L30 Hypothalamus and pituitary gland

Question 1

Pituitary gland is located in the sella tuirca and is connected to the hypothalamus by fragile pituitary stalk. What is the clinical implication of the fragile pituitary stalk? (1) What would be the expected results (2)?

Answer 1

Copmression of the stalk can be caused by head injury/craniopharyngioma (a para-pituitary tumor, from pituitary embryonic tissue)

> hypopituitarism + hyperprolactinemia

Question 2

Give 4 clinical presentations caused by a mass effect by a brain SOL on the pituitary gland.

Answer 2

1. Bitemporal hemianopia
   - compression on the optic chasm
2. Hypopituitarism
   - loss of all normal pituitary cell types (+/- isolated excess in hormone from the tumor)
3. Ophthalmoplegia
   - compression of CN3,4,6 within the carvenous sinus
4. Headache:
   - stretching of the diaphragm sella, obstruction of CSF drainage

Question 3

Hypoactive pituitary - we can use triple function tests to induce release of hormones.
List 3 examples.

Answer 3

1. Synacthen test: (ACTH) that induces release of cortisol
2. GnRH stimulation test: induces LH/FSH axis
3. TRH stimulation test: induces TSH, T4,T3 hormones and prolactin

Question 4

For Hypoactive pituitary, other than stimulating release of hormones, we can also test substances that induce pituitary activity.
3 examples.

Answer 4

1. Insulin tolerance test/ Glucagon stimulation test > glucagon causes increased BG > increase insulin > reactive hypoglycaemia > should have an increase in GH and cortisol (dual axis)
2. Amino acids intake > induce GH release
3. Water deprivation test: induce ADH release

Question 5

For hyperactive pituitary, what are the 2 principles of testing?

Answer 5

1. Inhibitory tests

2. Substances that are supposed to exert negative feedback.

Question 6

List 3 examples of inhibitory tests on hyperactive pituitary.

Answer 6

1. Bromocriptine (D2 agonist) on prolactin release
2. ONDST (Over night dexamethasone) > measure cortisol in the morning

• dexamethasone is a synthetic glucocorticoid that reduces ACTH release to distinguish ethology of Cushing’s
• not suppressed in Cushing’s syndrome

3. HDDST (high dose) > 50% for pituitary adenoma; not suppressed in ectopic ACTH/adrenal adenoma.

Question 7

Which test uses the principle of substances exerting negative feedback to test hyperactive pituitary gland?

Answer 7

• Oral glucose suppression test/somatostatin test

> should suppress GH

Question 8

What test to do if low ADH?

Expected results?

Answer 8

= suspect diabetes insidious

• Water deprivation test (+DDAVP - desmopressin ~mimics ADH) to differentiate cranial/nephrogenic DI
• If cranial DI > increase in urine osmolality (because can reabsorb water)
• if nephrogenic DI > no change

Question 9

Functions of prolactin (2) and stimulatory + inhibitory tests (2)?

Answer 9

Function

1. Lactation
2. Inhibit gonadotrophin release

Tests
Stimulatory
1. TRH to stimulate prolactin
2. D2 antagonist - Domperidone

Inhibitory

3. Dopamine D2 agonist - bromocriptine to increase dopamine and thus inhibit prolactin release
   - when suspect prolactinoma

Question 10

GH works with _________ to ?

Answer 10

IGF-1; promote growth

Question 11

What test to do in suspected dwarfism?

Answer 11

Stimulatory tests
1. Glucagon stimulation test (more preferred than insulin tolerance test due to safety)

2. Sleep
3. Amino acids (Bovril)
4. Heavy exercise

Question 12

What tests to do in suspected gigantism (before puberty) / acromegaly (after)?

Answer 12

Oral glucose tolerance test/ Somatostatin

- should inhibit GH

Question 13

Which of the following is true?
More likely to be non-functioning pituitary adenoma with hyperprolactinemia (NFPAH) rather than prolactinoma if?

A. The patient has older age
B. Relatively low prolactin level <5000 mIU/L
C. There is extrasellar tumor expansion
D. There is visual defect
E. There is GH deficiency

Answer 13

All of the above

Question 14

List 4 possible pre-analytical errors when measuring hormone levels.

Answer 14

1. Collection time
   - daily circadian rhythm e.g. cortisol (0600), GH (night(, TSH (night), testosterone(0600)
2. Menstrual cycle and menopause
   - estradiol, progesterone, LH, FSH
3. Venepuncture induces stress hormones release e.g. cortisol, prolactin > perform dynamic tests 30 mins after inserting a catheter
4. Labile hormones should be processed immediately e.g. ACTH, renin, PTH

Question 15

Hormones require sensitive methods to be analysed.

List 2 radioimmunoassays and 2 non-radioactive methods.

Answer 15

Radioimmunoassays: antibodies, radioisotopes

Non-radioactive: enzymes, flurophores

Question 16

What are the possible pitfalls when measuring glycoproteins (e.g. LH, FSH, TSH, hCG)?

Answer 16

They have the same alpha submit and specific beta subunit > cross-reactivity

• Also in prolactin family (prolactin, GH, human placental lactose hPL)
• GH increased in pregnancy

Question 17

Other than cross reactivity, suggest 2 other pitfalls in hormone assays.

Answer 17

Fragments of labile hormones may be immunoreactive but not biological active.
/
Radioisotopes given to patients for radiography may interfere with radioactive counting in radioimmunoassays