Lecture 8 - Pituitary disorders and treatment

Question 1

Why are LH/FSH level higher in elderly women?

Answer 1

The pituitary expresses higher levels to try affect the failing ovaries

Question 2

Congenital

Answer 2

Present at birth

Pituitary failures are mostly congenital

Question 3

Acquired

Answer 3

Develops after birth

Pituitary failures are less often acquired but may still occur

Question 4

Pituitary adenomas

Answer 4

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 5

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

Answer 5

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 6

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

Answer 6

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 7

Pituitary tumour treatment

Answer 7

• Surgery
• Radiotherapy:
• External beam radiotherapy
• Stereotactic radiosurgery
• Drug treatment
  Usually specific to the type of tumour (see Lecture 3)
  (Temozolomide chemotherapy for recurrent tumours)

Question 8

Transsphenoidal endoscopic pituitary surgery

Answer 8

Research

Question 9

Drugs for pituitary therapy

Answer 9

Hydrocortisone to replace cortisol
Levothyroxine to replace thyroxine

Question 10

Pituitary tumours

Answer 10

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

Question 11

Oncogene

Answer 11

A mutation in a gene means that gene then promotes cancerous growth

Question 12

Tumour suppressor gene

Answer 12

Mutation occurs in a gene that normally protects from cancer

Question 13

Types of germline pituitary tumour-causing mutations

Answer 13

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

Question 14

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

Answer 14

Mutations in the aryl hydrocarbon interacting protein (AIP)

Thought to function as a pituitary tumour suppressor gene

Autosomal dominant inheritance, variable penetrance.

Cause of ‘familial isolated pituitary adenomas’ (FIPA)

Question 15

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

Answer 15

X-linked acrogigantism

Also considered as 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 16

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

Answer 16

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)

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 17

Syndrome

Answer 17

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