Disorders of Adrenocortical Dysfunction Flashcards
What are the three stages of Cushing’s Disease investigation?
- Screening Tests, for when the disease is suspected
- Confirmation of the Diagnosis
- Differentiation of the Cause
What are the screening tests for Cushing’s Disease?
- Urinary-free cortisol
- Diurnal rhythm
- Overnight dexamethasone suppression testing
Describe the overnight low-dose dexamethasone suppression test.
- Cortisol is to be measured at 8 AM.
- 1 mg of dexamethasone is given at 11 PM. The cortisol levels are measured again at 8 AM the next morning.
- Cortisol suppression to <50 nmol/l is normal.
If the screening tests for Cushing’s Disease come back positive, there are 3 possibilities that could cause that.
What are these three possibilities? PART 1
TRUE CUSHING’S SYNDROME
PSEUDOCUSHING’S SYNDROME - common with:
- depression
- alcoholism
- anorexia nervosa
- obesity
If the screening tests for Cushing’s Disease come back positive, there are 3 possibilities that could cause that.
What are these three possibilities? PART 2
EXOGENOUS STEROIDS: found in everyday things such as
- inhalers
- eyedrops
- nasal drops
- skin creams
To remove the possibility of false positives, how do we change the overnight low-dose dexamethasone suppression test?
- Give 4 low-dose tablets a day for 2 days (0.5 mg of dexamethasone six-hourly for 48 hours).
- No cortisol left in their bloodstream.
- If cortisol is still detectable then the patient has Cushing’s Syndrome.
After the low-dose dexamethasone suppression test, what different diagnoses can be made?
CUSHING’S DISEASE:
- pituitary adenoma
ADRENAL TUMOUR:
- benign/ malignant
ECTOPIC ACTH PRODUCTION:
- benign/ malignant
After the low-dose dexamethasone suppression test, how can we differentiate between the different causes?
- high-dose dexamethasone suppression testing
- ACTH
- imaging
Describe the high-dose dexamethasone suppression test.
- High dose of 2 mg of dexamethasone is given every 6 hours for 48 hours.
- If cortisol suppresses to <50% of baseline, patient has Pituitary-Dependent Cushing’s Disease.
- If cortisol does not suppress, patient has ectopic ACTH production or adrenal tumour.
What are some laboratory features of cortisol excess?
- hypokalaemia
- metabolic alkalosis
- hyperglycaemia
For the CRH test, why would we measure CRH levels and not ACTH levels?
ACTH is present in the blood in fragments, making it difficult to measure.
Describe a CRH test.
- 0.1 μg/kg of human CRH is given.
- Blood assayed for ACTH and cortisol at set times: -15, 0, 15, 30, 45, 60, 90, 120 minutes.
Describe what different results of a CRH test indicate.
- If the ACTH doubles, indicates a normal response.
- If the ACTH is suppressed, indicates an adrenal tumour.
- If the ACTH level remains the same, indicates ectopic ACTH production.
- If there is an exaggerated ACTH response, indicates a pituitary tumour.
Tumours that produce hormones (in this case, ACTH) can be found in different places.
List the different scans/ tests done for each area/ condition to localise the tumour.
PITUITARY TUMOUR:
- MRI or IPSS
ADRENAL TUMOUR:
- CT or MRI
ECTOPIC ACTH PRODUCTION:
octreotide scan
ACTH sampling
What would be the treatment for a pituitary tumour?
- Excess cortisol causes patients to be hypertensive, immunosuppressed
- Risk factors for surgery, so given cortisol production blockers (e.g metyrapone/ ketoconazole).
- After surgery, patients require placement of other pituitary hormones until normal production resumed.
What would be the treatment for an adrenal tumour?
- Remove the source of an adrenal tumour.
- Patients will need to have steroid replacement tablets at time of and following surgery.
- Adrenal tumour suppresses the function of the normal gland
What are some of Addison’s clinical features?
- Weakness
- Weight loss
- Postural hypotension
- Myalgia
- Hyperpigmentation
- Hyponatraemia
- Hyperkalaemia
- Acidosis
- Hypercalcaemia
- Hypoglycaemia
- Increased urea and creatinine
- Eosinophilia
What are some causes of Addison’s Syndrome?
- Autoimmune diseases
- Steroid withdrawal
- Metastases
- Infiltration (amyloid, haemochromatosis)
- Waterhouse-Friedrichsen (bleeding in the adrenal glands)
- Apoplexy (bleeding within internal organs)
- Infection (fungal, viral)
- Enzyme defect (congenital adrenal hyperplasia, adrenoleukodystrophy, adrenomyeloneuropathy)
- Drugs
What would be the treatment of Addison’s disease?
- Replace the hormone.
- Use hydrocortisone; it mimics the diurnal rhythm, with last dose being given at 6 PM.
- Use fludrocortisone.
Describe 21-hydroxylase deficiency (classical) CAH.
- Autosomal recessive and HLA-linked.
- Patient cannot make aldosterone or cortisol, so build-up of 17-OH and progesterone
- Excess sex steroids cause virilisation, hirsutism, premature adrenarche, infertility, etc.
- No aldosterone - hyperkalaemia and hypotension.
Describe 11-hydroxylase deficiency (non-classical) CAH.
- Autosomal recessive and HLA-linked.
- Build-up of 11-deoxycortisol and deoxycorticosterone. Forms excess sex steroids
- Deoxycorticosterone has a partial action on the aldosterone receptor.
- So, instead of being hypotensive, patients become hypertensive and hypokalaemic.
How do we investigate for enzyme deficiencies in the making of cortisol and aldosterone?
- Synacthen test.
- No cortisol rise as there are increased 17-OH and progesterone levels.
How do we treat enzyme deficiencies in the making of cortisol and aldosterone? PART 1
- 11β- and 21-hydroxylase deficiency uses glucocorticoid therapy (with drugs e.g prednisolone).
- Acts partially on the mineralocorticoid receptor, providing negative feedback to ACTH.
- ACTH levels will fall, and the drive to produce testosterone will stop.
How do we treat enzyme deficiencies in the making of cortisol and aldosterone? PART 2
- Surgery possible to virilised female genitalia
- Treat the mother to prevent foetal virilisation.
