Pituitary Tumours Flashcards

1
Q
What are the names for a functioning pituitary tumour that releases the following anterior pituitary cells respectively:
somatotrophs 
lactotrophs 
thyrotrophs 
gonadotrophs 
corticotrophins
A
Acromegaly 
Prolactinoma 
TSHoma 
Gonadotrophinoma 
Cushing's disease (corticotroph adenoma)
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2
Q

How to classify pituitary tumours

A

Radiological size (MRI) - Size

Function - Excess secretion of a specific pituitary hormone OR no excess secretion of pituitary hormone (Non-functioning adenoma)

Benign or Malignant - Pituitary carcinomas – rare (<0.5% of pituitary tumours). Mitotic index measured using ki67 index - benign is <3%.
Pituitary adenomas can have benign histology but display malignant behaviour.

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3
Q

A pituitary MRI can be used to determine the size of the adenoma. What would the size of the adenoma for a micro and macro adenoma respectively?

A

Microadenoma <1cm (10mm)
Macroadenoma >1cm (10mm)

An adenoma compresses the optic chiasm manifesting as bitemporal hemianopia (fibres transmitted sensory modalities from the periphery decussate).
Supra-sellar or sellar
Invading the cavernous sinus or not.

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4
Q

Explain the process by which hyperprolactinaemia inhibits kisspeptin neurones.

A

Prolactin binds to prolactin receptors on kisspeptin neurons in the hypothalamus, exerting an inhibitory effect.
Impairs pulsatile secretion of kisspeptin.
Downstream inhibition of GnRH/LH/FSH/Oestrogen/Testosterone.
Oligo-amenorrhea/low libido/infertility/osteoporosis.

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5
Q

What is the commonest functioning pituitary adenoma?

A

Prolactinomas

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6
Q

What is the rough minimum threshold of serum prolactin to suggest a patient has a prolactinoma?

A

Usually serum [prolactin] >5000 mU/L

The larger the size of the tumour the higher the serum [prolactin] will be.

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7
Q

What would a patient with a prolactinoma present with?

A
Mental disturbance 
Erectile dysfunction 
Reduced libido 
Galactorrhoea 
Subfertility
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8
Q

List other causes of an elevated prolactin. Group them as physiological, pathological and iatrogenic.

A

Physiological:
Pregnancy/breastfeeding
Stress: exercise, seizure, venepuncture
Nipple/chest wall stimulation

Pathological:
Primary hypothyroidism, PCOS, chronic renal failure

Iatrogenic:
Antipsychotics, selective serotonin re-uptake inhibitors, anti-emetics, high dose of oestrogen, opiates

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9
Q

Where you see a mild elevation in serum prolactin, if the patient has no clinical features consistent with this (and you have reviewed their medication list), what are the 2 possible options?

A
  1. Macroprolactin - majority of circulating prolactin is monomeric & biologically active, however macroprolactin (sticky) is a polymeric variation.
    An antigen-Ab complex > monomeric prolactin and IgG (<5% of circulating prolactin). Recorded on assay – requires alternative method to confirm. Limited bioavailability and bioactivity CAN REASSURE THE PATIENT.
  2. Stress of Venepuncture
    Exclude by a cannulated prolactin series: sequential serum [Prolactin] measurement 20 minutes apart with an indwelling cannula to minimise venepuncture stress.
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10
Q

When should you organise a pituitary MRI for a prolactinoma?

A

Only once you have confirmed a true pathological elevation of serum prolactin should you organise a pituitary MRI.

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11
Q

Outline the treatment plan for a prolactinoma.

A

First-line treatment is medical not surgical. Dopamine receptor agonists are the mainstay of treatment - Cabergoline (bromocriptine). Aim is to normalise serum prolactin and shrink prolactinoma. Microprolactinomas will need smaller doses than macroplactinomas.

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12
Q

How do dopamine receptor agonists work?

A

D2-receptor agonists mimic the inhibitory effect of dopamine on lactotrophs – reducing the secretion of prolactin.

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13
Q

What causes acromegaly?

