Cushings Syndrome

Question 1

What is the estimated prevalence of cushings syndrome, which is a syndrome caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids?

1 - 4 million
2 - 14 million
3 - 40 million
4 - 140 million

Answer 1

3 - 40 million

Question 2

Cushings syndrome is a syndrome caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids. Is this more common in men or women?

Answer 2

• equal risk

Question 3

Cushings syndrome is a syndrome caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids. What age is this most common?

1 - 15-30
2 - 20-30
3 - 20-50
4 - >55

Answer 3

3 - 20-50

Question 4

The 3 main components that make up the Hypothalamic-pituitary-adrenal (HPA) axis are the hypothalamus, pituitary gland and adrenal gland. What does the hypothalamus secrete to stimulate the pituitary gland?

1 - adrenocorticotropic hormone
2 - thyrotropin releasing hormone
3 - corticotrophin releasing hormone
4 - thyroxine

Answer 4

3 - corticotrophin releasing hormone

Question 5

The 3 main components that make up the Hypothalamic-pituitary-adrenal (HPA) axis are the hypothalamus, pituitary gland and adrenal gland. What does the pituitary gland secrete to stimulate the adrenal gland?

1 - adrenocorticotropic hormone
2 - thyrotropin releasing hormone
3 - corticotrophin releasing hormone
4 - thyroxine

Answer 5

1 - adrenocorticotropic hormone

Question 6

The adrenal gland is made up of 2 key parts, the adrenal cortex (makes up 80-90%) and the medulla (makes up 10-20%). The adrenal cortex can be further divided into 3 parts. Label the image below with the names provided:

• zona glomerulosa
• zona reticularis
• zona fasciculata

Answer 6

1 = zona glomerulosa (outermost layer)
2 = zona fasciculata (middle layer)
3 = zona reticularis (innermost layer)

• the deeper you get the sweeter it gets

Question 7

The adrenal gland is made up of 2 key parts, the adrenal cortex and medulla. Embryonically, where does the adrenal cortex originate from?

1 - mesoderm
2 - ectoderm
3 - endoderm
4 - neural crests

Answer 7

1 - mesoderm
- medulla = neural crests

Question 8

Which 2 of the following does the medulla secrete?

1 - catecholamines (adrenaline and noradrenaline)
2 - corticosteroids
3 - enkephalins (involved in pain inhibition)
4 - mineralcorticoids

Answer 8

1 - catecholamines (adrenaline and noradrenaline)
3 - enkephalins (involved in pain inhibition)

Question 9

What are the key cells of the adrenal medulla that synthesis and secrete - catecholamines (adrenaline and noradrenaline) and enkephalins (involved in pain inhibition)?

1 - chief cells
2 - chromaffin cells
3 - parietal cells
4 - I cells

Answer 9

2 - chromaffin cells

Question 10

The cortex is stimulated by adrenocorticotropic hormone (released by the pituitary gland), stimulating what molecule that initiates the biosynthesis of the adrenal cortex secretions. What is this molecule?

1 - cholesterol
2 - vitamin B12
3 - folate
4 - LDL

Answer 10

1 - cholesterol
- forms the backbone of all steroids

Question 11

The cortex is stimulated by adrenocorticotropic hormone (released by the pituitary gland), stimulating cholesterol that initiates the biosynthesis of the adrenal cortex secretions. Which of the following is NOT a secretion of the adrenal cortex?

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]
4 - noradrenaline

Answer 11

4 - noradrenaline
- secreted by the medulla and not the cortex

Question 12

The image below shows how the adrenal gland is stimulated and and then the enzymes and reactions that take place to synthesise and secrete:

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]

Why is it important to understand these pathways?

Answer 12

• mutations/defects in any of these enzymes can lead to pathology

Question 13

There are 3 main hormones released by the adrenal gland, namely:

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]

Which of these is key in the following:

• Maintenance of homeostasis during stress (haemorrhage, infection, anxiety)
• Anti-inflammatory
• Energy balance / metabolism (increase and maintain glucose homeostasis)
• Formation of bone and cartilage
• Regulation of blood pressure
• Cognitive function, memory, conditioning

Answer 13

• glucocorticoids

Question 14

In a patient with a normal circadian rhythm with sleep/wake patterns, when would the peak and drop in cortisol be present?

