Cushing's Syndrome Flashcards
What is Cushing’s syndrome?
clinical manifestation of pathological hypercortisolism from any cause
What steroids do the adrenal cortex produce?
- Glucocorticoids
- Mineral corticoids
- Androgens
What is an example of a glucocorticoid?
cortisol
What do glucocorticoids do?
affect carbohydrate, lipid and protein metabolites
What is an example of a mineralcorticoid?
aldosterone
What do mineral corticoids do?
control sodium and potassium balance
What are androgens?
sex hormones converted to testosterone and dihydrotestosterone
What is the process by which cortisol is released?
- CRF from hypothalamus stimulates ACTH secretion from pituitary
- in turn stimulated cortisol and androgen production by adrenal cortex
What are causes of Cushing’s syndrome
- Pituitary or adrenal adenoma
- Ectopic ACTH production
- Adrenal carcinoma
- Exogenous corticosteroid use
What is cushing’s disease?
- pituitary or adrenal adenoma (Cushings disease) – bilateral adrenal hyperplasia
- peak age 30-50yrs
When might there be ectopic ACTH production?
- small cell lung cancer
- carcinoid tumour
What is most common cause of Cushing’s syndrome?
exogenous corticosteroid exposure
What is the majority of endogenous Cushing syndrome caused by?
ACTH secreting pituitary adenomas
What are the symptoms of Cushing’s syndrome?
- Increased weight
- Mood change
- Proximal weakness
- Gonadal dysfunction
What are signs of Cushing’s syndrome?
- Central obesity
- Plethoric moon faces
- Buffalo hump
- Supraclavicular fullness
- High glucose
- High BP
- Violaceous stria
What are some differential diagnosis of Cushing’s syndrome?
- obesity
2. metabolic syndrome
What are some complications of Cushing’s syndrome?
- Adrenal insufficiency secondary to adrenal suppression
- cardiovascular disease
- hypertension (pseudohyperaldosteronim)
- diabetes mellitus
- osteoporosis
- nephrolithiasis
What investigations may you do for Cushing’s syndrome?
- Urine pregnancy test
- Serum glucose
- Late-night salivary cortisol
- 1mg overnight suppression test
- 24hr urinary free cortisol
- 48h 2mg dexamethasone suppression test
What would serum glucose levels be like in Cushing’s syndrome?
elevated
What are 1st line investigations for Cushing’s syndrome?
- Lat night salivary cortisol
- 1mg overnight dexamethasone suppression test
- 24hr urinary free cortisol
What would late-night salivary cortisol levels be like in Cushing’s syndrome?
elevated
What would 1mg overnight dexamethasone suppression test for Cushing’s syndrome show?
morning cortisol >50 nanomol/L (>1.8 micrograms/dL)
What would 24hr urinary free cortisol be in Cushing’s syndrome?
> 50 micrograms/24 hour
What would 28hr 2mg dexamethasone suppression test be in Cushing’s syndrome?
morning cortisol >50 nanomol/L (>1.8 micrograms/dL)
If the dexamethasone test is positive what should you do and what would it show?
- ACTH Plasma Levels to figure out cause:
- If it is high, do high dose dex test and if there is no suppression CT for ectopic site
- if there is low ACTH MRI pituitary gland OR CRH stimulation test (if no rise, ectopic)
- (if rise, cushings disease)
How do you treat Cushing’s syndrome?
depends ont he cause
How do you manage ACTH secreting pituitary tumour (Cushings disease)?
Transsphenoidal pituitary adenomectomy
How would you treat ectopic ACTH or corticotrophin-releasing hormone (CRH) syndrome?
surgical resection or ablation of tumour and metastases
How would you treat ACTH-independent due to unilateral adrenal carcinoma or adenoma?
unilateral adrenalectomy or tumour resection
How would you treat ACTH- independent due to bilateral adrenal disease (hyperplasia or adenoma)?
bilateral adrenalectomy and permanent post-surgical corticosteroid replacement therapy
How do you manage Cushing’s syndrome due to steroids?
stop steroid use
What is the prognosis for Cushing’s syndrome?
untreated Cushing’s has high vascular mortality
What does dexamethasone do?
reduce ACTH release in normal ppl
What would a tumour in the zona fasiculata result in?
excess production of cortisol causing Cushingoid features to develop e.g. brusing
What are the 3 types of cushing’s syndrome?
- ACTH dependent
- ACTH independent
- Psudeo-Cushing’s
What are ACTH dependent causes of Cushing’s syndrome?
- Pituitary adenoma (Cushing’s Disease)
* Ectopic ACTH (SCLC)
What are ACTH independent causes of Cushing’s syndrome?
- Iatrogenic (MOST COMMON)
* Adrenal tumours
What are psudeo-cushing’s reasons for Cushing’s syndrome?
- Alcohol excess
- Severe depression
- Obesity
What is Psuedo-Cushing’s?
terms of signs, symptoms and hormone levels causing false positive dexamethasone suppression test
How do you differentiate psuedo-cushing’s from real cushing’s?
- insulin stress test to differentiate
- stimulating hypoglycaemia in a person without Cushings should cause a rise in cortisol levels
- If there is cortisol rise <170 nmol/L from basal suggests Cushing’s and not pseudo-Cushing’s because the tumour is not responsive to physiological mechanisms, the cortisol release is purely autonomous
What is involved in the low dose dex test?
- 9am cortisol (Monday) = 650nM
- 0.5mg dexamethasone every 6hrs for 48hours
- 9am cortisol (Wednesday) = >50nM
- FAILURE TO SURPRESS means a level that is either high or normal – you expect cortisol to be LOW due to negative feedback
How would a healthy person react to low dose dexa test?
- stimulation by giving dexamethasone should cause negative feedback on the HPA axis so surpress ACTH and thus cortisol production after 48hours
- LOW CORTISOL
How would a cushing’s syndrome person react to low dose dexa test?
will fail to surpress – can be normal or high
How do you distinguish between ACTH indpenet and dependent?
- High dose dex no longer used
- Inferior Petrosal Sampling
- MRI pituitary is IPS not able
What is IPS?
Measuring levels of ACTH in the pituitary to determine whether this is an ACTH dependent or independent cause
How do you distinguish IPS result?
- adrenal cause means the HIGH cortisol would suppress ACTH in the pituitary and so ACTH would be LOW
- pituitary cause, the ACTH is what is driving the HIGH cortisol so both would be RAISED
