Endoc- Pituitatry- Clin Manifestations Flashcards
(71 cards)
1
Q
The manifestations of pituitary disorders are as follows:
A
- Hyperpituitarism
- Hypopituitarism
- Local mass effects
2
Q
_____________
Arising from excess secretion of trophic hormones.
A
Hyperpituitarism:
3
Q
The causes of
hyperpituitarism include
A
- pituitary adenoma,
- hyperplasia and carcinomas of the anterior
pituitary,
- secretion of hormones by nonpituitary tumors, and
- certain hypothalamic
disorders.
4
Q
: Arising from deficiency of trophic hormones.
This may be caused by
destructive processes, including ischemic injury, surgery or radiation, inflammatory
reactions, and nonfunctional pituitary adenomas
A
Hypopituitarism
” Nmemonics: NADESTROY so cant produce!!!” Anything that destructs the gland HYPO!
5
Q
Local mass effects: Among the earliest changes referable to mass effect are radiographic abnormalities of the sella turcica,
A
including sellar expansion,
bony erosion,
and disruption of the diaphragma sella.
6
Q
Because of the close proximity of the optic nerves and chiasm to the sella, expanding pituitary lesions often compress decussating fibers in the optic chiasm. This gives rise to visual field abnormalities , classically in the form of defects in the lateral (temporal) visual fields, so-called _______________
A
bitemporal hemianopsia
7
Q
. In addition, a variety of other visual field abnormalities may be caused by asymmetric growth of many tumors. Like any expanding intracranial mass, pituitary adenomas can produce signs and symptoms of elevated intracranial pressure , including headache, nausea, and vomiting.
A
8
Q
The most common cause of hyperpituitarism is an ___________arising in the anterior lobe.
A
adenoma
9
Q
Pituitary adenomas are classified on the basis of hormone(s) produced by the neoplastic cells,
which are detected by immunohistochemical stains
A
10
Q
Some pituitary adenomas
can secrete two hormones (___________ being the most common combination), and rarely,
pituitary adenomas are plurihormonal.
A
GH and prolactin
Nmemonics: GP General Physician
11
Q
Pituitary adenomas can be_________i.e., associated
with hormone excess and clinical manifestations thereof) or ______________ (i.e.,
immunohistochemical and/or ultrastructural demonstration of hormone production at the tissue
level, without clinical symptoms of hormone excess).
A
- Functional
- nonfunctional
12
Q
Less common causes of hyperpituitarism
include ____________- and some hypothalamic disorders.
TABLE 24-1 – Classification of Pituitary Adenomas
A
pituitary carcinomas
13
Q
Large pituitary adenomas, and
particularly nonfunctioning ones, may cause ___________ as they encroach on and destroy
adjacent anterior pituitary parenchyma.
A
hypopituitarism
14
Q
TABLE 24-2 – Genetic Alterations in Pituitary Tumors
gene: Gsα
Activating mutation
A
GH adenomas
15
Q
TABLE 24-2 – Genetic Alterations in Pituitary Tumors
GAIN OF FUNCTION
LOSS OF FUNCTION
A
16
Q
What are the genes that cause
GAIN OF FUNCTION?
A
- Gsα
- Protein kinase A (PKA)
- Cyclin D1
- HRAS
17
Q
Protein kinase A (PKA)
Germline inactivating mutations of PRKARIA
(Carney complex), a negative regulator of PKA
A
GH and prolactin
adenomas
18
Q
Cyclin D1
Overexpression
A
Aggressive
adenomas
19
Q
HRAS
Activating mutation
A
Pituitary
carcinomas
20
Q
LOSS OF FUNCTION
A
- Menin
- CDKN1B (p27/KIP1)
- Aryl hydrocarbon receptor
interacting protein (AIP) - Retinoblastoma (RB)
protein
21
Q
Menin [*]
Germline inactivating mutations of MEN1
(multiple endocrine neoplasia, type 1)
A
GH, prolactin, and
ACTH adenomas
22
Q
*****CDKN1B (p27/KIP1) [*]
Germline inactivating mutations of CDKN1B
(“MEN-1-like” syndrome)
A
ACTH adenomas
23
Q
****Aryl hydrocarbon receptor interacting protein (AIP) [*]
Germline mutations of AIP (pituitary adenoma
predisposition [PAP] syndrome)
A
GH adenomas
24
Q
Retinoblastoma (RB)
protein
Methylation of RB gene promoter
A
Aggressive
adenomas
25
Genetic alterations associated with familial predisposition to pituitary adenomas.
