Endocrine Flashcards
What investigation results do you need to have to diagnose diabetes?
2 of: or 1 + symptoms:
random blood glucose over 11
fasting blood glucose over 7
more than 11 after glucose tolerance test
what is C peptide?
used to test for diabetes especially if atypical
Produced in the breakdown of insulin
So if T1DM there will be no C peptide
when should you take bolus insulin?
30 mins before a meal
what is the criteria for borderline diabetes?
oral glucose tolerance test above 7.8
fasting glucose above 6.1
hba1c above 42
what indications are there that metformin is not sufficient?
HbA1c is above 58
gliclazide is what type of drug, what does this do?
gliclazide = sulphonylurea
stimulate insulin release
= hypoglycaemia
what kind of drug is dapaglifozin?
SGLT2 inhibitor
glucose excretion into urine (fozin like urine)
exanatide is what kind of drug?
GLP-1 analogue
increase insulin and satiety
sitagliptin is what kind of drug?
DPP-4 inhibitor (prevents breakdown of GLP-1)
pioglitazone is what kind of drug?
thiazolidinedione
increased insuline sensitivity and decrease liver gluconeogenesis
CV side effects
in type II diabetes what type of insulin do you start with?
basal
what amount of glucose is level 2 hypoglycaemia?
3-3.9
diagnostic triad for hypoglycaemia?
symptomatic
biochemical
resolves with glucose
what is the pathophysiology of diabetic ketoacidosis?
lack of insulin = metabolise amino acids and triglycerides for energy
lipolysis = high serum levels of free fatty acids and alanine
glucagon stimulates ketogenesis (fatty acids – ketones)
= metabolic acidosis
what 3 things must there be in DKA?
hyperglycaemia
urinary ketones
metabolic acidosis
treatment of DKA?
slow rehydration
insulin
replace electrolytes
treat underlying cause
what can hyperosmolar hyperglycaemic state cause?
AKI
hypotension
coma
stroke etc (as hyperviscosity of blood because not enough water)
management of hyperosmolar hyperglycaemic state?
fluid (saline)! To dilute
insulin after that if still needed
3 macrovascular complications of diabetes?
stroke
IHD
heart failure
peripheral vascular disease
3 microvascular complications of diabetes?
neuropathy (inc autonomic = GI disturbance)
renal dysfunction
retinopathy
two stages of retinopathy and what briefly happens in them?
non proliferative: fluid leaks into macula = blurred vision
proliferative: new blood vessels try to grow but are not very strong
how does MODY1 present?
neonatal macrosomia and hyperglycaemia
what is MODY2?
GCK glucose sensor mutation
produces a mild diabetes
what is MODY-3?
most common
responds to sulphonylurea eg gliclazide
what is HNF MODY diabetes caused by?
decreased beta cell proliferation
how does adrenal disease impact glucose/diabetes?
acromegaly, cushings, increased adrenal activity = decreased insulin sensitivity – diabetes like picture
what is the simple function of thyroid hormone?
increases BMR, increases use of the body’s resources
what is the basic function of growth hormone?
breakdown of fat and carbs for growth
what is the basic function of cortisol?
mobilises glucose for fight or flight
what is the basic function of aldosterone?
increase BP, sodium and fluid retention
what is the effect of ADH on sodium?
high ADH = low sodium
what is Graves?
hyperthryoidism
because of antibodies to TSH receptors
what is toxic multinodular goitre?
high thyroid
in response to low iodine
what is Hashimoto’s?
hypothyroid
because of autoimmune attack of the thyroid gland
what is Conn’s syndrome?
high aldosterone
what is Addisons disease?
low aldosterone, cortisol and androgens
what is diabetes insipidus?
low ADH
what is the most common type of thyroid cancer?
papillary
what class of antibodies (MADGE) are in Graves disease?
IgG
are the affects of PTH mediated by osteoclasts or osteoblasts?
osteoblasts
osteoclasts haven’t got a PTH receptor
what kind of thyroid disturbance does tyhroiditis cause?
transient hyperthyroidism
amiodarone and lithium cause what endocrine disturbance?
hyperthyroidism
amiodarone can also cause hypothyroidism
a choriocarcinoma can cause what endocrine disturbance?
hyperthyroidism
choriocarcinomas secrete hCG
hCG increases thyroid hormone in preparation for pregnancy
5 symptoms of hyperthyroidism?
tremour increased heart rate yawning restlessness oligomenorrhoea irritability diarrhoea intolerance to heat sweating muscle wasting eyelid lad/stare
some symptoms of hyperthyroidism that indicate Grave’s is the cause?
