Principles Of Endocrine Disease And Its Assessment Flashcards
Where do peptide hormones act and why?
→ surface receptors because they are charged
Where do steroid hormones act and why?
→ nuclear receptors because they are aliphatic
What type of hormone is thyroid hormones?
→ steroid
What type of testing do you have to use for hormones and why?
→ dynamic
→ Hormones are pulsatile and vary during the day
How do you do a radioimmunoassay in the lab?
→ a labelled hormone that is a marker (radioactive)
→ antibody
→ Limited number of binding sites
→ centrifuge and measure how much radioactivity is in the bound fraction
→ do a standard curve
What is an advantage of a total hormone assay?
→ cheap
What are 2 disadvantages of a total hormone assay?
→ Hormones are found bound to proteins which affects the measurements and is not reflective of the true amount of hormone
Why is the total amount of hormone not a true indicator?
→ Only hormones that are not bound to protein have a true effect
What are advantages of a free hormone assay?
→ Representative of active hormone fraction
→ Not binding protein dependant
What are disadvantages of a free hormone assay?
→ Complex and expensive
→ Can have poor reproducibility
If you have more steps in an assay what does this do to the accuracy?
→ decreases the accuracy
→ transfer errors
How do you separate free hormones in an assay?
→ dialysis membrane
→ causing binding protein to precipitate out
What does the radiometric assay work on?
→ on peptide hormones
Why is measuring a peptide hormone difficult?
→ Peptide hormones have a very short half life
→ Enzymes cleave them
→ you have fragments of them in the circulation
How does a radiometric assay work?
→ antibody binds to amide end
→ sticks to test tube
→ wash test tube
How does tri iodothyronine get produced?
→ TRH is released from the hypothalamus
→ goes to the pituitary and causes the release of TSH
→ TSH acts on the thyroid
→ tri-iodothyronine is the biologically active hormone
How do you measure overproduction of thyroid hormone?
→ autoantibodies
→ Technetium scanning
→ Thyroid function
How do you measure underproduction of thyroid hormone?
→ Thyroid function
→ Autoantibodies
How do you check for thyroiditis?
→ Thyroid function
→ ESR(erythrocyte sedimentation rate)
→ Technetium
Why is thyroiditis sometimes mistaken for overproduction of thyroid hormone?
→ thyroid has about 18 months worth of thyroid hormone stored
→ If it gets infected it becomes leaky and releases the hormone
What do you measure if there is a suspected thryoid nodule?
→ Ultrasound
→ Fine needle aspiration biopsy
What is the diagnosis if T4 is high and TSH is high?
→ Check peripheral hormone
→ high - hyperthyroidism
→ decide whether primary or secondary
→ if T4 is high then TSH should be low (inhibits)
→ Has not happened so the problem is secondary
What is the negative feedback mechanism of thyroxine?
→ TSH sent to thyroid
→ Thyroid produces T3 and T4
→ T4 is end hormone so it inhibits TSH
If T4 and T3 is high and TSH is low what is the diagnosis?
→Hyperthyroidism
because peripheral hormones are high
→ primary because the TSH is low - correct functioning of the brain
If TSH is high and T3 and T4 are low what is the diagnosis?
→ Hypothyroidism
→Less negative feedback
→ TSH should increase
→ Primary because TSH is high - correct brain function
If TSH is low and T3 and T4 are low what is the diagnosis?
→ Hypothyroidism
→ TSH should increase
→ brain function incorrect
→ Secondary
If T4 is low, TSH is low and T3 is normal what is the diagnosis?
→ Sick Euthyroid
How should the dexamethasone suppression test be in normal people?
→ Cortisol level should decrease below 50
→ high dose should be 50% of baseline
Dethamethasone test in people with cushings disease?
→ low dose = not below 50
→high dose = more than 50% decrease
→ ACTH are high
Dexamethasone test in people with adrenal tumor?
→ low dose = not below 50
→ high dose = less than 50% decrease
→ ACTH is low
Dexamethasone test in people with ectopic ACTH?
→ low dose = more than 50
→ high dose = less than 50 decrease
→ ACTH very high
How do you test for Addisons?
→give synthetic ACTH
→ Cortisol level rises
What is the short synacthen test?
→ Shot of ACTH
→ Cortisol goes above 400
→ Diagnose adrenal failure
What is the long synacthen test used for?
→Blood taken over 24 hours
→ Diagnose secondary adrenal failure
What happens in the long synacthen test if it is pituitary vs Addisons?
→ Cortisol levels rise
→ can cause growth of adrenal gland
→ if addisons the cortisol wouldn’t be raised
What is done to test for growth hormone deficiency?
→ Large insulin dose
→ hypoglycaemia (less than 2.1)
→ cortisol should increase
What is the oral glucose tolerance test?
→ test for GH excess → 75g oral glucose → samples for GH taken → normal individuals GH fall → Acromegaly = rise
If the hormone is too high how do you test?
→ Suppress it
If the hormone is too low how do you test for it?
→ Stimulate it
What is involved in screening Cushing’s disease testing?
Urinary free cortisol
Diurnal Rhythm
Overnight dexamethasone suppression test
The Investigation of Cushing’s Disease is in Three Stages
- Screening
- Confirmation of the Diagnosis
- Differentiation of the cause
What is involved in differential diagnosis of Cushing’s?
- True Cushing’s
- Pseudocushing’s syndrome
- exogenous steroids
What do results of the CRH test mean?
- An exaggerated response indicates pituitary dependant Cushing’s Disease
- A flat response indicates ectopic ACTH production
What are some localisation techniques used on different glands?
1. Pituitary →MRI →Iinferior Petrosa; sinus sampling IPSS 2. Adrenal →CT or MRI 3. Ectopic →Octreotide Scan →ACTH Sampling
What are long and short Synacthen tests for?
Long: Used to diagnose secondary adrenal failure
Short: Used to diagnose primary adrenal failure
What is the gold standard for assessing adrenal reserve?
Insulin tolerance test
Insulin is administered to achieve hypoglycaemia with glucose less than 2.1 mmol/L
Hypoglycaemia stimulates the stress response which is mediated by the compensatory hormones for hypoglycaemia
What happens if the insulin tolerance test is contraindicated?
glucagon test can be used