Endocrine Disorders Flashcards
How can we investigate endocrine disorders?
Measure hormone levels: are they appropriate?
- The first is straightforward in some cases, if a hormone is very low or absent, or ridiculously high, but in other cases more interpretation is required
- Should this hormone level be lower or higher in this particular situation
Is endocrine tissue functional: dynamic tests of endocrine function
- The second involves testing the endocrine tissue that produces the hormone. Is it still responding?
- There are various tests aimed at stimulating endocrine tissue in ways known to normally stimulate or inhibit release of a hormone.
- We can measure how hormone levels change in response to such tests to see if the endocrine tissue that produces the hormone is still capable of responding.
- On the basis of such tests we can then attempt to correct the endocrine disorder, e.g., by replacing a hormone to try and mimic normal levels, or to intervene to stop over-production.
Recall the HPT axis.
The parvocellular neurons in specific hypothalamic nuclei synthesise and release the hormone TRH
Released from the axon terminals of these neurons, it diffuses into the portal veins which carries it to the pituitary gland where to binds to receptors on Thyrotrophs
These cells produce thyrotropin called TSH
TSH released into the general circulation will cause the thyroid to increase production of its hormones namely mostly T4 and T3
T3 is the biologically active
In the peripheral tissues T4 is converted to T3
T4 and T3 feed back negatively on the pituitary and hypothalamus
What is the hormonal difference between hypo and hyper-thyroidism?
Hypo Hyper
1° …. 2 …. 1° ….. 2°
T3/T4 L L H H
TSH H L/N L H
What some adrenal disorders?
Adrenal hyperfunction
- Excess cortisol causes Cushing’s syndrome
- Excess aldosterone causes for example Conn’s syndrome
Adrenal insufficiency
- Hypocortisolism
- Lack of aldosterone and cortisol (Addison’s)
Adrenocortical excess
Aldosterone excess
- Conn’s syndrome (also called primary hyperaldosteronism)
Cortisol excess
- Cushing’s syndrome (may be primary or secondary)
How is aldosterone secretion controlled?
Activated by
1. RAAS (have one flashcard describing the RAAS and how it maintain blood volume)*
2. Increased plasma [K+]
RAAS is activated by
1. Reduced renal perfusion
2. Increased sympathetic activity
Both interpreted as a fall in blood volume
How does secondary hyperaldosteronism occur?
Secondary hyperaldosteronism:
- Such as renal artery stenosis - A kidney is under perfused - Which is going to activate all the signals that activate RAAS - So there will be increased renin secretion which will increase angiotensin and therefore aldosterone activity
Give an overview of cortisol’s effects on the body
First, note that cortisol is essential for maintenance of normal blood pressure.
Second let’s look at some of its metabolic effects
It increases plasma glucose via several different mechanisms:
- It promotes insulin resistance in skeletal muscles so that muscles won’t take up glucose
- Promotes lipolysis so muscle can use fats instead of glucose
- Stimulates gluconeogenesis creating more glucose
Excess cortisol in the absence of such stress causes problems
The insulin resistance in the skeletal muscles will lead to hyperglycemia, as will increased gluconeogenesis
The increase in plasma glucose will lead to an increase in insulin and since plasma glucose is not taken up by the muscle the insulin will promote lipogenesis
The excess glucose will be turned to lipids and stored as fat which is why cushing’s disease symptoms include truncal/central adiposity and sometimes a thinning of the arms and legs from muscle wasting
What is the HPA axis and how does it work?
The hypothalamic-pituitary-adrenal axis
The hypothalamus secretes CRH which is carried via the portal vein to the pituitary where ACTH is secreted
ACTH stimulates the adrenal cortex to produce cortisol and the adrenal androgens
There is a negative feedback system in place so that cortisol binds in the pituitary and hypothalamus
Cortisol levels also fluctuate depending on the circadian rhythm (high in morning, low at night)
The circulating cortisol also exerts negative feedback onto vasopressin/ADH to a lower level
What is the most common cause of Cushing’s syndrome?
Exogenous glucocorticoids activate the 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
What is Cushing’s disease caused by and how?
Cushing’s disease is due to ACTH-secreting pituitary adenoma
- So there is more ACTH, more cortisol and also more negative feedback
How can Cushing’s syndrome be caused by an ectopic ACTH source?
Cushing’s syndrome may also be due to ectopic ACTH source
- Could be from a from a tumour elsewhere in the body that secretes ACTH
· ACTH from the pituitary will be low but the negative feedback does not affect the ectopic ACTH
- Or from a hyperfunction of the adrenal cortex
What is the differential diagnosis of Cushing’s syndrome?
Dexamethasone is a synthetic glucocorticoid which will activate the cortisol receptor in the hypothalamus and pituitary
With an intact feedback loop you would expect dexamethasone to supress cortisol levels
If you do the test in someone with Cushing’s syndrome the dexamethasone will not supress with a low dose
With a high dose you get suppression on the second or third day in people with Cushing’s disease because the feedback loop is intact but at a higher level
If the source is ectopic dexamethasone will not suppress the ectopic source; only the anterior pituitary
If there’s a problem with the adrenal cortex, the ACTH levels would be really low
What are the classifications of adrenal insufficiency?
Primary - Addison’s disease - Insufficient cortisol and aldosterone Secondary - Pituitary or hypothalamic disease - Insufficient cortisol
What are the clinical features of Addison’s?
Primary adrenal insufficiency clinical signs
- Hypotension
- Plasma [Na+]: normal to low- due to the absence of negative feedback causing increased ADH release, promoting pure water reabsorption
· This will have the effect of diluting electrolytes in the extracellular fluid
- Plasma [K+]: normal to high- aldosterone promotes potassium excretion so in its absence it can rise
· Does not always occur as vomiting can keep plasma K+ down
- High ACTH
- Elevated plasma renin due to lack of aldosterone and potential volume depletion
May be unmasked by significant stress or illness – which can lead to shock, hypotension, volume depletion (adrenal crisis)
What are the symptoms of Addison’s?
- Anorexia
- Weakness and fatigue
- Hyperpigmentation- as ACTH will cross react with the melanocortin receptor stimulating melanocytes
GI symptoms- nausea, vomiting, constipation, abdo pain
Hypotension
Salt cravings
Postural dizziness
Vitiligo
Muscle or joint pain
