Pituitary Gland Pathology

Question 1

The major way in which nonfunctioning pituitary pathology comes to attention is via mass effect. What are some manifestations of this mass effect?

Answer 1

Increased intracranial pressure —> headaches, nausea/vomiting, confusion, shallow breathing

Visual disturbances (bitemporal hemianopsia d/t compression of optic chiasm, blurred vision, diplopia, etc.)

Pituitary apoplexy

Underproduction of pituitary hormones

Hyperprolactinemia (not necessarily due to prolactin-producing tumor, just that inhibitors have been destroyed)

Question 2

What is pituitary apoplexy?

Answer 2

Hemorrhage into pituitary adenoma

Question 3

Types of cells found in anterior pituitary adenomas and the hormones they produce

Answer 3

Lactotroph — prolactin

Somatotroph — growth hormone

Corticotroph — ACTH

Gonadotroph — LH/FSH

Thyrotroph — TSH

Question 4

Most common secretory pituitary adenoma

Answer 4

Lactotroph adenoma (aka prolactinoma)

Question 5

Presentation of lactotroph adenoma (prolactinoma) in females

Answer 5

Menstrual irregularities (adenomas responsible for >20% of amenorrhea)

Galactorrhea

Diminished libido

Infertility

Mass effect

Question 6

Presentation of lactotroph adenoma (prolactinoma) in males

Answer 6

Decreased libido

Decreased sperm count

Mass effect [more likely to present as mass effect in males because hormone changes are more subtle — they don’t come to attention until very large]

Question 7

Lactotroph adenomas can be classified as sparsely granulated or densely granulated. Which is more common? Which one is more severe?

Answer 7

Sparsely granulated is more common

Densely granulated is more severe because they are associated with more secretory product

Question 8

Morphology and progression of lactotroph adenomas

Answer 8

Stromal hyalinization with psammoma bodies (calcifications)

Dense calcification progresses —> pituitary stone

Question 9

Treatment options for lactotroph adenoma

Answer 9

Dopamine agonist — Bromocriptine (Cabergoline)

Surgery (via trans-sphenoidal approach)

Question 10

What are some causes of hyperprolactinemia in the absence of an adenoma?

Answer 10

Pregnancy

Lactation/nipple stimulation

Loss of dopamine —> lactotroph hyperplasia (may occur with damage to neurons d/t stroke or head trauma, or d/t drugs like antipsychotics, antidepressants, verapamil, or metoclopramide)

Mass effect

Renal failure (increased production and decreased clearance of PRL)

Hypothyroid (increased TSH can stim PRL production)

Question 11

Somatotroph adenomas present differently based on what?

Answer 11

Whether the growth plate (epiphysis) has closed

Prior to closure, somatotroph adenomas manifest as gigantism

After closure, somatotroph adenomas manifest as acromegaly

Question 12

Clinical features of acromegaly

Answer 12

Enlargement of face and hands

Protruding jaw

Enlarged nose

Thickened lips

Joint pain/limited mobility

Enlarged viscera (including cardiomegaly)

Shortened lifespan (typically d/t CV complications)

Question 13

How is a diagnosis of somatotroph adenoma established?

Answer 13

Serum levels of IGF-1 (secreted by the liver and present in more stable, predictable amounts than GH)

If IGF-1 is elevated, an oral glucose tolerance test is done to check for GH response (in normal physiology, glucose should inhibit GH production, so if it remains high there is an abnormality)

Question 14

Treatment options for somatotroph adenoma

Answer 14

Somatostatin analogs

GH receptor antagonists

Surgical excision

Question 15

All adenomas tend to show _____ growth on histology. Somatotroph adenomas can be sparsely or densely granulated, and can be mixed with _____-secreting cells

Answer 15

Diffuse; PRL

[somatotroph adenomas combined with PRL-secreting cells are called mammosomatotroph adenomas]

Question 16

Cushing syndrome is different from Cushing disease. Which one is specifically derived from a pituitary corticotroph adenoma that produces ACTH?

Answer 16

Cushing disease

Question 17

Cushing syndrome refers to hypercortisolism and the associated symptoms. What are some of the associated symptoms?

Answer 17

Central obesity, hirsutism, moon facies, striae, thin skin, dorsocervical fat pad, edema, menstrual changes, decreased libido, headache, psychiatric disturbances, renal calculi, osteoporosis/fracture, abnormal glucose tolerance

Question 18

Major form of underlying cancer in cases of Cushing syndrome

Answer 18

Small-cell carcinoma of lung

[may also be due to pancreatic carcinoma or neural tumors]

Question 19

What is the most common cause of Cushing Syndrome?

Answer 19

Iatrogenic [d/t excess glucocorticoid administration]

Question 20

Workup for hypercortisolism NOT due to iatrogenic glucocorticoid administration

Answer 20

Check ACTH levels —

If high, it is ACTH-dependent hypercortisolism. Do inferior petrosal sinus sampling and MRI of the brain to determine whether d/t pituitary tumor or ectopic ACTH-producing tumor

If it is low, it is ACTH-independent hypercortisolism. Do CT/MRI of abdomen to determine whether adrenal adenoma/adrenal cancer or bilateral adrenal hyperplasia

[if ACTH levels are borderline, do a CRH stimulation test to clarify]

Question 21

T/F: Pituitary tumors retain some ability to be suppressed by corticosteroids, thus a high-dose dexamethasone suppression test can be used to help diagnose a pituitary microadenoma (Cushing disease)

Answer 21

True

[in contrast, a low-dose dexamethasone suppression test would fail to suppress ACTH]

Question 22

Treatment options for corticotroph adenoma

Answer 22

Somatostatin analogs

Bromocriptine

Surgical excision

[corticotroph adenomas can express dopamine receptors and somatostatin receptors]

Question 23

Condition characterized by large destructive pituitary adenoma that develops after surgical removal of the adrenal glands for treatment of Cushing syndrome

Answer 23

Nelson syndrome

[occurs most often d/t loss of inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma. Because the adrenals are absent, hypercortisolism does not develop, and pts present with mass effects due to the pituitary tumor. There can be hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes]

Question 24

Somatic gene mutation that can be seen in 40% of somatotroph adenomas (and rarely in corticotroph adenomas)

Answer 24

Mutation of GNAS gene — makes the alpha subunit of Gs lose its GTPase activity (so GDP isn’t there to keep it shut off; GTP will initiate cascade with cAMP-driven cell proliferation)

Question 25

Somatic genetic mutation associated with 36-62% of corticotroph adenomas, resulting in EGFR upregulation

Answer 25

USP8 mutation

Question 26

Familial gene mutation associated most commonly with somatotroph adenomas

Answer 26

AIP (FIPA)

—leads to what is known as Pituitary Adenoma Predisposition (PAP)

Question 27

Name some examples of causes of hypopituitarism

Answer 27

Tumors/mass lesions/cysts

TBI/hemorrhage

Apoplexy

Ischemic necrosis/Sheehan syndrome

Inflammatory disorders

Genetic defects

Question 28

Consequences of anterior hypopituitarism

Answer 28

No growth hormone —> increased body fat, decreased muscle mass, reduced strength

No gonadotropins —> poor libido/impotence, infertility, reduced facial and body hair (men); amenorrhea, dyspareunia, infertility, breast atrophy (women)

No TSH —> decreased energy, constipation, weight gain

No adrenocorticotropic hormone —> weakness, tiredness, hypoglycemia

No prolactin —> lactation failure

Question 29

What is Sheehan syndrome? Differentiate acute vs. chronic presentation

Answer 29

Postpartum ischemia/infarct/necrosis of the anterior pituitary

Acute — hypotension and lactation failure

Chronic — may result in any of the symptoms characterizing hypopituitarism

Question 30

A cystic mass derived from ____ ____ is a major cause of hypopituitarism when it expands and compresses the normal pituitary; it can also rupture and result in inflammation of the pituitary or meningitis

Answer 30

Rathke’s cleft cyst

Question 31

Primary vs. secondary empty sella syndrome

Answer 31

Primary: CSF leaks into the sella and compresses the pituitary

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

Question 32

Presentation of craniopharyngioma in kids age 5-15

Answer 32

Most often adamantinomatous craniopharyngiomas

Present with growth retardation from hypopituitarism

Question 33

Presentation of craniopharyngioma in adults >65

Answer 33

Usually papillary craniopharyngiomas

Present with signs of increased intracranial pressure or hypopituitarism

Question 34

Histology of craniopharyngiomas

Answer 34

Derived from Rathke’s pouch remnants — so it has squamous epithelium, “wet” keratin, and can present with calcified cyst

Question 35

Disease resulting from increased reclaimed free water from renal collecting system, leading to hyponatremia, hypernatriuria, mental status changes, muscle weakness, and seizures

Answer 35

SIADH

Question 36

Major causes of SIADH

Answer 36

Small cell carcinoma of the lung (other malignancies as well)

Traumatic brain injury/subarachnoid hemorrhage

Drugs (SSRIs)

Question 37

Disease resulting from decreased reclaimed free water from renal collecting system leading to hypernatremia, dilute urine, and polyuria

Answer 37

Diabetes insipidus

Question 38

What symptom is present in both SIADH and diabetes insipidus?

Answer 38

THIRST

In DI, it is due to a legitimate need to replace fluids

In SIADH, it is a direct effect of ADH on the brain resulting in inappropriate thirst