CP9-2 investigations of endocrine disease

Question 1

What are hormones?

Answer 1

Messenger molecules produced by endocrine glands which circulate around the body to elicit a response - short or long term - from a compatible target cell.

Question 2

What are the three main type of hormones? Where are they produced?

Answer 2

Peptide - produced in pituitary or parathyroid hormone
Steroid - produced in adrenal glands
Tyrosine-based - produced by thyroid gland

Question 3

What are all steroid hormones made from?

Answer 3

Cholesterol

Question 4

What are examples of peptide hormones?

Answer 4

PTH
ACTH
TSH

Question 5

What are the three ways that steroid hormones illicit a respons at the target cells?

Answer 5

Classical model
Receptor-mediated endocytosis
Signalling through cell-surface receptors

Question 6

What are examples of steroid hormones?

Answer 6

Testosterone
Oestradiol
Cortisol

Question 7

What are examples of tyrosine-based hormones?

Answer 7

Thyroxine (T4)
Triiodothyronine (T3)

Question 8

How is the endocrine system regulated?

Answer 8

By negative feedback

Question 9

What does thyroxine (T4) inhibit production of?

Answer 9

TRH and TSH

Question 10

What is the TSH pathway?

Answer 10

TRH produced by hypothalamus
Stimulates production of TSH at pituitary gland.
TSH stimulates the thyroid to produce

Question 11

What is the free hormone hypothesis?

Answer 11

Only unbound thyroxine is physiologically active and detected in a test, so if levels of thyroxine-binding globulin changes, the level of free hormone is affected. This then changes the measurement of hormone levels.

Question 12

When is cortisol level testing inacurrate?

Answer 12

Oestrogen contains contraceptive pill

Question 13

Where and what is the pathology if TSH is normal/low and thyroxine is low?

Answer 13

In the pituitary gland leading to secondary hypothyroidism

Question 14

Where and what is the pathology when TSH is high but the thyroxine levels are low?

Answer 14

in the thyroid gland leading to primary hypothyroidism usually due to Hashimoto’s

Question 15

Where and what is the pathology if TSH levels are low and thyroxine is high?

Answer 15

In the thyroid gland leading to primary hyperthyroidism usually due to Grave’s disease

Question 16

Where and what is the pathology if TSH is high and thyroxine is also high?

Answer 16

On the pituitary gland due to a TSH producing tumour

Question 17

What diagnosis can be missed if a normal TSH level is seen upon testing but no thyroxine testing is done?

Answer 17

Secondary hypothyroidism as around 84% of patients with this have normal TSH

Question 18

Why is thyroxine not measured for if TSH is normal but secondary hypothyroidism is suspected?

Answer 18

As very rare and often picked up on other tests

Question 19

Why should thyroid hormones not be tested for in acutely ill patients?

Answer 19

As TSH and thyroxine often drops and T3 increases but this is most likely to be due to their acute illness not a thyroid problem

Question 20

How often should TFTs be done?

Answer 20

Every 3 years in a healthy person
In hyperthyroidism when treating Graves’ disease, 1-2 months after radioactive iodine or 6-8 weeks post op after thyroidectomy
In hypothyroidism when minitoring treatment annually in long term thyroxine treatment or 2 months after change of dose

Question 21

How are hormones tested for in blood testes?

Answer 21

Immunoassays or mass spectrometry

Question 22

Why are immunoassays used to test for hormone levels more than mass spectrometry?

Answer 22

as its amenable to automation

Question 23

What are the two types of immunoassays?

Answer 23

Non-competitive
Competitive

Question 24

What can compromise immunoassays?

Answer 24

Interference

Question 25

What are phaeochromocytomas?

Answer 25

An adrenal medullary tumour of neuroendocrine chromaffin cells seen in adults

Question 26

What percentage of phaeochromocytomas are bilateral?

Answer 26

5%

Question 27

What percentage of phaeochromocytomas are malignant?

Answer 27

10%

Question 28

What percentage of phaeochromocytomas are in extra-adrenal neuroendocrine cells?

Answer 28

10%

Question 29

What are the clinical features of phaeochromocytoma?

Question 30

How is a phaeochromocytoma diagnoses?

Answer 30

Using plasmametanephrine levels 24 hour urine fractionates metanephrines Clonidine suppression test Plasma chromogranin A

Question 31

Why is it hard to diagnose phaeochromocytomas?

Answer 31

As it is not uncommon for false negative and false positive results of biochemical tests

Question 32

How is hypoglycaemia diagnosed?

Answer 32

Based on Whipple’s triad - low plasma glucose - signs and symptoms of hypoglycaemia - resolution of symptoms once glucose levels rise

Question 33

What are autonomic signs and symptoms of hypoglycaemia?

Answer 33

Hunger Sweating Anxiety Paresthesis Palpitations Tremulousness Pallor Tachycardia Widened pulse pressure

Question 34

What are neuroglycopenic signs and symptoms of hypoglycaemia?

Answer 34

weakness + fatigue dizziness headache confusion behavioural changes cognitive dysfunction blurred vision and diplopia --> cortical blindness hypothermia seizures coma

Question 35

What are endogenous causes of hypoglycaemia?

Answer 35

Insulin-mediated e.g. insulinoma Insulin-independent e.g. critical organ failure, sepsis, hormone deficiency, non-islet cell tumours

Question 36

What are exogenous causes of hypoglycaemia?

Answer 36

Alcohol Facetious Therapeutic drugs e.g. insulin

Question 37

What is an insulinoma?

Answer 37

Most common tumours arising from islets of langerhans?

Question 38

When should blood be taken for insulin and blood glucose tests?

Answer 38

when patient is hypoglycaemic

Question 39

What type of blood test is used in diagnosing insulinomas?

Answer 39

Fasting

Question 40

What results in blood tests are seen in patients with insulinomas?

Answer 40

Low blood sugar - less than 2.2 mmol/L High insulin - 6 micro units/ml or more High levels of C peptide - >0.2nmol/L

Question 41

What are features of Cushing’s?

Answer 41

Obesity - centrally and on shoulders and causes moon face Think skin with bruising and purple striate Hypertension Glucose intolerance Menstrual disturbances Thin limbs and muscle weakness Depression

Question 42

How is cortisol produced?

Answer 42

ACTH produced by pituitary gland causes adrenal glands to produce cortisol. Negative feedback of cortisol to the pituitary gland then inhibits ACTH production.

Question 43

What causes Cushing’s syndrome?

Answer 43

Excess cortisol production due to: - Cushing’s disease Pituitary gland tumour - adrenal gland tumours - exogenous gluticocorticoid therapy - Ectopic ACTH secreting tumours e.g. small cell carcinomas, islet cell tumours of the pancreas, medullary carcinoma of the thyroid, thymus gland tumours

Question 44

What causes the contralateral adrenal gland to shrink when there is a unilateral adrenal gland tumour?

Answer 44

excess cortisol production from affected adrenal gland inhibits ACTH production of the pituitary gland so the contralateral gland is not stimulated

Question 45

If adrenal insufficiency is suspected, what test is done?

Answer 45

Synactin test

Question 46

How do you test for Cushing’s syndrome?

Answer 46

Overnight dexamethasone supression test