MedEd Chem 1 Flashcards
describe the endocrine axis in the body
hypothalamus –> pituitary –> end organ
(tertiary) (secondary (primary)
- negative feedback from each to the one above
- external factors control the negative feedback
where is thyroid
inferior to larynx
vascular supply to thyroid
3 arteries (superior, inferior, thyroid ima) and veins (superior, middle, inferior)
2 functions of thyroxine and the R it acts on
acts on intranuclear receptor
regulates BMR
potentiating reponses to catecholamines
describe histology of thyroid gland
stroma (pale) with colloid (pink) surrounded by follicular cells (dark purple) and parafollicular cells between follicular cells
production of thyroxine
stimulated by TSH
thyroglobulin secreted by follicular cells
moved into colloid
oxygenation and iodination of thyroglobulin by thyroid peroxidase
makes t4
moves back into follicular cells
secreted into blood
what is free thyroxine
t4
t4 to t3 by which enzyme
deiodinase enzymes
how many iodine molecules does t4 have
2
what do parafollicular cells secrete
calcitonin
what does calcitonin do
regulates (reduces) calcium
sx of too much thyroxine
tremor
sweating
weight loss
palpitations
heat intolerance
goiter
anxiety
sx of hypothyroidism
weight gain
puffiness
reduced heart rate
constipation
depression
describe period dysfunction in hypo/hyperthyroidism & why
hypo = heavy periods
hyper = oligomenorrhoea with light periods
thyroxine has anti oestrogen effects - too much = blocks ovulation, too little = endometrial proliferation
what actually causes a goitre
high TSH causing proliferation
what types of thyroid issues cause goitre
primary hypothyroidism - TSH produced in response to low t4
secondary / tertiary hyperthyroidism - too much TSH produced
buzzword clinical features of specific thyroid diseases
pretibial myxoedema = graves
exopthalmus = hyperthyroidism (esp graves)
myxoedema coma = hypothyroidism
what scan is done in thyroid disease
radio iodine technetium scan
radio iodine scan of graves
butterfly thyroid - diffuse uptake through whole of thyroid
radio iodine scan of toxic multinodular goitre
discrete patches of uptake where the nodules are
radio iodine scan of toxic adenoma
single very dark spot showing intense uptake in one area over cancer
causes of hyperthyroidism
graves
de quervains
thyroid adenoma / ectopic
drug induced
toxic multinodular goitre
PP
iodine / jon basedow reaction
what is graves
AID hyperthyroidism due to auto ABs to TSH R
reaction to what drug can cause hyperthyroidism
amiodarone
causes of hypothyroidism
congenital /cretinism
primary atrophic
hashimotos
iodine deficiency
surgery / radio ablation
hypopituitarism
drugs
wolf chaikoff effect
what drugs can cause hypothyroidism
amiodarone, lithium, carbimazole
process of de quervain’s thyroiditis inc thyroidism level
infection / cancer / surgery / ITU stay etc –> inflammation of thyroid –> breakdown of gland –> release of all the hormones
hyper –> hypothyroid as hormones run out
why does amiodarone cause thyroid issues
amiodarone is a source of iodine
what is jon basedow reaction
chronic low thyroxine then given iodine causes hyperthyroidism due to body being used to low thyroxine
what is wolff chaikoff effect
give someone loads of iodine –> overloads the thyroid cells –> kills them off –> hypothyroidism
why is wolff chaikoff effect clinically relevant
explains why radio iodine in high doses can be used to treat toxic multinodular goitre etc
what is hashimotos thyroiditis
AID with ABs against TPO
(hypothyroidism)
what does ABs against TPO in hashimotos actually cause
inability to oxygenate and iodinate that thyroglobulin into t4 so no thyroxine produced
causes of cretinism
thyroid agenesis
thyroid dysgenesis
from where does the thyroid form embryologically
foramen caecum
(also forms part of tongue which is why if you have a thyroglossal cyst, it will move when you stick your tongue out)
features of cretinism
LDs
oedematous - puffy face, distended abdo
protruding tongue
stunted growth
hypothyroidism sx
Ix of thyroid issues
bedside - ECG, examination
bloods - FBC, U&Es, TFTs, ABs, lipids, BM, LFTs
imaging - USS, thyroid uptake / isotope scan, CT, MRI
ABs to screen for in ?thyroid issues
anti TSH
anti TPO
TSH low or high, free t4 high , t3 high. Dx?
