Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Physiology 1 > 64) Principles of endocrine disease and its assessment > Flashcards

64) Principles of endocrine disease and its assessment Flashcards

1
Q

What are the different layers of the endocrine system?

A
  • Primary: End organ. It is the end organ hormone production that defines the endocrine status of a person. They can either be hyperfunctional (overactive) and hypofunctional (underactive) or eufunctional (normal)
  • Secondary: The pituitary
  • Tertiary: The hypothalamus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the function of the hypothalamus?

A
  • It takes inputs from the brainstem (is the stomach empty or full?), the senses (what can I see around me?), higher centres (am I under threat?) and integrates them
  • They are then changed into an endocrine state by releasing a packet of hormones associated with the desired response (e.g. there will be a packet/group of hormones that bring about a stress response)
  • The hypothalamus then puts its hormones into the hypophyseal portal system where it travels to the pituitary
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the function of the pituitary?

A
  • The hormones secreted by the hypothalamus travel to the pituitary via the hypophyseal portal system
  • Here it amplifies the signal by releasing a large amount of premade hormones and releases them into circulation
  • They travel to the end organ and cause it to release their product
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why does the hypothalamus not secrete its hormones directly into the general circulation?

A
  • It produces a tiny amount of hormones that would not be strong enough to bring about a desired response
  • It must be amplified (by the pituitary) if we want to bring about a change in the body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does the endocrine system elicit a quick response?

A
  • The system is constantly running and regulated at a minimum level where we have a small amount of central and peripheral hormones in circulation
  • This is because if we were to produce the hormones and peptides only when we required them then it would take too long
  • When we need a response the regulation mechanism is inhibited and we are able to rapidly increase the level of hormones in circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why must the endocrine system be able to switch off quickly?

A
  • This is to ensure that one signal does not bleed into another signal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does the endocrine system switch off older signals quickly?

A
  • The end organ hormones produced inhibit the production of the central hormones (i.e. from the hypothalamus and pituitary)
  • This means that as soon as the endocrine response is happening it is working to switch itself off (negative feedback)
  • This allows the system to be dynamic and responsive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the pituitary gland?

A
  • The master gland that is located underneath the hypothalamus and sits in the Sella turcica
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the basis of hormone action?

A
  • Hormones act at receptors
  • These receptors can either be surface or nuclear
  • These hormones can either be peptides (charged) or steroids (aliphatic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What type of hormones work at each type of receptor?

A
  • Peptides work on surface receptors as they are charged and so are unable to pass into the membrane
  • Steroids work on nuclear receptors as they are aliphatic and so are able to pass into the membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What happens to hormone levels during the course of the day?

A
  • Most hormones are pulsatile and vary during the day
  • Therefore when measuring hormone levels we need to use more than one reading or dynamic testing (with an exception of thyroid hormones that have a long half life)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does “-trophin” mean and what does it tell us about the action of a pituitary hormone?

A
  • “-trophin” means food
  • Therefore hormones that have the suffix “-trophin” will trigger release of other hormones from target organs and maintains the secretions
  • For example: Gonadotrophin (food for the gonad) triggers the secretion of TSH and LH. Without gonadotrophin the gland will shirnk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the different hypothalamic, pituitary and final hormones in the body?

A

(Hypothalamic hormone –> Pituitary hormone –> Final hormone)

Gonadotrophin Releasing Hormone –> Gonadotrophin –> LH and FSH

Growth Hormone Releasing Hormone –> Somatotrophin –> Growth Hormone

Thyrotrophin Releasing Hormone –> Thyrotrophin –> TSH

Corticotrophin Releasing Hormone –> Corticotrophin –>ACTH

? –> Lactotrophin –> Prolactin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the principle of hormonal assays?

A
  • They are the law of mass action where we have a binding site (an antibody) along with the ligand (hormone) which exist in equilibrium with a bound complex
  • H + BG < = > H.BG
  • H: Hormone
  • BG: Binding globulin (site)
  • H.BG Bound hormone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What indicators do we use to measure the amount of hormones?