Protein kinase A (PKA) [\*]
Menin
CDKN1B (p27/KIP1) [\*]
```
Aryl hydrocarbon receptor
interacting protein (AIP) [\*]
```
26
Morphology.
The **typical pituitary adenoma** is a\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
soft, well-circumscribed lesion that may be confined to the sella turcica
27
**Larger lesions** typically **extend superiorly** through the **diaphragm sella** into the s**uprasellar region,** where they **often compress the optic chiasm** and a**djacent structure**s, such as some of the cranial nerves ( Fig. 24-4 ). As these adenomas expand, **they frequently erode the sella turcica** and **anterior clinoid processes**.
In as many as **30% of cases,** the **adenomas are not grossly encapsulated and infiltrate neighboring tissue**s such as the **cavernous and sphenoid sinuses, dura, and on occasion, the brain itsel**f. Such lesions are termed\_\_\_\_\_\_\_\_\_\_\_\_.
invasive adenoma
28
Not unexpectedly**, \_\_\_\_\_\_\_\_\_\_\_\_**tend to be **invasive more
frequently than smaller tumors**.
Foci of hemorrhage and necrosis are also more common in
these larger adenomas.
**macroadenomas **
29
Histologically, **typical pituitary adenomas** are composed of **relatively\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_-**.
* uniform, polygonal cells arrayed in sheets or cords
* **Supporting connective tissue, or reticulin, is sparse,**
* ****accounting for the **soft, gelatinous consistency of many of these lesions**.
* **Mitotic activity is usually sparse**.
* The **cytoplasm** of the constituent cells **may be acidophilic, basophilic, or chromophobic,** **depending on the type and amount of secretory product within the cells, *_but it is generally uniform throughout the tumor._***
30
What is the reason in accounting for the** soft, gelatinous consistency of many of these lesions** in pituitary adenomas?
Supporting connective tissue, or reticulin, is sparse,
31
\*\*\*\*\*What distinguish pituitary adenomas from non-neoplastic anterior pituitary parenchyma?
**This cellular monomorphism and the absence of a significant reticulin network distinguish pituitary adenomas from non-neoplastic anterior pituitary parenchyma ( Fig. 24-5 ).**
32
The **biologic behavior of the adenoma cannot always be reliably predicted from its histologic appearance**. T or F
T
33
A **subset of pituitary adenomas** demonstrates **brisk mitotic activity and staining of greater than 3% of the nuclei** with the **proliferation marker Ki-67**; these tumors **typically also demonstrat**e extensive **nuclear p53** immunoreactivity in the neoplastic cells, a **feature that correlates with the presence of p53 mutations**. It is recommended that adenomas with this profile **be classified** as \_\_\_\_\_\_\_\_\_\_\_\_\_\_, since these tumors have a higher propensity for aggressive behavior, including invasion and recurrence.
atypical adenomas
34
Clinical Course.
The signs and symptoms of pituitary adenomas include **endocrine abnormalities and mass effects**.
The effects of excessive secretion of anterior pituitary hormones are mentioned below, when the specific types of pituitary adenoma are described.
Local mass effects may be encountered in any type of pituitary tumor and have been discussed previously under clinical
manifestations of pituitary disease.
