Cushing's Syndrome Flashcards
What is Cushing’s syndrome?
It is defined as a condition in which there is prolonged elevation of endogenous or exogenous glucocorticoids – such as cortisol
What are the three classifications of Cushing’s syndrome?
Exogenous Cushing’s Syndrome
Endogenous Cushing’s Syndrome
Pseudo-Cushing’s
What is the most common classification of Cushing’s syndrome?
Exogenous Cushing’s Syndrome
What is exogneous Cushing’s syndrome?
It is caused by prolonged administration of glucocorticoids – such as prednisolone, hydrocortisone, etc
What are the two subclassifications of endogenous Cushing’s syndrome?
ACTH Dependent Cushing’s Syndrome
ACTH Independent Cushing’s Syndrome
What is ACTH dependent Cushing’s syndrome?
It is defined as elevated glucocorticoid levels related to excess ACTH production from the anterior pituitary gland
What are the two causes of ACTH dependent Cushing’s syndrome?
Cushing’s Disease
Paraneoplastic Syndrome
What is the most common cause of endogenous Cushing’s syndrome?
Cushing’s Disease
What is Cushing’s disease?
It is defined as a pituitary tumour, which secretes increased ACTH levels, resulting in adrenal hyperplasia, and therefore increased cortisol levels
What is paraneoplastic syndrome?
It refers to the production of increased ACTH related to ectopic secretion from tumours
What tumour is most commoly associated with Cushing’s syndrome?
Small cell lung cancer
What is ACTH independent Cushing’s syndrome?
It is defined as elevated glucocorticoid levels related to direct excess glucocorticoid secretion from the adrenal glands
What are the four causes of ACTH independent Cushing’s syndrome?
Adrenal Adenoma
Adrenal Carcinoma
Micronodular Adrenal Dysplasia
McCune Albright Syndrome
What is pseudo-Cushing’s?
It is defined as a group of conditions which mimics Cushing’s syndrome; however, is secondary to other factors
What are the two causes of pseudo-Cushing’s?
Alcoholism
Severe Depression
What are the thirteen clinical features associated with Cushing’s syndrome?
Moon Face
Central Obesity
Abdominal Striae
Buffalo Hip
Acne Vulgaris
Thin Skin
Hirsutism
Polyuria
Polydipsia
Peripheral Oedema
Low Mood
Decreased Libido
Hypertension
What is buffalo hip?
It is defined as the presentation of a fat pad on the patient’s upper back
What are the three specific clincial features associated with Cushing’s disease?
Headaches
Visual field defects
Galactorrhea
What are the nine investigations used to diagnose Cushing’s syndrome?
Blood Tests
Insulin Tolerance Test
Arterial Blood Gas (ABG)
24-Hour Urinary Free Cortisol
Low Dexamethasone Suppression Test (DST)
High Dexamethasone Suppression Test (DST)
Inferior Petrosal Sinus Sampling (IPSS)
Abdomen CT Scan
Pituitary MRI Scan
What three blood test results indicate Cushing’s syndrome?
Increased WCC Levels
Increased Sodium Levels
Decreased Potassium Levels
What underlying cause of Cushing’s syndrome is indicated with hypokalaemia?
Paraneoplastic Syndrome
What blood test can be used to identify the underlying cause of Cushing’s syndrome?
Serum ACTH
What underlying cause of Cushing’s syndrome is indicated by supressed ACTH levels?
ACTH independent cause, most commonly an adrenal adenoma
What underlying cause of Cushing’s syndrome is indicated by elevated ACTH levels?
ACTH dependent cause, most commonly Cushing’s disease (pituatary adenoma)
How is an insulin tolerance test used to investigate Cushing’s syndrome?
It is used to differentiate between Pseudo-Cushing’s and Cushing’s syndrome
What insulin tolerance test reuslt indicates pseudo-Cushing’s?
Elevated cortisol levels
What insulin tolerance test result indicates Cushing’s syndrome?
Suppressed cortisol levels
What ABG feature indicates Cushing’s syndrome?
Hypokalaemia metabolic alkalosis
What is a 24-hour urinary free cortisol?
It involves measurement of urinary cortisol levels over a 24 hour period
What 24-hour urinary free cortisol result indicates Cushing’s syndrome?
Cortisol levels three times the upper limit of normal - > 300mcg
What is the gold standard investigation used to diagnose Cushing’s syndrome?
Low dexamethasone suppression test (DST)
What is the low dexamethasone supression test (DST)?
