pituitary lecture 1 and 2 Flashcards
what would class a tumour as a microadenoma?
tumour that is 1 cm or less
what would class a tumour as a macroadenoma?
if the tumour is greater than 1 cm
what are physiological causes for raised prolactin?
- breast feeding
- pregnancy
- stress
what drugs may raise prolactin?
- dopamine antagonists e.g. metoclopramide
- antipsychotics e.g. phenothiazines
- antidepressants eg TCA, SSRIs
- Other: oestrogen, cocaine
what investigations would you do if you suspected prolactinoma?
- serum prolactin (would be high)
- MRI pituitary (would be too big)
- check visual fields (for bitemporal hemianopia)
- pituitary function tests (to see if other hormones are affected, in microprolactinoma it is unlikely to affect them but macroprolactinoma might)
what treatment is given for prolactinoma?
USE DOPAMINE AGONISTS!!
-Cabergoline (Dostinnex) is usually used due to least side effects, it is given once to twice per week orally
Other dopamine agonists:
- bromocriptine (3x per day orally)
- quinagolide (1x per day orally)
what are side effects of dopamine agonists?
- nausea/vomiting
- low mood
- fibrosis of heart valves/ retroperitoneal (however patients who are on meds for prolactinoma have such low dosage they wont experience this)
what effects do dopamine agonists have on prolactinoma?
- normalise prolactin levels
- tumour shrinkage
what causes acromegaly?
GH excess
how does acromegaly present?
- bones increase in size
- thickened soft tissues (skin, large jaw, sweaty, large hands)
- snoring/ sleep apnoea (due to thickened nasopharynx)
- hypertension
- cardiac failure
- headaches
- DM
- Hypopituitarism
- Visual field disturbances
- early CV death
- colonic polyps and colonic cancer
how is acromegaly diagnosed?
Gold standard= GTT suppression test, give 75g oral glucose and check GH every half hour for 2 hours, normally GH < 0.4 mg/l so if it doesn’t do this it suggests acromegaly
Blood serum:
-increased IGF1 (sometimes it is not that raised so dont always use this test)
what investigations should be done if there’s suspected acromegaly?
- GTT suppression test, if GH> 0.4mg/l then acromegaly is present
- check visual fields
- CT or MRI pituitary gland
- pituitary function test (to check the other hormones)
what is the treatment for acromegaly?
PITUITARY SURGERY = first line (90% cure if microadenoma and 50% cure if its macroadenoma)
DRUGS= second line
- Somatostatin analogues: Sandostatin and lanreotide
- Dopamine Agonists: Cabergoline (only works in 10-15% of patients)
- GH Antagonist: pegvisomant (most effective but expensive so last line)
-radiotherapy alone= third line (25% success at 3 years)
what are some examples of somatostatin analogues?
- sandosatin LAR
- lanreotide autogel
- pasireotide LAR
what effect do somatostatin analogues have on GH?
they reduce GH in most patients
what effect do somatostatin analogues have on the tumour?
- they shrink the tumour (by 30-60%)
- however the tumour will re expand 6 weeks after stopping somatostatin analogues
how long does it take for somatostatin analogues to work?
6-12 months
what are side effects of somatostatin analogues?
-local stinging
Short term:
- flatulence
- diarrhoea
- abdominal pain
long term:
-gall stones
what type of injection is Sandostatin LAR?
IM injection
what type of injection is pasireotide LAR?
IM injection
what type of injection is lanreotide autogel?
SC injection
what dose is Sandostatin LAR given?
1-30mg once a month
when would you choose to use a dopamine agonist in acromegaly?
- sometimes patients with acromegaly secrete GH and prolactin
- would use a dopamine agonist
what is an examples of a GH antagonist?
pegvisomant
how is pegvisomant administered?
SC injection 10-30mg per day
what is the mechanism of action of GH antagonists?
-bind to GH receptor blocking GH activity
what effect do GH antagonists have on tumour size?
-tumour size does not decrease, actually sometimes there is a small increase in tumour size
are GH antagonists expensive?
yes very
what is there excess of in cushings syndrome?
