Endocrine Flashcards
diagnosing and treating acromegaly
IGF-1
confirm with OGTT
> trans-sphenoidal resection of pituitary tumour
if surgery not appropriate:
dopamine agonist (bromocriptine, cabergoline, quinagolide, pergolide)
somatostatin analogues (ocreotide)
GH antagonist (pegvisamant)
- RTX
acromegaly aetiology and associations
95% GH secreting pituitary tumour
5% from ectopic GHRH secreting carcinoid tumour
IGF-1 secreted by liver in response to GH excess
associations:
McCune Albright
neurofibromatosis
MEN
FIPA (AIP mutation, younger)
causes of primary hypoadrenalism
Addisons (autoimmune destruction of adrenals)
TB
HIV
haemorrhage into adrenal glands
congenital adrenal hyperplasia
aldosterone action
binds to mineralocorticoid receptors in kidney
> Na retention
> K excretion
mechanism of secondary hypoadrenalism
exogenous steroids increase cortisol
> sensed by hypothalamus
> negative feedback regulation of pituitary adrenal axis to reduce secretion of corticotrophin releasing factor
> reduced levels of ACTH
> adrenal gland atrophies due to lack of stimulation
primary vs secondary hypoadrenalism features
hyperkalaemia and increased pigmentation only in primary hypoadrenalism
because ACTH is low in secondary hypoadrenalism, and there is still aldosterone secreted via RAAS
hypoadrenalism blood tests
raised urea, TSH, Ca, K
hypoglycaemia, hyponatraemia
eosinophilia
lymphocytosis
normocytic anaemia
short synacthen test:
cortisol will remain low after ACTH administration in primary (Addisons)
cortisol will rise after ACTH administration in secondary hypoadrenalism
hormone production in adrenals
cortex:
cortisol, aldosterone, DHEA
androgens
medulla:
catecholamines- adrenaline, noradrenaline, dopamine
adrenal cancer associated conditions
MEN2
Li Fraumeni
VHL
Neurofibromatosis-1
HNPCC
FAP
MIBG scan
chemical similar to adrenaline
uptaken by neuroendocrine tumour
scan 2/7 after injection
managing adrenal tumours
alpha blocker for phaeochromocytoma pre surgery
ketoconazole and metyrapone to reduce steroid
spiro to reduce aldosterone effects
mifepristone to reduce cortisol effects
tamoxifen to block oestrogen effects
mitotane CTx
causes of primary amenorrhoea
normal secondary sexual characteristics:
constitutional delay
pregnancy
GU malformations
hypo/hyperthyroid
hyperprolactinaemia
cushings
PCOS
androgen insensitivity
no secondary sexual characteristics:
primary ovarian insufficiency
CTx, RTx, autoimmune
hypothalamic dysfunction (incl weight loss, excessive exercise, chronic illness)
primary and secondary amenorrhoea definition
primary:
no menstruation by age 15y with normal secondary sexual characteristics
or no menstruation by age 13y with no secondary sexual characteristics
secondary:
no menstruation for 3-6 months with previously normal menses
or no menstruation for 6-12 months with previous oligomenorrhoea
oligomenorrhoea definition
bleeding < once per 35 days
amenorrhoea blood tests
FSH and LH- high in ovarian failure
PRL
testosterone
TSH
stimuli to release PTH
hypocalcaemia
hyperphosphataemia
low vit D
conversion of 25 hydroxy D3 to 1,25 hydroxyD3 is stimulated by what
high PTH
low PO4, low Ca
actions of active vitamin D
kidney: increased calcium and phosphate excretion
bone: increased mineralisation
small bowel: calcium and phosphate absorption
PTH-rP
acts on same receptors as PTH
secreted by tumours e.g. squamous cell, breast, kidney
sarcoid and vit D
excess production of active vit D by macrphages
> hypercalcaemia
familial hypocalciuric hypercalcaemia
auto dom
mutation in calcium receptor
does not require treatment
peptic ulcer from hypercalcaemia
due to excess gastrin
managing acute hypercalcaemia
Ca > 3
3-4L saline per day
IV bisphosphonates
congenital adrenal hyperplasia disorders
auto rec
21-hydroxylase def (cortisol +/- aldosterone def):
virilising, 70% salt losing
11-hydroxylase def (v rare):
virilising, HTN, hypokalaemia
17 hydroxylase def:
non virilising
classic- severe
non classic- milder with later onset
testing for CAH
17 hydroxyprogesterone- raised in 21 hydroxylase def
corticotropin stimulation test
CAH treatment
may not require any
glucocorticoids and mineralocorticoids
NaCl for infants w/ salt losing CAH
antenatal steroid to reduce genital ambiguity of female infants
causes of Cushings syndrome
ACTH dependent:
- Cushings disease (bilateral adrenal hyperplasia from pituitary adenoma secreting ACTH)
- ectopic ACTH e.g. small cell lung, carcinoid
- ectopic CRF (rare)
ACTH independent (low ACTH from negative feedback)
- steroids
- adrenal adenoma/cancer
- adrenal nodular hyperplasia
medical management of cushings
metyrapone if surgery not possibly
ketoconazole no longer used due to hepato tox
mitotane as adjunct CTx for adrenal cortical carcinoma
diagnosing cushings
phase 1:
loss of diurnal variation of cortisol
overnight dexamethasone suppression test
24h urinary free cortisol as alternative to dex sup test
phase 2:
if first line test is abnormal, do 48h low dose dex suppression test
phase 3 localisation:
ACTH> if detectable, do high dose dex sup test or CRH to differentiate between pituitary and ectopic > MRI pituitary/bilateral inferior petrosal sinus blood sampling if cushings disease likely
> if not detectable, adrenal gland tumour is likely > CT/MRI adrenal/adrenal vein sampling
cushings syndrome post op
cortisol should be undetectable during recovery period
will require steroids during recovery period
recovery may not occur
Nelsons syndrome
rapidly enlarging pituitary adenoma after bilateral adrenalectomy
occurs due to high ACTH from removal of neg feedback
> skin pigmentation, muscle weakness, mass effects
causes of secondary hypogonadism
(low FSH and LH)
hypogonadotropic hypogonadism
tumours
pituitary apoplexy
marijuana
haemochromatosis, sarcoid
hypothyroid, hyperprolactin, diabetes, cushings
