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
FSH action
stimulates sertoli cells > sperm production
stimulates follicular cells > ovulation
hypergonadotropic hypogonadism
results from gonadal disorders
elevated gonadotropins in absence of puberty at appropriate age
turner syndrome treatment of delayed puberty
GH and/or oxandrolone
IM testosterone side effects
polycythaemia
MODY genes
MODY1- HNF4AE
MODY2- glucokinase
MODY3- HNF1AE
MODY 4- IPF1
MODY 5- HNF1AE
diagnosing T1DM
random BM > 11 and typical symptoms
> same day referral
c peptide or autoantibodies if doubt
optimum plasma glucose for self monitoring
waking: 5-7
before meals other times of day: 4-7
90 mins after meals: 4-9
diagnosing T2DM
asymptomatic and HbA1c > 48 or 6.5% ideally tested twice
symptomatic and one abnormal HbA1c
fasting glucose 7 or more if Hba1c not appropriate e.g. pregnancy, children, T1DM, haemaglobinopathy
impaired glucose tolerance and impaired fasting glucose
OGTT 7.8-11.1 > IGTT
fasting BM 5.6-7 > impaired fasting glucose
fasting BM 7 or more > diabetes
T2DM management
- metformin
- add gliptin or sulfonylurea or SGLT2i
- consider triple therapy
- consider change to GLP1 mimetic or insulin
causes of diabetes insipidus
cranial:
idiopathic
craniopharyngiomas
trauma
pituitary surgery
lymphocytic hypophysitis
dysgerminomas
infiltrative process of hypothalamus e.g. sarcoid
renal:
x linked/dom ADHr abnormality (childhood onset)
hypercalcaemia, hypokalaemia
renal disease
demeclocycline, lithium
when to start dextrose with DKA pt
when glucose < 14
DKA indications for ITU/HDU
low GCS
hypokalaemia
ketones > 6
pH < 7.1
gigantism
acromegaly before puberty
increased height is main features
hyperaldosteronism
hypokalaemia, HTN, normal or mild hypernatraemia
- Conns > surgery
- adrenocortical hyperplasia > spiro or amiloride
causes of hyperaldosteronism
Primary, low renin:
conn syndrome (aldosterone producing adenoma)
b/l adrenocortical hyperplasia
adrenal carcinoma, GRA
secondary, high renin (due to renal hypoperfusion):
renal artery stenosis
accelerated HTN
CCF or hepatic failure
coarctation aorta
what drugs might affect renin/aldosterone tests?
ACEi
spironolactone
CCBc
ARB
treating hyperaldosteronism
adrenocortical hyperplasia
> spiro or amiloride
GRA > dex for 4/52
conn> lap adrenelectomy
causes of hyperparathyroidism
primary:
adenoma
hyperplasia
cancer
secondary:
CKD
low vit D
tertiary:
after prolonged secondary hyperparathyroidism, seen in CKD
drug causes of hypercalcaemia
lithium
thiazides
tertiary hyperparathyroidism
glands do not respond to normal feedback
occurs after prolonged secondary hyperparathyroidism
glands continue to produce excessive PTH though hypocalcaemia has been treated
primary vs secondary vs tertiary hyperparathyroid
primary:
hypercalcaemia
hypophosphataemia
PTH raised or normal
secondary:
hypocalcaemia
high PO4 in renal disease
raised PTH
tertiary:
hypercalcaemia
high PTH
PO4 often raised
predominantly increased TGs vs cholesterol
TG:
alcohol, obesity, T2DM
CKD, liver disease
high dose oestrogens, pregnancy
retinoids, beta blockers, thiazides
cholesterol:
smoking
hypothyroid
nephrotic syndrome, renal transplant
cholestasis
when to refer hypertriglyceridaemia
TG > 10
urgently if TG > 20 (if not due to poor glycaemic control or alcohol)
non HDL > 7.5
total cholesterol > 9
lipid lowering drugs side effects
simvastatin- potentiates warfarin and digoxin
gemfibrozil- absorption impaired by anion exchange resins
gemfibrozil and bezafibrate- potentiate warfarin
