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Y3 - Endocrine and metabolic > Cushings syndrome > Flashcards

Cushings syndrome Flashcards

1
Q

What is Cushings’s syndrome?

A

Cushing’s syndrome occurs because of prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids.
The condition is associated with significant morbidity and mortality, therefore rapid diagnosis, and management is essential.

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2
Q

What regulates glucocorticoid production in the body?

A

hypothalamic-pituitary-adrenal axis

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3
Q

What is the pathophysiology of Cushing’s syndrome?

A

Corticotropin-releasing hormone (CRH) is secreted from the hypothalamus. This release is influenced by stress levels, time of day and serum cortisol levels.
CRH travels in the blood and binds to specific receptors in the pituitary gland. This binding causes increased production of adrenocorticotropic hormone (ACTH).
ACTH is released into the bloodstream and travels to the adrenal glands, where it binds to specific receptors on the adrenal cortex.
This binding of ACTH to the receptors stimulates the adrenal cortex to release cortisol into the bloodstream, where it has a wide range of effects (see below).
Increased serum cortisol levels inhibit the production of CRH and ACTH via negative feedback, preventing the overproduction of cortisol.

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4
Q

What are the two types of corticosteroid hormones?

A

1) glucocorticoids e.g. cortisol
2) mineralocorticoids e.g. aldosterone

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5
Q

Where is cortisol produced?

A

in the adrenal glands

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6
Q

What is Cushing’s disease?

A

a pituitary adenoma secretes excessive ACTH which stimulates excessive cortisol from the adrenal glands

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7
Q

What pituitary hormone stimulates the adrenal glands to produce cortisol?

A

adrenocorticotropic hormone (ACTH)

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8
Q

What hypothalamus hormone stimulates the pituitary gland to produce ACTH?

A

CRH

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9
Q

Give 7 presentations associated with Cushing’s syndrome:

A

1) moon face
2) central/truncal obesity
3) abdominal striae
4) enlarged fat pad on the upper back (buffalo hump)
5) proximal limb muscle wasting
6) hirsutism (male pattern of facial hair on women)
7) easy bruising and poor skin healing

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10
Q

In what cases would hyperpigmentation be seen in Cushing’s?

A

raised ACTH e.g. pituitary tumour or ectopic ACTH producing tumour

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11
Q

What is the function of cortisol?

A
  1. The synthesis of glucose from non-carbohydrate sources (known as gluconeogenesis), resulting in increased levels of glucose in the blood.
  2. Promoting the breakdown of proteins, which can result in muscle wasting in chronic states of cortisol elevation
  3. An initial surge in cortisol levels trigger lipolysis, however, chronically elevated cortisol promotes lipogenesis
  4. Inhibition of the production of several inflammatory cytokines causing downregulation of the immune response
  5. Reduction in bone formation (chronically elevated levels of cortisol can result in osteoporosis.)
  6. In high concentrations, cortisol exhibits mineralocorticoid effects, increasing sodium and water retention whilst increasing potassium excretion.
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12
Q

Give 5 metabolic complications associated with Cushing’s:

A

1) hypertension
2) cardiac hypertrophy
3) type 2 diabetes
4) dyslipidaemia
5) osteoporosis

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13
Q

Give 3 mental health complications associated with Cushing’s:

A

1) anxiety and depression
2) insomnia
3) psychosis

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14
Q

Give the 4 causes of Cushing’s syndrome (CAPE):

A

1) Cushing’s disease (pituitary adenoma)
2) adrenal adenoma (secretes XS cortisol)
3) paraneoplastic syndromes e.g. ectopic ACTH secretion
4) exogenous steroids (taking long term steroid medications)

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15
Q

What cancer most commonly produces ectopic ACTH?

A

small cell lung cancer

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16
Q

What is primary adrenal insufficiency?

A

where inadequate cortisol from the adrenal glands is produced with a lack of negative feedback to the pituitary

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17
Q

What is the most common cause of Cushing’s syndrome?

A

The most common cause of Cushing’s syndrome is the use of exogenous glucocorticoids (e.g. prednisolone, hydrocortisone).

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18
Q

What 2 types of endogenous Cushing’s syndrome are there?

A
  1. corticotropin- dependent
  2. Corticotropin-independent
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19
Q

What is the most common cause for corticotropin -dependent cushing’s syndrome?

A

Corticotropin-dependent Cushing’s syndrome accounts for 80-85% of cases.2

Pituitary adenomas account for 80% of corticotropin-dependent Cushing’s syndrome (known as Cushing’s disease).

Ectopic production of corticotropin (e.g. small cell lung cancer) accounts for around 20% of corticotropin-dependent Cushing’s syndrome.

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20
Q

What are the 2 most common causes for corticotropin-independent cushing’s syndrome?

A
  1. Adrenal adenomas
  2. Adrenal carcinomas
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21
Q

What are the typical symptoms of Cushing’s syndrome?

A

Weakness
Facial fullness
Weight gain
Low mood
Decreased libido
Polydipsia
Polyuria
Increased frequency of infections

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22
Q

What are the typical clinical findings in Cushing’s syndrome?

A

Truncal obesity
Buffalo hump
Supraclavicular fat pads
Moon facies
Proximal muscle wasting
Hypertension
Oedema
Headaches, visual field defects and galactorrhoea (in Cushing’s disease)

23
Q

What are the relevant lab investigations for Cushing’s syndrome?

