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1 - Pituitary Gland Flashcards

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1
Q

How does the hypothalamus communicate with the anterior pituitary gland?

A

Neurohormones

Through a specialised portal vascular system.

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2
Q

Do direct neural connections exist between the hypothalamus and the anterior pituitary gland?

A

No.

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3
Q

How does the hypothalamus communicate with the posterior pituitary gland?

A

Through axons that originate within hypothalamic neuronal cell bodies.

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4
Q

What are the two inhibitory neurohormones produced by the hypothalamus?

A

Dopamine

Somatostatin

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5
Q

What anterior pituitary hormones does dopamine inhibit?

A

FSH
LH
Prolactin
TSH

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6
Q

What anterior pituitary hormones does somatostatin inhibit?

A

Growth Hormone

TSH

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7
Q

What hormone does POMC (pro-opiomelanocortin) give rise to?

A

ACTH

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8
Q

POMC and MSH (melanocyte-stimulating hormone) result in what change? And occur in what disease?

A

Hyperpigmentation

Addison’s disease
Nelson syndrome

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9
Q

Where does vasopressin (ADH) act and how does it work?

A

Distal tubule

Increases permeability to water

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10
Q

At high concentrations, what can ADH cause?

A

Vasoconstriction

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11
Q

What are the two main stimuli of ADH secretion?

Sensed by which receptors?

A

Increased osmotic pressure + volume depletion.

Osmoreceptors (within hypothalamus) and baroreceptors.

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12
Q

What 4 locations are baroreceptors located?

A

Carotid sinus
Aortic arch
Left atrium
Pulmonary veins

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13
Q

A lack of ADH results in what condition?

A

Central diabetes insipidus

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14
Q

What pathology occurs in nephrogenic diabetes insipidus?

A

Inability of kidney to respond to ADH.

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15
Q

What are the two target areas of oxytocin?

A

1) Uterine smooth muscle

2) Myoepithelial cells within the breast

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16
Q

What stimulates oxytocin release?

A

1) Suckling

2) Increases gradually throughout pregnancy

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17
Q

What 6 hormones are produced by the anterior pituitary gland?

A 
ACTH
GH
TSH
LH
FSH
Prolactin
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18
Q

What 2 hormones are produced by the posterior pituitary gland?

A

Oxytocin

ADH (vasopressin)

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19
Q

What are the two possible effects arising from pituitary tumours?

A

1) Mass effect (headache, visual loss)

2) Hormonal effects (hormone overproduction)

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20
Q

What is a clonal tumour?

A

A tumour made up of all the same cells.

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21
Q

What pathology arises as as a result of a clonal tumour of somatotrophs?

A

Acromegaly (GH excess)

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22
Q

What features are present in acromegaly?

A

Tall stature
Enlarged hands, feed
Metabolic effects: HTN + diabetes
Sweating (gland proliferation)

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23
Q

What is a clonal tumour of lactotrophs called?

A

Prolactinoma

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24
Q

What symptoms occurs as a result of a prolactinoma?