Briefly, these include\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Acute hemorrhage into an adenoma is sometimes associated with pituitary apoplexy , as was noted above.
With this general introduction to pituitary adenomas, we proceed to a discussion of the individual types of tumors.
1. **radiographic abnormalities of the sella turcica,**
2. **visual field abnormalities,**
3. ** signs and symptoms of elevated intracranial pressure,**
4. **and occasionally hypopituitarism. **
35
PROLACTINOMAS
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are the **most frequent type of hyperfunctioning pituitary**
**adenoma,** accounting for about **30% of all clinically recognized cases**.
These lesions range from
**small microadenomas to large**, expansile tumors associated with **substantial mass effect.**
PROLACTINOMAS
Prolactinomas (lactotroph adenomas
36
Microscopically, the **overwhelming majority of prolactinomas** are composed of **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** ;
**weakly acidophilic
or chromophobic cells** (**sparsely granulated prolactinoma**
37
rare prolactinomas are
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ ( Fig. 24-6 ).
strongly acidophilic (densely granulated prolactinoma)
38
Prolactin can be demonstrated within the secretory granules in the cytoplasm of the cells using immunohistochemical stains.
Prolactinomas have a propensity to **undergo dystrophic calcification**, **ranging from\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**
Prolactin secretion by functioning adenomas is usually efficient (**even microadenomas secrete
sufficient prolactin to cause hyperprolactinemia**) and proportional, in that serum prolactin
concentrations tend to correlate with the size of the adenoma
** isolated psammoma bodies** to **extensive calcification** of virtually the** entire tumor mass (“pituitary stone”).**
39
Increased serum levels of prolactin, or prolactinemia, cause \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
amenorrhea,
galactorrhea,
loss of libido,
and infertility
40
The **diagnosis of an adenoma** is made **more readily in women than in me**n, especially between the ages of **20 and 40 years,** presumably **because of the\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ **
Prolactinoma underlies almost **a quarter of cases of amenorrhea**. In contrast, in men and older women, the hormonal manifestations may be subtle, allowing the tumors to reach considerable size **(macroadenomas) before being detected clinically.**
** sensitivity of menses to disruption by hyperprolactinemia.**
41
Hyperprolactinemia may result from causes other than prolactin-secreting pituitary adenomas .
Physiologic hyperprolactinemia occurs in \_\_\_\_\_\_\_\_\_\_\_\_\_
.
1. pregnancy;
2. serum prolactin levels increase throughout pregnancy, reaching a peak at delivery.
3. Prolactin levels are also elevated by **nipple stimulation**, as occurs during suckling in lactating women,
4. and as a response to many types of stress
42
Pathologic hyperprolactinemia can also result from** **
1. **lactotroph hyperplasia,** such as when there is** interference with normal dopamine inhibition of prolactin secretion**.
* This may occur as a r**esult of damage to the dopaminergic neurons of the hypothalamus**, damage to **the pituitary stalk** (e.g., due to head trauma), or **drugs that block dopamine receptors on lactotroph cells. **
2. **Any mass in the suprasellar compartmen**t may disturb the normal inhibitory influence of the hypothalamus on prolactin secretion, **resulting in hyperprolactinemia. \*\*\*\*\*Therefore, a mild elevation in serum prolactin in a person with a pituitary adenoma does not necessarily indicate a prolactin-secreting tumor.**
3. **Other causes of hyperprolactinemia include several classes of drugs (such as dopamine antagonists), estrogens, renal failure, and hypothyroidism. **
43
How is prolactinomas treated?
Prolactinomas are treated by surgery or, more commonly, with bromocriptine, a dopamine receptor agonist that causes the lesions to diminish in size.
44
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are the second most common type of **functioning pituitary adenoma.**
GH-secreting tumors
45
Somatotroph cell adenomas may be quite large by the time they come to clinical attention because\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
the manifestations of excessive GH may be subtle
46
Histologically, **pure GH cel**l –containing adenomas are also classified into **two subtypes**:
1. densely granulated and
2. sparsely granulated.
