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Finals: Medicine > Cushing's Syndrome > Flashcards

Cushing's Syndrome Flashcards

1
Q

Define Cushing’s syndrome

A

Cushing’s syndrome is caused by prolonged exposure to an excess of glucocorticoids

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2
Q

The cause of excess glucocorticoids may be endogenous or exogenous.

Define the term exogenous

A

The source is derived externally

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3
Q

The cause of excess glucocorticoids may be endogenous or exogenous.

Define the term endogenous

A

The source is derived internally

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4
Q

What is the most common cause of excess glucocorticoids

a) Exogenous
b) Endogenous

A

a) Exogenous

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5
Q

What is the most common cause of Cushing’s syndrome secondary to exogenous glucocorticoid

A

Long term high dose steroid medication

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6
Q

The causes of Cushing’s syndrome may be divided based on location.

Name these groups

A

ACTH dependent - those that are caused by pituitary problem

ACTH independent - those that are independent on the pituitary

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7
Q

What is the most common cause of Cushing’s syndrome secondary to endogenous glucocorticoid

A

ACTH dependent causes e.g. Cushing’s disease

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8
Q

Name 3 causes of ACTH dependent Cushing’s syndrome

A
  • Cushing’s disease
  • Paraneoplastic Cushings
  • Ectopic CRH production
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9
Q

What is the most common cause of ACTH dependent Cushing’s syndrome

A

Cushing’s Disease

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10
Q

Define the term Cushing’s disease

A

Excess glucocorticoid production as a result of a pituitary adenoma secreting excess ACTH.

Accounts for the majority of endogenous causing cases

Remember Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.

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11
Q

Define paraneoplatic Cushing’s

A

Excess ACTH is released from a cancer somewhere other than the pituitary (known as ectopic ACTH production).

The ectopic ACTH stimulates excessive cortisol release.

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12
Q

What is the most common cause of paraneoplastic Cushings

A

Small cell lung cancer

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13
Q

Define Ectopic CRH production (cause of ACTH dependent Cushing’s Syndrome)

A

Rarely Corticotrophin-releasing hormone (CRH) may be produced by malignant tissue resulting in increased ACTH and cortisol production.

CRH is secreted by the hypothalamus - stimulates the release of ACTH from the pituitary, which in turn causes cortisol production (hypothalamic-pituitary-adrenal axis)

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14
Q

ACTH independent is Cushing’s Syndrome in the presence of normal ACTH production

Name the 2 main causes of this

A
  • Therapeutic corticosteroid administration - results in the suppression of CRH and ACTH
  • Primary adrenal lesions - hormone secreting adrenal tumours that result in cortisol excess and thus negative feedback suppresses CRH and ACTH
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15
Q

Name the symptoms of Cushing’s syndrome

A

The clinical features associated with Cushing’s syndrome are related to the effects of excess cortisol.

  • Symptoms
  • Easy bruising
  • Thin skin
  • Purple striae
  • Hirsutism – presence of coarse pigmented hair on the face, chest, upper back or abdomen in a female as a result of hyperandrogenism (excessive production of androgen)
  • Weight gain
  • Amenorrhoea
  • Reduced libido
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16
Q

Name the signs of Cushing’s syndrome

A
  • Thinner arms and legs (due to proximal muscle weakness) with a central adiposity
  • Proximal muscle weakness in both the upper and lower libs
  • Central obesity
  • Moon face
  • Plethora
  • Buffalo hump
  • Metabolic complications including diabetes mellitus, dyslipidaemia, metabolic bone disease, and hypertension
  • Hyperpigmentation (in ACTH dependent causes only)- noted in oral mucosa and palmar creases
17
Q

Two of four tests should be used as a first-line diagnostic test in patients to establish a diagnosis of Cushing’s syndrome.

Name the 4 first line diagnostic tests

A
  1. 24-hour urinary free cortisol
  2. Spot urine cortisol: creatinine ratio (completed 3 times)
  3. Dexamethasone suppression test either overnight or over 48-hours
  4. Late-night salivary cortisol
18
Q

Describe the 24 hour urinary free cortisol test used for Cushing’s syndrome

A

Three or more collections are usually needed.

