Cushing's Syndrome Flashcards
Define Cushing’s syndrome
Cushing’s syndrome is caused by prolonged exposure to an excess of glucocorticoids
The cause of excess glucocorticoids may be endogenous or exogenous.
Define the term exogenous
The source is derived externally
The cause of excess glucocorticoids may be endogenous or exogenous.
Define the term endogenous
The source is derived internally
What is the most common cause of excess glucocorticoids
a) Exogenous
b) Endogenous
a) Exogenous
What is the most common cause of Cushing’s syndrome secondary to exogenous glucocorticoid
Long term high dose steroid medication
The causes of Cushing’s syndrome may be divided based on location.
Name these groups
ACTH dependent - those that are caused by pituitary problem
ACTH independent - those that are independent on the pituitary
What is the most common cause of Cushing’s syndrome secondary to endogenous glucocorticoid
ACTH dependent causes e.g. Cushing’s disease
Name 3 causes of ACTH dependent Cushing’s syndrome
- Cushing’s disease
- Paraneoplastic Cushings
- Ectopic CRH production
What is the most common cause of ACTH dependent Cushing’s syndrome
Cushing’s Disease
Define the term Cushing’s disease
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.
Define paraneoplatic Cushing’s
Excess ACTH is released from a cancer somewhere other than the pituitary (known as ectopic ACTH production).
The ectopic ACTH stimulates excessive cortisol release.
What is the most common cause of paraneoplastic Cushings
Small cell lung cancer
Define Ectopic CRH production (cause of ACTH dependent Cushing’s Syndrome)
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)
ACTH independent is Cushing’s Syndrome in the presence of normal ACTH production
Name the 2 main causes of this
- 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
Name the symptoms of Cushing’s syndrome
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
Name the signs of Cushing’s syndrome
- 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
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
- 24-hour urinary free cortisol
- Spot urine cortisol: creatinine ratio (completed 3 times)
- Dexamethasone suppression test either overnight or over 48-hours
- Late-night salivary cortisol
Describe the 24 hour urinary free cortisol test used for Cushing’s syndrome
Three or more collections are usually needed.
If urine cortisol levels are high (3-4x normal) it is highly suggestive of Cushing’s syndrome.
Describe the Spot urine cortisol:creatinine ratio test used for Cushing’s syndrome
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
Describe the Dexamethasone suppression test used for Cushing’s syndrome
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
In normal physiology, what time of day should the cortisol level be at its highest and lowest
Highest - in the morning
Lowest - at night
Describe the Late night salivary cortisol test used for Cushing’s syndrome
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.
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]
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
1st line investigations - Diagnosis of Cushing
2nd line investigation - ACTH independent
What is the third line investigation
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.
1st line investigations - Diagnosis of Cushing
2nd line investigation - ACTH dependent
What is the third line investigation
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
What is the management on Cushing’s syndrome
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
What is the gold standard treatment of Cushing’s disease
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
What is the management of exogenous Cushing’s
Gradual withdrawal of the glucocorticoid.
Pituitary irradiation may be used to treat Cushing’ disease
In which group of patients would this be suitable for
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
Name the various surgical options for Cushing’s disease
- Trans-sphenoidal surgery (gold standard)
- Adrenalectomy - removal of adrenal glands. Requires lifelong glucocorticoid and mineralcorticoid replacement
- Unilateral adrenalectomy
- Bilateral adrenalectomy
