Pituitary/Hypothal - HG

Question 1

List 4 things that may lead to inaccurate IGF-1 levels?

Answer 1

1. Malnutrition
2. Hepatic disease
3. Renal disease
4. Puberty (if reference range not appropriate for tanner stage)
5. Uncontrolled diabetes
6. Hypothyroidism

Question 2

What is the best screening test for acromegaly/gigantism? What is the confirmatory test?

Answer 2

Screening: IGF-1 level

Confirmatory: GH suppression with oral glucose.

Healthy subjects suppress GH levels to less than 1 ng/mL 2 hours after an oral glucose load (75 g).

Question 3

List 5 instances in which the GH suppression test with oral glucose (for diagnosis of GH excess) may be unreliable.

Answer 3

1) Diabetes mellitus
2) Hepatic or renal disease
3) Obesity
4) Pregnancy
5) Patients on estrogen supplements

Question 4

Why do dopamine agonists work in treating prolactinomas?

Answer 4

Dopamine agonists bind to the pituitary-specific D2 dopamine receptors on the cell membrane of prolactin-secreting cells, decreasing intracellular levels of cAMP and Ca2+. This process inhibits the release and synthesis of prolactin.

Note: The action of dopamine agonists on D1 dopamine receptors in the brain has the side effects nausea and dizziness; dopamine agonists with more D2 specificity, such as cabergoline, are less likely to have these
side effects.

Question 5

Which pituitary hormones share an alpha subunit?

Answer 5

TSH, FSH, and LH.

The beta subunit is specific to each hormone.

Question 6

Treatment of one pituitary deficiency can unmask others. List 3.

Answer 6

1) Treating GH-deficiency can unmask hypothyroidism.
- GH converts T4 to T3; when GH is absent, children have “normal” T4 levels but low T3.
- When treatment is initiated, T4 converts to T3, “unmasking” the low T4.

2) Treating GH-deficiency can unmask adrenal insufficiency (usually only in mild disease).
- GH deficiency leads to increase activity of 11b-hydroxysteroid dehydrogenase type 1
- This results in lower cortisol to cortisone conversion
- Treating with GH increases the conversion to cortisone, “unmasking” low cortisol levels

3) Treating adrenal insufficiency can unmask DI
- Low cortisol levels are associated with water retention which may have a protective effect in DI
- Treatment with GC leads to loss of free-water, “unmasking” DI.

4) Treating hypothyroidism can unmask adrenal insufficiency
- Thyroid hormone increases the metabolic clearance of cortisol and increases metabolic demand.
- Treatment with thyroid hormone can precipitate an adrenal crisis.

Question 7

List 3 syndromes that can predispose to GH-excess (Gigantism or Acromegaly)

Answer 7

1. MEN-1
2. McCune Albright
3. Carney Complex

Question 8

Which are prolactin levels often mildly elevated in patients with pituitary adenomas/tumours?

Answer 8

The release/transport of dopamine to the pituitary is affected by mass effect. As dopamine down-regulates prolactin production, the absence of dopamine leads to higher levels of PRL.

Question 9

While GH-secreting tumours are usually treated surgically, list 3 options for medical management.

Answer 9

1) Somatostatin analogs (octreatotide/lanreotide)
2) GH receptor antagonist (pegvisomant; acts on peripheral GH receptors)
3) Dopamine agonists (limited efficacy)

Note: Approximately 40% to 60% of GH macroadenomas are not controlled by surgery alone, and adjuvant
therapy is indicated.

Question 10

How can you distinguish between thyroid

hormone resistance and a TSH-secreting tumour (biochemical test, non-dynamic)?

Answer 10

TSH tumors may secrete alpha-subunit in excess of whole TSH. Therefore, the molar ratio of serum a-SU to TSH is increased in many patients with TSH tumours but is normal in those with thyroid hormone resistance.

TRH stimulation and T3 suppression are 2 other tests (dynamic) that can be done.

Question 11

What is Nelson syndrome?

Answer 11

The development of an aggressive ACTH secreting pituitary tumour, post bilateral adrenalectomy.

Nelson syndrome occurs in up to 30% of patients post adrenalectomy (sometimes years later).