Pituitary Flashcards
what clinical syndromes may arise as a result of functional pituitary tumours
- acromegaly (GH)
- Cushing’s disease (ACTH)
- prolactinoma (PRL)
- TSHoma
how might non-functioning pituitary tumours present
- hypopituitarism
- compression of local structures
what is the pattern of hormone imbalance in hypopituitarism and why does this arise
all hormones go down except prolactin which increases
- disinhibtion hyperprolactinaemia
how might pituitary tumours affect vision
compression of the optic chiasm –> bi-temporal hemianopia
assessment of visual fields mandatory part of clinical exam as it is the usual indication for surgery in non-functioning tumours
at what time of day can prolactin and TSH be checked
do not fluctuate much so can be checked at any time of day
what hormones should be checked in patients with suspected pituitary disease
fT4 and TSH
- TSH usually normal in secondary hypothyroidism
when should LH/FSH be measured in women vs men
- women: within 1st 5 days of menstrual cycle
- men: 0900 in fasting state
when should cortisol levels be checked if deficiency is suspected
0900
what molecule is a marker of GH
IGF-1
- low levels suggest GH deficiency
when should the synacthen test NOT be used
after 2 weeks of ACTH deficiency, atrophy of adrenal cortex leads to inadequate response to synacthen
- test should not be used to measure ACTH reserve in an acute situation e.g. pituitary apoplexy or immediately post pituitary surgery
what is the gold standard test of ACTH and GH reserve
insulin tolerance test
in which patients should the insulin tolerance test not be performed
patients with ischaemic heart disease or epilepsy due to risk of triggering coronary ischaemic and seizures
what is the imaging modality of choice for the pituitary gland
MRI (CT where MRI not possible)
- injection of contrast to highlight difference between tumour and normal gland
how are pituitary tumours classified
> 1cm = macro adenoma
< 1cm = micro adenoma
what should be excluded before further investigation of hyperprolactinaemia
pregnancy
in large pituitary tumours, what does a prolactin > 5000iU/L suggest
active secretion of prolactin (prolactinoma) rather than pituitary stalk compression from non functioning adenoma
what are the features of micro-prolactinomas
- <1cm
- commonest pituitary tumour
- menstrual disturbances or hypognadism in men
- galactorrhoea but infertility may be the only feature
how is PCOS differentiated from prolactinoma
- presence of androgens symptoms
- less elevated prolactin levels <1000 min/L
- absence of pituitary lesion on MRI
what are the features of macro-prolactinoma
- > 1cm and may be very large
- more common in men
- PRL >5000miU/L
what is the Hook Effect of prolactin levels
When levels of PRL are very high, the immuno-assay can give inaccurately low results so may be necessary to dilute the sample to achieve more accurate result
how are prolactinomas treated
D2 agonists e.g. cabergoline or bromocriptine
how is cabergoline prescribed
given once or twice weekly and better tolerated than bromocriptine which is given daily
what are common side effects of D2 agonists
- nausea
- postural hypotension
- rarely psychiatric disturbance
what is a rare complication of treating macro-prolactinomas
CSF leak due to rapid reduction in size of lesion which gives potential risk of meningitis
what are pituitary causes of high PRL
- prolactinoma
- non functioning adenoma
- hypophysitis
- stalk section
what are hypothalamic causes of high PRL
- tumours
- infiltration disease
what are physiological causes of high PRL
- pregnancy
- breast stimulation
- stress
what are medications causing high PRL
- antipsychotic
- anti emetics
- anti HTN
- oestrogen
what are the functions of PRL
- stimulates breast development
- stimulates milk production
what is the definitive treatment of pituitary adenomas
transsphenoidal surgery
what risks/complications are associated with untreated acromegaly
- premature death from CVD (cardiomyopathy)
- inc risk of bowel cancer (colorectal)
- HTN
- diabetes >10%
what is the cause of acromegaly
excess GH secondary to pituitary adenoma in 95% cases
- minority caused by ectopic GHRH or GH production by tumours e.g. pancreatic
what are the clinical features of acromegaly
- coarse facial appearance
- spade like hands, puffiness
- increase in shoe size
- large tongue, progathism, interdental spaces
- excessive sweating and oily skin
- features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
what are the main diagnostic investigations of acromegaly and what will they show
serum IGF-1 levels & oral glucose tolerace test (OGTT) with serial GH measurements
* in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
* in acromegaly there is no suppression of GH
