Pituitary Pathology

Question 1

What symptoms/processes occur due to the mass effect of pituitary lesions? (5)

Answer 1

Increased intracranial pressure - HA, N/V, HTN, bradycardia, papilledema.

Visual field disturbances - BL temporal hemianopsia.

Pituitary apoplexy - hemorrhage into the adenoma.

Underproduction of pituitary hormones.

Hyperprolactinemia

Question 2

Sizes of the following pituitary adenomas:

< 1 cm
1-4 cm
> 4 cm

Answer 2

< 1 cm: microadenoma
1-4 cm: macroadenoma
> 4 cm: giant adenoma

Question 3

What is the most common secretory pituitary adenoma (30%)?

Answer 3

Lactotroph adenoma (prolactinoma)

Question 4

Lactotroph adenoma (prolactinoma) presentation in women (5) vs. men (3)

Answer 4

Women: menstrual irregularities (responsible for >20% of cases of amenorrhea), galactorrhea, diminished libido, infertility and mass effect.

Men: decreased libido, decreased sperm count, mass effect.

Question 5

What are the 2 classifications of lactotroph adenomas? Which is more common?

Answer 5

Sparsely granulated - most common

Densely granulated - rare

Question 6

What is the progression of lactotroph adenomas?

Answer 6

Stromal hyalinization w/ psammoma bodies (calcifications) can progress to dense calcifications and eventually a pituitary stone.

Question 7

What are the 2 major treatments for lactotroph adenomas?

Answer 7

Dopamine agonists - Bromocriptine, Cabergoline

Surgery

Question 8

What can cause Hyperprolactinemia in the absence of adenoma? (5)

Answer 8

Pregnancy

Lactation/nipple stimulation

Loss of DA -> lactotroph hyperplasia (damage to neurons (stroke, trauma, etc.), drugs, mass effect.

Renal failure (increased production and decreased clearance of PRL.

Hypothyroidism (increased TSH can stimulate PRL production)

Question 9

What 2 diseases will somatotroph adenomas lead to?

Answer 9

Gigantism and Acromegaly

Question 10

What are some features of Acromegaly?

Answer 10

Enlargement of the face and hands
Protruding jaw
Enlarged nose
Thickened lips

Joint pain/limited mobility
Enlarged viscera
Shortened lifespan (due to CV complications)

Question 11

How is Acromegaly diagnosed?

How is it treated? (3)

Answer 11

Elevated serum levels of IGF-1 prompts an oral glucose tolerance test for GH response.

Somatostatin analogs
GH receptor antagonists
Surgical excision

Question 12

What type of growth is characteristic of all pituitary adenomas?

What helps confirm a diagnosis?

Answer 12

Diffuse growth

Confirmation made w/ GH immunochemistry

Question 13

What is the pathological findings of somatotroph adenomas?

Answer 13

Can be sparsely or densely granulated. May be mixed with PRL-secreting cells.

Question 14

What occurs as a result of a corticotroph adenoma?

Answer 14

ACTH induces hypercortisolism - Cushing’s syndrome

Question 15

What is difference between Cushing syndrome and Cushing’s disease?

Answer 15

Cushing syndrome - obesity, DM, hirsutism, adrenal hyperplasia (basically anything that can occur due to hypercortisolism).

Cushing’s disease - derives from pituitary ACTH (Corticotroph adenoma).

Question 16

Which 3 malignancies can cause Cushing syndrome as a paraneoplastic feature?

Answer 16

Small-cell lung carcinoma

Pancreatic carcinomas

Neural tumors

Question 17

What is the most common cause of Cushing syndrome?

Answer 17

Iatrogenic Cushing syndrome - due to corticosteroid administration.

Question 18

What happens on the high-dose dexamethasone suppression test in a corticotroph adenoma?

What happens during the CRH stimulation test?

Answer 18

Suppression of ACTH

There is an elevated response, meaning they retain their responsivity to CRH.

Question 19

What is the treatment for a Corticotroph adenoma? (3)

Answer 19

Somatostatin agalogs
DA agonists (Bromocriptine)
Surgical excision

Question 20

What is Nelson’s syndrome?