If urine cortisol levels are high (3-4x normal) it is highly suggestive of Cushing’s syndrome.

19
Q

Describe the Spot urine cortisol:creatinine ratio test used for Cushing’s syndrome

A

Early morning sampling of the urine

Ratio raised is suggestive of Cushing’s syndrome

Needs to be completed 3 times

Creatinine levels also need to be measured as the variation in levels between samples indicates that the test needs to be repeated

20
Q

Describe the Dexamethasone suppression test used for Cushing’s syndrome

A

Either overnight dexamethasone suppression test or low dose dexamethasone suppression over 24 hours.

A dose of dexamethasone (a synthetic glucocorticoid steroid) is taken at night.

Cortisol and ACTH is measured in the morning

The dexamethasone should suppress the normal morning spike of cortisol.

Low level of cortisol = normal

Normal or high level of cortisol = suggestive of Cushing’s syndrome

21
Q

In normal physiology, what time of day should the cortisol level be at its highest and lowest

A

Highest - in the morning

Lowest - at night

22
Q

Describe the Late night salivary cortisol test used for Cushing’s syndrome

A

Cortisol exhibits diurnal variation i.e. the plasma concentration of cortisol levels varies during a 24 hour period.

Cortisol levels will be at its highest in the morning and lowest at night

Late night salivary cortisol should be undetectable or very low therefore if the level is not low it is suggestive of Cushing’s syndrome.

23
Q

Once a diagnosis of Cushing’s syndrome is established a cause of the Cushing’s syndrome must be found.

What is the 1st line investigation to detect the cause of the Cushing’s syndrome

[This will be the 2nd line investigate for Cushing’s syndrome because the 1st line investigations are establish a diagnosis]

A

The first thing that is done to establish a cause is to determine if the Cushing’s is ACTH dependent or independent

This is done by a blood test i.e. plasma ACTH level

Suppressed ACTH = indicate ACTH-independent Cushing syndrome

Unsuppressed ACTH = indicate ACTH-dependent Cushing syndrome

24
Q

1st line investigations - Diagnosis of Cushing

2nd line investigation - ACTH independent

What is the third line investigation

A

CT adrenal glands.

This is because the vast majority of endogenous ACTH independent Cushing’s is caused by adrenal pathology.

Further tests may include MRI adrenal glands and PET/CT.

25
Q

1st line investigations - Diagnosis of Cushing

2nd line investigation - ACTH dependent

What is the third line investigation

A

3rd line investigation: High dose dexamethasone suppression test

Used to distinguish a pituitary adenoma from ectopic ACTH sources

In pituitary adenomas - the high levels will cause suppression of ACTH and cortisol

Ectopic ACTH - ACTH and cortisol will remain high as it is independent on the hypothlamaus and pituitary gland

26
Q

What is the management on Cushing’s syndrome

A

The management depends on the underlying cause

Exogenous causes: gradually reduce the glucocorticoid dose - do not abruptly stop as that can cause Addisonian crisis

Endogeneous causes: surgery is the mainstay of treatment

  • Trans-sphenoidal (through the nose) removal of pituitary adenoma
  • Surgical removal of adrenal tumour
  • Surgical removal of tumour producing ectopic ACTH
27
Q

What is the gold standard treatment of Cushing’s disease

A

Trans-sphenoidal surgery - through the nose removal of pituitary adenoma

Remember Cushing’s Disease refers to excess glucocorticoid production as a result of a pituitary adenoma

28
Q

What is the management of exogenous Cushing’s

A

Gradual withdrawal of the glucocorticoid.

29
Q

Pituitary irradiation may be used to treat Cushing’ disease

In which group of patients would this be suitable for

A

This may be used in children and young people or those in whom surgical techniques have failed.

Effects are not immediate and takes around 6-12 months to have maximal effect

30
Q

Name the various surgical options for Cushing’s disease

A
  • Trans-sphenoidal surgery (gold standard)
  • Adrenalectomy - removal of adrenal glands. Requires lifelong glucocorticoid and mineralcorticoid replacement
  • Unilateral adrenalectomy
  • Bilateral adrenalectomy

Finals: Medicine (91 decks)

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