ezetimibe- headache, abdo pain, thrombocytopaenia, myositis, pancreatitis, abnormal lfts
anion exchange resins- abnormal lfts, impaired absorption of dig, warfarin, thyroxine, fat soluble vits
probucol- eosinophilia, long qt
whipple’s triad
non diabetic hypoglycaemia
- clinical symptoms
- BM< 3.3
- resolution of symptoms after glucose is corrected
causes of non diabetic hypoglycaemia
insulin, sulfonylureas
GH or adrenal insufficiency (hypopituitarism or addisons)
hyperthyroid
malnutrition, alcohol
insulinoma, fibroma, sarcoma, renal cell ca (IGF 1 secretion)
large liver tumours (increased gluc consumption)
nesidioblastosis, islet hypertrophy
beta blockers, fluoroquinolones, heparin, ppi, sulfonylureas, tramadol, quinine, haloperidol
what is released in response to hypoglycaemia
GH
cortisol
glucagon
adrenaline
inflammatory and infiltrative causes of hypopituitarism
lymphocytic hypophysitis
haemochromatosis
sarcoid, TB, langerhand histiocytosis
ipilumab, tremelimumab
presentation of pituitary apoplexy
sudden onset headache, visual changes and ophthalmoplegia
palsies of CN III, IV, VI
secondary hypothyroidism
low T3, T4 due to reduced TSH
pituitary cause
c peptide hyperinsulinaemia
low in exogenous
high in endogenous
liddle syndrome
auto dom
dysfunctional Na channels in collecting duct
HTN, hypokalaemic metabolic alkalosis, hypernatraemia
appears like primary hyperaldosteronism but renin and aldosterone are suppressed
indications for FSH testing to diagnose menopause
> 45y with atypical symptoms
40-45y with menopausal symptoms and change in cycle
< 40y if menopause suspected
MEN
MEN1: Parathyroid, Pituitary, Pancreas
auto dom, 11q13
MEN2A: Parathyroid, Phaeochromocytoma, Medullary thyroid
auto dom, RET 10q11.12
MEN2B: Phaeochromocytoma, Medullary thyroid, Marfinoid, Mucosal neuromas
auto dom, RET
diagnosing medullary thyroid ca
raised calcitonin
should you biopsy a suspected phaeochromocytoma?
no
familial phaeochromocytoma conditions
MEN (usually bilateral)
neurofibromatosis
VHL
phaeochromocytoma triad
headache
palpitations
sweating
phaeochromocytoma catecholaminergic effects
alpha:
- increased BP and cardiac contractility
- gluconeogenesis, glycogenolysis
- intestinal relaxation
beta:
- increased HR and contractility
consequences of hyperinsulinaemia in PCOS
- reduced hepatic DHBG > increased free T
- increased androgen production > anovulation, oligo/amenorrhoea
- weight gain
blood tests in PCOS
T may be high
high LH:FSH
raised HbA1c
normal to low SHBG
PRL may be mildly elevated
drug treatment for premature ejaculation
dapoxetine SSRI
turner syndrome cardiac problems
bicuspid aorta
coarctation
partial anomalous venous drainage
chemo for thyroid ca
tyrosine kinase inhib
lenvatinib and sorafenib for locally advanced or metastatic differentiated cancer if radioiodine did not work
cabozantinib for medullary ca that has spread or not operable
phases of thyroid eye disease
active- 6-24 months
inactive- chronic fibrotic phase, further changes are unlikely but proptosis remains
when to admit or get urgent advice for thyroid eye disease
dysthyroid optic neuropathy (reduced acuity or colour discrimination)
history of globe subluxation
risk of corneal ulceration (sclera or cornea visible when eyes are closed)
radioiodine uptake in thyroxoticosis
increased or normal uptake:
Graves
toxic multinodular
toxic/hot nodule
reduced uptake:
excess thyroxine ingestion
thyroiditis (dequervains, post partum, silent)
ectopic thyroid tissue
iodine administration
