Cushing's Syndrome Flashcards
1
Q
Describe the hypothalamic pituitary axis for cortisol
A
2
Q
What is the role of cortisol?
A
- It’s your body’s main stress hormone.
- It works with certain parts of your brain to control your mood, motivation, and fear.
- Manages how your body uses carbohydrates, fats, and proteins
- Keeps inflammation down
- Regulates your blood pressure
- Increases your blood sugar (glucose)
- Controls your sleep/wake cycle
- Boosts energy so you can handle stress and restores balance afterward
3
Q
What is cushings syndrome?
A
- It is a clinical state caused by chronic glucocorticoid excess and loss of the body’s normal negative feedback mechanism of the hypothalamic-pituitary-adrenal axis
- There is also loss of circadian rhythm of cortisol as cortisol is highest in the mornings
4
Q
What are the main causes of cushing’s syndrome?
A
- Oral Steroids
- Endogenous causes are rare:
- Increased ACTH
- Pituitary adenoma (Cushings disease) is the commenest cause
- Increased ACTH
5
Q
What are the ACTH dependent causes of cushings syndrome?
A
- Cushings disease
- Bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma
- Ectopic ACTH production
- Small cell lung cancer
- Carcinoid tumours
- Ectopic CRF production (RARE)
- Some thyroid and prostate cancers
6
Q
What are the ACTH independent causes of cushings syndrome?
A
- Iatrogenic
- Pharmacological doses of steroids
- Adrenal adenoma/cancer
- Adrenal nodular hyperplasia
7
Q
What are some specific features of ectopic ACTH production causing cushings syndrome?
A
- Hyperpigmentation (due to increased ACTH)
- Hypokalaemic metabolic alkalosis (increased cortisol leads to mineralocorticoid activity
- Weight loss
- Hyperglycaemia
- The classical features of cushings are often absent
8
Q
What are the symptoms of Cushings syndrome?
A
- Weight gain
- Mood change
- Depression
- Lethargy
- Irritability
- Psychosis
- Proximal weakness
- Gonadal dysfunction
- Irregular menses
- Hirsutism
- Erectile dysfunction
- Occasional virilisation if female
- Acne
- REcurrent achilles tendon rupture
9
Q
What are the signs of Cushings syndrome?
A
- Central obesity
- Moon face
- Buffalo hump
- Purple abdominal striae
- Supraclavicular fat distribution
- Skin and muscle atrophy
- Osteoporosis
- Hypertension
- Hyperglycaemia
- Infection prone
- Poor healing
10
Q
How is suspected Cushing syndrome investigated?
A
- Raised plasma cortisol (can be misleading depending on illness, time of day and stress - venepuncture)
- Localise the source on the basis of lab testing (Is ACTH raised ?)
- Use imaging studies to confirm the likely source (although many tumours are too small to be detected on MRI)
- CT
- MRI
- 1st Line test
- Overnight dexamethasone suppression test
- 24hr free urinary cortisol
- 2nd line tests
- 48hr dexamethasone suppression test
- 48hr high dose dexamethasone suppression test
- Midnight cortisol
- Localisation tests
- Plasma ACTH
- Adrenal vein sampling
- Corticotropin-releasing hormone test
- MRI imaging
- Bilateral inferior petrosal sinus
11
Q
When are false negatives seen in the dexamethasone suppression test?
A
- Depression
- Obesity
- Alcohol Excess
- Inducers of liver enzymes
12
Q
How does the dexamethasone suppression test work?
A
- Dexamethasone is a manmade version of cortisol.
- After you take a dose of it, your body should make less cortisol.
- If the patient does not have cushings syndrome then there should be a drop in ACTH and cortisol production due to negative feedback
- In Cushings syndrome, there is no suppression of cortisol
- Usually, the test is done overnight, but it can also be done over 2 days.
- In the overnight test, you give dexamethasone at midnight and measure cortisol at 8am
- If the overnight test (1st line treatment) is abnormal, you do the 2 day dexamethasone suppression test
- You give dexamethasone 6hourly and measure cortisol at 0 and 48hr
- The last test should be 6hr after the last dose
- The midnight cortisol testshould be low if normal as cortisol works on a circadian rhythm where is is lowest at midnight and highest in the early morning
- There are two doses you can take for the test: low dose and high dose. The low-dose test helps you find out if you have Cushing syndrome or not. You typically get 1 mg of dexamethasone.
- You’d get the high-dose test once you know you have Cushing syndrome. It’s done to find out whether it’s caused by a tumor on your pituitary gland. The high dose is typically 8 mg.
13
Q
How do the localisation tests work for cushings syndrome?
A
- Plasma ACTH
- If its undetectable –> adrenal tumour –> therefore do a CT of the adrenal glands to check
- If there is no mass on CT, proceed to adrenal vein sampling or adrenal scintigraphy
- If ACTH is detectable, you have to distinguish between a pituitary adenoma and ectopic ACTH production via high dose dexamethasone suppression test
- If there is complete or partial suppression of cortisol then it is caused by a pituitary adenoma as the pituitary retains some negative feedback regulation but the ectopic is not under any feedback control
-
A corticotropin releasing hormone test would also help here
- Cortisol would rise with pituitary disease as the pituitary gland would directly be stimulated by the CRH
- But cortisol would not rise with ectopic ACTH production
- Therefore is tests show that cortisal responds to manipulation, Cushinds disease is likely
- If its undetectable –> adrenal tumour –> therefore do a CT of the adrenal glands to check
- To confirm Cushings disease:
- Image the pituitary (MRI)
- If no mass is seen –> bilateral inferior petrosal sinus blood sampling may help to confirm a pituitary adenoma
- If tests confirm that the cortisol does not respond to manipulation, hunt for the ectopic
- MRI of neck, thorax and abdomen (small ACTH secreting carcinoid tumours)
- IV contrast CT of chest, abdomen and pelvis
14
Q
What is cushings disease?
A
- Cushing’s disease is caused by a tumour in the pituitary gland (usually a pituitary microadenoma).
- The pituitary tumour produces high levels of adrenocorticotropic hormone (ACTH) which, in turn, causes the adrenal glands to produce excessive amounts of the hormone, cortisol.
- In most cases, the cause of the tumour cannot be identified.
- Cushings disease can also be due to excess production of hypothalamus CRH (corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism) that stimulates the synthesis of cortisol by the adrenal glands.
15
Q
How is Cushings syndrome treated?
A
- Depends on the cause
- Iatrogenic - Stop medication if possible
- Cushings disease:
- Remove pituitary adenoma (transphenoidal surgery)
- Bilateral adrenolectomy is source is unlocatable or there is a recurrence post-op)
- Adrenal adenoma/carcinoma:
- Adrenolectomy - this cures the adenoma but rarely sorts out the cancer
- Follow up with radiotherapy and adrenolytic drugs (mitotane) if its a carcinoma
- Ectopic ACTH
- Surgery if tumour is located and has not spread
- Metyrapone, ketoconazole and fluconazole decrease cortisol production if pre-op of if awaiting effects of radiation
- Intubatoin and mifepristone and etomidate may be needed in severe ACTH-associated psychosis
