Pituitary Tumours Flashcards
-> Function of endocrine glands: Summarise the function of the key endocrine glands, including the synthesis, regulation and physiological effects of their hormones. -> Endocrine disorders: Describe the clinical features and treatment options of endocrine disorders.
Somatotrophs release:
Growth hormone
Lactotrophs release:
Prolactin
Thyrotrophs release:
Thyroid stimulating hormone (TSH)
Gonadotrophs release:
- Luteinising hormone (LH)
- Follicle stimulating hormone (FSH)
Corticotrophs release:
ACTH
A functioning pituitary tumour on somatotrophs can lead to:
Acromegaly
A functioning pituitary tumour of the lactotrophs is referred to as?
Prolactinoma
A functioning pituitary tumour of the thyrotrophs is referred to as?
TSHoma
A functioning pituitary tumour of the gonadotrophs is referred to as?
Gonadotrophinoma
A functioning pituitary tumour of the corticotrophs is referred to as?
Corticotroph adenoma
Cause of Cushing’s Disease
What are pituitary tumours classified by (radiologically) (4)?
- Size
- Suprasellar (situated or rising above the sella turcica) or not
- Compressing optic chiasm or not
- Invading cavernous sinus or not
What is the size classification of a microadenoma?
- < 1Omm (1cm)
What is the size classification of a macroadenoma?
- > 1cm (10mm)
What are pituitary tumours classified by (in terms of function) (2)?
- Excess secretion of a specific pituitary hormone
- No excess secretion of pituitary hormone (non-functioning adenoma)
What are pituitary tumours classified by (in terms of malignancy) (2)?
Benign: Adenomas
Malignant: Carcinomas (very rare (< 0.5%))
* Mitotic index measured using Ki67 index – benign is < 3%
Pituitary adenomas can have benign histology but display malignant behaviour
How is the malignancy (mitotic index) of a pituitary adenoma measured?
ki67 index
Describing how many cells are dividing
< 3% is considered benign
What ki67 mitotic index classifies a pituitary adenoma as benign?
- < 3%
What are the clinical presentations of a prolactinoma (5)?
- Menstrual disturbance
- Erectile dysfunction
- Reduced libido
- Galactorrhoea
- Subfertility
How do the symptoms of prolactinoma arise (5 steps)?
- Prolactinoma leads to hyperprolactinaemia
- Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
- Inhibits kisspeptin pulsative release
- Decreases in downstream GnRH/LH/FSH/T/Oest
- Oligo-amenorrhoea/Low libido/Infertility/Osteoporosis
Which hormone inhibits the pulsatile action of kisspeptin neurones?
- Prolactin
What are the physiological causes of an elevated prolactin (3)?
- Pregnancy / breast feeding
- Stress: exercise, seizure, venepuncture (stress induced can lead to an increase in prolactin levels)
- Nipple / chest wall stimulation
What are the pathological causes of elevated prolactin other than a prolactinoma (3)?
- Primary hypothyroidism (Due to increased TRH release)
- Polycystic ovarian syndrome (PCOS)
- Chronic renal failure
What are the iatrogenic causes of elevated serum prolactin (5)?
- Antipsychotics
- Selective serotonin re-uptake inhibitors (SSRIs)
- Anti-emetics
- High dose oestrogen
- Opiates
What investigations are recommended in suspection of prolactinoma (2)?
- Serum [prolactin]
- Pituitary MRI
What parameter of serum prolactin is associated with a prolactinoma?
- > 5000mu/L
Serum prolactin is proportional to tumour size
How is the majority of prolactin transported within the serum?
- Monomeric prolactin that is biologically active
What are the two possible outcomes of an elevation of serum prolactin yet there are no clinical consistent features (false positives)?
- Macroprolactin
- Stress of venipuncture
What is macroprolactin?
- A polymeric form of prolactin (An antigen-antibody complex of monomeric prolactin and IgG)
Normally < 5% of circulating prolactin
How can a stress of venepuncture be excluded from true elevation in serum prolactin?
- Exclude by a cannulated prolactin series
- Sequential serum prolactin measurement 20 minutes apart with an indwelling cannula to minimise venepuncture stress
How is a true pathological elevation of serum prolactin diagnosed?
- Conduct pituitary MRI
What is the first line of treatment in regards to prolactinomas?
- Dopamine receptor agonists (cabergoline or bromocriptine)
What is the aim with using cabergoline to manage prolactinoma?
- Normalise serum prolactin and shrink prolactinoma
How do dopamine receptor agonists work in the management of prolactinoma?
- Bind to D2 receptors on lacotrophs therefore exerting an inhibitory effect on prolactin release
What are the symptoms associated with acromegaly (8)?
- Sweatiness
- Headache
- Coarsening of facial features: Macroglossia / Prominent nose
- Large jaw - prognathism
- Increased hand & feet size
- Snoring & obstructive sleep apnoea
- Hypertension
- Impaired glucose tolerance / diabetes mellitus
What is the main risk that is increased in patients with untreated acromegaly?
- Increased cardiovascular risk
Which factors are released from the liver upon stimulation of growth hormone (2)?
- IGF-1
- IGF-2
How can acromegaly be diagnosed (3)?
- Elevated serum IGF-1
- Failed suppression of GH following oral glucose load (OGTT) - paraxodical rise
- Once confirm GH excess, pituitary MRI to visualise pituitary tumour
GH pulsatile -> so random measurement unhelpful
What is the first line of treatment in patients with acromegaly?
- Trans-sphenoidal pituitary surgery
Aim to normalise serum GH and IGF-1
What pharmacological treatments can be prescribed for acromegaly?
- Somatosatin analogues (octreotide)
- Dopamine agonists (cabergoline)
GH secreting pituitary tumours frequently express D2 receptors
What is Cushing’s syndrome?
An excess cortisol
What is Cushing’s disease?
- Cushing’s Syndrome due to a corticotroph adenoma
What are the clinical features Cushing’s syndrome (13)?
- Mental changes (depression)
- Osteoporosis
- Impaired glucose tolerance (diabetes)
- High BP
- Proximal myopathy
- Red cheeks
- Fat pads
- Thin skin
- Easy bruising
- Moon face
- Purple striae
- Pendulous abdomen
- Poor wound healing
What are the causes of Cushing’s disease divided into (2)?
- ACTH Independent
- ACTH Dependent
What are the ACTH independent causes of Cushing’s syndrome (2)?
- Oral corticosteroids
- Adrenal adenoma or carcinoma
What are the ACTH dependent causes of Cushing’s syndrome (2)?
- Corticotroph adenoma (Cushing’s Disease)
- Ectopic ACTH (Lung cancer)
What is the most common cause of Cushing’s syndrome?
- Oral corticosteroids
How is Cushing’s syndrome investigated (3)?
- Elevation of 24h 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) increased cortisol secretion
If Cushing’s syndrome is confirmed, how can one distinguish between ACTH dependent / ACTH independent cause?
- Once confirmed hypercortisolism, measure ACTH
- If ACTH high, pituitary MRI ACTH dependent
What is the main clinical feature often presented alongside a non-functioning pituitary adenoma?
- Bitemporal hemianopia
What are the not-so-common clinical features presented alongside a non-functioning pituitary adenoma?
- Hypopituitarism
- Serum prolactin can be raised
How are non-functioning pituitary adenomas managed?
- Trans-sphenoidal surgery needed for larger tumours, particularly if visual disturbance
