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Year 3 > Cushing's syndrome (E&M) > Flashcards

Cushing's syndrome (E&M) Flashcards

1
Q

Define Cushing’s syndrome.

A

Syndrome associated with chronic inappropriate elevations of free circulating cortisol (pathological hypercortisolism from any cause)

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2
Q

How can we classify Cushing’s syndrome?

A
  • ACTH dependent (80%)
    • pituitary adenoma (Cushing’s disease) –> excess ACTH
    • ectopic ACTH (small cell lung cancer, pulmonary carcinoid tumour)
  • ACTH independent (20%)
    • adrenal adenoma (benign)
    • adrenal carcinoma
    • oral steroids - chief cause
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3
Q

Which groups does Cushing’s syndrome happen most commonly in? (2)

A
  • F>M
  • 20-40 years old
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4
Q

What are some risk factors for Cushing’s syndrome? (4)

A
  • exogenous corticosteroid use (most common cause)
  • pituitary adenoma (Cushing’s disease)
  • adrenal adenoma
  • adrenal carcinoma
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5
Q

What else can mimic Cushing’s syndrome? (2)

A
  • excess alcohol consumption (pseudo-Cushing’s)
  • metabolic syndrome (central obesity with insulin resistance and hypertension)
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6
Q

What are the clinical features of Cushing’s syndrome? (16)

A
  • thin, easily bruisable skin with ecchymoses
  • stretch marks (striae)
  • proximal myopathy (muscle weakness)
  • central obesity
  • moon face
  • facial plethora
  • intracapsular fat pad - buffalo neck hump
  • fatigue
  • acne & hirsutism
  • hyperpigmentation (if ACTH-dependent)
  • lethargy & depression
  • osteopenia & osteoporosis
  • hypertension
  • hyperglycaemia
  • gonadal dysfunction & low libido
  • increased susceptibility to infection
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7
Q

What are the discriminatory features of Cushing’s syndrome? (6)

A
  • bruising and thin skin
  • purple striae >1cm wide
  • myopathy (proximal)
  • DM, HTN, osteoporosis at young age
  • facial plethora
  • supraclavicular fat pads
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8
Q

What are the first-line, high sensitivity investigations for Cushing’s syndrome? (4)

A
  • late-night salivary cortisol
  • 1mg overnight low-dose dexamethasone suppression test
  • 24h urinary free cortisol
  • high-dose dexamethasone suppression test
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9
Q

What is the first-line and most sensitive test for diagnosing Cushing’s syndrome?

A

Low-dose (1mg) overnight dexamethasone suppression test

  • patient given 1mg dexamethasone at 11pm and plasma cortisol measured the following morning at 8am
  • Cushing’s syndrome - failure to suppress morning cortisol spike (>50nmol/L)
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10
Q

What does late night salivary cortisol or 24-hour free cortisol show in Cushing’s syndrome?

A

Elevated

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11
Q

What test can we use to distinguish between adrenal Cushing’s syndrome, Cushing’s disease and ectopic ACTH production?

A

High-dose dexamethasone suppression test

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12
Q

How does the high-dose dexamethasone suppression test work in Cushing’s syndrome?

A

High-dose dexamethasone inhibits excess ACTH production from pituitary, but autonomous cortisol production from adrenals is not inhibited

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13
Q

What are the results of high-dose dexamethasone suppression test in different forms of Cushing’s syndrome?

A
  • Cushing’s syndrome due to adrenal adenoma/carcinoma/steroids: ACTH suppressed, cortisol NOT suppressed
  • Cushing’s disease (pituitary adenoma): ACTH AND cortisol suppressed
  • ectopic ACTH: NEITHER ACTH nor cortisol suppressed
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14
Q

What do we check for in bloods for Cushing’s syndrome? (4)

A
  • hyperglycaemia
  • hypokalaemia - ectopic ACTH production due to SCLC
  • hypernatraemia
  • metabolic alkalosis - increased H+ excretion and HCO3- reabsorption
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15
Q

What might ABG show in Cushing’s syndrome?

