2. Robbins: Pituitary Gland Flashcards
(53 cards)
1
Q
Embryonic development of the pituitary gland
A
- Infundibular process => posterior pituitary, which connects directly to the hypothalamus.
- Rathke’s pouch (oral ectoderm) => anterior pituitary, which makes the hypophyseal portal circulation.
2
Q
- Neurohypophysis => _____ pituitary gland.
- Adenohypophysis => _____ pituitary gland.
A
- Neurohypophysis => posterior pituitary gland.
- Adenohypophysis => anterior pituitary gland.
3
Q
Histology of the Anterior Pituitary
A
- Made up of: nests and glands.
- Cytoplasm is made up of
- 1. Acidophils (eosinophillic cytoplasm) => secrete GH and prolactin
- 2. Basophils (basophillic cytoplasm) => secrete TSH, LH/FSH, ACTH
- 3. Chromophobes (poor staining cytoplasm) => secrete anything
- *but any of these can secrete anything
4
Q
Histology of the Posterior Pituitary
A
- Looks like brain tissue
- - Axonal neurons
- - Supportive pituicytes (neuroglial cells)
5
Q
AP contains 6 cells. What do they secrete?
- Somatotrophs
- Mammosomatotrophs
- Lactotrophs
- Corticotrophs
- Thyrotrophs
- Gonadotrophs
A
- Somatotrophs => GH
- Mammosomatotrophs => GH and prolactin
- Lactotrophs => prolactin
- Corticotrophs => ACT, POMC (pro-opiomelanocortin), MSH (melanocyte-stimulating hormone)
- Thyrotrophs => TSH (thyroid-stimulating hormone)
- Gonadotrophs => FSH and LH
6
Q
What are the functions of LH and FSH?
A
- LH => causes ovulatation and formation of corpora lutea in ovary.
- FSH => forms graafian follicle in ovary
- Both regulate spermatogenesis and testosterone production in males
7
Q
How does pituitary pathology come to attention?
A
- Hyperpituitarism (usually due to adenoma)
- Hypopituitarism
- Mass effect
8
Q
What is mass effect?
A
-
Non-functioning adenomas (those without clinical symotoms of hormone excess) can get large, protrude from sella turcica and cause mass effect
- 1. Increased intracranial pressure (ICP) => HTN, HA, N/V bradycardia, shallow breathing, papilledema*
- 2. Bilateral temporal hemianopsia => loss of lateral FOV due to compression of the optic chiasm
- 3. Pituitary apoplexy => hemorrage into adenoma, a surgical MRGNC that can cause death.
- Underproduction of pituitary hormones (bc encroach on adjacent AP parenchyma) and OVERproduction of prolactin
9
Q
What is pituitary apoplexy?
A
Hemorrage into the adenoma caused by mass effect of a non-functioning adenoma
10
Q
Mass effect can cause an overproduction of one hormone. What is that hormone and why?
A
- Overproduction of prolactin, because DA (which inhibits prolactin) cannot bind.
- DA cannot bind => cannot prevent prolactin secretion => hyperprolactinemia.
11
Q
Hyperpituitarism:
- Most common cause:
- Other causes:
A
- Adenoma in the AP
- Hyperplasia, carcinoma, secretion from non-pituitary tumors, certain hypothalamic disorders.
*
12
Q
- Microadenoma => ____
- Macroadenoma => ____
- Giant adenoma => ____
A
- Microadenoma => less than 1cm
- Macroadenoma => 1-4cm
- Giant adenoma => bigger than 4cm
13
Q
Pituitary Adenoma
- MC in who?
- Types?
- Sporadic or familial?
- Histologically, a typical pituitary adenoma is made up of what type of cells and how are they arranged?
A
- 35-60 YO
- Functional (secrete excess hormones) vs non-functional (do not have clinical sx of too much hormone)
- Majority are sporadic, but 5% are familial.
- Uniform, polygonal cells arranged in sheets or cords
14
Q
What 2 morphological features of pituitary adenomas distinguish them from non-neoplastic anterior pituitary parenchyma?
A
- Cellular monomorphism
- Absence of a reticulin (CT) network, making them soft (bc no CT/reticulin)
15
Q
Which genetic mutation is seen in many pituitary adenomas, especially somatotroph cell adenomas (40%); leads to what signaling effects?
