ___ diseases.

Answer 22

autoimmune

Question 23

What are the features of Addison’s disease?

Answer 23

Anorexia

Weight loss

Pigmentation

Dizziness and hypotension

Abdominal pain, vomiting, diarrhoea

Question 24

What kind of pigmentation is common in people with Addison’s disease?

Answer 24

Buccal pigmentation

Question 25

What will be seen on biochemical tests of people with Addison's disease?

Answer 25

**Hyponatraemia** **Hyperkalaemia** **Hypoglycaemia**

Question 26

Which stimulation test is used to diagnose adrenal insufficiency?

Answer 26

**Synacthen test**

Question 27

In primary adrenal insufficiency, ACTH levels will be very **(high / low)**.

Answer 27

**high** causing skin pigmentation

Question 28

In secondary adrenal insufficiency, what will the patient's ACTH be like? Will they be pigmented?

Answer 28

**Normal or low** **No pigmentation**

Question 29

Why are aldosterone levels low in people with Addison's?

Answer 29

**Destruction of adrenal cortex**

Question 30

How should Addison's disease be managed?

Answer 30

**IV hydrocortisone** (to replace cortisol) **Fludrocortisone** (to replace aldosterone)

Question 31

What is the maintenance dose of oral hydrocortisone in patients with Addison's disease?

Answer 31

**15-30mg**

Question 32

How many doses of hydrocortisone (15-30mg) in total are given to patients with Addison's disease?

Answer 32

**Two** to mimic diurnal rhythm if you give after 6pm patient will be insomniac

Question 33

What must be monitored in patients being treated for Addison's disease?

Answer 33

**Blood pressure** **Potassium level**

Question 34

As in diabetes, patients with Addison's disease must be educated on how to take their medication under which circumstance?

Answer 34

**Sick days**

Question 35

What is the emergency presentation of Addison's disease?

Answer 35

**Addisonian crisis**

Question 36

What causes **primary adrenal insufficiency?**

Answer 36

Disease of adrenal gland itself

Question 37

What causes **secondary adrenal insufficiency**?

Answer 37

**Problems with hypothalamic-pituitary axis** **Iatrogenic** (surgery, radiotherapy) **WITHDRAWAL OF HIGH DOSE STEROID THERAPY**

Question 38

What is the most common cause of secondary adrenal insufficiency?

Answer 38

**Withdrawal of high dose steroids**

Question 39

How does high dose steroid cessation cause secondary adrenal insufficiency?

Answer 39

**As they are similar to cortisol, they inhibit CRH/ACTH release by negative feedback and the adrenal glands atrophy** So when you take the patient off them, their adrenal glands aren't capable of producing enough cortisol \> Insufficiency

Question 40

Are patients with secondary adrenal insufficiency pigmented?

Answer 40

**No** normal / low ACTH

Question 41

What happens to aldosterone secretion in secondary adrenal insufficiency?

Answer 41

**Nothing** no adrenal cortex damage

Question 42

How is secondary adrenal insufficiency treated?

Answer 42

**Hydrocortisone** (cortisol replacement)

Question 43

Patients with central obesity, i.e lemon on matchsticks appearance, should tip you off to which adrenal disorder?

Answer 43

**Cushing's disease/syndrome**

Question 44

What causes Cushing's syndrome?

Answer 44

**Excess cortisol secretion by adrenal cortex**

Question 45

What are the features of Cushing's syndrome?

Answer 45

**Central obesity, abdominal striae** **Acne** **Moon face** **Hypertension** **Easy bruising** **Proximal myopathy** i.e lots

Question 46

Cushing's syndrome is either ACTH ___ or \_\_\_.

Answer 46

**dependent** , **independent**

Question 47

What causes 70% of Cushing's disease?

Answer 47

**Pituitary adenoma** producing ACTH

Question 48

As Cushing's disease is caused by cortisol excess, how is it diagnosed?

Answer 48

**Dexamethasone suppression test**

Question 49

If a patient **passes** a low dose dexamethasone suppression test, they don't have Cushing's. If a patient **fails** the test, what is done next?

Answer 49

**More tests** e.g overnight dexamethasone suppression test

Question 50

What is the commonest cause of **cortisol excess**?

Answer 50

**Prolonged high dose steroid therapy** causes atrophy of ACTH-producing cells and adrenal atrophy must be weaned off steroids otherwise they will develop adrenal insufficiency

Question 51

Patients presenting with hypertension under the age of 40 should always be checked for ___ adrenal disorders.

Answer 51

**secondary**

Question 52

Which adrenal diseases produce a) hypotension b) hypertension with hyperglycaemia c) hypertension with hypokalaemia?

Answer 52

a) Adrenal insufficiency b) Cushing's disease c) Conn's syndrome / primary aldosteronism

Question 53

What is primary aldosteronism?

Answer 53

Excess aldosterone production unregulated by renin-angiotensin system

Question 54

Why does primary aldosteronism cause hypokalaemia?

Answer 54

**Loads of K+ excreted by kidneys**

Question 55

As it causes hypertension, many patients with Conn's syndrome die of ___ disease.

Answer 55

**cardiovascular**

Question 56

What are the main features of primary aldosteronism?

Answer 56

**Hypertension** **Hypokalaemia** **Metabolic alkalosis** (as H+ ions leave with potassium)

Question 57

What are the two main causes of primary aldosteronism?

Answer 57

**Adrenal adenoma** - CONN'S SYNDROME ## Footnote **Bilateral adrenal hyperplasia**

Question 58

Primary aldosteronism can be caused by mutations for which channels?

Answer 58

**Potassium channels**

Question 59

Which tests are used first and second-line to diagnose primary aldosteronism?

Answer 59

**1. Aldosterone / renin ratio (A/R), abnormal if raised** **2. Saline suppression test** give patient 2L saline IV, if aldosterone doesn't drop by at least 50% then they have PA

Question 60

Once you have confirmed that a patient has primary aldosteronism, how do you find out the cause?

Answer 60

**Adrenal CT scan**

Question 61

Which scan shows the metabolic activity of cells and can be combined with a CT to confirm primary aldosteronism?

Answer 61

**PET-CT scan** Gold-standard for diagnosing primary aldosteronism

Question 62

If a **PET-CT scan** shows adrenal hyperplasia to be a) unilateral (or an adrenal adenoma) b) bilateral how is it treated?

Answer 62

**a) Unilateral adrenalectomy** **b) Aldosterone antagonists**

Question 63

What is an aldosterone antagonist used to treat primary aldosteronism caused by bilateral adrenal hyperplasia?

Answer 63

**Spironolactone**

Question 64

Apart from PET-CT, what test can be done to confirm if adrenal disease causing primary aldosteronism is unilateral or bilateral?

Answer 64

**Adrenal vein sampling**