other autoimmune eg diabetes etc bulging eyes acropathy pretibial myxedema Goitre
What do the individual levels of T3/T4 mean?
high T3 and T4 = hyperthyroidism
high T3 = hyperthyroidism
normal T3 high T4 - not significant
what antibodies are there in Graves?
anti TSHR IgG
may see:
anti TPO (thyroid peroxidase)
anti thyroglobulin
how can you look at the thyroid gland to see the type of goitre?
radioactive iodine uptake scan
what drug is used for hyperthyroidism?
carbimazole
what is gestational thyrotoxicosis?
nausea and vomitting
wernickes encephalopathy
no goitre or autoimmunity, low TSH high T4
what can happen in pregnancy if too much thyroid hormone?
poor foetal growth low birth weight pre eclampsia miscarriage still birth
what is atropic thyroiditis?
an extreme form of hashimotos, = hypothyroidism
symptoms of hypothyroidism?
weight gain cold intolerance oedema slow cerebration delayed reflexes fatigue dry cold skin loss of lateral aspect of eyebrows goitre
what antibodies are there in Hashimoto’s?
anti-TPO
what is subclinical hypothyroidism?
high TSH but (inappropriately) normal T4
what is the drug for hypothyroidism?
levothyroxine
what can happen if not enough thyroid hormone in pregnancy?
hypertension placental abruption post partum haemorrhage low birth weight (this can also happen if hyperthyroid) preterm neonatal goitre neonatal resp distress If you take levothyroxine you need to increase the dose in pregnancy
3 signs/symptoms of thyroid cancer?
trachial deviation dysphagia hoarse voice palpable nodule in thyroid raised or decreased thyroid hormone or symptoms of that
what 2 types of thyroid cancer secrete thyroglobulin?
papillary and follicular
thyroglobulin is used to make T3 and T4
what cells is medullary thyroid cancer from?
the C cells that make calcitonin
what are the 3 effects of grehlin?
increases hunger
increases fat deposition
stimulates growth hormone
What inhibits growth hormone release? - 3
somatostatin (from hypothalamus)
glucose
dopamine
high IGF-1 or GH, by negative feedback
what organ produces IGF-1?
liver
3 effects of IGF-1?
Cartilege formation
bone growth
protein synthesis
cell proliferation
apart from acral enlargement, give 5 other features of acromegaly?
sweating large hands/feet carpal tunnel arthralgia headache bitemporal hemianopia hypogonadal dysfunction diabetes like - polyuria polydipsia hyperprolactinaemia
3 tests for acromegaly?
GH - pulsatile so high GH means little but very low GH suggests is not a tumour
GnRH - if high suggests a problem in hypothalamus
glucose tolerance test.
- glucose inhibits GH release
- glucose = fall in IGF-1 normally, if not could be acromegaly
pituitary MRI after you have pos results, to find the tumour
what treatment is first line for acromegaly caused by pituitary tumour?
transsphenoidal pituitary surgery
give 3 drugs you could give for acromegaly?
somatostatin analogue eg octroetide
dopamine agonist eg bromocriptine
pegvisomant: GH antagonist
Cushings disease vs syndrome?
cushings disease = pituitary tumour
cushings syndrome = glucocorticoid excess from any other cause
two primary causes of cushings?
adrenal adenoma
adrenal hyperplasia
micronodular adrenal dysplasia
carney complex syndrome
what is a carney complex syndrome?
multiple benign tumours
myxomas (in conn tissue esp heart)
tumours in endocrine glands (– Cushings etc)
spotty skin
5 signs / symptoms of Cushings disease?
moon face bufallo hump purple striae muscle wasting central obesity achne bloating weiight gain tiredness menstrual irregularity
how does cortisol affect the BMR?
cortisol decreases metabolism, this is why cushings = weight gain
what is dexamethasone an analogue of?
cortisol
how does the dexamethasone test work, what do you use it for?
use it to investigate high cortisol
dexamethasone = cortisol analogue
so AcTH should decrease in response to it (neg feedback)
if AcTH does not decrease is pathological
Cushings disease – only responds to high dose dexamethasone
ectopic AcTH secreting tumour (eg small cell lung cancer) – still no response to v high dexamethasone
in Cushings when is the best time to measure cortisol?
