ChemPath: Pituitary

Question 1

Why doesn’t hypopituitarism cause low blood pressure?

Answer 1

The adrenals are still able to produce aldosterone

Question 2

Which hypothalamic hormones affect prolactin release?

Answer 2

Dopamine → negative

TRH → positive

NOTE: hypothyroidism causes hyperprolactinaemia (Primary hypothyroidism causes elevated thyrotropin-releasing hormone (TRH) levels that can result in thyrotroph and lactotroph hyperplasia)

Question 3

How might a pituitary macroadenoma present in women?

Answer 3

Amenorrhoea and galactorrhoea

(this is due to compression of the pituitary stalk, reduction in the inhibitory effects of dopamine and increased release of prolactin)

Question 4

What physical manifestation might a macroadenoma of the pituitary gland (>1cm) cause?

Answer 4

Bitemporal hemianopia

NOTE: this can be tested using a visual field test

Question 5

What is the main problem with prolactinomas?

Answer 5

It might reduce/stop the production of other pituitary hormones (e.g. FSH and LH) or affect the axis

High prolactin in itself is not much of an issue.

Question 6

What is the CPFT?

Answer 6

Combined Rapid Anterior Pituitary Evaluation Panel

Test for pituitary function

Question 7

Which three stimuli of pituitary hormone secretion are used in the CPFT (what drugs are administered)?

Answer 7

• Hypoglycaemia (via insulin) - increases CRH/ACTH and increases GHRH/GH
• TRH - increases TSH and prolactin
• LHRH (aka GnRH) - increases LH and FSH

Question 8

What safety precautions must you take before subjecting a patient to hypoglycaemia?

Answer 8

• No cardiac risk factors (needs a normal ECG)
• No history of epilepsy
• Ensure good IV access

Question 9

Describe the manifestations of increasing hypoglycaemia?

Answer 9

• Initially, the activation of the sympathetic nervous system will result in sweating, tachycardiac etc.
• When the blood glucose reaches <1.5mM, neuroglycopaenia may occur (loss of consciousness and confusion)

Question 10

What blood glucose concentration is normally required to stimulate the pituitary gland?

Answer 10

<2.2mM

Question 11

How should a patient be rescued if they experience severe hypoglycaemia during this CPFT?

Answer 11

50ml 20% dextrose

Question 12

How much insulin should a patient be administered to induce hypoglycaemia during a CPFT test?

Answer 12

0.15 U/kg

Question 13

Outline the dosing of various drugs in the CPFT.

Answer 13

• 5mL syringe
• Insulin (0.15 U/kg)
• TRH 200 µg
• LHRH 100 µg

NOTE: the patient may experience a warm flush and vomit when the drug is administered

Question 14

What should be measured in the blood?

Answer 14

• Glucose
• Cortisol (caused by insulin)
• GH (caused by insulin)
• LH and FSH (caused by GnRH)
• TSH (caused by TRH)
• Prolactin (casued by TRH)

Question 15

How frequently should hormone levels in the blood be measured?

Answer 15

• Every 30 mins for 60 mins - LH, FSH, TSH, prolactin
• Every 30 mins for 120 mins - glucose, GH, cortisol

Question 16

Describe the response you would expect from a normal pituitary gland undergoing the CPFT?

Answer 16

Blood sugar will go down but then it will rise again without any external help. This is due to production of GH and ACTH (and hence cortisol) in response to the metabolic stress.

Question 17

What should be done if a response isn’t observed at a plasma glucose of 2.2 mM?

Answer 17

Give more insulin

Question 18

What level of cortisol and GH is considered a normal response?

Answer 18

Cortisol >550nM

GH >10 IU/L

Question 19

List the order of hormone replacement in someone with panhypopituitarism.

Answer 19

• Hydrocortisone
• Thyroxine
• Oestrogen
• GH

NOTE: Fludrocortisone is not necessary because the adrenals can still produce aldosterone

Question 20

How should a patient with a prolactinoma be treated?

Answer 20

Dopamine agonists (e.g. cabergoline)

This reduces the size of the tumour and can avoid surgery

Question 21

What is disconnection hyperprolactinaemia?

Answer 21

Compression of the pituitary stalk by a tumour cuts off the negative effect of dopamine on pituitary prolactin secretion

This results in hyperprolactinaemia

Question 22

Why do non-functioning adenomas need surgery?

Answer 22

They do NOT respond to dopamine agonists

Question 23

Why might prednisolone replace hydrocortisone as the first-line steroid replacement agent?

Answer 23

It has a longer half-life meaning that once daily dosing is possible

Question 24

How should you investigate a child with poor growth who is suspected of having a GH deficiency?

Answer 24

• Take a random plasma GH measurement (GH is pulsatile but if you happen to measure it during a pulse and they have detectable GH then it shows that they are produing GH)
• Excercise test
• Insulin tolerance test (effective but dangerous so should NOT be done straight away)

Question 25

Name two tests that may be used to investigate suspected acromegaly.

Answer 25

• Oral glucose tolerance test
• IGF-1 levels

NOTE: the normal ranges for IGF-1 are not fuly resolved and they vary with age

Question 26

What are the management options for acromegaly

Answer 26

1. Pituitary Surgery
2. Others
   
   1. Pit radiotherapy
   2. Cabergoline
   3. Ocreotide