A

Acromegaly arises due to an adenoma of somatotrophs leading to an unregulated secretion of growth hormone into the systemic circulation.

  • Insidious presentation > Mean time to diagnosis from onset of symptoms = 10 years.
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14
Q

What does a patient with acromegaly present with?

A
SWEATINESS 
HEADACHE 
Coarsening of facial features: Macroglossia, prominent nose,
large jaw (prognathism)
Increased hand and feet size
Snoring & obstructive sleep apnoea
Hypertension
Impaired glucose tolerance/diabetes mellitus
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15
Q

Explain the mechanism of growth hormone action.

A

Growth hormone exerts anabolic effects on the growth of tissues (muscle and bone) supporting the development of an individual. Potentiates the release of insulin-like growth factor (Somatomedin) – IGF-I (and IGF-2) from the liver.

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16
Q

Explain how you can diagnose acromegaly.

A

There is a pulsatile action of growth hormone (random measurements are therefore unhelpful)

  • Elevated serum IGF-I
  • Failed suppression (paradoxical rise) of GH following oral glucose load – oral glucose tolerance test.
  • Prolactin can be raised – co- secretion of GH and prolactin.
  • Once confirm GH excess – pituitary MRI to visualise tumour.
17
Q

Are dopamine receptor agonists safe to be used on pregnant women?

A

Yes

18
Q

Is there an increased cardiovascular risk in untreated acromegaly?

A

Yes

19
Q

Outline the treatment of acromegaly.

A
  1. First line treatment is SURGICAL > Trans-sphenoidal pituitary surgery
    Aim to normalise serum GH and IGF-I.
  2. Can use medical treatment prior to surgery to shrink tumour or if surgical resection is incomplete: administer somatostatin analogues – octreotide (endocrine cyanide) + Dopamine agonists (Cabergoline) (GH secreting pituitary tumours express D2 receptors)
  3. Radiotherapy can be done but is a slow procedure.
20
Q

What is Cushing’s syndrome?

A

Cushing’s is defined as an excess of cortisol/glucocorticoid.

21
Q

List the causes of Cushing’s syndrome. Categorise the causes into ACTH dependent and ACTH independent.

A

ACTH dependent:
Pituitary dependent Cushing’s disease (pituitary adenoma)
Ectopic ACTH (lung cancer)

ACTH independent:
Taking steroids by mouth (most common cause)
Adrenal adenoma or carcinoma

22
Q

What is the difference between Cushing’s syndrome and Cushing’s disease?

A

Cushing’s syndrome = excess cortisol

Cushing’s disease is due to a pituitary corticotroph adenoma secreting ACTH.

23
Q

List the symptoms a patient with Cushing’s disease may present with.

A

Mental changes (depression)
Osteoporosis
Impaired glucose tolerance (diabetes) – high blood pressure
Proximal myopathy (Muscle weakness)- thin arms and legs
Pendulous abdomen
Poor wound healing, easy bruising
Purple striae, thin skin, fat pads, red cheeks and moon face.

24
Q

Explain how to investigate a patient for Cushing’s disease.

A

Elevation of 24 urine free cortisol – increased cortisol secretion.
Elevation of late-night cortisol – salivary or blood test – loss of diurnal rhythm

Failure to suppress cortisol after oral dexamethasone (exogenous glucocorticoid suppresses ACTH secretion).
Once confirmed hypercortisolism, measure ACTH.
If ACTH high do a pituitary MRI. This determines whether cause is ACTH dependent (Cushing’s disease) or ACTH independent (Cushing’s syndrome).

25
Q

Is Cushing’s disease ACTH dependent?

A

Yes

It is not ACTH independent (i.e. taking steroids by mouth; adrenal adenoma/carcinoma).

26
Q

What is a non-functioning pituitary adenoma?

What do they often present with?

A

Tumour not secreting any specific hormone.
Often present with visual disturbance (bitemporal hemianopia).

Can present with hypopituitarism (Serum prolactin raised since dopamine is unable to travel down the pituitary stalk from hypothalamus).

27
Q

How can you treat a non-functioning pituitary adenoma?

A

Trans-sphenoidal surgery required for large tumours.