* may also demonstrate impaired glucose tolerance which is associated with acromegaly
what is the 1st line treatment for acromegaly
transsphenoidal surgery
if a pituitary tumour causing acromegaly is inoperable or surgery is unsuccessful, what medication may be indicated (3)
- somatostatin analogue: e.g. octreotide directly inhibits release of GH
- pegvisomant: GH receptor antaognist prevents dimerisation of GH receptor, OD s/c administration
- dopamine agonists: e.g. bromocriptine
what are other treatment options for acromegaly
- stereotactic RT
- external beam RT
how does stereotactic RT work and what are long term side effects
provides more targeted treatment at higher dose but only suitable for lesions well away from the optic chiasm
how is disease activity of acromegaly monitored following surgery and why is this important
- after initial surgery, repeat OGTT will indicate if there is persistent disease
- long term follow up important to ensure adequate control of GH & IGF-1 levels and to exclude recurrence
- also periodic screening colonoscopy due to strong risk of neoplasia
patients should be intermittently assessed for sleep apnoea, diabetes, cardiovascular risk and symptoms of recurrence
how do NFPAs present
visual field loss
headache
hypopituitarism
what are the 2 forms of hypopituitarism
congenital
acquired
how might hypopituitarism preset
non specific symptoms: lethargy, weight gain, sexual dysfunction
- may present as an acute hypo-adrenal crisis + hypoNa and hypotension (medical emergency!!)
- in children, short stature may be presenting feature
how is hypopituitarism investigated
priority is assessment exclusion of adrenal insufficiency
how is each component of hypopituitarism treated
- ACTH: hydrocortisone replacement leads to immediate inc energy and appetite
- TSH: thyroxine replacement
- gonadotropin: in men give testosterone via gel or injection
- GH: daily subcut injection
how does Cushing’s disease present
- central obesity
- dorso-cervical fat pad
- increased roundness of face
- plethora
- thin skin
- easy bruising
- prox myopathy
- HTN
- premature osteoporosis
- DM
why is untreated Cushing’s syndrome dangerous
associated with significant morbidity and has a 5 year mortality approaching 50%
what are the 3 broad categories of causes of Cushing’s syndrome
- endogenous ACTH dependent causes
- exogeous ACTH independent
- pseudo-Cushing’s
what are endogenous causes of cushing’s syndrome
- Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
- ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
what are exogenous causes of cushing’s syndrome
- iatrogenic: steroids
- adrenal adenoma (5-10%)
- adrenal carcinoma (rare)
- Carney complex: syndrome including cardiac myxoma
- micronodular adrenal dysplasia (very rare)
what is pseudo-cushing’s
- mimics Cushing’s
- often due to alcohol excess or severe depression
- causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
- insulin stress test may be used to differentiate
what are appropriate screening tests for cushing’s disease and what are their results
- 24hr urine free cortisol
- low dose dexamethasone suppression tests/overnight
- 24h UFC will be elevated, and failure to suppress cortisol to < 50nmol/l after LDDST or overnight DST suggest Cushing’s syndrome
- Elevated late night salivary cortisol levels are a new convenient outpatient screening test.
explain the dexamethasone suppression tests
- normal respose to dex is suppressed cortisol due to negative feedback
- so a lack of cortisol suppression in respose to dex suggests cushing’s syndrome
what are the 3 types of dexamethasone suppression tests and state in what situations they are appropriate to use
- Low-dose overnight test (used as a screening test to exclude Cushing’s syndrome)
- Low-dose 48-hour test (used in suspected Cushing’s syndrome)
- High-dose 48-hour test (used to determine the cause in patients with confirmed Cushing’s syndrome)
what are the results of dexamethasone suppression tests in various causes of cushing’s syndromes
what are treatment options for cushing’s syndrome
primary objective is to remove the underlying cause
* Trans-sphenoidal (through the nose) removal of pituitary adenoma
* Surgical removal of adrenal tumour (lap adrenalectomy)
* Surgical removal of the tumour producing ectopic ACTH (e.g., small cell lung cancer), if possible
* Metyrapone/ ketoconazole reduces the production of cortisol in the adrenals and is occasionally used
what is Nelson’s syndrome
the development of an ACTH-producing pituitary tumour after the surgical removal of both adrenal glands due to lack of cortisol and -ve feedback
- causes skin pigmentation (high ACTH), bitemporal hemianopia and hypopituitarism
what is an indication for surgery of a non functioning pituitary tumour
- visual disturbances
- secreting hormones