Midnight, when it should be lowest
If cortisol is still high at this time you know there is a problem
In Cushings when should you measure AcTH, what will the results tell you?
measure at 9am
as cortisol is highest at 9am, ACTH should be lowest
If it is low the problem could be with the adrenals
If it is high the ACTH is being produced when it shouldnt be so the problem is secondayr
3 causes of pseudocushings?
alcohol
depression
obesity
pregnancy
what is secondary hyperaldosteronism caused by?
high renin, eg
- renal artery stenosis
- heart failure (resulting in poor renal perfusion)
how does renin cause aldosterone release?
renin = angiotensinogen – AT1
AT 2 = aldosterone release from the adrenals
what does aldosterone do in the kidney?
increases Na+K+ channels on the luminal membrane of principle cells in the DCT
increases ENaC on the apical membrane of principle cells in the DCT
= increased sodium reabsorption and increased potassium excretion
Increases H+K+ excretion pump = potassium excretion & alkalosis
some symptoms of Conns syndrome?
Conns = too much aldosterone
resistant hypertension
alkalosis
hypokalaemia – cramps
lethargy
how would you find renal artery stenosis?
CT angiography
doppler
magnetic resonance angiography (MRA)
first line investigation for hyperaldosteronism?
renin:aldosterone ratio
is Conns primary or secondary?
Conns is primary hyperaldosteronism, caused by an adrenal tumour/hyperplasia etc
treatment for hyperaldosteronism?
aldosterone antagonist - spironolactone, eplerenone
percutanous renal artery angioplasty/stent - if renal artery stenosis
adrenalectomy - if problem is a unilateral tumour
low dose glucocorticoids for familial hyperaldosteronism
in this country what is the most common cause of adrenal insufficiency?
Autoimmune adrenalitis
antibodies against glands or enzymes especially 21 a hydroxylase
3 causes of Addisons disease?
autoimmune adrenalitis TB congenital metastatic tumour haemorrhage amyloidosis
what is the most common cause of tertiary adrenal insufficiency?
steroids
what stimulates AcTH release from the anterior pituitary?
CRH release from the hypothalamus
give 4 physiological functions of cortisol?
increases HR increases BP bronchodilation glycogenolysis decreases digestion decreases urine output decreases BMR
symptoms of Addisons disease?
hyperpigmented patches of skin weight loss muscle wasting fatigue poor recovery from inf hypotension hyponatraemia hyperkalaemia vitiligo hair loss dehydration
symptoms of addisonian crisis?
metabolic acidosis hyperkalaemia hyponatraemia hypovolaemic shock confusion
when do you measure cortisol if you suspect adrenal insufficiency and what result indicates adrenal insufficiency?
measure at 9am when it should be highest, if low is bad!
100 = hospitalise
more than 500 = fine
what is synacthen and how can you use it as a test?
AcTH analogue
should stimulate AcTH receptors = cortisol release
if cortisol is not released in response there is a problem with the adrenals (primary adrenal insufficiency / Addisons disease)
why should you measure aldosterone if there is low cortisol?
aldosterone is also released from the adrenals but not under pituitary control
so if aldosterone is normal, problem is with AcTH - pituitary, hypothalamus, steroids
if aldosterone is low the problem is primary, a problem with the adrenals
3 causes of hyperkalaemia?
adrenal insufficiency renal dysfunction tumour lysis syndrome rhabdomyolysis/ trauma / burns metabolic acidosis diabetic ketoacidosis potassium sparing diuretics eg spironolactone ACEi because they decrease aldosterone diet NSAIDs because they impair renal function
normally is potassium intracellular or extracellular?
potassium lives in the cell
what ECG signs do you see in hyperkalaemia?
tall tented T waves
flat P
wide QRS
symptoms of hyperkalaemia?
arrythmia weakness paresthesia lightheadedness tachycardia diarrhoea hyper reflexia
a traumatic blood taking can alter the level of what electrolyte?
potassium
because it is released from lysed cellls
what drug for mild (below 6) hyperkalaemia?
calcium resonium
what drugs for bad hyperkalaemia?
insulin/dextrose
calcium gluconate
nebulised salbutamol
IV fluid
sodium bicarb
5 causes of hypokalaemia?
conns
cushings
nephrotic syndrome = low kidney BP = RAAS
inadequate diet / malabsorption / laxative
potassium wasting diuretics
renal failure
genetic - barrters / liddles / gietelmans
alkalosis
alcohol
5 symptoms of hypokalaemia?
arrythmia / palpitations / ectopic beats muscle weakness / hypotonia rhabdomyolysis paralytic ileus hypotension respiratory depression tetany
ECG changes in hypokalaemia?
