Pathology of the Pituitary Gland Flashcards
Give the components of the adenohypophysis and the neurohypophysis.
Adenohypophysis - Pars tuberalis (on stalk), pars intermedia, pars distalis
Neurohypophysis - pars nervosa and infundibulum (pituitary stalk)
What gives rise to the anterior and posterior pituitary?
Anterior - Rathke’s pouch - an evaination of the oropharyngeal ectoderm
Posterior - ventral diencephalon / median eminence of hypothalamus
Starts functioning by 6-8 weeks
What are the cells which make up the posterior pituitary?
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
What structures are most likely to be directly affected by pituitary tumors?
Structures directly adjacent to the sella turcica
- 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.
- Optic chiasm -> sits directly above sella
- Sphenoid sinus
- Diaphgrama sellae, sits above and prevents CSF access into the sellae
How is most surgery of the pituitary gland done and why?
Via transnasal trans-sphenoidal approach
- > this is because the sphenoid sinus lies directly below the pituitary.
- > can enter the brain thru the nasal cavity
Give the primary cells which produce each of the following hormones of the anterior pituitary: GH, PRL, ACTH, FSH, LH, TSH, and MSH.
GH - Somatotroph PRL - Lactotroph ACTH - Corticotroph FSH / LH - Gonadotroph TSH - Thyrotroph MSH - Corticotroph -> also produced via POMC like ACTH
What is a chromophobe? What hormone does it make?
An inactive or depleted cell -> can really make any hormone type, we just don’t know what granule they will develop yet.
What is a null cell?
A non-committed resting or stem cell of the anterior pituitary
What hormones are produced more in the lateral vs medial portions of the anterior pituitary and why does this make sense?
Lateral - GH / PRL
Medial - TSH / ACTH
-> makes sense because stress hormones and metabolic hormones are more critical to life
What cell types are derived from stem cells of Rathke’s pouch?
Corticotrophs, somatotroph stem cells, and gonadotrophs
What cell lines are derived from somatotroph stem cells?
Thyrotrophs, mammosomatrophs, and somatrophs
What cell lines are derived from mammosomatrophs?
Lactotrophs and somatotrophs
Is a tumor more likely to secrete ACTH + FSH/LH or GH + PRL and why?
More likely to be GH + PRL
-> lactotrophs and somatotrophs have a closer common cell lineage
What are Herring bodies?
Dilated nerve endings in the pars nervosa containing neurosecretory granules
What is the most common pituitary tumor and which condition is thought to predispose to it?
Pituitary adenoma -> benign epithelial neoplasm derived from anterior pituitary cells
Associated with Multiple Endocrine Neoplasia 1 (MEN-1)
Where do pituitary adenomas typically arise and where else could they be?
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)
What is microadenoma vs macroadenoma?
Microadenoma - tumor <1 cm
Macroadenoma - tumor >1 cm
What is a functional vs nonfunctional pituitary adenoma? What nomenclature is used with the latter?
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.
What is the classical presentation of a nonfunctional pituitary adenoma (patient symptoms)? How much tissue must be lost to cause hypopituitarism?
Symptoms due to mass effect:
- Bitemporal heteronymous hemianopsia - “tunnel vision”
- Hypopituitarism - due to compression of normal pituitary tissue - requires loss of 75% of normal adenohypophysis
- Headache
What can happen if pituitary adenomas disrupt the hypothalamus / neurohypophysis?
Central diabetes insipidus or syndrome of inappropriate antidiuretic hormone (SIADH)
What is the typical presentation of GH adenoma in children vs adults?
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)
What is Cushing’s syndrome vs Cushing’s disease?
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)
What is an invasive adenoma? Why does this matter?
Tumors showing gross tumor invasion into the dura or bone
Increased likelihood of recurrence. But remember, these cannot metastasize (these are benign adenomas).
What is an atypical adenoma vs pituitary carcinoma? How is the diagnosis of the latter made?
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
How is pituitary hyperplasia different than pituitary adenoma?
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
What is the most common cause of pituitary hyperplasia?
Prolactin cell hyperplasia of pregnancy
-> This is a regular and normal thing as the pituitary is preparing the mammary glands for da bb
What is pituitary apoplexy and what is the general underlying cause?
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)
What will the pituitary gland look like after pituitary insufficiency (and on MRI) and what are two common direct causes of this?
Pituitary becomes hemorrhagic and necrotic
- Pituitary adenoma
- Pituitary hyperplasia of pregnancy with complicated pregnancy / hypotension
-> it will be enlarged on MRI and have areas of heterogeneity due to necrosis
What is lymphocytic hypophysitis and what causes it?
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
What does sarcoidosis do to the pituitary / hypothalamus? What is this considered one type of, and what condition does it mimic?
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
What is a Rathke cleft cyst and how can it cause problems?
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
What is empty sella syndrome / how does it occur?
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
What is primary vs secondary empty sella syndrome and who does it occur in? How does it present?
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
Is empty sella syndrome usually clinically significant?
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
What is the most common sellar tumor in children and what might is be confused with?
Craniopharyngioma - a tumor derived from Rathke’s epithelium
May be confused with pituitary adenoma -> both present with headache, hypopituitarism, and bitemporal hemianopsia
What does the pathology of craniopharyngioma look like?
“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.
What fluid is in the cysts of craniopharyngioma and what is its prognosis?
Cholesterol crystals in a “motor oil”-like fluid
Prognosis is poor -> tumor is locally aggressive and it frequently recurs after surgery
What is a chordoma? Where does it occur? Who tends to get it?
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.
What does the histology of chordoma look like?
Physaliphorous cells - prominent vacuolization of cells as they produce extracellular matrix resembling cartilage + myxoid stroma
-> just looks like bands of cells producing cartilage.
Why do we talk about chordoma in this unit?
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