A

Metabolic alkalosis - increased H+ excretion and HCO3- reabsorption

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16
Q

What do tests show for ACTH-dependent Cushing’s syndrome?

A
  • high plasma ACTH
  • pituitary MRI if Cushing’s disease suspected
  • CXR and bronchoscopy if SCLC suspected
  • high-dose dexamethasone suppression test negative - both cortisol and ACTH suppressed
17
Q

How do we differentiate between pituitary and ectopic ACTH secretion in Cushing’s syndrome?

A
  • petrosal sinus sampling of ACTH
  • CRH stimulation - cortisol rises if pituitary, no change if ectopic/adrenal
18
Q

What do tests show for ACTH-independent Cushing’s syndrome (adrenal cause)?

A
  • low plasma ACTH
  • CT/MRI of adrenals
  • high-dose dexamethasone suppression test = ACTH suppressed, cortisol not suppressed
19
Q

How can we differentiate between Cushing’s and pseudo-Cushing’s?

A

Insulin stress test

20
Q

How can we differentiate between primary and secondary aldosteronism?

A

Look at renin levels - if renin is high, then a secondary cause is more likely e.g. renal artery stenosis

Cushing’s syndrome = plasma renin would not be high

21
Q

What are some differential diagnoses for Cushing’s syndrome? (2)

A
  • obesity
  • metabolic syndrome
  • (both lack: facial plethora, unexplained bruising, proximal myopathy, violaceous striae, supraclavicular fullness and osteoporotic fractures)
22
Q

How do we manage Cushing’s syndrome due to excess steroid use?

A

Discontinue steroids / use lower dose / use steroid-sparing agent

23
Q

What medical management is there for Cushing’s syndrome?

A

Steroidogenesis inhibitors: consider prior to surgery, only short-term use for severe hypercortisolism

  • metyrapone (11b-hydroxylase inhibitor –> N&V, hypoadrenalism)
  • ketoconazole (17a-hydroxylase inhibitor –> N&V, alopecia, liver damage)

(Dopamine agonist - cabergoline, glucocorticoid receptor antagonist - mifepristone, somatostatin analogue - pasireotide etc)

24
Q

How do we manage Cushing’s disease?

A
  • transsphenoidal pituitary adenomectomy
  • consider post-op corticosteroid replacement (hydrocortisone) and hormonal replacement (pituitary hormones)
  • if unsuccessful, try medical therapies alone or pituitary radiotherapy or bilateral adrenalectomy (with hormone replacement)
25
Q

How do we manage Cushing’s syndrome due to adrenal adenoma/carcinoma?

A

Adrenalectomy (unilateral if possible)

26
Q

How do we manage ectopic ACTH Cushing’s syndrome?

A
  • surgical resection with bridging medical therapy +/- chemo and radiotherapy
  • second-line: bilateral adrenalectomy with replacement
  • third-line: medical therapy only
27
Q

What are some complications of Cushing’s syndrome? (9)

A
  • diabetes
  • osteoporosis (excess bone exposure to glucocorticoids = decreased osteoblast activity, increased osteoclast activity)
  • hypertension
  • predisposed to infections
  • adrenal insufficiency (secondary to adrenal suppression)
  • CVD
  • nephrolithiasis
  • Nelson syndrome (after bilateral adrenalectomy - progression of pituitary adenoma –> intracranial mass effect and elevated ACTH)
  • treatment-related central hypothyroidism/GH deficiency/adrenal insufficiency/hypopituitarism/hyponatraemia/hypogonadism/diabetes insipidus
28
Q

Describe the prognosis of Cushing’s syndrome.

A
  • untreated disease has poor survival rate of 50% at 5 years
  • patients may have decreased QoL after treatment

Year 3 (145 decks)

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