Adrenal Flashcards
Name 8 causes glucocorticoid excess / Cushing syndrome
ACTH dependant
• Pituitary adenoma (Cushing disease ) ! (70%)
• ectopic ACTH secretion eg bronchial cancer! (10%)
• ectopic CRH or related peptides
• ACTH therapy
ACTH independent
• adrenal adenoma or carcinoma! (20%)
• micronodular hyperplasia (partially ACTH dependent)
Pseudo-cushings: obesity, alcoholism, depression, anxiety
Exogenous glucocorticoids
Name 3 investigations for suspected Cushing’s (screen)
• Low dose dexamethasone suppression test (not suppressed )
• 24h urinary free cortisol (increased)
• late night salivary cortisol (increased)
Also: midnight serum cortisol increased, diurnal rhythm lost
Name 3 most common causes Cushing’s syndrome NB
ACTH dependent (do CRH test)
• pituitary ACTH incr = Cushing’s disease. Eg pituitary adenoma (most common ) (do MRI pituitary)
• ectopic ACTH secretion eg bronchial cancer
ACTH independent (do CT adrenal, adrenal vein sampling)
• adrenal tumour adenoma or carcinoma
Name 2 causes pseudo-cushings and how to confirm dx
• Suspected alcohol - abstinence
• depression - CRH (corticotropin releasing hormone) test
Name 5 other less important tests for cushings
• Potassium: hypokalemic acidosis (feature of ectopic ACTH production due to increased output of mineralocorticoids or high cortisol, with renal loss K and H)
• selective venous sampling
• pituitary function tests
• tumour markers: ectopic ACTH
• glucose tolerance test: steroid induced diabetes
Name 5 investigations for suspected catecholamine tumour
Demonstrate excessive production:
• plasma free metadrenalines
• urinary fractionated metadrenalines
• less sensitive tests: urine catecholamines, urine total metadrenalines, urinary vmA
What does high ACTH, low cortisol and lack of cortisol response to Synacthen test indicate
Primary adrenal failure
Test for antibodies to see if autoimmune
Measure cortisol before and after inject synthetic ACTH
How diagnose primary hyper aldosteronism (3)
High aldosterone to renin ratio (AKA low renin)
Aldosterone > 400
Confirm with saline suppression test (aldosterone should decrease with admin of 2L over 4h)
Can be due to Conn’s syndrome (adrenal carcinoma causing hyperaldosteronism)
What should be done if Suspect hyperaldosteronism and patient has hypoK
Correct hypoK because can suppress aldosterone leading to false negative
What is the most common enzyme deficiency in newborns with congenital adrenal hyperplasia and how diagnose
21 hydroxylase deficiency!
Will have markedly elevated 17-OH-progesterone
How differentiate Cushings, adrenal tumour and ectopic ACTH secreting tumour? (All will have high cortisol, suppresses diurnal rhythm, low dose dexamethasone suppression test not suppressed) (3)
Cushings: plasma ACTH normal/high, high dose dexamethasone suppressed, CRH test increased response
Adrenal tumour: ACTH not detectable, high dose dexamethasone not suppressed, CRH test no response
Ectopic ACTH secreting tumour: plasma ACTH very high, high dose dexamethasone not suppressed, CRH test no response
Name 7 causes of primary adrenal insufficiency
- autoimmune
. Infective - secondary tumour
-Infiltrative - congenital adrenal hyperplasia
- adrenoleukodystrophy
- drugs
Name 8 causes of secondary adrenal insufficiency
(Secondary to pituitary insufficiency)
• congenital
• tumours
• infection
• secondary tumour deposits
• vascular lesions
• trauma
• iatrogenic
• secondary to hypothalamic disease
Summarise the diurnal rhythm of the adrenal gland (5)
• Hypothalamus: corticotrophin releasing hormone
• anterior pituitary: ACTH
• adrenal cortex: free cortisol (negative feedback to hypothalami’s ) and bound cortisol to CBG
• androgens (cortex)
• aldosterone (cortex)
Medulla: catecholamines and peptides
How investigate (screen for) adrenal insufficiency? (2)
- If no glucocorticoid therapy: cortisol morning, urea and electrolytes
- If glucocorticoids: short synacthen test (inject ACTH)
Name 5 causes primary hyperaldosteronism (Conn’s syndrome)
• Mostly: idiopathic or bilateral adrenal hyperplasia
• unilateral adenoma (conn’s syndrome)
Rare:
• glucocorticoid suppressible hyper aldosteronism
• primary adrenal hyperplasia
• aldosterone producing carcinoma
Investigation of primary hyperaldosteronism (3)
• Aldosterone: renin increased! (Suppressed renin)
(- urine 18 hydroxy cortisol
- Genetic testing cyp 11B2)
Also hypo k!
Hyper na!
HT, alkalosis
Dynamic function test: saline infusion test!
CT/MRI
How diagnose secondary hyperaldosteronism and what causes it?
Most common cause hyperaldosteronism
High renin! Thus low aldosterone: renin (due to excessive activation of RAAS)
Causes: Renin producing tumour, renal artery stenosis, CHF, cirrhosis, nephrotic syndrome
Treat: diuretics
Where is ACTH produced, what curses its release and where does it act
Anterior pituitary
Stimulated by crh from hypothalamus
Stimulate adrenal cortex to release cortisol
What is produced by adrenal cortex (3)
- Sex hormones: androgens, oestrogens (zona reticularis)
- Mineralocorticoid’s: corticosterone, aldosterone (salt balance) (zona glomerulosa)
- glucocorticoids: cortisol, cortisone (zona fasciculata)
What is produced by adrenal medulla (2)
Catecholamines: epinephrine, norepinephrine
Peptides: somatostatin, substance p
Cortisone vs cortisol?
Cortisone = inactive - medications. Converted in liver
Cortisol = biologically active. Produced by adrenal glands.
How screen for phaechromocytoma (tumour adrenal) (3)
- high catecholamines (plasma or urinary metanephrines - normetadrenaline and metadrenaline)
- provocative testing/dynamic function tests: if above test inconclusive but high clinical suspicion. Give clonidine then measure plasma or urinary metanephrines
- imaging: CT, MRI
What do next if one of the Cushing’s syndrome screening test is positive?
ACTH level
- suppressed = adrenal cause
→ do CT adrenal +/- adrenal vein sampling angiography +/- pet scan - not suppressed = ACTH dependent
→ do CRH test, 48h high dose dexamethasone suppression +- inferior petrosal sinus sampling
> pituitary source: MRI
> ectopic: CXR, CT chest abdo, tumour markers +/- multiple venous sampling for ACTH
Name 2 factors that indirectly stimulate aldosterone
- Low renal blood flow
- hyper K
Name 2 functions aldosterone
- Reabsorb Na
- excrete K
Name 3 hormones affected by adrenal insufficiency causing clinical effects
- Low aldosterone → high urea + K, low Na
- low cortisol
- low androgens
- high ACTH → stimulate melanocytes → hyperpigmentation
Next investigations if confirmed adrenocortical insufficiency with screening tests? (3)
ACTH
- high: primary adrenocortical insufficient
→ CT abdomen, adrenal auto-antibodies, adrenal androgens / urine steroid profile ( if cah suspected) - low: secondary
→ first exclude glucocorticoid therapy
→ pituitary function tests +/ - insulin hypoglycaemia test (if pan hypopituitarism suspected) + /- pituitary MRI