47
The **densely granulated adenomas** are composed of cells that are \_\_\_\_\_\_\_\_\_\_\_\_\_in routine sections**, retain strong cytoplasmic GH reactivit**y on immunohistochemistry, and demonstrate **cytokeratin staining** in a **perinuclear distribution.**
monomorphic and acidophilic
48
In contrast, the **sparsely granulated variants** are composed of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
chromophobe cells with considerable nuclear and cytologic pleomorphism and focal, weak staining for GH.
49
**Bihormonal mammosomatotroph adenomas** that expres**s both GH and prolactin** are being increasingly recognized with the availability of better immunohistochemical reagents; morphologically, **most bihormonal adenomas resemble the** \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
densely granulated pure somatotroph adenomas.
50
_Persistently_ **elevated levels of GH** stimulate the **hepatic secretion** of **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_,** which causes **many of the clinical manifestations.**
**insulin-like growth factor 1 (IGF-1 or somatomedin C)**
51
If a somatotrophic adenoma appears in **children before the epiphyses have closed**, the **elevated levels of GH (and IGF-1) result in\_\_\_\_\_\_\_\_\_\_\_\_**
This is characterized by a **generalized increase in body size** with **disproportionately long arms and legs**.
** gigantism**.
52
If the **increased levels of GH** are **present after closure** of the **epiphyses**, patients develop \_\_\_\_\_\_\_\_.
In this condition, growth is **most conspicuous in skin** and **soft tissues; viscera (thyroid, heart, liver, and adrenals**); and **bones of the face, hands, and feet**.
Bone density may be increased (hyperostosis) in **both the spine and the hips.**
Enlargement of the jaw results in **protrusion (prognathism**), with **broadening of the lower face**.
The hands and feet are enlarged with **broad, sausage-like fingers.**
In **most instances gigantism is also accompanied by evidence of acromegaly.** Thes**e changes develop for decades before being recognized**, hence the opportunity for the adenomas to reach substantial size**. **
acromegaly
53
GH excess is also correlated with a variety of other disturbances, including
1. gonadal dysfunction,
2. diabetes mellitus,
3. generalized muscle weakness,
4. hypertension, arthritis,
5. congestive heart failure, an
6. an increased risk of gastrointestinal cancers.
54
The diagnosis of pituitary GH excess relies on **documentation of\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**.
** elevated** serum GH and IGF-1 levels
55
In addition,\_\_\_\_\_\_\_\_\_\_\_\_ is one of the **most sensitive tests for acromegaly**.
failure to suppress GH production in response to an oral load of glucose
56
What is the treatment pituitary adenoma?
The underlying pituitary adenoma can be **either removed surgically or treated via pharmacologic means**.
The latter includes **somatostatin analogs** (recall that s**omatostatin has an inhibitory effect on pituitary GH secretion)** or the **use of GH receptor antagonists,** which **prevent hormone binding to target organs** such as the liver.
When effective control of high GH levels is achieved, the characteristic tissue overgrowth and related symptoms gradually recede, and the metabolic abnormalities improve.
57
\_\_\_\_\_\_\_\_\_\_\_\_\_ are usually **small microadenomas** at the time of **diagnosis.** These tumors are **most often basophilic (densely granulated)** and **occasionally chromophobic** (**sparsely granulated)**. Both **variants stain positively with periodic acid–Schiff** (PAS) because of the **presence of carbohydrate in POMC,** the **ACTH precursor molecule**; in addition, they **demonstrate variable immunoreactivity for POMC and its derivatives, including ACTH and β- endorphin.**
Corticotroph adenomas
58
**Excess production of ACTH** by the **corticotroph adenoma** leads to **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**and the **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.**
This syndrome is discussed in more detail later with the diseases of the adrenal gland.
It can be caused by a wide variety of conditions in addition to ACTH-producing pituitary tumors.