A

Lactation

Amenorrhoea

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25
What pathology arises as as a result of a clonal tumour of corticotrophs?
Cushing's disease | ACTH-secreting pituitary tumour from POMC
26
What are the characteristic features of Cushing's disease?
``` Moon face (fat deposition) Striae Recession of hair Hirsutism Bruising ```
27
Which two clonal tumours are termed 'non-functioning' adenomas? And why?
Gonadotroph adenomas Thyrotroph adenomas Both very rare
28
What are craniopharyngiomas?
Rare, benign tumours Form as solid tissue, cysts or calcified nodules.
29
Name 3 destructive lesions which result in hypopituitarism
Rathke's cleft cyst Meningiomas Gliomas
30
Hypopituitarism lesions results in which 3 hormones insufficiencies?
Hypoadrenalism Hypothyroidism Hypogonadism
31
Polyclonal tumours arise from what pathology?
Hormone dysregulation resulting in hyperplasia | e. g. high-dose estrogen = PRLoma (e. g. Transgenic GH-RH excess = GHoma)
32
What are the 4 candidates for protein mutation in polyclonal tumours?
Receptors G-protein subunits Kinases Nuclear proteins (cell signalling capital)
33
What two receptors result in a prolactinoma if mutated?
Dopamine D2 receptor (K/o studies get them because Dopamine is an important inhibitor of prolactin secretion) FGF4-Receptor (splice variant may be associated, but not causative)
34
What are the 5 diseases involving adenomas?
1) McCune-Albright Syndrome 2) Multiple Endocrine Neoplasia (MEN) 1 3) Familial isolated pituitary adenoma 4) X-linked acromegaly 5) Carney complex
35
What is the underlying pathophysiology of McCune-Albright Syndrome?
G-protein activating mutation in the protein GSP, resulting in excess GH.
36
How does a GSP mutation result in excess GH?
GalphaS mutation (GSP) 1) Inhibition of GTP-ase activity 2) Constitutive activation of adenylate cyclase 3) LOTS OF cAMP 4) Protein kinase A activation 5) CREB phosphorylation 6) Excess gene expression
37
In what % of GHomas is a GSP mutation found?
40%
38
What inheritance trait is the GSP mutation?
Dominant
39
As a result of its effect, what type of gene is GSP?
Oncogene
40
MEN-1 is what kind of gene?
Tumour suppressor gene
41
For MEN-1 to manifest, however, given its TSG trait, what has to occur?
Two-hit hypothesis
42
What is the difference in protein expression between the 1st and 2nd hit?
1st = reduced protein expression 2nd = NO Protein expressed (phenotype)
43
MEN-1 results in tumours forming in which 3 glandular organs?
Pituitary Parathyroid Pancreas
44
What NUCLEAR protein does MEN-1 gene code for?
Menin
45
What inheritance pattern does MEN-1 have?
Autosomal dominant trait (occurs even in heterozygous) **High-penetrance
46
On what chromosome is MEN-1 mutation found?
Chromosome 11 | 11q33
47
Describe what happens in the process of ubiquination?
Protein targeting for degradation.
48
What kind of protein is USP8?
A de-ubiquitinase
49
A mutation in USP8 results in what condition?
Cushing's disease
50
How does Cushing's disease arise from a USP8 mutation?
Increases de-ubiquitination of EGFR. Rescues EGFR from lysosomal degradation. Increase in EGFR signalling. Increase in ERK Increased ATH production.
51
Explain the combined model of pathogenesis in regards to pituitary adenomas.
Hormonal / environmental induced proliferation occurring. More divisions = more likely for mutation. Incidental mutation (e.g. GSP / USP8) results in monoclonal tumour forming.
52
What are the 3 main modalities to treat pituitary tumours?
1) Surgery 2) Radiotherapy 3) Drug therapy
53
What type of surgery is used to remove pituitary tumours?
Transsphenoidal adonectomy
54
Name two important structures that need to be avoided in Transsphenoidal surgery
Optic nerve | Internal carotid artery
55
Possible complications from pituitary surgery?
Visual field defects Various endocrine complications CSF leak
56
Radiotherapy is often an adjuvant. What consequence will occur after therapy?
Hypopituitarism
57
What 3 consequences occur from a prolactinoma?
Anovulation Amenorrhoea Galactorrhoea
58
Name 3 drugs that can cause prolactinaemia
Dopamine antagonists (metoclopramide) SSRI (e.g. fluoxetine) Tricyclic anti-depressants
59
What pharmaceutical therapy can be used to treat prolactinomas / hyperprolactinaemia?
Dopamine agonists (e.g. bromocriptine)
60
Name a few side effects of bromocriptine
12% get them Nausea Postural hypotension Abdo pain
61
Name one novel dopamine agonist And why is it better?
Quinagolide (similar to bromocriptine) Less common SE
62
What pharmaceutical therapy can be used to treat acromegaly?
Somatostain receptor agonists OR GH antagonists
63
Name a GH antagonist
Pegvisomant
64
What is the mechanism of action of Pegvisomant?
Binds to one half of the GH-receptor, inhibiting the binding of GH and subsequent dimerisation. Reduces levels of IGF-1 and GH production.
65
Pegvisomant is a modified GH molecule. It is also pegylated for two reasons - what are they?
Decrease immunogenicity Increase half-life

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