hyperthyroidism
TSH high or low, free t4 low, t3 low. Dx?
hypothyroidism
TSH low or normal, free t4 low, t3 low. Dx?
sick euthyroid
TSH low, free t4 high or low, t3 high or low. Dx?
subacute thyroid
TSH normal or high, free t4 low, t3 low. Dx?
subclinical hypothyroid
TSH normal or low, free t4 high, t3 high. Dx?
subclinical hyperthyroid
mx of hyperthyroid and reason why for each
propanolo - sx control
thioamides - inhibit TPO
radioiodine - wolf chaikoff effect
surgical resection
mx of hypothyroidism
oral levothyroxine
mx of myxoedema coma
IV liothyronine
how is levothyroxine titrated
to normal TSH with 6 weekly check ups until stable
ensuring not over replacing –> palpitations
higher in preg / nephrotic syndrome etc
what is sick euthyroid
severe illness causes body to try and shut down metabolism to conserve energy so low t3/4 –> initially high TSH then low
most common type of thyroid tumour
papillary 70%
which thyroid tumour has best prognosis
papillary
3 buzzwords for papillary thyroid tumour
psammoma bodies
orphan annie nuclei
lymphatic invasion
2nd most common thyroid tumour
follicular 20%
what is prognosis of follicular tumour (good / bad / very bad)
good
2 buzzwords for follicular tumour
encapsulated
vascular invasion
2 associations of medullary thyroid cancer (buzzwords)
c-cells that produce calcitonin
MEN2
what thyroid condition is a risk factor for developing lymphoma
hashimotos
2 buzzword gene associations of lymphoma with thyroid
DLBCL
CD20
who gets anaplastic thyroid tumour
elderly people
prognosis of anaplastic thyroid tumour (good / bad / very bad)
very bad
histology of anaplastic thyroid tumour
rapid growth
giant and spindle shaped cells
Mx of papillary and follicular thyroid tumours
surgery +/- radio-iodine
replace thyroxine to completely suppress TSH
monitor thyroglobulin / calcitonin
50F with recent coryzal Sx. Now has hyperthyroidism sx with tender neck. low TSH and high T4. poor uptake on technetium scan. Dx?
de quervain’s thyroiditis
which blood marker is used to monitor for recurrence of medullary thyroid cancer
calcitonin
Mx for thyrotoxic crisis
beta blocker, steroid, thioamide
why is steroid given in thyrotoxic crisis
prevents peripheral conversion of t4 to t3
where does pituitary sit
sella turcica
list anterior pituitary hormones
growth hormone
FSH / LH
ACTH
TSH
list hypothalamic hormones which act on AP
TRH
VP
CRH
GnRH
GHRH
somatostatin
how is GnRH released
pulsatile wave forms
2 types of pituitary masses with definition of each
macroadenoma >1cm (non functional)
microadenoma <1cm (functional)
sx related to macroadenoma in pituitary
bitemporal hemianopia - superior quadrantopia
headache
hormone related - mainly prolactin
clinical features of acromegaly
soft tissue growth - large hands / feet / tongue
organomegaly
HF / HTN
DM
carpal tunnel
Ix of acromegaly
plasma IGF-1 1st line
OGTT
GH measurement
MRI pituitary
Mx of acromegaly
trans sphenoidal surgical resection - 1st line
somatostatin analogue
CVD risk factor modification
monitor serum GH
colonoscopy surveillance
what is gigantism
acromegaly before puberty (epiphysis haven’t fused so get rlly tall)
clinical features of prolactinoma
galactorrhoea
gynaecomastia
oligo / amenorrhoea
loss of libido
impotence
ix of prolactinoma with key result
serum prolactin (>6000)
MRI pituitary
mx of prolactinoma