A
GNAS mutations —> α subunit of Gs loses GTPase activity—> GTP stays bound and GDP does NOT shut off pathway => ↑↑↑ cAMP => cellular proliferation
16
Q
GNAS mutations are not seen in what type of adenomas?
A
- Thyrotroph
- Lactotroph
- Gonadotroph
17
Q
Some pituitary adenomas can secrete 2 hormones, what is the most common combination?
A
GH and prolactin = Bihormonal mammosomatotroph adenoma
18
Q
Functional vs. Non-functional adenomas: which are most likely to come to be diagnosed as macroadenomas?
A
Non-functional adenomas, because they are most likely to come to attention at a later stage.
19
Q
Large pituitary adenomas, particularly nonfunctioning ones, may cause hypopituitarism how?
A
By encroaching on and destroying adjacent anterior pituitary parenchyma
20
Q
Gross morphology of a typical pituitary adenoma?
A
Soft and well-circumscribed
- Small => confined to the sella turica. If expands, erodes sella turcica.
- Large => extend through diaphragm sella and compress optic chiasm and adjacent structures.
21
Q
Gross morphology of a invasive adenoma
A
- Not grossly encapsulated and infiltrate neighboring tissue
- Hemorrhage and necrosis = more common.
22
Q
Atypical adenomas have a higher propensity for aggressive behavior and are associated with mutations in which gene?
A
TP53
23
Q
What is the most common secretory pituitary adenoma?
A
Lactotroph adenoma
24
Q
What is the 2nd most common pituitary adenoma?
A
Somatotroph adenoma (secretes GH)
25
What is the most common cause of **Cushing syndrome**?
**Iatrogenic** Cushing syndrome due to glucocorticoid administration **(giving a patient long-term steroids)**
26
Corticotroph adenomas stain positively with what stain due to the presence of POMC?
PAS
27
What are the 3 major types of cancer associated with paraneoplastic secretion of ACTH or ACTH-like substance leading to Cushing Syndrome?
1. **- Small-cell carcinoma of lung**
2. **- Pancreatic carcinoma**
3. **- Neural tumors**
28
If **Cushings syndrome** is diagnosed, how do we find out the etiology?
* **_Check ACTH levels_**
1. **Low ACTH =\>** ACTH-independent: _problem with adrenal glands_ (adrenal Cushings)
1. CAT scan/MRI
1. =\> Adrenal adenoma or adrenal cancer
2. =\> Bilateral adrenal hyperplasia
2. **High ACTH** =\> ACTH-dependent: _problem with AP/ectopic source_
1. Inferior petrosal sinus sampling and MRI of brain
1. Pituitary tumor (Cushings disease)
2. Ectopic ACTH source
29
**Non-functioning** pituitary adenomas are often called what?
**Silent** or **null-cell adenomas** because they are not noticed till large and presenting with **mass effect.**
30
**_Pituitary carcinoma_**
* How common and dangerous?
* Essential conditions for prescence: _______ and \_\_\_\_\_\_
* Most are _functional/non-functional_
* Most commonly secrete \_\_\_\_\_\_\_\_
* **RARE** and can metastasize, spread through brain
* **Craniospinal** or **systemic metastases**
* **Functional**
* **Prolactin** and **ACTH**
31
Which mutation is associated with **familial** pituitary adenomas, causing **pituitary adenoma predisposition (PAP) syndrome**?
**LOF** of **AIP,** most commonly in **somatotroph adenomas**
32
What are the most common mutations seen in **_somatic/sporadic_** pituitary adenomas?
1. **GNAS**
2. **USP8** (in 36-62% of corticotroph adenomas)
1. =\> **upregulation of EGFR**
33
Where are AIP mutations more common?
**Ireland/Irish**
34
Causes of **hypopituitarism** (which can be d/t hypothalamus or pituitary)
1. Tumors and mass lesions in sella
2. TBI and subarachnoid hemorrhage =\> **MCC\***
3. Pituitary surgery or radiation
4. **Pituitary apoplexy**
5. Ischemic necrosis of pituitary and **Sheehan syndrome**
6. **Rathke cleft cyst**
7. **Empty sella syndrome**
8. **Hypothalamic lesion** (craniopharyngioma and metastasis from breast and lung cancer)
35
What are 2 other **AP neoplasias (derived from AP epithelium?**
1. **Rathkes Cleft Cyst**
2. **Craniopharyngioma**
36
**Pituitary apoplexy** in its most dramatic presentation produces sudden onset of what sx's?
1. **- Excruciating HA**
2. **- Diplopia**
3. **- Hypopituitarism**
37
What is the **most common form** of clinically significant **ischemic necrosis of the anterior pituitary**?