-cortisol
what is the effect of excess cortisol on protein?
Protein loss
what can protein loss cause?
- myopthy (wasting)
- osteoperosis (fractures)
- thin skin (striae, bruising)
what effect does excess cortisol have on carbohydrate/lipid metabolism?
-it alters carbohydrate/lipid metabolism causing high blood glucose
what effect does cushings syndrome have on mineralcorticoid?
-it creates excess mineralcorticoid leading to hypertension and oedema
what effect does cushings syndrome have on androgen?
-it causes excess androgen leading to virilism, hirsutism, ane and oligo/amenorrhoea
how does chushings present?
- thin skin
- proximal myopathy
- frontal balding in women
- conjunctivital oedema
- osteoperosis
what tests are used for diagnosing Cushings?
Overnight 1mg dexamethasone supression test (oral):
- cortisol <50nmol/l next morn= normal
- cortisol > 130nmol/l next morn= abnormal
Urine free cortisol (24 hr urine collection)
- total <250 is normal
- cortisol/creatinine ratio of <25 is normal
Diurnal cortisol variation (midnight/8am)
- loss of diurnal variation suspicious of Cushing’s
- serum/saliva/ spot urine collection
Diagnostic test (low dose DST)
- 2 day 2mg/day dexamthesone suppression test
- cortisol <50 nmol/l 6 hours after last dose indicates no Cushings
- cortisol >130nmol/l = cushings
what is the difference between cushings disease and cushings syndrome?
cushings disease= tumour in the pituitary causing excess cortisol
cushings syndrome= tumour elsewhere causing excess cortisol
what else apart from tumours in pituitary gland can cause cushings?
- adenoma of the adrenal gland
- ectopic ACTH production in thymus, lung or pancreas can cause Cushings
- alcohol, depression and certain steroid hormones
what would a low dexamethasone test show for cushings caused by pituitary tumour, adrenal adenoma or an ectopic tumour?
abnormal results
what would ACTH levels be if someone had cushings caused by a pituitary tumour?
25-300
what would ACTH levels be if someone had cushings caused by an adrenal tumour?
<1
what would ACTH levels be if someone had cushings caused by an ectopic tumour?
> 300
what would CRF (corticol releasing hormone/factor) test show in a patient with cushings caused by a pituitary tumour?
ACTH raised by 50%
Cortisol raised by 20%
what would treatment for cushings caused by pituitary tumour?
-pituitary endoscopic surgery
what would treatment for cushings caused by pituitary tumour?
first line= transphenoidal hypophysectomy
if it reaccurs= radiotherapy
if radiotherapy unsuccesful= bilateral adrenalectomy
what would treatment for cushings caused by adrenal tumour?
first line=transphenoidal surgery
second line=
third line=
what would treatment for cushings caused by adrenal tumour?
-adrenalectomy
what would treatment for cushings caused by an ectopic tumour?
-remove source
OR
-bilateral adrenalectomy
what drug treatment is given for cushings disease?
Metyrapone= if other treatment fails and while waiting for radiotherapy to work
Pasireotide LAR
Ketoconazole (not commonly used as hepatotoxic)
what are side effects of Metyrapone?
nausea and vomiting are common
why is Ketoconazole not commonly used to treat cushings?
-as its hepatotoxic
what is pan hypopituitarism?
-a condition in which all production and synthesis of hormones in the pituitary gland is reduced
what does absence of GH due to pan hypopituitarism cause?
-growth failure
what does absence of TSH due to pan hypopituitarism cause?
-hypothyroidism
what does absence of LH/FSH due to pan hypopituitarism cause?
-hypogonadism
what does absence of ACTH due to pan hypopituitarism cause?
-hypoadrenal
what does absence of posterior pituitary function due to pan hypopituitarism cause?
-diabetes insipidus
what are the causes of hypopituitarism? (EDIT)
- pituitary tumours
- other local brain tumours
- iatrogenic: surgery
- granulomatous diseases: TB, histiocytes X, sarcoidosis
- Vascular disease: polyarteritis
