Lecture 8 - Pituitary disorders and treatment I

Question 1

A 71-year-old patient complains about tiredness and dizziness and has the following results from a blood test, what is her diagnosis:
TSH - low
fT4 - low
LH - low
FSH - low
Cortisol - low/normal
Prolactin - normal

Answer 1

Acquired pituitary failure - not expected to be a natural decline as the levels are too low to be normal

Question 2

Why are LH/FSH levels higher in elderly women?

Answer 2

The pituitary expresses higher levels to try affect the failing ovaries

Question 3

Congenital: what does it mean, how frequent are these types of pituitary failures, and what are the main causes?

Answer 3

Present at birth

Congenital pituitary failures are less frequent than acquired

• Birth trauma
• Midline defects
• Genetic mutations

Question 4

Acquired: what does it mean, how frequent are these types of pituitary failures, and what are the main causes?

Answer 4

Develops after birth

Pituitary failures are more often acquired

• Head injury, brain insult, surgery
• Cancer treatments
• Pituitary infarction/haemorrhage
• Pituitary inflammation/infiltration
• Infection
• ‘Empty sella syndrome’
• Mass lesions - pituitary tumours, cysts, other tumours, etc

Question 5

Pituitary adenomas: how are they categorised, what are the different types. and what hormone do they produce?

Answer 5

Size:
* Microadenoma - <1cm
* Macroadenoma - >1cm

Hormone production:
* Corticotroph adenoma -> ACTH over-production
* Somatotroph adenoma -> GH over-production
* Lactotroph adenoma -> Prolactin over-production
* ‘Non-functioning’ pituitary adenomas don’t result in functional hormone excess

Question 6

Pituitary adenomas: why are they dangerous, do they grow quickly, are they malignant, do they damage surrounding structures, etc?

Answer 6

They can result in overproduction of hormones

They are slow growing, benign tumours, but they can compress nearby structures (the optic nerve, for example, affecting the vision)

Question 7

Craniopharyngiomas: what are they, what are they composed of, what is their origin, and when are they mostly present?

Answer 7

Rare, ‘benign’ tumours - can be problematic because of size and recurrence

Can contain solid, cystic, or calcified elements

Thought to develop from the remnants of Rathke’s pouch

Bimodal incidence: childhood and late adult onset

Question 8

Pituitary tumour treatment: what are the types?

Answer 8

Surgery

Radiotherapy:
* External beam radiotherapy
* Stereotactic radiosurgery

Drug treatment - Usually specific to the type of tumour, Temozolomide chemotherapy is used for recurrent tumours

Question 9

Transsphenoidal endoscopic pituitary surgery (ER): what is it and what is the process?

Answer 9

The most common surgery used to remove pituitary tumours

Removes tumours from the pituitary gland through the nose and sphenoid sinus

Question 10

Drugs for pituitary therapy: what are they and what are they used to replace?

Answer 10

Hydrocortisone to replace cortisol
Levothyroxine to replace thyroxine

Question 11

Pituitary tumours: are they sporadic or genetic

Answer 11

Most pituitary tumours are sporadic, but about 5% can be attributed to genetics

Question 12

Oncogene

Answer 12

Genes in which a mutation means that cancerous growth is promoted

Question 13

Tumour suppressor gene

Answer 13

Genes that act to prevent tumour formation

Question 14

FIPA: what does it mean and what are some examples?

Answer 14

Familial-isolated pituitary adenomas - tumours with a genetic origin that only results in pituitary adenomas and no other tumour type

• AIP mutations
• XLAG

Question 15

Types of germline pituitary tumour-causing mutations

Answer 15

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

Question 16

AIP mutations: what are they, what does the gene normally do, how is it inherited, and what tumours do they cause?

Answer 16

Mutations in the aryl hydrocarbon interacting protein (AIP)

Thought to function as a pituitary tumour suppressor gene - supported by the fact most pituitary tumours caused by this are LoF

Autosomal dominant inheritance, variable penetrance

Cause of ‘familial isolated pituitary adenomas’ (FIPA)

Question 17

XLAG: what is it, what type of condition is it, how does it cause tumours, and what type of adenomas does it cause?

Answer 17

X-linked acrogigantism - condition only occurring in men

Also considered a FIPA condition

Microduplications of GPR101 (Xq26.3) cause gain-of-function in a G-protein coupled receptor

Mechanism incompletely understood, but this appears to result in early onset pituitary adenomas secreting growth hormone (and prolactin)

Question 18

MEN1 syndrome: what is it, what type of adenomas are the most common for it to produce, what organs are affected, how severe is it, what is its inheritance, and how do we try to prevent it?

Answer 18

Mutations in MENIN (MEN1) gene (11q13), a tumour-suppressor gene

Prolactin-producing pituitary adenomas (prolactinomas) are the commonest pituitary tumour in MEN1

Multiple organs affected - pituitary, pancreas, parathyroid (but also skin, adrenal)

Quite severe - predisposition for tumours is high so watching this is very necessary every few years or so

Autosomal dominant pattern of inheritance, high penetrance

Regular screening in people with known MEN1 mutations aims to detect MEN1 tumours early, and intervene before they cause problems

Question 19

Syndrome: what is it?

Answer 19

A set of symptoms or conditions that occur together and suggest the presence of a certain disease or an increased chance of developing the disease