Endocrine Disorders Flashcards
What can we do when investigating endocrine disorders
- Measure hormone levels: are they appropriate?
- Is endocrine tissue functional: dynamic tests of endocrine function
Describe the Hypothalamic- pituitary-thyroid axis
- The hypothalamus releases TRH which stimulates the primary gland to release TSH
- TSH triggers the production of T4 and T3 in the thread glands
- T4 being the precursor of T3 and T3 being the biologically active hormone
- Increased T3/T4 concentration negatively feedbacks onto the hypothalamus and pituitary to produce less TRH and TSH
What is meant by primary Hypothyroidism
- Autoimmune destruction of the thyroid
- Reduced production of thyroid hormone from the gland itself
- Hashimotos disease
Low T3/T4 levels but High TSH levels
What is meant by secondary hypothyroidism
Reduced thyroid production by under-stimulation from the pituitary
Low T3/T4 levels and Low/None TSH levels
What is meant by primary Hyperthyroidism
Increased production of hormones from the gland itself
- Grave’s disease - antibody stimulation of thyroid
High T3/T4 levels and Low TSH levels
What is meant by secondary Hyperthyroidism
Increased stimulation of thyroid gland due to overactive pituitary
High T3/T4 levels and High TSH levels
List the adrenal steroids
- Mineralocorticoids
(aldosterone) - Glucocorticoids (cortisol)
- Adrenal androgens
What are the adrenal disorders
Adrenal hyperfunction:
- Excess cortisol (Cushing’s
syndrome) - Excess aldosterone (e.g.
Conn’s syndrome)
Adrenal Insufficiency:
- Hypocortisolism (lack of cortisol)
- Lack of aldosterone and
cortisol (Addison’s)
What controls the secretion of aldosterone
- RAAS
- Increased plasma Potassium concentration
Describe the RAAS pathway (REVISION)
- The macula dense senses perfusion pressure and salt concentrations
- Juxtaglomerular cells release renin when activated by the macula densa
- Renin converts angiotensin, made in the liver, to angiotensin 1
- Angiotensin 1 is converted to angiotensin 2 by ACE
- Angiotensin 2 causes vasoconstriction and stimulates aldosterone secretion
What activates the RAAS pathway
- Reduced renal perfusion
- Increased sympathetic activity
Both interpreted as reduced blood volume
What effects will excess aldosterone have on RAAS activation
- Hypertension
- Hypokalaemia
How can we diagnose aldosterone related diseases
- Measure the plasma aldosterone and renin concentrations and compare the ratio with normal readings
- High aldosterone: low renin is characteristic of primary aldosteronism
- High aldosterone: high renin is characteristic of secondary aldosteronism - Renal artery stenosis
What are the main actions of cortisol in the body
- Immunosuppression
- Maintain BP
- Promote gluconeogenesis
Promotes lipolysis - Preserves plasma glucose
Excess can cause muscle wastage, hyperglycaemia and hypertension
Describe the Hypothalamic-pituitary-adrenal axis
- The hypothalamus secretes CRH and VP which stimulates the pituitary to release ACTH
- ACTH acts on the adrenal glands to produce androgens and cortisol
Describe the blood cortisol concentration changes over 24hrs in a patient
- Peaks in the morning
- Lowest at midnight
- Difficult to measure plasma cortisol levels as it changes frequently over the day
What is the most common cause of Cushing’s syndrome
Iatrogenic - as a result of medical therapy
- 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
Weaned gradually off glucocorticoid therapy
What are the two causes of excess cortisol
- ACTH-secreting pituitary adenoma
- Ectopic release of ACTH
How does ACTH-secreting pituitary adenoma cause excess adrenal gland activity
- The increased ACTH causes excess stimulation of the adrenal cortex which causes excess production of cortisol and androgens
- The excess cortisol and androgens cause negative feedback on the hypothalamus and pituitary to produce less ACTH
- However the negative feedback has little effect on the release of ACTH
How does Ectopic ACTH cause excess adrenal gland activity
- Ectopic ACTH stimulates the production of cortisol and androgens
- Negative feedback on the hypothalamus and pituitary causes less ACTH production
- However, the adrenal cortex responds to the ectopic ACTH and not the pituitary ACTH
How can we do a differential diagnosis for Cushing’s syndrome
- Test plasma cortisol concentrations at times we know what value it should be
- 24-hour urine sample analysis and compare to reference values
- Dexamethasone suppression test
Describe how the dexamethasone suppression test works
- Administer the glucocorticoid dexamethasone in patients and test cortisol concentration
- Normally expect cortisol to be suppressed in the morning but not in cushing’s
- Repeat with a high dose of dexamethasone for 4 days
- Suppression at 2nd or 3rd days if from adrenal gland
- If no suppression it is ectopic
Describe primary adrenal insufficiencies
- Addison’s disease
- Insufficient cortisol and aldosterone
- Inappropriate VP levels
Describe secondary adrenal insufficiencies
- Pituitary or hypothalamic disease
- Insufficient cortisol
- Inappropriate VP levels
What are the clinal features of Addison’s disease
- Hypotension
- Plasma sodium concentration: low to high - Increased ADH and water excretion
- Plasma potassium concentration: normal to high - Decreased aldosterone
- High ACTH - decreased aldosterone and increased negative feedback
- Elevated plasma renin - decreased kidney perfusion
What are the signs and symptoms of Addison’s disease
- Anorexia
- Weakened/ fatigue
- Hyperpigmentation
- GI symptoms
How can we diagnose Addison’s disease
- Dynamic ACTH stimulation test
What is the dynamic ACTH stimulation test
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