A
  • We use hormones we detectors on them
  • These detectors can either be radioactive (e.g. iodine), a fluorescent dye (which gives off light) or a dye that changes colour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do we measure hormone levels?

A
  • In order to measure the amount of hormones we have to construct a standard curve
  • In the tube we add a solution where there will be some hormones that does not have the detector and some hormones with detectors attached to the assay
  • The binding sites in the assay are limited and at equilibrium all binding sites are occupied
  • After adding the solution we separate the free hormones from the bound hormones and we measure the amount of detector in the bound fraction
  • After constructing the standard curve we can measure the amount of hormone in an unknown sample by carrying out an assay of the sample and measuring the amount of detector
  • We then use our curve to determine the hormone levels from the amount of detector present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Why do we construct a standard curve everyday?

A
  • This is because there are many factors (e.g. the person carrying out the assay and the temperature) which can make changes to the data
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does the standard curve tell us?

A
  • The standard curve shows us how the binding of radioactively labelled hormones decreases as we add more and more unlabelled hormones
  • Therefore when measuring the amount of hormone in a sample we can measure the % of labelled hormone and use the graph to work out the amount of unlabelled hormone (i.e. hormone in the sample)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the different categories of hormone assays?

A
  • Total hormone assays

- Free hormone assays

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are total hormone assays?

A
  • Dependent on binding protein levels
  • This is because most hormones travel in the blood stream bound to a binding protein
  • However this means they are not always reflective of free hormone levels
  • They are cheap and reliable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are free hormone assays?

A
  • We measure the free and biologically active hormone
  • It is not binding protein dependent
  • They involve a separation step which means they are expensive and complex
  • They are also difficult to automate and so in many routine biochemical tests they are not suitable
  • Becuase of the extra steps of separation they may have poor reproducibility which limits their use in a clinical setting
22
Q

How can we separate the bound hormones from the free hormones?

A
  • We can use a semi-permeable membrane which will only allow the free hormones to cross and so we can measure the level of the free hormones that have crossed.
  • We can also add a chelating agent which binds to the proteins and chelates them causing them to fall out of circulation leaving behind the free hormones to be measured
23
Q

Why is the measurement of parathyroid hormones harder?

A
  • It has a very short half life in the plasma
24
Q

How do we measure the amount of peptide hormones?

A
  • We develop antibodies for both ends of the peptide hormones
  • The antibody for one end is attached to the test tube and the sample is then added to the test tube
  • The N terminal ends of the peptides bind to the antibodies in the test tube.
  • The test tube is then washed where all the unbound fragments are washed away
  • Detecting antibodies are then added which bind to the other end of the hormone and so we can then measure the amount of biologically active hormone present using the detectors
  • This is called an immunometric assay
25
Q

What are the hormones involved in thyroid action and its negative feedback system?

A
  • The hypothalamus releases Thyrotropin Releasing Hormone (TRH) which causes the pituitary to release Thyrotrophin/ Thyroid Stimulating Hormone (TSH) into circulation
  • TSH stimulates the release of triiodothyronine and thyroxine/ tetraiodothyronine to inhibit hypothalamic and pituitary release
26
Q

What do we look for in each type of thyroid disease?

A
  • Over production: Thyroid function test, autoantibodies test and do a technetium scanning
  • Under production: Thyroid function test and autoantibodies test
  • Thyroiditis (irritation of thyroid gland): Thyroid function test, ESR and technetium scanning
  • Thyroid Nodule: Ultrasound Scan, FNA and a CT of the neck
  • Goitre: Thyroid Function test, ultrasound scan, CXR, CT/MRI and flow Volume Loop
27
Q

What are the features from an ultrasound which give suspicion of cancer?

A
  • We have a U-classification going from U1 to U5

- The greater the score the greater the suspicion of cancer

28
Q

What are the features from an cytology which give suspicion of cancer?

A
  • There is a Thy-classification going from Thy1 to Thy5
  • The higher the Thy score the higher the suspicion of caner
  • Anybody with Thy3 or above should have the nodule removed by surgery
29
Q

What are the different stages of investigating Cushing’s disease?

