61 - Hormone Measurement and Interpretation

Question 1

Reference range of free thyroxine

Answer 1

9-25 pmol/L

Question 2

Reference range of TSH

Answer 2

0.4-0.7mIU/L

Question 3

TSH and free T4 levels in the failing thyroid gland

Answer 3

Get an initial slight decrease in free T4, which is compensated by an increase in TSH.
Eventually pituitary gland can no longer stimulate thyroid gland enough to keep up normal production of FT4.
This leads to a steep decline in FT4 and symptoms of hypothyroidism.

Question 4

Most useful test for detecting early thyroid disease

Answer 4

TSH, as increases early in disease, before FT4 has dropped.

Question 5

Dynamic tests

Answer 5

Sampling at multiple points in time.

May involve stimulating or suppressing something(EG thyroid gland) and seeing if it responds appropriately.

Question 6

Uses of dynamic testing

Answer 6

• Subclinical Disease.
A diseased system may appear to function normally under basal conditions but show abnormalities if stressed.
• Investigating Abnormal Results.
Is an abnormal hormone result due to a physiological or pathological cause?

Used less frequently now, as very sensitive assays are more widely available now.

Question 7

Examples of dynamic hormone tests

1-6

Answer 7

• Glucose Tolerance Test
• Dexamethasone Suppression Test
• Synacthen stimulation Test
• Combined Pituitary Function Test
• GH suppression Test
• GH stimulation test

Question 8

Glucose tolerance test

Answer 8

When a patient has a borderline diabetic fasting blood glucose.
Give 75g glucose orally.
Take blood measurements at 0, 1 hour and 2 hours
Expect a slight increase then decrease in a normal person.
In diabetic, get big increase in blood glucose

Question 9

Dexamethasone suppression test
1
2
3

Answer 9

Use if patient has a high cortisol level
• Patient takes dexamethasone at midnight.
• This steroid should suppress normal adrenal production of cortisol.
• Measure cortisol before and after dexamethasone. If normal, cortisol should be low.

Question 10

Role of dexamethasone in suppression test

Answer 10

Inhibits adrenocorticotrophic hormone.

Question 11

When is a synacthen stimulation test used?

Answer 11

When adrenal underactivity is suspected

Question 12

Synacthen

Answer 12

Synthetic ACTH

Question 13

Synacthen stimulation test
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2
3
4

Answer 13

• Stimulate the gland with ACTH and measure cortisol levels.
• 250 ug Synacthen IM at time 0 min.
• Blood cortisol at 0, 30 and 60 min.
• Cortisol levels should rise if normal. Will not rise if adrenal underactivity problem.

Question 14

Combined pituitary function test

Answer 14

Give insulin, TRH, LHRH at time 0 min.
Performed under medical supervision.
Rarely performed today

Insulin leads to hypoglycaemia, leads to hormonal response (ACTH should rise, leading to cortisol rise)

TRH (should cause TSH rise, leading to thyroxin rise)

LHRH (should stimulate prolactin and LH release)

Question 15

GH stimulation test

Answer 15

Cases where GH production is suspected
Stimulate GH release and see if increases.
Stimulus may be exercise, hypoglycaemia,
arginine (arginine insulin test)

Question 16

GH suppresion test

Answer 16

Perform glucose tolerance test with GH levels.
Elevated glucose should cause suppression of GH
Rarely used as now have good GH and IGF-1 assays

Question 17

Techniques often used for hormone measurements

Answer 17

Immunoassays (because need to be able to detect extremely low levels of hormones)

Question 18

Competitive immunoassay

Answer 18

Competition between specimen hormone and added labeled hormone for limited amount of antibody.
When measuring label, less label indicates more specimen hormone binding.
Compare levels of signal from label to a standard curve.

Question 19

Sandwich immunoassay

Answer 19

Antibody against hormone is fixed. Wash serum sample over it. Wash with a second, labelled antibody against hormone. Wash free antibody away. Measure amount of signal.

Question 20

Advantages and disadvantages of monoclonal and polyclonal antibodies

Answer 20

Polyclonal have strong binding, can lack specificity.

Monoclonal can have weaker binding, but good specificity.

Question 21

Tags on most antibodies used now

Answer 21

BIoluminescence.

Question 22

Problem with antibodies

Answer 22

Antibody specificity.

EG Cortisol and other steroid hormones have similar structures, and can be detected as the same thing.

Question 23

Possible effect of patient autoantibodies on hormone testing

Answer 23

This is a rare event in practice.
May have differing effects depending on type
of assay used and how the antibody binds.

Naturally occurring autoantibody which binds to normal hormone.
This may effect
- hormone half life
- biological effects
- response in immunoassays
-eg macroprolactin

Question 24

Heterophilic antibody interference

Answer 24

If a patient has antibodies against mice, can cross link antibodies used in sandwich assays, leading to a false positive