endocrine

Question 1

How do we investigate endocrine disorders?

Answer 1

1. measure levels : are they appropriate?

2. Is endocrine tissue functional : dynamic tests of endocrine function - designed to stimulate levels of hormone

Question 2

hypothalamic -pituitary -thyroid - axis (negative feedback)

Answer 2

hypothalamus (TRH)
pituitary (TSH)
Thyroid gland (T3 and T4)
peripheral tissues (T4 -> T3)

Question 3

hypothyroidism/hyperthyroidism

Answer 3

=>hypothyroidism:
- Hashomoto’s
-thyroid gland doesn’t produce T4 and T3
=> Hyperthyroidism
-Grave’s disease
- antibodies bind to thyroid gland and stimulate more production of T3 and T4.
=>primary disease - bc the problem is in thyroid gland itself

Question 4

What are disorders of adrenocortical function?

Answer 4

-excess cortisol (eg: Cushing’s syndrome)
-excess aldosterone (eg: Conn’s syndrome)
-Adrenal insufficiency
=>hypocortisolism
=>lack of aldosterone and cortisol (Addison’s)

Question 5

how is aldosterone secretion controlled?

Answer 5

Activated by: 
1. RAAS 
2. Increased plasma [K+] 
RAAS is activated by 
1. Reduced renal perfusion 
2. increased sympathetic activity 
Both interpreted as fall in blood volume.

Question 6

RAAS

function to maintaining blood volume not salt conc

Answer 6

• decreased perfusion, increased SNS activity , decreased Na+, Cl- in distal tubule.
• macula densa can sense salt in tubular fluid and communicate with juxtaglomerular cells and release renin
• Angiotensinogen -> angiotensin 1 (by renin)
• angiotensin 1 -> angiotensin 2 by ACE
• Angiotensin 2 binds to Angiotensin 2 receptors on adrenal cortex(increase aldosterone secretion, to increase sodium reabsorption, because sodium brings water in so net effect is increased water not salt concentration, to increase blood volume) and blood vessels (increase vasoconstriction)

Question 7

What are disorders of RAAS?

Answer 7

-hyperaldosteronism
leads to hypertension
hypercalemia
=> diagnosis of primary hyperaldosteronism
-measure plasma aldosterone and renin ratio
-high aldosterone : low renin

Question 8

What is the most common cause of Cushing’s syndrome?

Answer 8

• iatrogenic
• exogenous gluccocorticoids activate cortisol receptor
• at high doses will shut down HPA Adrenal cortex atrophies with lack of ACTH stimulation
• several days may be required for adrenal gland to become responsive to ACTH again .

Question 9

What is diagnostic test for Cushing’s syndrome?

Answer 9

• Dexamethansone
• measure suppression at high and low doses and plasma ACTH
• Cushing’s = no suppression at low and high suppression at high , plasma ACTH high
• Adrenal tumour = no suppression in high and low dose, plasma ACH low
• ectopic ACTH = no suppression in both both high and low and very high plasma ACTH

Question 10

What is differential diagnosis test for Addisons’s?

Answer 10

=> asses he ability of adrenal gland to to produce cortisol in response to ACTH short synacthen test(synthetic ACT

1. short synthacthen test: measure baseline cortisol and 30 minutes after
   - if cortisol is increased by >200 or >550 after 30 minutes it is a secondary adrenal insufficiency (not primary = problem with the adrenal gland)
2. long synacthen test
   - 3 days
   - absence of stimulation by ACTH time needed to regain responsiveness.