A
  • Screening
  • Confirmation of Diagnosis
  • Differentiation of Cause
30
Q

How do we screen and confirm the diagnosis of Cushing’s Syndrome?

A
  • Urinary free cortisol
  • Diurnal Rhythm
  • Over night dexamethasone suppression testing
31
Q

How does the level of cortisol in the blood stream in normal people compare with patients with a tumour?

A
  • In normal patients it is highest in the morning and when we sleep it is virtually undetectable
  • When there is a tumour present they have higher productions of cortisol during the whole course of the day
  • Hence if cortisol is detected at midnight it shows that there may be a problem
32
Q

How does the level of cortisol filtered in the urine in normal people compare with patients with a tumour?

A
  • Normally about 3-5% of the cortisol levels within the blood is freely filtered out the kidney and is found in the urine
  • When there is a tumour we will find higher concentrations of cortisol in the urine as more is produced so more will be filtered out
  • This only occurs when we have normal renal function
33
Q

What is the dexamethasone suppression test?

A
  • If we wish to inhibit the production of cortisol then we must add cortisol (due to the negative feedback system)
  • However we will not know if we are measuring the amount of cortisol made by the body or the amount of cortisol we administered
  • Instead we can administer dexamethasone as the brain cannot tell the difference between dexamethasone and cortisol
  • Dexamethasone inhibits the production of ACTH without directly contributing to cortisol levels
  • In a normal person cortisol production stops
34
Q

How is the overnight dexamethasone suppression test carried out?

A
  • We give a milligram of dexamethasone to the patient at night and the next morning cortisol levels should be undetectable in a normal person
35
Q

What are the different possibilities of Cushing’s Syndrome

A
  • True Cushing’s Syndrome
  • Pseudocushing’s Syndrome: This is where we have a false positive which can be caused by depression, alcoholism, anorexia nervosa and obesity
  • Exogenous steroids: They might be taking steroids. We can ask for a direct history and some examples could be inhalers, eyedrops, nasal drops and skin creams
36
Q

How does the level of cortisol in the blood in normal people compare with patients with pseudocushing’s syndrome after an overnight dexamethasone suppression test?

A
  • After the overnight dexamethasone suppression test in normal patients we see cortisol levels to fall below a certain threshold
  • In pseudocushing’s syndrome the patient is stressed and so they have higher baseline cortisol
  • Hence after the overnight dexamethasone suppression test the patients cortisol levels will fall but will remain at a higher level compared to the results found in the normal patient
37
Q

How do we confirm that a person has true Cushing’s syndrome?

A
  • We use the low dose dexamethasone suppression test.
  • Instead of giving a tablet of dexamethasone we give four tablets a day for four days
  • At the end of this test if the patient’s cortisol level falls below the same threshold as those found with healthy patients then we know that the patient does not have Cushing’s syndrome and so has pseudocushing’s syndrome
  • If it remains higher than the threshold then they truly have Cushing’s Syndrome
38
Q

What are the differential diagnosis after confirming the patient has true Cushing’s syndrome?

A
  • Cushing’s Disease: Pituitary adenoma
  • Adrenal Tumour: Benign or malignant
  • Ectopic ACTH production: Benign or malignant
39
Q

How do we investigate what type of True Cushing’s Syndrome the patient has?

A
  • We can use a high dose dexamethasone suppression test to see whether Cushing’s disease (a tumour) is present
  • We give a dose that is about four times higher and at the end of the two days we will see cortisol levels to fall if it is Cushing’s disease (a tumour)
  • If the levels do not fall then it is not Cushing’s disease and hence the cause of the true Cushing’s syndrome may be either an adrenal tumour or ectopic ACTH production
  • If it is not pituitary then we can look at the ACTH levels
  • If ACTH levels are low then it is an adrenal tumour
  • If ACTH levels are high then it is ectopic ACTH
40
Q

What are the laboratory features of Cushing’s syndrome?