flat inverse T wave
U wave
ST depression
prolonged QU
what is the oral potassium replacement called?
sandok
3 causes of nephrogenic diabetes insipidus?
lithium CKD post obstructive uropathy hypokalaemia hypercalcaemia inherited V2 receptor defect diabetes mellitus
3 causes of cranial diabetes insipidus?
brain tumour head injury hypophysitis meningitis sarcoidosis pregnancy
is ADH released when serum osmolarity is high or low?
released when it is high
this means the blood is concentrated and we dont want to be losing anymore water so we will secrete ADH to keep the water
presentation of diabetes insipidus?
polyuria polydipsia dehydration postural hypotension hypernatraemia concentrated blood, diluted urine
what is desmopressin an agonist of and how is desmopressin used as a test?
desmopressin = V2 agonist
test for diabetes insipidus
what can you use as a marker of DI instead of desmopressin?
copeptin
released in the production of ADH
water deprivation should induce copeptin release
treatment for DI? Is this for cranial or nephrogenic?
desmopressin
works well in cranial
no good treatment for nephrogenic but can try desmopressin
symptoms of hyponatraemia?
nausea anorexia lethargy headache weakness myalgia ataxia confusion seizures LOC myoclonus respiratory arrest
3 causes of SIADH?
head injury brain abscess guillian barre pneumonia asthma drugs eg carbamazepine small cell lug cancer
what is the difference in presentation of Addisons and SIADH?
both have low serum sodium and high urine sodium
in addisons there is usually hypovolaemia but in SIADH the body compensates for this
In addisons there are dark patches on the skin
in addisons ACTH is high
in addisons you also lack cortisol
what happens if the person is hyponatraemic and you give them sodium too quickly?
osmotic demyelination
treatment for SIADH?
replace sodium with hypertonic saline
tolvaptan
fluid restrict
furosemide
If you suspect acromegaly, what are the 1st, 2nd and 3rd line tests?
1st line: IGF-1
2nd : oral glucose tolerance test
3rd: pituitary function tests inc prolactin
4th: MRI pituitary
what is the gold standard test for phaeochromocytoma?
elevated free plasma metanephrine
3 cancers that cause SIADH?
small cell lung
prostate
pancreatic
thymus
lymphoma
complications of acromegaly?
obstructive sleep apnoea carpal tunnel diabetes cardiomyopathy HTN stroke
what is the most common cause of primary hyperparathyroidism?
solitary adenoma
in hyperaldosteronism what is the most obvious electrolyte distubance?
hyperkalaemia
how does carbimazole work?
prevents thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin
what cells is a phaeochromocytoma made of?
chromaffin cells
4 causes of hypocalcaemia?
- low vit D
- low PTH (surgery/ digeorge / magnesium deficiency)
- pseudohypoparathyroidism (mutation in PTH receptor)
- kidney disease (so cant reabsorb it)
- osteomalacia
pancreatitis
resp alkalosis
rhabdomyolysis
how does calcium affect QT?
lOng = hypOcalcaemia short = hypercalcemia
two signs of hypocalcaemia?
Trousseau: hand spasm with BP cuff
Chovstek: face twitch
parasthesia, spasm, long QT, seizures and basal ganglia calcification suggest high or low calcium?
low
low calcium = everything more excitable, the QT interval is opposite to what you’d think
thirst, hyporeflexia, short QT, pyrexia, hypertension suggest high or low calcium?
high
primary vs secondary hyperparathyroidism?
primary: high PTH = high Ca
secondary = low Ca = high PTH
how does high calcium affect the neurones?
high calcium = hyperpolarisation = slow and sluggish neurones
symptoms of high calcium?
bones (pain)
stones (kidney)
moans (depression)
thrones (constipation)
hyporeflexia hypertension vomitting confusion - coma pyrexia
what happens in hypercalcaemia of malignancy?
tumour produces ectopic PTHrP
what happens in carcinoid syndrome?
tumour produces serotonin, bradykinin and histamine = vasodilation itching SOB diarrhoea
plasma chromogranin A and urinary 5-HIAA are tests for what?
carcinoid syndrome
a drug for carcinoid syndrome?
octreotide
3 causes of decreased pituitary function?
adenoma metastates developmental cyst - rathkes or mucocoele syphilis sarcoidosis granulomatosis with polyangiitis anneurysm autoimmune perisellar meningeoma
what cells is prolactinoma a tumour of?
what are some symptoms of prolactinoma?
lactotroph
inhibits FSH and LH = infertility, amenorrhoea
galactorrhoea
low libido
