Week 4 - B - Pituitary physiology - tumours and disorders Flashcards by Chris Egubjo

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

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What are the two categories for cells of the anterior pituitary gland?

The acidophils and basophils cells

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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

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Where are the anterior pituitary hormones synthesised?

In the capillaries of the anterior pituitary gland

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Where are the posterior pituitary hormones synthesised?

ADH and oxytocin and synthesised within the body of the nerve cells in the hypothalamus

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How do ADH and oxytocin travel from the hypothalamus to the posterior pituitary gland?

They travel via axomplasmic flow

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What is the other, more common name for thyrotropin?

Thyroid stimulating hormone

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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

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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

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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

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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

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What hormone triggers ovulation in females? What does it stimulate the production of in males?

luteinizing hormone (LH)

Stimulates production of testosterone

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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

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What is the test used to diagnose adrenal insufficiency in a disease such as Addison’s disease?

Synacthen test

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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

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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

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What is the size difference regarding pituitary tumours in a Microadenoma and Macroadenoma?

≤ 1cm: Microadenoma

> 1cm: Macroadenoma

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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