Lecture 10 - Pituitary disorders and treatment II

Question 1

Possible genetic causes of pituitary tumours

Answer 1

• AIP mutations (FIPA)
• X-linked acrogigantism (XLAG)
• MEN1 syndrome

Question 2

Anterior pituitary: what is it called and what are some examples of the tumours?

Answer 2

Adenohypophysis

• Somatotroph
• Corticotroph
• Gonadotroph
• Thyrotroph
• Lactotroph

Question 3

Somatotroph: what does it cause to be in excess, is it silent, and what does it cause?

Answer 3

Functional growth hormone excess

Rarely silent.

Causes gigantism or acromegaly.

Question 4

Corticotroph: what does it cause to be in excess, is it silent, and what does it cause?

Answer 4

Functional ACTH excess

Can be silent

If functional, causes Cushing’s disease

Question 5

Gonadotroph: what does it cause to be in excess, is it silent, and what does it cause?

Answer 5

Gonadotrophin hormone excess

Rarely functional

Functional LH/FSH hypersecretion can cause ovarian hyperstimulation or testicular enlargement

Question 6

Thyrotroph: what does it cause to be in excess, how common is it, what is it also known as, and what does it cause?

Answer 6

Can cause TSH excess

Very rare

AKA ‘TSH-oma’

Functional TSH causes clinical picture of hyperthyroidism

Question 7

Lactotroph: what does it cause to be in excess, how common is it, what is it also known as, and what does it cause?

Answer 7

Functional prolactin excess

Commonest type of functional pituitary adenoma

AKA ‘prolactinomas’

The major effect of a prolactinoma is decreased levels of some sex hormones — namely, estrogen and testosterone

Question 8

Can you get posterior pituitary tumours?

Answer 8

Yes, but way way less common - may be mis-diagnosed as non-functioning pituitary adenomas

They include:
* Pituicytomas (infundibulomas), * Granular cell tumours
* Spindle cell oncocytomas

Question 9

Growth hormone excess manifest: how does it manifest pre-pubertal and post pubertal and what general consequences occur due to it?

Answer 9

Pre-pubertal - tall stature (gigantism)

Post-pubertal - enlarged peripheries (acromegaly), excess soft tissue growth and excess sweating

• High blood pressure.
• Raised blood sugars (diabetes mellitus)
• Other consequences of having a pituitary mass

Question 10

Pituitary tumour diagnosis

Answer 10

• Clinical symptoms and signs of growth hormone excess.
• Blood test for IGF-1
• Growth hormone suppression testing
• Blood tests to assess remainder of pituitary function.
• Pituitary gland imaging.
• Genetic testing

Question 11

Pituitary tumour treatment

Answer 11

Surgery:
* Selective transsphenoidal operation to remove tumour
* First-line treatment

Drug treatment:
* Somatostatin receptor agonists
* GH receptor antagonist (Pegvisomant)
* Second-line treatment

Pituitary radiotherapy:
* Last-line treatment

Question 12

Somatostatin receptor agonists

Answer 12

Bind to somatostatin receptors and inhibit growth hormone secretion and inhibit adenoma cell proliferation

Question 13

Growth hormone receptor antagonist treatment: what is used, why is it preferred as treatment, what does it do, and what does it mainly affect?

Answer 13

‘Pegvisomant’ - highly selective growth hormone receptor antagonist

Modified human GH molecule (9 amino acid substitutions, pegylated to reduce immunogenicity and increase half-life)

Prevents GH receptor dimerisation, and so reduces IGF-1 production

Aimed at reducing the effects of excess GH, rather than targeting the pituitary tumour itself.

Question 14

GH excess: what hidden effects should be looked for?

Answer 14

• Colonoscopy to look for colonic polyps
• Echocardiogram to look for left ventricle hypertrophy and other cardiac manifestations of GH excess
• Regular assessment of blood pressure, blood glucose and lipid profiles, to minimise metabolic disease risk

Question 15

Prolactin: what things cause there to be high levels of it

Answer 15

Normal physiological situations:
* Pregnancy
* Breastfeeding
* Stress

Medications - especially those prescribed to treat psychosis and depression

Chest wall stimulation

Other endocrine conditions:
* Hypothyroidism
* Acromegaly

Pituitary pathology:
* Lactotroph adenoma (prolactinoma)
* Pituitary stalk disconnection

Question 16

Prolactinoma: what are the consequences?

Answer 16

Direct effects of excess prolactin:
* Galactorrhoea (milk leakage from the breasts)

Effects of gonadal axis suppression:
* Cessation of periods (amenorrhoea), anovulation
* Loss of libido, sexual dysfunction, erectile dysfunction

Effects of tumour mass:
* Headache
* Visual disturbance

Question 17

Dopamine receptor agonists: what are examples and what do they do?

Answer 17

• Bromocriptine
• Cabergoline
• Quinagolide

Apoptosis, tumour shrinkage, prolactin reduction, etc

Question 18

Bromocriptine: what is it, what receptor does it interact with, what does it do, and what side effects may it cause?

Answer 18

Dopamine receptor agonist

D2 receptor agonist (ergot alkaloid)

Greatest effect in first 3 months of treatment, but continues thereafter:
* Tumour shrinkage
* Prolactin reduction
* Restoration of gonadal function

Side effects:
* Nausea
* Mood change
* Hypotension
* Abdominal pain

Question 18

Cabergoline and quinagolide: what are they, what do they do, and why are they preferred over bromocriptine?

Answer 18

Dopamine receptor agonists

Newer D2 receptor agonists that cause tumour shrinkage

Not without side effects, but better tolerated than bromocriptine

Question 19

Pituitary hormone excess vs loss

Answer 19

Numerous medical problems can cause loss of pituitary function

Pituitary hormone excess is rarer, but can have significant impact on people’s health and wellbeing

Pituitary tumours can cause both loss and gain of pituitary function, and may be due to genetic predisposition