Adrenal Issues Flashcards
What is Addison’s disease?
Autoimmune destruction of the adrenal glands
What is the commonest cause of hypoadrenalism in the UK
Addison’s disease
Autoimmune destruction of the adrenal glands is the commonest cause of primary hypoadrenalism in the UK, accounting for 80% of cases.
Addison’s disease and results in reduction of which hormones
reduced cortisol and aldosterone being produced.
Which electrolyte disturbances will occur as a result of Addison’s disease?
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
Addison’s disease sx
lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
hyperpigmentation (especially palmar creases)*, vitiligo, loss of pubic hair in women, hypotension
crisis: collapse, shock, pyrexia
Addisons disease causes hypo or hyperglycaemia
hypoglycaemia
What are the primary causes of hypoadrenalims?
primary addison's tuberculosis metastases (e.g. bronchial carcinoma) meningococcal septicaemia (Waterhouse-Friderichsen syndrome) HIV antiphospholipid syndrome
What are the secondary causes of hypoadrenalims?
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
Hypoadrenalism always causes hyperpigmentation
false
Primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
In a patient with suspected Addison’s disease the definite investigation is
ACTH stimulation test (short Synacthen test)
Describe ACTH simulation test
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
If an ACTH stimulation test is not readily available (e.g. in primary care) then what test can be useful:
9 am serum cortisol
Describe results of 9am serum cortisol for addisons
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
Patients who have Addison’s disease are usually given what therapy.
both glucocorticoid and mineralocorticoid replacement
hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the first half of the day
fludrocortisone
Describe patient education in Addison’s disease?
emphasise the importance of not missing glucocorticoid doses
consider MedicAlert bracelets and steroid cards
patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
discuss how to adjust the glucocorticoid dose during an intercurrent illness
Management of intercurrent illness in addisons?
in simple terms the glucocorticoid dose should be doubled
the Addison’s Clinical Advisory Panel have produced guidelines detailing particular scenarios - please see the CKS link for more deta
Causes of addisonian crisis?
sepsis or surgery
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
Outline management of addisonian crisis?
hydrocortisone 100 mg im or iv - continue hydrocortisone 6 hourly until the patient is stable.
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Describe the which hormones are released from the parts of the cortex?
Zona glomerulosa – produces and secretes mineralocorticoids such as aldosterone.
Zona fasciculata – produces and secretes corticosteroids such as cortisol. It also secretes a small amount of androgens.
Zona reticularis – produces and secretes androgens such as dehydroepiandrosterone (DHES). It also secretes a small amount of corticosteroids.
What is Cushing’s Syndrome?
is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol.
What is Cushing’s disease?
specific condition where a pituitary adenoma (tumour) secretes excessive ACTH. Cushing’s Disease causes a Cushing’s syndrome, but Cushing’s Syndrome is not always caused by Cushing’s Disease.
Endogenous are the commonest causes of cushings disease
FALSE
exogenous causes of Cushing’s syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones.
ACTH dependent causes of cushings?
Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
ACTH independent causes of cushings?
iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
What is Pseudo-Cushing’s?
mimics Cushing’s
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
What test differentiates cushings and pseudocushings?
insulin stress test may be used to differentiate
How is cushings investigated?
Investigations are divided into confirming Cushing’s syndrome and then localising the lesion.
Metabolic acidosis/alkalosis seen in cushings
hypokalaemic metabolic alkalosis
How does cushings affect glucose?
impaired glucose tolerance
Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with
very low potassium levels.
Tests to confirm Cushing’s syndrome
The two most commonly used tests are:
overnight dexamethasone suppression test (most sensitive)
24 hr urinary free cortisol
Localisation test in Cushings?
first-line 9am and midnight plasma ACTH (and cortisol) levels
Both low- and high-dose dexamethasone suppression tests may be used to localise the pathology resulting in Cushing’s syndrome.
When measuring 9am and midnight plasma ACTH (and cortisol) levels - If ACTH is suppressed then what is most likely?
non-ACTH dependent cause is likely such as an adrenal adenoma
In cushings what would Normal results look like? (low dose, high dose dexamethasone & ACTH?)
Cortisol following
low-dose dexamethasone: Low
Cortisol following
high-dose dexamethasone: Low
ACTH: Normal
What would Cushing’s syndrome due to other causes (e.g. adrenal adenomas) show on localisation tests?
Cortisol following
low-dose dexamethasone: Normal
Cortisol following
high-dose dexamethasone: Normal
ACTH: Low
What would Cushing’s disease (i.e. pituitary adenoma → ACTH secretion) show on localisation tests?
Cortisol following
low-dose dexamethasone: Normal
Cortisol following
high-dose dexamethasone: Low
ACTH: High
What would Ectopic ACTH syndrome likely show on localisation tests?
Cortisol following
low-dose dexamethasone: Normal
Cortisol following
high-dose dexamethasone: Normal
ACTH: High
What can differentiate between pituitary and ectopic ACTH secretion?
Petrosal sinus sampling of ACTH
In Cushing’s what would CRH stimulation tests show?
if pituitary source then cortisol rises
if ectopic/adrenal then no change in cortisol
Primary hyperaldosteronism most commonly caused by?
bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases
Primary hyperaldosteronism extremely rare cause?
Adrenal carcinoma
Features of Primary hyperaldosteronism?
hypertension hypokalaemia e.g. muscle weakness this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients alkalosis
What is first line investigation for Primary hyperaldosteronism? What would this show?
plasma aldosterone/renin ratio is the first-line investigation
should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone)
What other tests should be done in Primary hyperaldosteronism?
plasma aldosterone/renin ratio is the first-line investigation
following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
Adrenal Venous Sampling (AVS) can be done to identify the gland secreting excess hormone in primary hyperaldosteronism
Primary hyperaldosteronism mx
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
What is Phaeochromocytoma
rare catecholamine secreting tumour
Phaeochromocytoma inheritance
10% are familial
Phaeochromocytoma associations?
MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
10% rules in phaeo?
bilateral in 10%
malignant in 10%
extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
Features in phaeo are typically
episodic
sx phaeo
hypertension (around 90% of cases, may be sustained) headaches palpitations sweating anxiety
24 hr urinary collection of catecholamines test for phaeo
false
metanephrines
test for phaeo?
24 hr urinary collection of metanephrines (sensitivity 97%*)
Surgery is first line in phaeo
false
stabilized with medical management
Outline management in Phaeo?
patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
(a before b)
Surgery is the definitive management
What is Von Hippel-Lindau (VHL) syndrome?
autosomal dominant condition predisposing to neoplasia. It is due to an abnormality in the VHL gene located on short arm of chromosome 3
Features of VHL?
haemangiomas manifesting in subarachnoid haemorrhages, vitreous haemorrhage
phaeochromocytoma
clear-cell renal cell carcinoma
Cysts: renal cysts (premalignant), extra-renal cysts: epididymal, pancreatic, hepatic
endolymphatic sac tumours
