Week 4 - B - Pituitary physiology - tumours and disorders Flashcards
What is the other name for the pituitary stalk and what does this stalk connect?
Pituitary stalk is also known as the infundibulum - connects hypothlamus to pituitary gland
What are the two categories for cells of the anterior pituitary gland?
The acidophils and basophils cells
What are the acidophil cells and what are the basophil cells of the anterior pituitary?
Acidophil cells - the non-tropics being GH and prolactin
Basophil cells - the tropics being FSH, LH, TSH and ACTH
Where are the anterior pituitary hormones synthesised?
In the capillaries of the anterior pituitary gland
Where are the posterior pituitary hormones synthesised?
ADH and oxytocin and synthesised within the body of the nerve cells in the hypothalamus
How do ADH and oxytocin travel from the hypothalamus to the posterior pituitary gland?
They travel via axomplasmic flow
What is the other, more common name for thyrotropin?
Thyroid stimulating hormone
How does exposure to cold cause the temperature to increase? (in relevance to pituitary and hypothalamus)
Exposure to cold causes the hypothalamus to release thyrotropin releasing hormone (TRH) which signals the anterior pituitary to release TSH which causes the thyroid gland to release T3 and T4
T3 and T4 account for 30% of thermogenesis and therefore produce heat to warm up the body
What is released from the hypothalamus ending up in the release of cortisol? Where is cortisol released from?
Hypothalamus releases corticortophin releasing hormone (CRH) which stimulates the pituitary to release ACTH which stimulates the release of cortisol
From the adrenal cortex
What is released from the hypothalamus ending up in the release of thyroxine? Where is thyroxine released from?
Hypothalamus releases thyrotropin releasing hormone (TRH) which stimulates the pituitary gland to release TSH which stimulates the release of thyroxine
From the thyroid gland
What hormone from the hypothalamus stimulates the release of LH/FSH? What do these hormones stimulate the production of?
Gonadotropin releaseing hormone (GnRH)
LH and FSH stimulate the production of estradiol and testosterone
What hormone triggers ovulation in females? What does it stimulate the production of in males?
luteinizing hormone (LH)
Stimulates production of testosterone
What hormone stimulates the anterior pituitary to release growth hormone? What hormone from the hypothalamus inhibits the release of prolactin?
Growth hormone releasing hormone
Dopamine
What is the test used to diagnose adrenal insufficiency in a disease such as Addison’s disease?
Synacthen test
How is Addison’s disease distinguished from 2º adrenal insufficiency? (mineral and clinical finding)
2º adrenal insufficiency is due to ↓ACTH production, which has no skin hyperpigmentation & no hyperkalemia
What does an insulin stress test test for?
Tests to see the response in levels of cortisol and GH when a patient is basically driven into a hypo
Will be able to find if there is a deficiency
What is the size difference regarding pituitary tumours in a Microadenoma and Macroadenoma?
≤ 1cm: Microadenoma
> 1cm: Macroadenoma
In a non-functioning pituitary tumour, what can be compressed? What is the most common visual defect due to this compression?
Can compress the optic chiasm causing a bitemporal hemianopia (usually superior temporal quadrantanopia which spreads to the inferior temporal quadrants)
In bitemporal hemianopia, where is vision missing? What can a non-functioning pituitary adenoma do the the pituitary gland secretions? (what disease associated with ADH)
Vision is absent in the outer half of both the right and left eye
Can decrease secretions causing
- Hypoadrenalism
- Hypothyroidism
- Hypogonadism (Diabetes Insipidus)
- GH deficiency
In hypopituitarism caused by a non-functioning adenoma, what can happen to the prolactin levels?
Can lead to compression of the pituitary stalk causing the dopamine inhibition of prolactin not to work therefore causing a hyperprolactinaemia
What are physiological reasons for a raised prolactin? (4 reasons)
Breast feeding
Pregnancy
Stress
Sleep
What are 3 pathological reasons for a raised prolactin? (two are drugs)
Dopamine antagonists - metaclopramide
Hypothyroidism - increased TRH levels can cause production of prolactin Prolactinoma
Some antidepressants
What is the most common functioning pituitary adenoma? What about the 2nd and 3rd most common?
Most common pituitary adenoma - prolactinoma
2nd most common - Growth hormone cell adenoma
3rd most common - ACTH producing adenoma
How may a pituitary stalk lesion cause a raised prolactin?
A pituitary stalk lesion can block the inhibiting effect of dopamine on the release of prolactin therefore causing the levels of prolactin to increase
What are the early presentation signs of a hyperprolactinaemia in females? What about males?
