Endocrine disorder

Question 1

What can we do if we think there an endocrine disorder?

Answer 1

1. Measure hormone levels: are they appropriate?
2. Is endocrine tissue functional: dynamic tests of endocrine function
3. Always interpret with respect to controlling variable
   Attempt to correct if necessary

Question 2

Describe the HPA axis with respect to thyroid

Answer 2

On image

Question 3

What is thyroid hormone needed for?

Answer 3

Thyroid hormone is needed for:
• Normal growth and development
• Increase metabolic rate – ATP, heat production, glucose release and upregulates the cardiovascular system

Question 4

Define hypothyroidism

where does primary and secondary occur?

Answer 4

Hypothyroidism – too little thyroid hormone. To diagnose this we measure TSH levels in the blood.

(primary in the thyroid gland/ secondary in the hypothalamus)

Question 5

Define hyperthyroidism

Answer 5

Hyperthyroidism – too much thyroid hormone

Question 6

Describe the release from neuroscretory cells in the hypothalamus of thyrotrophin

Answer 6

In the hypothalamus there are neurosecretory cells (parvocellular neurones) within specific nuclei and release thyrotrophin releasing hormone, these neurones have short axons and terminate on the capillary base of the hypothalamus release TRH into local capillaries which collect in the portal vein carrying TRH to the anterior pituitary gland which activates TSH synthesising cells, TSH is then released into the circulation where it binds to receptors on the thyroid gland stimulating production of T4 and T3. This system is under negative feedback (refer to image).

Question 7

Describe the structure of the adrenal glands

Answer 7

• The adrenal glands sit on top of the kidney.
• The adrenal gland consists of an out layer of cells called the cortex and an inner layer called the medulla
• The cortex is divided into 3 zones: the outer secretes mineralocorticoids (aldosterone), middle secretes the glucocorticoids (cortisol) the inner secretes the adrenal androgens.
• Blood flows from the outer surface of the cortex to the inner medulla

Question 8

Describe adrenal hyperfunction

Answer 8

Adrenal hyperfunction
• Excess cortisol (Cushing’s syndrome) (primary hyperaldosteronism)
• Excess aldosterone (e.g. Conn’s syndrome)

Question 9

Describe adrenal insufficiency

Answer 9

Adrenal insufficiency
• Hypocortisolism
• Lack of aldosterone and cortisol (Addison’s)

Question 10

What controls aldosterone secretion?

Answer 10

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

Question 11

How is plasma aldosterone/ renin ratio is useful in diagnosis of primary hyperaldosteronism?

Answer 11

Source of excess aldosterone is adrenal (e.g., aldosterone-secreting adenoma)

Question 12

What effect will excess aldosterone have on RAAS activation?

Answer 12

Hyperaldosteronism is a disease in which the adrenal gland(s) make too much aldosterone which leads to hypertension (high blood pressure) and low blood potassium levels.

Question 13

What are the actions of cortisol?

Answer 13

On image

Question 14

Describe the HPA axis with respect to the adrenal glands

Answer 14

On image

Question 15

What is the most common cause of cushings syndrome?

Answer 15

Most common cause of Cushing’s syndrome is iatrogenic
• Exogenous glucocorticoids 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 to become responsive to ACTH again

Question 16

Give another cause of cushings syndrome

Answer 16

Cushing’s syndrome may also be due to ectopic ACTH source

Question 17

Have a look at the differential diagnosis of cushings disease

Answer 17

On image

Question 18

What causes primary and secondary adrenal insufficiency?

Answer 18

Primary 
•	Addison’s disease 
•	Insufficient cortisol and aldosterone
Secondary 
•	Pituitary or hypothalamic disease
•	Insufficient cortisol

Question 19

What are the clinical features of addisons (primary adrenal insufficiency)?

Answer 19

Primary adrenal insufficiency
•	Hypotension 
•	Plasma [Na+]: normal to low
•	Plasma [K+]: normal to high 
•	High ACTH
•	Elevated plasma renin

May be unmasked by significant stress or illness – shock, hypotension, volume depletion (adrenal crisis)

Question 20

Describe the acth stimulation test and long synacthen test

Answer 20

ACTH stimulation test
Assess ability of adrenal to produce cortisol in response to ACTH
Short synacthen test
• Measure baseline cortisol (9am) and 30 min after 250 µg synacthen (synthetic ACTH) i.m.
• Adrenal insufficiency is excluded by an increase in cortisol of >200 nmol/L and/or a 30 min value >550
Long synacthen test
• Adrenal cortex ‘shuts down’ in absence of stimulation by ACTH – time needed to regain responsiveness
• 3-day stimulation with synacthen
• In secondary (but not primary) adrenal insufficiency cortisol increases by >200 nmol/L over baseline
• Long test not often necessary since ACTH assay can distinguish