1 - 5am
2 - 9am
3 - 12pm
4 - 6pm

Answer 14

2 - 9am
- peak is typically 35-45 minutes after waking, but 9am is the standard peak
- levels drop in the evening

Question 15

In a patient with a normal circadian rhythm with sleep/wake patterns, cortisol peaks early morning 35-45 minutes after waking and drops in the evening. When assessing a patients adrenal function at baseline, what is an important question to ask the patient and taking into account?

1 - age
2 - sleep history
3 - profession and hours
4 - family history

Answer 15

3 - profession and hours
- shift patterns alter circadian rhythm

Question 16

What is the clinical term given to a patient with excessive cortisol levels?

1 - Addisons disease
2 - Cushings disease
3 - Hashimoto disease
4 - Graves disease

Answer 16

2 - Cushings disease

Question 17

What is the primary cause of elevated cortisol in the body?

1 - pituitary adenoma
2 - exogenous steroids
3 - adrenal adenoma
4 - hypothalamus cortisol toxicity

Answer 17

2 - exogenous steroids
- 80% of endogenous causes is due to pituitary adenoma

Question 18

If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH dependent cushings would we see raised or normal levels of ACTH?

Answer 18

• raised levels
• increased ACTH means the issue is secondary and not a problem with the adrenal gland

Question 19

If a patient presents elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH dependent cushings we would expect to see raised levels of ACTH. Which 2 of the following are most likely to be the 2 main causes of this?

1 - pituitary adenoma
2 - other cells outside of pituitary can create ACTH such as lung cancer
3 - mass in hypothalamus
4 - increase hypersensitivity of adrenal cortex to
adrenocorticotropic hormone

Answer 19

1 - pituitary adenoma
- most common
2 - other cells outside of pituitary can create ACTH such as lung cancer
- common in small cell lung cancer

• both result in adrenal hyperplasia

Question 20

If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH independent cushings would we see raised or normal levels of ACTH?

Answer 20

• low or normal levels of ACTH
• issue is not caused by pituitary gland
• likley to due to adenoma of the adrenal gland

Question 21

If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH independent cushings we would see normal or low level of ACTH. What are the 2 main causes that may be causing this?

1 - increase hypersensitivity of adrenal cortex to
adrenocorticotropic hormone
2 - adrenal tumour
3 - hyperplasia of adrenal cortex
4 - long standing steroid therapy

Answer 21

2 - adrenal tumour
4 - long standing steroid therapy
- this is most common

Question 22

Which of the following is NOT a typical symptom of cushings syndrome?

1 - muscle wasting and think extremities
2 - skin thinning, bruising and striaes
3 - increased risk of fractures
4 - buffalo hump
5 - weight loss
6 - round full moon shaped face
7 - mental disturbances
8 - gonadal dysfunction

Answer 22

5 - weight loss
- typically causes central obesity

Question 23

Which of the following is NOT a typical clinical sign of cushings syndrome?

1 - hypotension
2 - hyperglycaemia
3 - osteoporosis
4 - increased risk of infection and poor wound healing

Answer 23

1 - hypotension

Question 24

If a patient presents elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. Weight gain is a common clinical presentation, where does this weight tend to increase?

1 - limbs
2 - neck and face
3 - chest cuainsg gynaecomastia
4 - abdomen and bum

Answer 24

4 - abdomen
- insulin increases lipoprotein lipase that signals adipocytes in abdomen and bum to take up more lipids

Question 25

If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. Pigmentation can be a common symptom, but only when it is cushings syndrome that is dependent on ACTH. Why is this?

Answer 25

- ACTH activates the pro-opiomelanocortin (POMC) pathway - ACTH binds to the melanocortin 1 receptor on the surface of dermal melanocytes ALSO PRESENT IN BOTH PRIMARY AND SECONDARY ADRENAL INSUFFICIENCY

Question 26

Does excessive cortisol levels cause hyper or hypokalaemia?

Answer 26

- hypokalaemia - cortisol can bind to the mineralocorticoid receptor on the collecting tubule, promoting K+ excretion and Na+ reabsorption

Question 27

Does excessive cortisol levels cause metabolic acidosis or alkalosis?

