ChemPath 22: 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 hence hypothyroidism causes hyperprolactinaemia

Question 3

How might pituitary failure present in women?

Answer 3

Amenorrhoea and galactorrhoea

Question 4

What physical manifestation might a macroadenoma of the pituitary gland (> 1 cm) 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. ACTH, TSH, GH)

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 do they increase

Answer 7

Hypoglycaemia – increases CRF/ACTH and increases GHRH/GH

TRH – increases TSH and prolactin

LHRH – 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, activation of the sympathetic nervous system will result in sweating, tachycardia etc.

When the blood glucose reaches < 1.5 mM, neuroglycopaenia may occur (loss of consciousness and confusion)

Question 10

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

Answer 10

< 2.2 mM

Question 11

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

Answer 11

50 mL 20% dextrose

Question 12

How much insulin should the patient receive in CPFT?

Answer 12

0.15 U/kg

Question 13

Outline the dosing of various drugs in the CPFT - what adverse reaction can happen when this is administered

Answer 13

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

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

Question 14

What should be measured n the blood during CPFT? How often?

What result is expected?

Answer 14

Glucose

Cortisol 
GH 
LH and FSH 
TSH 
Prolactin 

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

Everything should rise except glucose which goes down

Question 15

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

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

Answer 15

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

Cortisol > 550 nM
GH > 10 IU/L

Question 16

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

Answer 16

Give more insulin

Question 17

List the order of hormone replacement in someone with panhypopituitarism.

Answer 17

HYDROCORTISONE
Thyroxine
Oestrogen
GH

NOTE: fludrocortisone is not necessary because the adrenals can still produce aldosteron

Question 18

How should a patient with a prolactinoma be treated?

What hormones should be replaced in prolactinoma + how? Which is most important?

Answer 18

Dopamine agonists (e.g. cabergoline) - This reduces the size of the tumour and can avoid surgery

ACTH - Corticosteroids (MOST IMPORTANT - Otherwise Addisonian crisis)
GH - GH
TSH - T4
LH /FSH - Oestrogen/ testosterone/progesterone

Question 19

What is disconnection hyperprolactinaemia?

Answer 19

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

This results in hyperprolactinaemia

Question 20

Why do non-functioning adenomas need surgery?

Answer 20

They do NOT respond to dopamine agonists

Question 21

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

Answer 21

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

Question 22

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

Answer 22

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 producing GH)

Exercise test

Insulin tolerance test (effective but dangerous so should NOT be done straight away)

Question 23

What hormones are released by the hypothalamus and what is their action on the ANTERIOR pituitary? + where do their products act and how?

Answer 23

GNRH -> GH (nb: inhibited by somatostatin) -> IGF-1, IGF-2 (Liver)

CRH -> ACTH -> Cortisol (Adrenals)

TRH -> TSH -> T3/T4 (Thyroid)
TRH -> Prolactin -> Breast milk + inhibits FSH+LH

Dopamine -> Inhibits Prolactin -> Produce breast milk + inhibits FSH+LH

GnRH (LHRH) -> LH/FSH -> Testosterone / Oestrogen (Gonads)

Question 24

What is released by the hypothalamus and what is their action on the POSTERIOR pituitary?

Answer 24

Neuronal signals in hypothalamus -> Oxytocin and Vasopressin (ADH)

Oxytocin - Expresses breast milk (breast) + Uterine contractions (Uterus)

Vasopressin - Vasoconstriction (V1) + Water reabsorption (V2)

Question 25

Causes of hypopituitarism?

Answer 25

Infection - Meningitis (TB)

Inflammation - Sarcoidosis

Malignancy - Pituitary adenoma (func + non-func), Craniopharygiomas (hypothalamic)

Vascular - Sheehans syndrome (pituitary apoplexy)

Iatrogenic - Surgery, radiation

Question 26

What is the most common type of pituitary adenoma? Finding?

Answer 26

Prolactinoma - Usually has prolactin >6000

Note- doesnt always have to be that highly raised

Question 27

Size of macroadenomas?

Answer 27

> 1cm

Question 28

How do non-funcitoning macroadenomas vary to prolactinomas in how they cause the same issue?

Answer 28

They compress the pituitary stalk -> decreased dopamine hence increased prolactin

Question 29

How do prolactinomas and non-functioning macroadenomas cause hypopituitarism?

Answer 29

Non-func macroadenoma:
- Compression of stalk -> less dopamine (hence less inhibition) -> Prolactin inhibits FSH/LH

Prolactinoma:
- Compression of nearby hormone producing cells
- Prolactin inhibiting FSH/LH
(This can also cause inhibition of other hormones in a similar way)

Question 30

Signs + Symptoms of Acromegaly?

Answer 30

Symptoms (insidious onset)

• Headaches
• Hyperhidrosis

Signs

• Spade-like hands
• Prominent supraorbital ridges
• Increased interdental spaces
• Macroglossia
• Prognathism
• Bitemporal hemianopia

Question 31

Ix of Acromegaly?

Answer 31

Increased IGF-1
Combined pituitary function test (CPFT)
Oral glucose tolerance test - Measure GH after this (should be high in acromegaly)

MRI pituitary

Question 32

Mx of Acromegaly?

Answer 32

1st Line = Trans-sphenoidal surgery

D2 receptor agonists (cabergoline/octreotide)
Somatostatin analogues (octreotide/lanreotide)
GH receptor antagonists (pegvisomant)

Question 33

Why do anti-psychotic medications cause high prolactin levels?

Answer 33

They are dopamine antagonists (D2 receptors)

and dopamine normally inhibits prolactin

Question 34

Tolvaptan - What is it’s mechanism of action?

Answer 34

Tolvaptan (vaptan) is a medication used to treat SIADH

hence MoA is V2-receptor antagonist

Question 35

A 31 year old lady is 38 weeks pregnant. Whilst in labour, she had a prolonged 2nd stage which required induction and subsequently caused blood loss of 900 ml. Over the next 48 hours, she complains of headache, lethargy and she is unable to breast feed.

What is the likely cause?

Answer 35

Sheehan’s syndrome

Question 36

A woman presents with headache and bitemporal hemianopia. She is found to have a 2 cm pituitary adenoma on MRI. Her blood results reveal the following:
Raised Prolactin (1400), rest is normal

What is the most likely diagnosis?

Answer 36

Non-functioning pituitary macroadenoma - raised prolactin = secondary to reduced dopamine due to compression of pituitary stalk

Question 37

A woman presents with headache and bitemporal hemianopia. She is found to have a 6 mm pituitary adenoma on MRI. Her blood results reveal the following:
Raised Prolactin (24000), rest is normal

What is the most likely diagnosis?

Answer 37

Prolactinoma

Question 38

A woman presents with headache and bitemporal hemianopia. She is found to have a 4 mm pituitary adenoma on MRI. Her blood results reveal the following:
Raised Prolactin (1400), rest is normal

What is the most likely diagnosis?

Answer 38

Prolactinoma