Adrenal

Question 1

Name 8 causes glucocorticoid excess / Cushing syndrome

Answer 1

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

Question 2

Name 3 investigations for suspected Cushing’s (screen)

Answer 2

• 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

Question 3

Name 3 most common causes Cushing’s syndrome NB

Answer 3

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

Question 4

Name 2 causes pseudo-cushings and how to confirm dx

Answer 4

• Suspected alcohol - abstinence
• depression - CRH (corticotropin releasing hormone) test

Question 5

Name 5 other less important tests for cushings

Answer 5

• 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

Question 6

Name 5 investigations for suspected catecholamine tumour

Answer 6

Demonstrate excessive production:
• plasma free metadrenalines
• urinary fractionated metadrenalines
• less sensitive tests: urine catecholamines, urine total metadrenalines, urinary vmA

Question 7

What does high ACTH, low cortisol and lack of cortisol response to Synacthen test indicate

Answer 7

Primary adrenal failure
Test for antibodies to see if autoimmune

Measure cortisol before and after inject synthetic ACTH

Question 8

How diagnose primary hyper aldosteronism (3)

Answer 8

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)

Question 9

What should be done if Suspect hyperaldosteronism and patient has hypoK

Answer 9

Correct hypoK because can suppress aldosterone leading to false negative

Question 10

What is the most common enzyme deficiency in newborns with congenital adrenal hyperplasia and how diagnose

Answer 10

21 hydroxylase deficiency!
Will have markedly elevated 17-OH-progesterone

Question 11

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)

Answer 11

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

Question 12

Name 7 causes of primary adrenal insufficiency

Answer 12

• autoimmune
  . Infective
• secondary tumour
  -Infiltrative
• congenital adrenal hyperplasia
• adrenoleukodystrophy
• drugs

Question 13

Name 8 causes of secondary adrenal insufficiency

Answer 13

(Secondary to pituitary insufficiency)
• congenital
• tumours
• infection
• secondary tumour deposits
• vascular lesions
• trauma
• iatrogenic
• secondary to hypothalamic disease

Question 14

Summarise the diurnal rhythm of the adrenal gland (5)

Answer 14

• 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

Question 15

How investigate (screen for) adrenal insufficiency? (2)

Answer 15

• If no glucocorticoid therapy: cortisol morning, urea and electrolytes
• If glucocorticoids: short synacthen test (inject ACTH)

Question 16

Name 5 causes primary hyperaldosteronism (Conn’s syndrome)

Answer 16

• Mostly: idiopathic or bilateral adrenal hyperplasia
• unilateral adenoma (conn’s syndrome)

Rare:
• glucocorticoid suppressible hyper aldosteronism
• primary adrenal hyperplasia
• aldosterone producing carcinoma

Question 17

Investigation of primary hyperaldosteronism (3)

Answer 17

• 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

Question 18

How diagnose secondary hyperaldosteronism and what causes it?

Answer 18

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

Question 19

Where is ACTH produced, what curses its release and where does it act

Answer 19

Anterior pituitary

Stimulated by crh from hypothalamus

Stimulate adrenal cortex to release cortisol

Question 20

What is produced by adrenal cortex (3)

Answer 20

• Sex hormones: androgens, oestrogens (zona reticularis)
• Mineralocorticoid’s: corticosterone, aldosterone (salt balance) (zona glomerulosa)
• glucocorticoids: cortisol, cortisone (zona fasciculata)

Question 21

What is produced by adrenal medulla (2)

Answer 21

Catecholamines: epinephrine, norepinephrine

Peptides: somatostatin, substance p

Question 22

Cortisone vs cortisol?

Answer 22

Cortisone = inactive - medications. Converted in liver

Cortisol = biologically active. Produced by adrenal glands.

Question 23

How screen for phaechromocytoma (tumour adrenal) (3)

Answer 23

• 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

Question 24

What do next if one of the Cushing’s syndrome screening test is positive?

Answer 24

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

Question 25

Name 2 factors that indirectly stimulate aldosterone

Answer 25

• Low renal blood flow
• hyper K

Question 26

Name 2 functions aldosterone

Answer 26

• Reabsorb Na
• excrete K

Question 27

Name 3 hormones affected by adrenal insufficiency causing clinical effects

Answer 27

• Low aldosterone → high urea + K, low Na
• low cortisol
• low androgens
• high ACTH → stimulate melanocytes → hyperpigmentation

Question 28

Next investigations if confirmed adrenocortical insufficiency with screening tests? (3)

Answer 28

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