**Sheehan syndrome** aka postpartum necrosis
38
List some **conditions** which may be associated with **pituitary necrosis**
1. - DIC
2. - Sickle cell anemia
3. - ↑ ICP
4. - Traumatic injury
5. - Shock
39
What are **Rathke cleft cysts** lined with and how can they lead to **hypopituitarism**?
**Ciliated cuboidal epithelium** w/ some **goblet cells** and anterior pituitary cells
=\> Hypopituitarism
1. Accumulate proteinaceous fluid and expand=\> compress NL pituitary.
2. If rupture =\> inflammation of pituiary and meningitis.
40
**Craniopharyngiomas** may be seen in which 2 age groups;
* Types and dysfunction caused in each?
- **Kids** **(5-15 y/o)** = _adamantinomatous_ craniophryngiomas that cause [growth retardation from hypopituitarism]
- **Adults** **(\>65 y/o)** = _papillary_ craniopharyngiomas that cause [↑ ICP or hypopituitarism]
41
**Gross craniopharyngiomas**
Usually **cystic** and **multiloculated**
42
4 histological findings of **adamantinomatous craniopharyngiomas**?
1. **Nests/cords of stratified squamous epithelium** embedded in spongy "reticulum" w/ "palisading" at the periphery
2. **"Wet"/lamellar keratin formation = DIAGNOSTIC FEATURE**
3. **Dystrophic calcification** =\> calcified cyst
4. Cholesterol-rich, thick brownish yellow fluid ("machine oil")
43
What do the **papillary** **type** of **craniopharyngiomas** _lack_ histologically?
Usually lack **keratin, calcification**, and **cysts**
44
What occurs in **primary empty sella syndrome?**
**Defect in diaphragma sella** causes **arachnoid mater** + **CSF** to **leak into sella** =\> **expand** the sella =\> **compress** the pituitary
45
**Primary empty sella syndrome** is most commonly seen in whom?
**Obese women** w/ a hx of **multiple pregnancies**
46
How do individuals with **primary empty sella syndrome** commonly present?
**Visual field defects** and occasional endocrine abnormalities such as **hyperprolactinemia**
47
What occurs in **secondary empty sella** syndrome?
Pituitary adenoma enlarges the sella and is then either surgically removed or undergoes infarction --\> **loss of pituitary function + empty space**
48
**Anterior hypopituitarism =\>**
1. ↓ GH
2. ↓ gonadotropin
3. ↓ TSH
4. ↓ prolactin
1. **↓ GH**
1. Increase body fat, ↓ muscle and strength
2. **↓ gonadotropin**
1. M: ↓ sex drive, facial and body hair and infertility
2. W: amenorrhea, dysparenia, infertility, breast atrophy
3. **↓ TSH**
1. ↓ NRG, hypoglycemia and tiredness
4. **↓ prolactin**
1. cannot lactate
49
What is an example of an inflammatory disorder and infection which can involve the **hypothalamus** and cause _deficiencies of anterior pituitary hormones_ and _diabetes insipidus?_
1. **- Sarcoidosis**
2. **- Tuberculous meningitis**
50
What is **Sheehan syndrome (post-partum necrosis)?**
NL, during pregnancy, AP grows 2x size, however**, BS and space does not increase** =\> **compressed** and **relative hypoxia** =\> **ischemia and infarctaion** during labor and delivery.
51
What does **posterior pituitary** secrete?
1. **ADH**
2. **Oxytocin**
52
What are **hypothalamic suprasellar tumors** and what can they cause?
**Gliomas** and **craniopharyngiomas**.
Cause: hypofunction/hyperfunction, of AP, DI or a combination of both.
53
How do craniophargiomas come to attention?
* **Children**: growth retardation due to hypopituitarism and GH deficiency
* **Adults**: HA/visual disturbances.