dopamine agonist - 1st line
trans sphenoidal resection
serum prolactin for monitoring
causes of hypopituitarism
cancer - pituitary adenoma, craniopharyngioma
infection - TB / syphillis
infiltration - sarcoid / lymphoma
iatrogenic - surgery / trauma / radiation
infarct - Sheehan’s / apoplexy
tertiary - kallman’s
signs / sx of hypopituitarism
generic - lethargy, weight gain, low BP, hair loss, myalgia
sex hormones - impotence, loss of libido, no periods (GnRH)
addisons crisis (ACTH)
myxoedema coma (TSH
in what order are the hormones lost in SOL compressing pituitary
(kind of the order of how important they are except prolactin)
GH first to go
FSH / LH
ACTH
TSH
prolactin last to go (TRH stimulates prolactin, so when TSH goes then prolactin goes up)
screening of hypopituitarism
9am cortisol
TFTs
serum testosterone / oestrogen
Ix of hypopituitarism and what this involves
combine pituitary function test
- administer LHRH, TRH and induce hypoglycaemia (give insulin)
- measure LH, FSH, TSH, ACTH and GH for 2 hours every 30 mins.
CT / MRI
mx of hypopituitarism
replace end hormones - cheaper and easier
- hydrocortisone
- thyroxine
- oestrogen / testosterone
give steroids if infiltration cause
which hormone needs to be replaced first and why in hypopituitarism
hydrocortisone - can precipitate a thyrotoxic crisis otherwise
BV supply to adrenals
3 arteries
1 vein
3 layers of adrenal cortex and what does each secrete
glomerulosa = aldosterone
fasicularta = cortisol
reticularis = sex hormones
medulla = catecholamines
(remember it as GFR outer to inner)
3 layers of adrenal cortex and what does each secrete
glomerulosa = aldosterone
fasicularta = cortisol
reticularis = sex hormones
medulla = catecholamines
(remember it as GFR outer to inner)
what does 21 hydroxylase do
progesterone –> deoxycorticosterone (ald pathway)
AND
17 OH progesterone –> 11 deoxycortisol (cortisol pathway)
what does 17a hydroxylase do
progesterone –> 17 OH progesterone
AND
pregnenolone –> 17 OH prognenolone
(both in aldosterone to cortisol pathway shunt)
21a hydroxylase deficiency clinical picture
CAH
clinical features of 11 beta hydroxylase deficiency
HTN
hypernatraemia
hypokalaemia
clinical features of 21 hydroxylase deficiency
hypotensive addisons crisis
low Na, high K
causes of adrenal insufficiency
primary
- iatrogenic
- Addisons (AID)
- TB
- waterhouse friedrichson syndrome
- infarct
- malignancy
- AIPE syndromes 1&2
secondary
- hypopituitarism
what is waterhouse friedrichson syndrome
septicaemia causing haemorrhagic adrenals infarcts
which bug / condition most commonly causes waterhouse friedrichson syndrome
neisseria meninigitidis meningitis
clinical features of adrenal insufficiency
postural sx
weight loss, anorexia
abdo pain, N&V
fatigue
vomitting, salt craving
skin / mucosal pigmentation
decreased arm / pubic hair
addisonian crisis
Ix for adrenal insufficiency
9am cortisol
U&Es - Na, K
serum ACTH
glucose
CT abdomen
SynthACTHen test
how is synthACTHen test done
IV/IM ACTH given
check cortisol at 0,30,60 mins
what 9am cortisol reading would exclude Addisons
> 350
in which type of adrenal insufficiency cause would synthACTHen test be positive (cortisol rises)
secondary disease
Mx of adrenal insufficiency
hydrocortisone (glucocorticoid + weak mineralo)
fludrocortisone (mineralocorticoid)
causes of hyperaldosteronism
