Lecture 8 - Pituitary disorders and treatment I Flashcards
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
Acquired pituitary failure - not expected to be a natural decline as the levels are too low to be normal
Why are LH/FSH levels higher in elderly women?
The pituitary expresses higher levels to try affect the failing ovaries
Congenital: what does it mean, how frequent are these types of pituitary failures, and what are the main causes?
Present at birth
Congenital pituitary failures are less frequent than acquired
- Birth trauma
- Midline defects
- Genetic mutations
Acquired: what does it mean, how frequent are these types of pituitary failures, and what are the main causes?
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
Pituitary adenomas: how are they categorised, what are the different types. and what hormone do they produce?
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
Pituitary adenomas: why are they dangerous, do they grow quickly, are they malignant, do they damage surrounding structures, etc?
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)
Craniopharyngiomas: what are they, what are they composed of, what is their origin, and when are they mostly present?
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
Pituitary tumour treatment: what are the types?
Surgery
Radiotherapy:
* External beam radiotherapy
* Stereotactic radiosurgery
Drug treatment - Usually specific to the type of tumour, Temozolomide chemotherapy is used for recurrent tumours
Transsphenoidal endoscopic pituitary surgery (ER): what is it and what is the process?
The most common surgery used to remove pituitary tumours
Removes tumours from the pituitary gland through the nose and sphenoid sinus
Drugs for pituitary therapy: what are they and what are they used to replace?
Hydrocortisone to replace cortisol
Levothyroxine to replace thyroxine
Pituitary tumours: are they sporadic or genetic
Most pituitary tumours are sporadic, but about 5% can be attributed to genetics
Oncogene
Genes in which a mutation means that cancerous growth is promoted
Tumour suppressor gene
Genes that act to prevent tumour formation
FIPA: what does it mean and what are some examples?
Familial-isolated pituitary adenomas - tumours with a genetic origin that only results in pituitary adenomas and no other tumour type
- AIP mutations
- XLAG
Types of germline pituitary tumour-causing mutations
- AIP mutations
- X-linked acrogigantism (XLAG)
- MEN1 syndrome
AIP mutations: what are they, what does the gene normally do, how is it inherited, and what tumours do they cause?
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)
XLAG: what is it, what type of condition is it, how does it cause tumours, and what type of adenomas does it cause?
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)
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?
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
Syndrome: what is it?
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