Answer 27

- metabolic alkalosis - cortisol can bind to the mineralocorticoid receptor on the collecting tubule - promotes H+ excretion and HCO3- reabsorption that lowers pH

Question 28

When investigating a patient with suspected cushing syndrome, what would be the first 2 simple measures that can be done biochemically? 1 - midnight cortisol level measurement 2 - adrenalcorticoid hormone levels 3 - FBC 4 - 24h urine cortisol measurement

Answer 28

1 - midnight cortisol level measurement 4 - 24h urine cortisol measurement

Question 29

When investigating a patient with suspected cushing syndrome, the first 2 simple measures that can be done biochemically include cortisol measurement at midnight and then a 24h urine cortisol measurement. If these are inconclusive we can then do dynamic testing, which is where we can attempt to suppress cortisol using which drug? 1 - Carbimazole 2 - Propylthiouracil 3 - Dexamethasone 4 - Lithium

Answer 29

3 - Dexamethasone - used as a suppression test - similiar structure to cortisol, so if levels are high it should reduce adrenocrticotropin hormone (ACTH) - BUT if it does not lower cortisol levels than the issue is in the adrenal cortex

Question 30

When investigating a patient with suspected cushing syndrome, the first 2 simple measures that can be done biochemically include cortisol measurement at midnight and then a 24h urine cortisol measurement. If these are inconclusive we can then do dynamic testing, which is where we can attempt to suppress cortisol using dexamethasone. What are the 3 protocols that can be used here?

Answer 30

- Overnight Dexamethasone Suppression Test (ONDST) - Low Dose Dexamethasone Suppression Test (LDDST) - High Dose Dexamethasone Suppression Test (HDDST)

Question 31

When investigating a patient with suspected cushing syndrome, the first 2 simple measures that can be done biochemically include cortisol measurement at midnight and then a 24h urine cortisol measurement. If these are inconclusive we can then do dynamic testing, which is where we can attempt to suppress cortisol using dexamethasone. There are 3 protocols that can be used here: - Overnight Dexamethasone Suppression Test (ONDST) - Low Dose Dexamethasone Suppression Test (LDDST) - High Dose Dexamethasone Suppression Test (HDDST) If a cortisol levels decrease in response to HDDST, is this generally diagnostic of a primary or secondary increase in cortisol levels?

Answer 31

- primary cause - specifically linked to cushings disease - caused by pituitary tumour or ectopic ACTH release from another malignancy

Question 32

When investigating a patient with suspected cushing syndrome, the first 2 simple measures that can be done biochemically include cortisol measurement at midnight and then a 24h urine cortisol measurement. If these are inconclusive we can then do dynamic testing, which is where we can attempt to suppress cortisol using dexamethasone. There are 3 protocols that can be used here: - Overnight Dexamethasone Suppression Test (ONDST) - Low Dose Dexamethasone Suppression Test (LDDST) - High Dose Dexamethasone Suppression Test (HDDST) If a cortisol levels decrease in response to HDDST, this generally diagnostic of cushings disease and indicates increased ACTH is due to pituitary tumour or another malignancy. What would be the first imaging of choice in this instance? 1 - ultrasound 2 - X-ray 3 - CT scna 4 - MRI

Answer 32

4 - MRI - need to also request a special MRI to get lots of small slices of pituitary gland as it is small and can be missed by standard head MRIs - CT may be useful if imaging the adrenal glands

Question 33

If a patient has cushing syndrome the treatment is dependent on the cause. If a patient has cushing syndrome that is independent of adrenocorticotrophin hormone (ACTH) due to steroids, should these steroids be stopped immediately?

Answer 33

- no - slowly reduce the steroid - stopping steroids immediately can cause adrenal crisis - look for alternative treatment option

Question 34

If a patient has cushing syndrome the treatment is dependent on the cause. Patients can have raised cortisol that is independent of adrenocorticotrophin hormone (ACTH) or dependent to ACTH. If it is ACTH dependent due to a tumour on the pituitary or adrenal gland, which of the following would be viable treatment options? 1 - transsphenoidal adenectomy (tumour removal from pituitary gland) 2 - adrenalectomy (surgery to remove one or both adrenal glands) 3 - chemotherapy and radiotherapy 4 - all of the above

Answer 34

4 - all of the above