Pituitary Pathophysiology

Question 1

4 categories of disease of the hypothalamus and pituitary?

Answer 1

Tumors
Infiltrative diseases
Meningitis
Trauma

Question 2

3 broad types of tumors that affect the hypothalamus and pituitary?

Answer 2

Adenomas of the ant. pituitary.
Tumors from embryological remnants (eg. Rathke’s cleft cells).
Metastases to the hypothalamus.

Question 3

3 infiltrative diseases that can affect the hypothalamus and/or pituitary? Where does each affect?

Answer 3

Hemochromatosis - pituitary.
Sarcoidosis - hypothalamus.
Langerhans cell histiocytosis - hypothalamus.

Question 4

What’s the only kind of pituitary disease that can cause hypersecretion?

Answer 4

Pituitary Adenoma

In contrast… pretty much any problem can cause hyposecretion.

Question 5

3 effects of GH deficiency? (there may be more)

Answer 5

Shortened stature (if occurs prior to epiphyseal closure).
Reduced muscle mass, increased fat mass.
Decreased bone mineral density.

Question 6

What’s the one pituitary hormone we can’t currently replace?

Answer 6

Prolactin

Question 7

How does hormone structure relate to the presentation of pituitary adenomas?

Answer 7

“-trophs” that make peptides are more likely to present with signs of hormone imbalance. (GH, PRL, ACTH)
“-trophs” that make glycoproteins are less likely to produce functional hormones, and thus more often don’t present until tumor is causing a mass effect. (FSH, LH, TSH)
(obviously this is not 100%)

Question 8

2 clinical syndromes caused by somatotroph adenomas? What determines the difference between the two?

Answer 8

Gigantism and acromegaly.

Gigantism occurs when GH levels are high before the closure of epiphyseal plates.

Question 9

What does somebody with acromegaly look like?

Answer 9

Enlarged facial features - supraorbital ridge, jaw, nose etc.
Bigger feet, bigger fingers.

Question 10

Two lab tests for a GH-secreting somatotroph adenoma?

Answer 10

See if GH/IGF-1 is suppressed in response to glucose load - won’t be suppressed if adenoma.
Measure IGF-1 - will be elevated if adenoma.

Question 11

6 bad to life-threatening consequences of acromegaly?

Answer 11

Severe osteoarthritis.
Cancer, esp of the colon.
CV disease.
Diabetes mellitus.
Neuropathy - esp. things like carpal tunnel syndrome.
Sleep apnea (due to thickened pharyngeal tissues).

Question 12

3 types of Tx for somatotroph adenoma?

Answer 12

Surgery.
Medications.
Radiation.

Question 13

3 pharmacologic treatment of somatotroph adenoma?

Answer 13

Dopamine agonists (paradoxical effect).
Somatostatin analogues.
GH receptor antagonists.

Question 14

What’s the deal with using dopamine agonists for somatotroph adenoma?

Answer 14

Dopamine leads to GH release in normal somatotropes.

But in somatotroph adenomas, dopamine suppresses GH release.

Question 15

What’s the name of the dopamine agonist mentioned as being used for acromegaly (and for hyperprolactinema)?

Answer 15

Cabergoline. (ergot derivative. Ergotism -> delirium / psychosis due to dopamine activity…)

Question 16

What’s one GH receptor antagonist?

Answer 16

Pegvisomant (binds to dimerized GH receptor)

Question 17

Difference in lactotroph adenoma presentation in pre-menopausal vs. post-menopausal women? Why?

Answer 17

Pre-menopausal: amenorrhea / oligomenorrhea, galactorrhea.
Post-menopausal: mass effect neuro symptoms.
Post-menopausal women don’t have periods to mess up and apparently breast tissue isn’t responsive to PRL, and thus tumors present later.

Question 18

Effects of lactotroph adenoma in men?

Answer 18

Decreased libido, fertility, potency.

Question 19

4 normal causes of PRL release?

Answer 19

Pregnancy
Nursing
Exercise (?)
Stress (physical and psychological)

Question 20

Are lactotroph adenomas the only cause of hyperprolactinemia? One way to distinguish?

Answer 20

Nope, can be caused by lots of things, esp. dopamine antagonists, estrogens, opiates, etc.
PRL levels from lactotroph adenomas will typically be much greater than from other causes.

Question 21

2 clinical syndromes associated with corticotroph adenomas?

Answer 21

Neuro effects from mass effect.

Cushing’s syndrome.

Question 22

What’s a pharmacological treatment for thyrotroph adenoma?

Answer 22

Somatostatin analogues.

Question 23

Most common presentation of gonadotroph adenoma?

Answer 23

Neuro signs and symptoms due to mass effect.

Question 24

2 hormonal syndromes that can be caused by gonadotroph adenoma?

Answer 24

Precocious puberty in males due to LH.

Ovarian hyperstimulation in pre-menopausal women due to high FSH.

Question 25

Visual defect commonly seen in pituitary adenoma?

Answer 25

Bitemporal hemianopsia. (upper quadrants tend to be lost first, as tumor is compressing optic chiasm from the bottom)

Question 26

What do hormone levels look like in the presence of a gonadotroph adenoma?

Answer 26

Elevated subunits, eg. alpha subunit, LH-beta, but there are often not elevated levels of intact gonadotropins. (but sometimes it happens)

Question 27

You suspect a woman has PCOS and you give her leuprolide (GnRH analogue). But she really has a gonadotroph adenoma. What will happen?

Answer 27

This will actually massively increase gonadotropins and estrogen levels. Gonadotroph adenomas are apparently stimulated, not suppressed, by exogenous GnRH.