Answer 20

Nelson’s syndrome is a rare disorder and occurs in patients who have had both adrenal glands removed owing to Cushing syndrome

Question 21

What type of adenoma are Gonadotroph adenomas considered?

How do they present?

Answer 21

Non-functioning - “silent” or “null cell” adenomas

Present w/ mass effect. They typically show minimal function.

Question 22

What genetic change is associated with pituitary adenomas? What changes as a result?

Is it somatic or familial?

Which adenoma is it most commonly seen in? Which one is it rarely seen in?

Answer 22

GNAS - makes the alpha subunit of Gs lose its GTPase activity. The signaling cascade is not turned off, so there is constant cAMP-driven cell proliferation.

Somatic

Exists in 40% of Somatotroph adenomas and rarely in Corticotroph adenomas.

Question 23

What mutation occurs in Corticotroph adenomas?

Somatic or familial?

Answer 23

USP8 - mutation results in EGFR upregulation.

Somatic

Question 24

What mutation often effects Somatotroph adenomas?

Somatic or familial?

Answer 24

AIP (FIPA)
PAP - pituitary adenoma predisposition

Familial

Question 25

What is the morphology of a pituitary adenoma generally?

What happens in aggressive adenomas?

Answer 25

Well circumscribed, may erode bone, may bleed.

Aggressive adenomas are poorly circumscribed and may invade brain if they get big enough.

Question 26

What is a Rathke’s cleft cyst?

What can occur as a result?

Answer 26

Cystic mass derived from Rathke’s pouch.

Can expand and compress a normal pituitary. It can rupture and result in inflammation of the pituitary or meningitis.

Question 27

Two groups of Craniopharyngiomas:

Kids (5-15 y/o)

Adults (>65 y/o)

Answer 27

Kids (5-15 y/o): most often adamantinomatous craniopharyngiomas. GR results from the hypopituitarism.

Adults (>65 y/o): papillary craniopharyngiomas. Signs of increased intracranial pressure or hypopituitarism.

Question 28

What are Craniopharyngiomas derived from?

What are 3 histological findings?

Answer 28

Rathke’s pouch remnants.

Squamous epithelium
“Wet” keratin
Calcified cyst

Question 29

What is the cause of primary empty sella syndrome?

What is the cause of secondary empty sella syndrome?

Answer 29

Primary - CSF leaks into the sella and compresses the pituitary.

Secondary - the pituitary expands and infarcts within the sella, leaving an empty space.

Question 30

What are symptoms of anterior hypopituitarism? (5)

Answer 30

Loss of GH - increased fat, decreased muscle, reduced strength.

Loss of gonadotropins - (men) poor libido/impotence, infertility, reduced facial/body hair; (women) amenorrhea, dyspareunia, infertility, breast atrophy.

Loss of TSH - fatigue, constipation, weight gain.

Loss of ACTH - weakness, fatigue, hypoglycemia.

Loss of PRL - lactation failure.

Question 31

What is Sheehan’s syndrome?

Answer 31

Post-partum necrosis of the pituitary gland.

Question 32

Which 2 hormones are secreted by the posterior pituitary?

Answer 32

Oxytocin and ADH

Question 33

Diabetes insipidus =

What are 3 features a patient might notice?

Answer 33

Decreased reclaimation of free water from the renal collecting system.

Increased serum Osm (hypernatremia)
Dilute, excessive urinate
Polyuria

Question 34

What happens when DDAVP is given to patients with central DI vs. nephrogenic DI?

Answer 34

Central DI - kidneys respond w/ increased water retention and increased urine Osm/Na+.

Nephrogenic DI - no response by the kidneys.

Question 35

What occurs in SIADH?

What are 3 features a patient might notice?

What are 3 major causes?

Answer 35

Inappropriate ADH secretion; increased reclaimed free water from renal collecting system.

Decreased serum Osm (hyponatremia)
Concentrated urine (hypernatriuria)
Mental status changes, muscle weakness, seizures

Causes:

• small cell lung carcinoma
• traumatic brain injury/subarachnoid hemorrhage
• drugs (SSRIs)