Endocrinology Flashcards
What is Cushing’s syndrome?
The clinical state caused by glucocorticoid excess + the loss of normal feedback mechanisms of the HPA axis
What are the causes of Cushing’s syndrome?
- ACTH-dependent causes
- Cushing’s disease
-Ectopic ACTH production
- Ectopic CRF production - rare - ACTH-independent causes:
- Adrenal adenoma / cancer
- Adrenal nodular hyperplasia
- Iatrogenic - steroid use
- Carney complex - rare
- McCune-Albright syndrome- rare
What is Cushing’s disease?
Bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma.
- Affects females > males
- Peak age 30-50 years
Describe ectopic ACTH production
Occurs most commonly with small cell lung cancer and carcinoid tumours.
Specific features are
- pigmentation due to raised ACTH
- hypokalaemic metabolic alkalosis
- weight loss
- Raised BM
- Clinical features of Cushing’s are often absent
What are the symptoms of Cushing’s syndrome?
- weight gain
- mood changes (depression, lethargy, irritability, psychosis)
- proximal weakness
- gonadal dysfunction (irregular menses, hirsuitism, erectile dysfunction)
- acne
- recurrent Achilles tendon rupture, occasionally virilisation
What are the signs of Cushings syndrome?
- central obesity
- plethoric moon face
- buffalo neck hump
- supraclavicular fat distribution
- skin and muscle atrophy
- bruises
- purple abdominal striae
- osteoporosis
- hypertension
- hyperglycaemia
- infection prone
- porr healing
What is the overall aim of testing for Cushing’s syndrome?
- Confirm raised plasma cortisol
- Localise source
How is raise plasma cortisol confirmed in suspected Cushing’s syndrome?
- Overnight dexamethasone supporession test
- 24hour urinary free cortisol (normal <280nmol/24 hours)
- If these are abnormal the proceed to a 48 hour dexamethasone suppression test
Describe an overnight dexamethasone suppression test if suspecting Cushing’s syndrome
1mg dexamethasone at midnight, followed by cortisol level at 8am.
- In health this causes a -ve feedback with reduced ACTH and cortisol to <50nmol/l
- In Cushing’s syndrome there’s no cortisol suppression
Describe the 48 hours dexamethasone suppression test in suspected Cushing’s syndrome
Done after confirming raised cortisol either with a 24-hour urinary free cortisol level or an overnight dexamethasone suppression test.
Give 0.5mg QDS for 48 hours and measure cortisol at 0 and 48 hours
- In Cushing’s syndrome there is failure to suppress cortisol
How is Cushing’s syndrome localised?
- Plasma ACTH - if undetectable an adrenal tumour is most likely -> CT scan
- If plasma ACTH is detectable then a high-dose dexamethasone suppression test is carried out. If it’s Cushing’s disease then there will be partial supporession as there’s still some negative feedback. If it’s an ectopi source then there will be no suppression.
- MRI brain - detects 70% of adenomas (rest are too small)
- Bilateral inferior petrosal sampling may help confirm a pituitary adenoma
- CT C/A/P if ectopic tumour suspected.
How is Cushing’s syndrome managed?
- Stop exogenous steroids if possible
- Resection of pituitary adenomas
- Adrenalectomy for adrenal tumours
- Surgery to remove ectopic ACTH tumour
- Drugs to suppress cortisol production
What drugs can be used to manage Cushing’s syndrome?
- Pituitary-directed drugs -> control cortisol production from adenomas e.g. cabergoline or pasireotide
- Steroid synthesis inhibitors e.g. ketoconazole, osilodrostat
- Mifepristone - blocks effects of cortisol on the tissues