A
  • These include hypokalaemia, metabolic alkalosis and hyperglycaemia.
  • This is due to the activation of the mineralocorticoid receptor which causes K+ and H+ to be taken into the cell and Na+ to be released from the cell
  • This increased activation is a result of the usual defence mechanism which stops cortisol acting on a mineralocorticoid receptor (11-Beta Hydroxysteroid Dehydrogenase) is overwhelmed by the amount of cortisol in circulation
  • This means the cortisol can then access the receptor
41
Q

What is the Corticotrophin Releasing Hormone (CRH) test?

A
  • Instead of giving an inhibitory hormone this time we are giving patients a stimulatory hormone CRH and measuring changes in ACTH levels
  • When a healthy person is given CRH their ACTH levels in the blood doubles
  • In Cushing’s disease there is an excessive response and so we will see a massive increase in ACTH levels (about 4 times the level at base line)
  • If there is an adrenal adenoma there is a strong negative feedback and hence ACTH levels are low. Even if they are given the stimulatory hormone (CRH) the ACTH levels remain suppressed
  • With ectopic ACTH the ACTH levels are high but since the source of ACTH are not pituitary cells they will not be able to respond to CRH and so ACTH levels remains constantly high
42
Q

After confirming the type of true Cushing’s syndrome what do we do next?

A
  • We localise the problem using imaging
  • Pituitary: MRI or Inferior Petrosa sinus sampling (IPSS)
  • Adrenal: CT scan or MRI
  • Ectopic ACTH: Octreotide Scan or ACTH Sampling
43
Q

Why do we have to distinguish the type of True Cushing’s syndrome before localising?

A
  • Many people may have a coincidental tumour on their adrenals or on their pituitary which may not be the cause of the Cushing’s syndrome
  • So to ensure we know where the source of the excess ACTH production is located
44
Q

How do we test for adrenal insufficiency?

A
  • 9 AM cortisol screening test
  • ACTH levels in the blood
  • Electrolytes: Looking for hyponatremia with hyperkalaemia
  • Adrenal imaging
  • Infection screen
  • Adrenal anti-bodies
  • Investigations for other causes of adrenal failure
  • Imaging for cancer
45
Q

How do we test for low cortisol reserve?

A
  • We use the Synacthen test: Can be short (used to diagnose primary adrenal failure) or long (used to diagnose secondary adrenal failure)
  • The short Synacthen test uses a smaller dose of Synacthen than a long Synacthen test
  • Synacthen is synthetic ACTH
46
Q

How do we conduct the short Synacthen test?

A
  • We give an injection of Synacthen into a patient and see how much cortisol the glands can produce
47
Q

How do we conduct the long Synacthen test?

A
  • If there is secondary adrenal failure (lack of ACTH) the adrenal gland shrinks
  • Although it produces the hormone it is too small to achieve its function
  • In the long Synacthen test we give a large dose of Synacthen which allows for some recovery of the gland and hormone production
48
Q

What is the stress test?

A
  • If we give a stress to the body it stimulates the production of CRH and ACTH
  • We can measure the amount of hormones produced at any stage of the cortisol feedback loop
  • In the stress test we are testing the brains ability to react to stimuli directly
49
Q

What is the insulin tolerance test?

A
  • It is a stress test in which the patient is put in a hypoglycaemic episode
  • We do this by giving them a large dose of insulin and we see how the hormone levels respond
  • It is the Gold standard for assessing adrenal reserve
  • However since it is a stress test we are unable to do it on someone with heart disease, epilepsy, severe cortisol deficiency, very old/young people or on pregnant people
  • Where the insulin tolerance test is contraindicated the glucagon test can be used
50
Q

How do we test for acromegaly?

A
  • We conduct an oral glucose tolerance test.
  • Here we give an oral glucose load and we look to see what happens to the growth hormone (GH) levels
  • In a normal person the GH levels falls
  • In acromegaly the level of GH does not fall but instead rises
51
Q

What are endocrine diseases caused by?

A
  • Too much hormone

- Too little hormone

52
Q

How do we test for hormone levels?

A
  • Since hormone levels vary physiologically we have to use dynamic testing methods rather than static testing methods
  • If hormone levels are too high we suppress it
  • If hormone levels are too low we stimulate it

Physiology 1 (64 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions