Pathology of the Pituitary Gland

Question 1

Give the components of the adenohypophysis and the neurohypophysis.

Answer 1

Adenohypophysis - Pars tuberalis (on stalk), pars intermedia, pars distalis

Neurohypophysis - pars nervosa and infundibulum (pituitary stalk)

Question 2

What gives rise to the anterior and posterior pituitary?

Answer 2

Anterior - Rathke’s pouch - an evaination of the oropharyngeal ectoderm

Posterior - ventral diencephalon / median eminence of hypothalamus

Starts functioning by 6-8 weeks

Question 3

What are the cells which make up the posterior pituitary?

Answer 3

Mostly glial cells, since the large portion of axons in the pars nervosa are ADH / oxytocin producing neurons from the supraoptic / paraventricular nuclei.

Glial cells = Pituicytes

Question 4

What structures are most likely to be directly affected by pituitary tumors?

Answer 4

Structures directly adjacent to the sella turcica

1. Cavernous sinus - directly adjacent, includes distal portions of internal carotid arteries, cranial nerves 3, 4, V1/V2, and 6, with 6 most likely to be damaged.
2. Optic chiasm -> sits directly above sella
3. Sphenoid sinus
4. Diaphgrama sellae, sits above and prevents CSF access into the sellae

Question 5

How is most surgery of the pituitary gland done and why?

Answer 5

Via transnasal trans-sphenoidal approach

• > this is because the sphenoid sinus lies directly below the pituitary.
• > can enter the brain thru the nasal cavity

Question 6

Give the primary cells which produce each of the following hormones of the anterior pituitary: GH, PRL, ACTH, FSH, LH, TSH, and MSH.

Answer 6

GH - Somatotroph
PRL - Lactotroph
ACTH - Corticotroph
FSH / LH - Gonadotroph
TSH - Thyrotroph
MSH - Corticotroph -> also produced via POMC like ACTH

Question 7

What is a chromophobe? What hormone does it make?

Answer 7

An inactive or depleted cell -> can really make any hormone type, we just don’t know what granule they will develop yet.

Question 8

What is a null cell?

Answer 8

A non-committed resting or stem cell of the anterior pituitary

Question 9

What hormones are produced more in the lateral vs medial portions of the anterior pituitary and why does this make sense?

Answer 9

Lateral - GH / PRL
Medial - TSH / ACTH
-> makes sense because stress hormones and metabolic hormones are more critical to life

Question 10

What cell types are derived from stem cells of Rathke’s pouch?

Answer 10

Corticotrophs, somatotroph stem cells, and gonadotrophs

Question 11

What cell lines are derived from somatotroph stem cells?

Answer 11

Thyrotrophs, mammosomatrophs, and somatrophs

Question 12

What cell lines are derived from mammosomatrophs?

Answer 12

Lactotrophs and somatotrophs

Question 13

Is a tumor more likely to secrete ACTH + FSH/LH or GH + PRL and why?

Answer 13

More likely to be GH + PRL

-> lactotrophs and somatotrophs have a closer common cell lineage

Question 14

What are Herring bodies?

Answer 14

Dilated nerve endings in the pars nervosa containing neurosecretory granules

Question 15

What is the most common pituitary tumor and which condition is thought to predispose to it?

Answer 15

Pituitary adenoma -> benign epithelial neoplasm derived from anterior pituitary cells

Associated with Multiple Endocrine Neoplasia 1 (MEN-1)

Question 16

Where do pituitary adenomas typically arise and where else could they be?

Answer 16

Typically within the sella turcica, but can be suprasellar (i.e. stalk region) or infrasellar (arising from glandular rests of Rathke’s pouch which did not involute during develoment)

Question 17

What is microadenoma vs macroadenoma?

Answer 17

Microadenoma - tumor <1 cm

Macroadenoma - tumor >1 cm

Question 18

What is a functional vs nonfunctional pituitary adenoma? What nomenclature is used with the latter?

Answer 18

Functional - can secrete hormone and produces symptoms based on this

Nonfunctional - may or may not be producing hormone, but will have no symptoms caused by hormones. This could also be due to a loss in end-organ response.
These are described as “silent”. I.e. silent corticotroph adenoma.

Question 19

What is the classical presentation of a nonfunctional pituitary adenoma (patient symptoms)? How much tissue must be lost to cause hypopituitarism?

Answer 19

Symptoms due to mass effect:

1. Bitemporal heteronymous hemianopsia - “tunnel vision”
2. Hypopituitarism - due to compression of normal pituitary tissue - requires loss of 75% of normal adenohypophysis
3. Headache

Question 20

What can happen if pituitary adenomas disrupt the hypothalamus / neurohypophysis?

Answer 20

Central diabetes insipidus or syndrome of inappropriate antidiuretic hormone (SIADH)

Question 21

What is the typical presentation of GH adenoma in children vs adults?

Answer 21

Children - Gigantism - linear bone growth because tumor occurred before closing of epiphyses

Adults - Acromegaly - overgrowth of soft tissues with organomegaly -> cardiac failure or secondary diabetes mellitus (GH induces gluconegenesis and decreased glucose uptake into cells)

Question 22

What is Cushing’s syndrome vs Cushing’s disease?

Answer 22

Cushing’s syndrome - syndrome of features associated with prolonged exposure to cortisol

Cushing’s disease - Cushing’s syndrome due to ACTH oversecretion by anterior pituitary (may be due to pituitary or hypothalamic dysfunction)

Question 23

What is an invasive adenoma? Why does this matter?

Answer 23

Tumors showing gross tumor invasion into the dura or bone

Increased likelihood of recurrence. But remember, these cannot metastasize (these are benign adenomas).

Question 24

What is an atypical adenoma vs pituitary carcinoma? How is the diagnosis of the latter made?

Answer 24

Atypical adenoma - Tumors showing increased proliferative activity

Pituitary carcinoma - very rare entity, made by showing a systemic metastatic spread -> no reliable means of predicting behavior by histology

Question 25

How is pituitary hyperplasia different than pituitary adenoma?

Answer 25

Pituitary hyperplasia occurs in response to production of hypothalamic releasing hormones, whether those hormones are ectopically made or normally made in response to lack of negative feedback. Pituitary adenoma is increased cell proliferation in the absence of stimulus

Question 26

What is the most common cause of pituitary hyperplasia?

Answer 26

Prolactin cell hyperplasia of pregnancy | -> This is a regular and normal thing as the pituitary is preparing the mammary glands for da bb

Question 27

What is pituitary apoplexy and what is the general underlying cause?

Answer 27

Sudden development of pituitary insufficiency due to the growth of the pituitary outstripping its blood supply (it is a very vascular organ and requires lots of oxygen)

Question 28

What will the pituitary gland look like after pituitary insufficiency (and on MRI) and what are two common direct causes of this?

Answer 28

Pituitary becomes hemorrhagic and necrotic 1. Pituitary adenoma 2. Pituitary hyperplasia of pregnancy with complicated pregnancy / hypotension -> it will be enlarged on MRI and have areas of heterogeneity due to necrosis

Question 29

What is lymphocytic hypophysitis and what causes it?

Answer 29

Autoimmune inflammation of adenohypophysis caused by infiltration of lymphocytes, leading to destruction of anterior pituitary with fibrosis. Usually occurs in women during late pregnancy or shoftly after delivery

Question 30

What does sarcoidosis do to the pituitary / hypothalamus? What is this considered one type of, and what condition does it mimic?

Answer 30

Generally causes non-necrotizing granulomatous inflammation involving the pituitary stalk and hypothalamus - > considered one type of granulomatous hypophysitis - > mimics non-functioning pituitary adenomas as it presents with symptoms of mass effect

Question 31

What is a Rathke cleft cyst and how can it cause problems?

Answer 31

Non-neoplastic epithelial cysts derived from glandular rests of Rathke's pouch -> generally occur in pars intermedia. If they are large (>1 cm) they can produce all the features of a non-functioning macroadenoma

Question 32

What is empty sella syndrome / how does it occur?

Answer 32

Syndrome where pituitary appears missing +/- loss in pituitary function due to compression by herniation of the subarachnoid space with CSF into the sella (area of bone). -> Pituitary is normally not surrounded by CSF because the diaphragma sellae is a piece of dura which forms a covering and disallows CSF from leaking in

Question 33

What is primary vs secondary empty sella syndrome and who does it occur in? How does it present?

Answer 33

Primary - protrusion of a diverticulum of arachnoid membrane into sella. Occurs in middle-aged women, often with obesity and hypertension (same demographic as pseudotumor cerebri) -> presents as headache. Secondary - pituitary fails to take up entire space of sella which allows CSF to seep in, follows surgical resection, apoplexy, or radiation treatment of sellar tumor

Question 34

Is empty sella syndrome usually clinically significant?

Answer 34

No. Often the gland is reduced in size and is just a thin layer around the edge of the sella, but this can be seen as an incidental finding and nothing is done

Question 35

What is the most common sellar tumor in children and what might is be confused with?

Answer 35

Craniopharyngioma - a tumor derived from Rathke's epithelium May be confused with pituitary adenoma -> both present with headache, hypopituitarism, and bitemporal hemianopsia

Question 36

What does the pathology of craniopharyngioma look like?

Answer 36

"Adamantinomatous" - squamous epithelium which appears cystic due to fluid accumulation between squamous epithelial cells. Calcification is extremely common (remember pathoma's mnemonic about this being derived from mouth and teeth have calcium). "Wet keratin" - keratin pearls appear overly plump.

Question 37

What fluid is in the cysts of craniopharyngioma and what is its prognosis?

Answer 37

Cholesterol crystals in a "motor oil"-like fluid Prognosis is poor -> tumor is locally aggressive and it frequently recurs after surgery

Question 38

What is a chordoma? Where does it occur? Who tends to get it?

Answer 38

A moderately malignant tumor derived from embryonic notochord - type of sarcoma. Arises in sacrum (nucleus pulposus) or spheno-occipital bones (typically around the clivus of the occipital bone) typically in middle-aged men.

Question 39

What does the histology of chordoma look like?

Answer 39

Physaliphorous cells - prominent vacuolization of cells as they produce extracellular matrix resembling cartilage + myxoid stroma -> just looks like bands of cells producing cartilage.

Question 40

Why do we talk about chordoma in this unit?

Answer 40

Although they generally arise in the bone, they are common in the sellar region, and can produce similar symptoms such as pituitary dysfunction, headache, and CN3 deficits