It involves the administration of 1mg of dexamethasone, which is a synthetic glucocorticoid, at night
In the morning, their serum cortisol levels are then measured
What is a normal low dexamethasone suppression test result? Explain
Decreased cortisol levels
The dexamethasone administration will result in stimulation of the negative feedback system on the hypothalamus and pituitary gland, resulting in decreased secretion of CRH and ACTH levels
Ultimately, this leads to a simultaneous decrease in cortisol levels
What low dexamethasone suppression test result indicates Cushing’s syndrome? Explain
Elevated serum cortisol levels > 50nmol/L
There is loss of this negative feedback inhibition and therefore serum cortisol levels remain elevated with dexamethasone administration
When is the high dexamethasone suppression test (DST) used to investigate Cushing’s syndrome?
It is recommended following a positive low dexamethasone suppression test, in order to differentiate between the underlying cause
What is the high dexamethasone suppression test (DST)?
It involves the administration of 1mg of dexamethasone, which is a synthetic glucocorticoid, at night
In the morning, their serum cortisol and ACTH levels are then measured
What high dexamethasone suppression test result indicates Cushing’s syndrome related to Cushing’s disease? Explain
Suppressed serum cortisol levels
Suppressed serum ACTH levels
This is due to the fact that dexamethasone administration will result in negative feedback inhibition of the hypothalamus and pituitary gland
What high dexamethasone suppression test result indicates Cushing’s syndrome related to an adrenal adenoma? Explain
Not suppressed serum cortisol levels
Suppressed serum ACTH levels
This is due to the fact that there is direct excess glucocorticoid secretion from the adrenal glands, and therefore dexamethasone administration will further increase these levels
However, there will be negative feedback inhibition of the hypothalamus and pituitary, so ACTH levels will be suppressed
What high dexamethasone suppression test result indicates Cushing’s syndrome related to paraneoplastic syndrome? Explain
Not suppressed serum cortisol levels
Not suppressed serum ACTH levels
This is due to the fact that ACTH levels are secreted independent of the hypothalamus-pituitary-adrenal axis, and therefore there will be no negative feedback inhibition of the hypothalamus and pituitary
When is inferior petrosal sinus sampling (IPSS) used to investigate Cushing’s syndrome?
It is used to differentiate between the underlying cause of Cushing’s syndrome when neuroimaging and high dexamethasone suppression tests are insufficient
What is IPSS?
It involves sampling veins that drain the pituitary gland, in order to directly measure ACTH levels
These ACTH levels are compared with peripheral ACTH levels, in order to determine whether the Cushing’s syndrome is ACTH-dependent due to a pituitary adenoma
What are the two features of Cushing’s syndrome on abdomen CT scan?
Adrenal adenomas
Small cell lung cancer
What is a feature of Cushing’s syndrome on pituatary MRI scans?
Pituitary adenoma
What is the management option of exogneous Cushing’s syndrome?
We review the patient’s glucocorticoid treatments and alter accordingly – often stopping, reducing or administrating an alternative steroid-sparing immunosuppressive agent
What is the pharmacological management option of endogenous Cushing’s syndrome?
Glucocorticoid Synthesis Inhibitors
When are glucocorticoid synthesis inhibitors used to manage endogenous Cushing’s syndrome?
They are used to temporarily reduce glucocorticoid levels, in order to prepare the patient for definitive therapy
In some cases, they can be administered chronically for those who are unfit to undergo definitive surgical management
Name three glucocorticoid synthesis inhibitors used to manage endogenous Cushing’s syndrome
Ketoconazole
Metyrapone
Mitotane
What are the two surgical management options of Cushing’s syndrome?
Trans-Sphenoidal Surgery
Laparoscopic Adrenalectomy
When is trans-sphenoidal surgery used to manage endogenous Cushing’s syndrome?
It is used to manage Cushing’s syndrome related to Cushing’s disease
What is trans-sphenoidal surgery?
It involves removal of the pituitary adenoma through the sphenoid sinus
When is laparoscopic adrenalectomy used to manage endogenous Cushing’s syndrome?
It is used to manage Cushing’s syndrome related to adrenal adenomas
What is laparoscpic adrenalectomy?
It involves laparoscopic removal of the adrenal tumour
In cases of bilateral adrenalectomy, what pharmaoclogical management option should be administered?
Immediate steroid replacement therapy
What are the six complications of Cushing’s syndrome?
Hypertension
Heart Failure
Type Two Diabetes Mellitus
Obesity
Metabolic Syndrome
Osteoporosis
