Cushings Syndrome Flashcards
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
3 - 40 million
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?
- equal risk
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
3 - 20-50
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
3 - corticotrophin releasing hormone
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
1 - adrenocorticotropic hormone
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
1 = zona glomerulosa (outermost layer)
2 = zona fasciculata (middle layer)
3 = zona reticularis (innermost layer)
- the deeper you get the sweeter it gets
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
1 - mesoderm
- medulla = neural crests
Which 2 of the following does the medulla secrete?
1 - catecholamines (adrenaline and noradrenaline)
2 - corticosteroids
3 - enkephalins (involved in pain inhibition)
4 - mineralcorticoids
1 - catecholamines (adrenaline and noradrenaline)
3 - enkephalins (involved in pain inhibition)
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
2 - chromaffin cells
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
1 - cholesterol
- forms the backbone of all steroids
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
4 - noradrenaline
- secreted by the medulla and not the cortex
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?
- mutations/defects in any of these enzymes can lead to pathology
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
- glucocorticoids
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
2 - 9am
- peak is typically 35-45 minutes after waking, but 9am is the standard peak
- levels drop in the evening
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
3 - profession and hours
- shift patterns alter circadian rhythm
What is the primary cause of elevated cortisol in the body?
1 - pituitary adenoma
2 - exogenous steroids
3 - adrenal adenoma
4 - hypothalamus cortisol toxicity
2 - exogenous steroids
- 80% of endogenous causes is due to pituitary adenoma
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?
- raised levels
- increased ACTH means the issue is secondary and not a problem with the adrenal gland
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
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
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?
- low or normal levels of ACTH
- issue is not caused by pituitary gland
- likley to due to adenoma of the adrenal gland
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
2 - adrenal tumour
4 - long standing steroid therapy
- this is most common
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
5 - weight loss
- typically causes central obesity
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
1 - hypotension
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
4 - abdomen
- insulin increases lipoprotein lipase that signals adipocytes in abdomen and bum to take up more lipids
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?
- 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
Does excessive cortisol levels cause hyper or hypokalaemia?
- hypokalaemia
- cortisol can bind to the mineralocorticoid receptor on the collecting tubule, promoting K+ excretion and Na+ reabsorption
Does excessive cortisol levels cause metabolic acidosis or alkalosis?
- metabolic alkalosis
- cortisol can bind to the mineralocorticoid receptor on the collecting tubule
- promotes H+ excretion and HCO3- reabsorption that lowers pH
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
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
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
4 - all of the above
