Chemical Pathology - Pituitary

Question 1

Does pituitary failure cause hypotension?

Answer 1

No - because as long as your adrenal glands are intact, you can still produce aldosterone

*Sometimes doctors miss pituitary failure because BP is normal, but that doesn’t matter*

*Pituitary failure leads to a lack of ACTH but that only really affects cortisol*

Question 2

What are the 6 anterior pituitary hormones and which hypothalamic hormones control their release?

Answer 2

GHRH -> GH

TRH -> TSH and prolactin

Dopamine REDUCES prolactin

LHRH/GnRH -> LH and FSH

CRH -> ACTH

*Different cells produce different hormones so removing a portion of the pituitary gland should spare some of the other hormones*

Question 3

How does pituitary failure present?

Answer 3

Not many symptoms: galactorrhea, amenorrhoea, bitemporal hemianopia (if >1cm macroadenoma pressing on optic chiasm)

Question 4

How are visual fields assessed?

Answer 4

Humphreys 30-2 visual fields test (using a machine)

Question 5

If a patient has a pituitary adenoma and the prolactin is over 6000, what is the cause?

Answer 5

MUST BE A PROLACTINOMA (only cause of such a high prolactin)

*Prolactinomas aren’t usually a problem unless they’re causing visual field defects or impairing the production of other pituitary hormones -> must perform pituitary function testing*

Question 6

What is the CPFT?

Answer 6

Combined pituitary function testing - to ensure that the pituitary is responding adequately to a metabolic stress (by producing ACTH and GH) and to see whether gonadotrophs and thyrotrophs are working properly:

Insulin hypoglycaemic stress -> should increase CRH and therefore ACTH (so that cortisol leads to glucose production), also increase GHRH and thus GH (which leads to glucose production)

TRH -> should stimulate TSH and prolactin

GnRH/LHRH -> should increase LH and FSH

Question 7

What is the caution of pituitary function test?

Answer 7

Causing hypoglycaemia can be dangerous

*Need to ensure there are no cardiac risk factors, angina and that the ECG is normal*

*Need to ensure there is no history of epilepsy as a hypo can cause a fit*

Question 8

How do you avoid dangerous hypos in the pituitary function test?

Answer 8

Ensure good IV access from the beginning so 50ml of 20% dextrose can be given to reverse issues

*Remember that low glucose below 2mM causes sympathetic activation to occur first -> makes patients aggressive and difficult to gain IV access at this point*

*Really low glucose below 1.5mM leads to neuroglycopaenia -> patient loses consciousness and becomes confused

Question 9

What level of hypoglycaemia is adequate in the insulin stress test?

Answer 9

Below 2mM

Question 10

What is the method for CPFT?

Answer 10

Fast patient overnight

Ensure good IV access

Weigh patient and calculate dose required (0.15 units of insulin per kg)

Mix the following in 5ml syringe: insulin 0.15 units/kg, TRH 200mcg, LHRH 100mcg

Take bloods for glucose, cortisol, GH, LH, FSH, TSH, prolactin and T4 for every 30 minutes up to 60 minutes (also measure glucose, cortisol and GH at 90 and 120 mins)

Question 11

What is a normal and abnormal response to CPFT testing?

Answer 11

Normal = glucose drops below 2.2mM and then recovers, cortisol reaches 450mM, GH reaches 10IU/L

*Glucose drop raises TRH which in turn raises prolactin*

Abnormal = reduced production of all hormones

Question 12

Which hormone treatment must be urgently given if the pituitary function is impaired?

Answer 12

HYDROCORTISONE (needed to respond to stress)

*Other replacement therapies include thyroxine, then oestrogen, then GH*

Question 13

What is the treatment to shrink a prolactinoma?

Answer 13

Dopamine D2 agonist e.g. bromocriptine or cabergoline (cabergoline is more specific and only needed once a week compared to 3x a day for bromocriptine)

Question 14

How can a non-functioning pituitary adenoma cause high prolactin? e.g. 2800 - lower than 6000

Answer 14

Adenoma compresses pituitary stalk and prevents dopamine from reaching anterior pituitary

*Common question in path exam - note the difference between prolactin above or below 6000*

Question 15

What is the treatment for a stalk-compressing pituitary adenoma?

Answer 15

Replacement hormones because all the other hypothalamic hormones are also prevented from reaching anterior pituitary:

Hydrocortisone, thyroxine, oestrogen, GH

ALSO potentially worth giving bromocriptine/cabergoline to bring down prolactin and enable fertility -> however, it is a non-functioning tumour so can only be eliminated by SURGERY

Question 16

Does a patient with pituitary failure need fludrocortisone?

Answer 16

NO - this is an aldosterone replacement but RAAS and aldosterone production is unaffected in pituitary failure

Question 17

What is the difference between prednisolone and hydrocortisone?

Answer 17

Prednisolone is more potent and has a longer half-life (more resistant to degradation)

Prednisolone can be given once daily - matches circadian rhythm better and will be used more in the future

Question 18

What are the tests for acromegaly?

Answer 18

Oral glucose tolerance test = gold standard: 75g of glucose and measure GH levels in 2 hours -> GH should drop with glucose administration but you get a paradoxical rise in acromegaly

High measured IGF-1 to confirm diagnosis (produced by the liver in response to GH to promote tissue and bone growth)

Question 19

What are the treatment options for acromegaly - and which is the best?

Answer 19

Order in which options are offered:

Pituitary surgery = BEST (transphenoidal hypophysectomy - certain cautions if the tumour is near blood vessels etc.)

Pituitary radiotherapy

Cabergoline (many acromegalies express D2 receptors)

Octreotide (somatostatin analogue which reduces GH production)

Question 20

What do the adrenals look like?

Answer 20

Mercedes shape, small (like 3cm length)