**adrenal hypersecretion of cortisol**
development of hypercortisolism (also known as** Cushing syndrome).**
59
When the hypercortisolism is **due to excessive production of ACTH by the pituitary,** the process is designated \_\_\_\_\_\_\_\_\_\_\_\_\_\_
Cushing disease.
60
**Large destructive adenoma**s can develop in patients after **surgical removal of the adrenal glands** for **treatment of Cushing syndrome.** This condition, known as\_\_\_\_\_\_\_\_\_\_\_\_\_-occurs most often because of a **loss of the inhibitory effect of adrenal corticosteroids** on a preexisting corticotroph microadenoma.
Because the a**drenals are absent in persons with this disorder,** **hypercortisolism does not develop**.
In contrast, patients present with mass effects of the pituitary tumor. In addition**, there can be hyperpigmentation** because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes.
Nelson syndrome,
61
OTHER ANTERIOR PITUITARY ADENOMAS
1. Gonadotroph (LH-producing and FSH-producing) adenomas
2. Thyrotroph (TSH-producing) adenomas
3. Nonfunctioning pituitary adenomas
4. Pituitary carcinomas
62
Pituitary adenomas may elaborate more than one hormone. For example, prolactin may be
demonstrable by immunolabeling of somatotroph adenomas. In other cases, unusual
plurihormonal adenomas are capable of secreting multiple hormones; these **tumors are usually
aggressive.** A few comments are made about several of the less frequent functioning tumors.
63
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_can be difficult to recognize because they **secrete hormones inefficiently and variably,** and the **secretory products usually do not cause a recognizable clinical syndrome (non-functioning adenomas, see below).**
* are most frequently found in **middle-aged men and women** when they **become large enough to cause neurologic symptoms**, such as **impaired vision, headaches, diplopia, or pituitary apoplexy.**
Gonadotroph (LH-producing and FSH-producing) adenomas
64
**In Gonadotroph ,Pituitary hormone deficiencies** can also be found, most commonly impaired secretion of \_\_\_\_\_\_\_\_\_\_\_.
This causes **decreased energy and libido in men** (**due to reduced testosterone**) and **amenorrhea in premenopausal women**.
LH.
65
Thus, gonadotroph adenomas are **paradoxically associated with** \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
. The neoplastic cells usually demonstrate immunoreactivity for the common gonadotropin α-subunit and the specific β-FSH and β-LH subunits; **FSH is usually the predominant secreted hormone.**
secondary gonadal hypofunction
66
\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are rare, accounting for approximately 1% of all
pituitary adenomas. **Thyrotroph adenomas are a rare cause of hyperthyroidism.**
Thyrotroph (TSH-producing) adenomas
67
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_are a heterogeneous group that constitutes approximately **25% to 30% of all pituitary tumors.**
Their lineage can be established by immunohistochemical staining for hormones or by biochemical demonstration of cell type-specific transcription factors.
In the past, many such tumors have been called **silent variants or null-cell adenomas**.
Not surprisingly, the **typical presentation of nonfunctioning adenomas is mass effects.**
These lesions may **also compromise the residual anterior pituitary sufficiently to cause hypopituitarism**.
This may occur as a r**esult of gradual enlargement of the adenoma or after abrupt enlargement of the tumor because of acute hemorrhage (pituitary apoplexy).**
Nonfunctioning pituitary adenomas
68
\_\_\_\_\_\_\_\_\_\_\_\_ are quite rare, accounting for less than 1% of pituitary tumors.
Pituitary carcinomas
69
The demonstration of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is a sine qua non of a pituitary carcinoma.
craniospinal or systemic metastases
70
The **majority of pituitary carcinoma**s are functional neoplasms, with prolactin and
ACTH being the most common secreted products. Metastases usually appear late in the
course, following multiple local recurrences
functional neoplasms, with prolactin and
ACTH
71