A

Full blood count (white cell count may be raised due to glucocorticoid effects)
Urea and electrolytes (hypokalemia, hypernatraemia)

24
Q

What is the main investigation for Cushing’s syndrome?

A

dexamethasone test

25
Q

True or false: the dexamethasone test can be used for all types and causes of Cushing’s

A

false (it can only be used to diagnose Cushing’s syndrome caused by an internal problem - no point using it to diagnose exogenous steroid Cushing’s)

26
Q

Describe the normal effect of dexamethasone on cortisol levels:

A

dexamethasone causes negative feedback on the hypothalamus reducing CRH and therefore ACTH and cortisol (cortisol is suppressed)

27
Q

What result in the dexamethasone test indicates Cushing’s

A

resistance to cortisol suppression

28
Q

What are the three types of dexamethasone tests?

A

1) Low dose overnight test
2) low dose 48hr test
4) high dose 48hr test

29
Q

What is the low dose overnight dexamethasone test used for?

A

screening to exclude Cushing’s syndrome

30
Q

Describe the low dose overnight dexamethasone test:

A

1mg of dexamethasone is given at night and cortisol is checked the following morning

31
Q

What is the low dose 48hr dexamethasone test used for?

A

when Cushing’s is suspected and diagnosis needs to be confirmed

32
Q

Describe the low dose 48hr dexamethasone test:

A

0.5mg of dexamethasone is given every 6 hours for 8 doses and cortisol is checked after this period

33
Q

What is the high dose 48hr dexamethasone test used for?

A

to determine the cause of raised cortisol in patients with confirmed diagnoses of Cushing’s syndrome
This test is indicated if ACTH levels are detectable.

The test is useful for differentiating between pituitary and ectopic ACTH production.

A reduction of basal urinary free cortisol of greater than 90% supports a diagnosis of a pituitary adenoma (ectopic ACTH causes less suppression).

34
Q

Describe the high dose 48hr dexamethasone test:

A

2mg of dexamethasone is given every 6 hours for 8 doses and cortisol is checked after this period

35
Q

In what cause of Cushing’s would cortisol be low on high dose dexaethasone testing?

A

pituitary adenoma

36
Q

What type of variation does levels of ACTH have?

A

Levels of ACTH have a diurnal variation, with the plasma concentration being highest at 8am and lowest at midnigt

37
Q

What does An elevated ACTH suggest?

A

An elevated ACTH level alongside a raised serum cortisol level suggests a diagnosis of ACTH-dependent Cushing’s syndrome

38
Q

What does an undetected ACTH level suggest?

A

An undetectable ACTH level alongside a raised serum cortisol level suggests a diagnosis of ACTH-independent Cushing’s syndrome

39
Q

What is Inferior Petrosal Sinus Sampling?

A

Inferior petrosal sinus sampling
Inferior petrosal sinus sampling (IPSS) is an invasive procedure in which ACTH levels are sampled from veins that drain the pituitary gland.

These ACTH levels are compared with peripheral ACTH levels to determine whether a pituitary tumour is responsible for ACTH-dependent Cushing’s syndrome.

This method is used when neuroimaging along with the previous investigations has been insufficient to reach a diagnosis (e.g. no visible lesion on neuroimaging of the pituitary).

40
Q

What is the relevant imaging used to investigate Cushing’s syndrome?

A

MRI of the pituitary: to confirm the presence of an adenoma
CT chest and abdomen: to identify suspected adrenal tumours or other sources of ectopic ACTH production

41
Q

Would ACTH be high or low in adrenal adenomas?

A

Low

42
Q

Would ACTH be high or low in pituitary adenomas?

A

High

43
Q

Would ACTH be high or low in ectopic ACTH production?

A

High

44
Q

Give an alternative to the dexamethasone test:

A

24 hours urinary free cortisol (testing urinary cortisol for 24 hours)

45
Q

What surgery is used to remove pituitary adenomas?

A

trans-sphenoidal removal

46
Q

What management is used when cortisol/ACTH tumours cannot be removed?

A

bilateral adrenalectomy with life-long steroid replacement therapy

47
Q

What is the management for exogenous Cushing’s syndrome?

A

involves reviewing the patient’s current glucocorticoid treatments and reducing doses where possible (often with steroid-sparing immunosuppressive agents).

48
Q

What medical management can be used for endogenous Cushing’s syndrome?

A

Ketoconazole, metyrapone and mitotane all directly inhibit glucocorticoid synthesis and secretion in the adrenal gland.7

As a result, these medications can be used to temporarily reduce glucocorticoid levels to help prepare the patient for definitive therapy.

In some cases, these medications can be used long-term for patients who are too unfit to undergo definitive surgical management.

49
Q

Name a common complication of bilateral adrenalectomy:

A

Nelson’s syndrome

50
Q

What is Nelson’s syndrome?

A

development of an ACTH producing pituitary tumour after removal of both adrenal glands with the lack of cortisol resulting in a lack of negative feedback to the pituitary gland, causing tumour development

51
Q

Give 3 presentations associated with Nelson’s syndrome:

A

1) skin pigmentation
2) bitemporal hemianopia
3) symptoms associated with lack of other pituitary hormones

52
Q

Name a drug that reduces cortisol:

A

metyrapone

53
Q

Name 5 complications of Cushing’s syndrome?

A

Hypertension
Diabetes
Obesity
Metabolic syndrome
Osteoporosis

Y3 - Endocrine and metabolic (20 decks)

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