* Galactorrhea
* Menstrual irregularity
* Ammenorrhoea
* Infertility
* Dry vagina
Males - decreased libido and headache and erectile dysfunction
On an MRI scan of prolactinoma, what should be looked for?
Size of tumour - mirco or macro prolactinoma (greater or less than 1cm)
Pituitary stalk compression
Optic chiasm
What is the most common dopamine agonist given for prolactinoma?
cabergoline - D2 receptor agonist
Bromocriptine can also be given
Dopamine (D2) agonist have are 1st line treatments for prolactinoma What is the second line treatment for a prolactinoma? Why is it reserved for 2nd line?
Surgery (trans-sphenoidal surgery is usually the first line type of pituitary surgery) - high success rate but risks of permanent hormone deficiency and prolatinoma recurrence so reserved as 2nd line
What can a tumour secreting excess amounts of growth hormone cause?
Can cause acromegaly (gigantism in children, acromegaly in adults)
What does acromegaly do to Respiratory? Cardiac? GI?
Respiratory - causes snoring and sleep apnoea
Cardiac - causes hypertension and can lead to cardiac failure
GI - causes colonic polyps and colon cancer
Increased shoe size, ‘spade hands’, wedding ring too tight What is this? What are other symptoms of this condition?
Acromegaly
Excessive sweating and large jaw
Growth hormone causes liver gluconeogensis What can a growth hormone secreting adneoma therefore cause?
Can cause secondary diabetes mellitus
What test is used to screen for acromegaly and what is used to diagnose it?
Why cant the growth hormone level just be measured?
Measuring IGF1 (insulin-like growth factor 1) - used to screen
Glucose tolerance test (GTT) - used to diagnose
75g of glucose is given orally The GH levels are checked every 30mins for 2 hours (this is the glucose tolerance test used in acromegaly) In acromegaly, what do you expect to see?
The growth hormone levels do not fall when glucose is introduced
State again how growth hormone affects/is affected by glucose and insulin like growth hormone 1 (IGF-1)?
State what happens in the screening and diagnostic tests for acromegaly
When blood sugar is low, hypothalamus releases growth hormone releasing hormone (GHRH) which causes the anterior pituitary to release growth hormone (GH)
GH promotes the secretion of IGF-1 which decreases blood sugar levels
- Screening test - IGF-1 - levels are raised due to the excessive growth hormone production increaseing gluconeogenesis which increases IGF1 production
- GH is raised in glucose tolerance test when it should not be (negative feedback) due to excessive growth hormone production
How does acromegaly potentially lead to diabetes?
Excess GH:
1) stimulates gluconeogenesis and lipolysis, causing hyperglycemia and elevated free fatty acid levels;
2) leads to both hepatic and peripheral insulin resistance, with compensatory hyperinsulinemia. Conversely, IGF-1 increases insulin sensitivity.
What is the first line treatment for acromegaly?
Surgery
What is an example of a somatosatin anolgue used in acromegaly if surgery is not able to work? How do somatostatin analogues work?
Ocreotide
They slow down the production of many hormones, including gut hormones and growth hormone
Pituitary surgery for acromegaly 90% achieved if microadenoma (i.e. <1cm diameter) 50% achieved if macroadenoma Can work well alongside radiotherapy How long do somatostatin anologues tae to shrink tumour? What can happen 6weeks after stopping?
Takes 6 months - 12m
re-expansion 6 weeks after stopping
What can usually be given pre-op in acromegaly? and why?
A somatostatin anlogue
Relieves headache within an hour and improves outcome
What are potential side effects of treatment with somatostatin analogues?
Short term - Flatulence Diarrhoea Abdominal pains
Long term - Gastritis < 60% Gallstones 60%
What is the last line pharmacological treatment for acromegaly? First line, surgery, followed by radiation Somatostatin anolgue - eg ocreotide Finally…?
Last line treatment is growth hormone receptor antagonists
Example is pegvisomant
Very expensive and does not decrease tumour size
What are the safe levels of GH post-GTT? (done to check follow up in acromgealy treatment)
GH <0.4ug/l (post GTT)
True or false:
Dopamine inhibits release of prolactin?
ACTH exerts its peripheral effect via IGF-1?
Surgery is the first line treatment for prolactinoma?
Acromegalic headache is usually due to tumour compression?
True
False, ACTH exerts its peripheral effect via cortisol, GH exerts its peripheral effect via IGF-1
False, dopamine agonsits is first line treatment for prolactinoma
True, compression of nearby brain tissue
