Hyperpituitarism

Question 1

What is the most common etiology of hyperpituitarism?

Answer 1

Pituitary neuroendocrine tumors (PitNETs), previously known as pituitary adenoma

Question 2

What are non-functional macro-PitNETs?

Answer 2

Large, non-functional PitNETs at least 1 cm in size (hence, the name “macro”) that starves anterior pituitary of blood and its input from the hypophyseal portal system via compression of the pituitary stalk

ROADBLOCK

Question 3

What are the consequences of non-functional macro-PitNETs?

Answer 3

1. Ischemia due to compression of vasculature supplying anterior pituitary and other structures
2. Decreased trophic (stimulating) hormone levels due to lack of portal import to anterior pituitary, which is caused by compression of the pituitary stalk
3. Increased prolactin due to inability of dopamine to exert its effects (dopamine must travel through hypophyseal portal system in pituitary stalk to reach the anterior pituitary)

Question 4

What are lactotroph-derived PIT-1 tumors?

Answer 4

Nonfunctional PitNETs derived from lactotrophs whose cells over-express PIT-1 (transcription factor)

There is loss of the inhibitory effects of dopamine due to reduced D2 receptor expression, loss of normal signaling downstream of dopamine (low cAMP), or autonomous (dopamine-independent) secretion

Loss of inhibitory effects of dopamine leads to increase in prolactin (hyperprolactinemia), which manifests as galactorrhea, amenorrhea, and decreased libido

Question 5

What are somatotroph-derived PIT-1 tumor?

Answer 5

Nonfunctional PitNETs derived from somatotrophs whose cells over-express PIT-1 (transcription factor)

A mutation in the GNAS gene leads to increased growth hormone secretion, causing acromegaly (adults) and gigantism (children)

Question 6

What are T-PIT tumors?

Answer 6

Nonfunctional PitNETs derived from corticotrophs whose cells over-express T-PIT (transcription factor)

Increased ACTH secretion causes ACTH-dependent Cushing’s syndrome

Silent variant only exerts local mass effect

Question 7

What are SF-1 tumors

Answer 7

Silent PitNETs derived from gonadotrophs whose cells over-express SF-1 (transcription factor)

Tumors cells exhibit immunohistochemical stain indicating increased FSH and LH secretion, although secretion is not clinically significant

Cause local mass effect only
Rarely, ovarian hyperstimulation and macro-orchidism occur due to increased FSH and LH