primary
- bilateral idiopathic hyerplasia
- adrenal adenoma
- familial GRA
secondary
- RAS
- FMD
- CCF
sx / signs of hyperaldosteronism
HTN
low K
high Na
polyuria and polydipsia
ix of hyperaldosteronism
bloods - U&Es, plasma ald:renin ratio
CT abdo
adrenal vein sampling
mx of hyperaldosteronism
aldosterone antagonists (spironolactone)
surgical resection
causes of cushing syndrome
primary
- adrenal tumour
secondary
- pituitary adenoma (cushings DISEASE)
- ectopic / paraneoplastic ACTH - SCC lung Ca
iatrogenic
- xs steroids
mccune albright syndrome
cushings sx
moon face
red face
buffalo hump
lemon on sticks etc
ix of cushings
24hr urinary cortisol / 9am cortisol
low dose dex suppression test
high dose dex suppression test
CT CAP / MRI pituitary
purpose of 24hr urinary cortisol / 9 am cortisol for ?cushings
confirms raised cortisol
purpose of low dose vs high dose dex suppression test for ?cushings
low dose = confirms true cushings syndrome (ie not exogenous steroids)
high dose = confirms cushings DISEASE
mx of cushings due to exogenous steroids
gradual tapering
mx of cushings disease
trans sphenoidal resection
mx of cushings due to adrenal tumour
monitoring
resection
radiotherapy
mx of cushings due to ectopic tumour
radio / resection
ketoconazole / metyrapone / mifepristone
what are phaeos associated with
MEN2
NF 1
VHL
what is the clinical rule of phaeos
10%
malignant
extra adrenal
bilateral
normotensive
clinical features of phaeo
episodes of panic / impending doom
resistant HTN
triad: throbbing headache, palpitations, sweating
ix of phaeo
BP, ECG
** urinary metanephrins ** buzzword
U&Es, LFTs, catecholamines
CT abdo / MIBG scan
what can cause false positives in urinary metanephrins test
TCAs
CCBs
beta blockers
mx of phaeo
alpha blockade - phenoxybenzamine
beta blockade
surgery
chemo
labelled MIBG
phaeos are tumours of what
adrenal medulla
what is conns syndrome
adrenal hyperplasia / tumour causing HTN, high Na and low K
what Ix is high in conns
aldosterone:renin ratio
tx of conns
spironolactone
adrenalectomy
features of MEN1
pituitary adenoma
parathyroid hyperplasia
pancreatic tumour
3Ps
features of MEN2a
parathyroid hyperplasia
medullary thyroid cancer
phaeo
2Ps 1M
features of MEN2b
mucosal neuromas
marfanoid body habitus
medullary thyroid cancer
phaeo
1P 3Ms
Dx of pre DM with values for each
fasting BG 6.1-6.9
OGTT 7.8 - 11
HbA1c 42 - 47
random BM 7.8 - 11
Dx of DM with values for each
Sx + one of these // no Sx + 2 of these:
fasting BG >7
OGTT >11.1
HbA1c >48 (6.5%)
random BM >11.1
mx of t1dm
lifestyle advice - inc alcohol
DM nurse review
dietary advice
insulin
metformin if BMI >25
surgical - pancreas kidney transplant
outline tx ladder of t2dm (7)
diet and lifestyle
exercise
metformin
+ sulphonylurea / DPP4 agonist / SGLT2 inhibitor
+ GLP1 antagonist or 2 of above
insulin
surgical - bariatric
buzzword for DKA breathing
kussmals breathing
enzyme deficiency in acute intermittent porphyria
PBG deaminase
Ix of acute intermittent porphyria
urinary / serum levels of PBG and ALA
sx of acute intermittent porphyria
acute abdo pain
GI Sx
neuropsych Sx - confusion, hallucinations, sensory loss / weakness
what is PCT
porphyria cutanea tarda
enzyme deficiency in PCT
uroporphyrinogen decarboxylase
Ix of PCT
urinary uroporphyrinogen III is raised
sx of PCT
photosensitive rashes and blisters
