endocrine Flashcards
when do pregnant hypothyroid women need to change their their thyroxine and by how much
increase their thyroid hormone replacement dose by up to 50% as early as 4-6 weeks of pregnancy
Acromegaly CFs
large tongue, hands, face
XS sweating
signs of hypopituitarism- headache, bitemporal hemianopia
which clinical problems assiciated with acromegaly
HTN, Cardiomyopathy, diabetes
what is acromegaly caused by
XS GH secreted
95% caused by pit adenoma
MEN1
Investigations acromegaly
GOLD STANDARD;
Serum IGF-1 levels
If IGF-1 raised- OGTT
what would show on Ix for acromegaly
acromegaly: no supression of GH in hyperglycaemia
MRI brain - check for pit adenoma
first line management acromegaly and what adjunct
trans sphenoid surgery
ocreotide= adjunct when awaiting surgery a somatostatin analogue which is often used as an adjunct to surgery resulting in reduced growth hormone levels and reduction in tumour size.
(bromocriptide DO agonist is only for medical management alone_
management acromegaly:
- trans sphenoid surgery
- somatostatin analogue eg octreotide, directly inhibits the release of growth hormone
- pegvisomant——GH receptor antagonist
- dopamine agonists——bromocriptine (now last line)
what is addisons disease and what does it cause
how does it affect electrolytes
and CFs
what causes addisons
primary hypoadrenalism
causes reduced cortisol and reduced aldosterone
low Na
high K
loss of pubic hair
CFs
axillary hair thinning
pubic hair thinning
vitiligo
salt craving
hypotension
hypoglycaemia
addisonian crisis
caused by autoimmune destruction of adrenal glands
primary hypoadrenalism =????
addisons disease
eg biguanide
metformin
what type of meds are DPP4 inhibitors and their MOA
gliptins eg sitagliptin
DECREASE GLP 1 breakdown
pros of biguanides and MOA
eg metformin-
no risk of hypoglycaemia
works by DECREASE hepatic glucose production
and
INCREASE peripheral insulin sensitivity
how do gliptins work
DPP4 inhibitor
increase post prandial insulin
eg sulpohonylurea
glicazide, glibenclamide
work by:
increase pancreatic insulin secretion
ATPk CLOSES CHANNEL
which type of diabetes medicine causes weight gain
sulphonylurea== AVOID IN OBESE PATIENTS
WHAT Type of diabetes medicine can cause hypoglycaemia
sulphonylureas- eg gliclazide
eg thiazolidinediones
and MOA
eg pioglitazone
moa= PARRY gamma
TRIAD symptoms of DKA
- blood glucose>11
- capillary ketones >3 or >2+ in urine
- pH<7.35
initial DKA TX
IV FLUIDS- and Fixed rate insulin infusion
5OU actrapid in 50ml 0.9%NaCl
HHS presentation and cause
CFS
Tx
characteristic of T2DM, severe hyperglycaemia in absense of ketosis causing hyperosmolar state
Tx HHS
agressive iV fluids
consider potassium replacement if hypokalemc
Treatment thyrotoxicosis
propylthiouracil
Propanolol
high dose steroids- dex 4mg iv
iodine
supportive measuresd
which medication can cause thyroidtoxicosis
amiodarone
TRAb antibody sensitive and specific for which thyroid problem?
Grave’s disease
which thyroid antibody is tested in Grave’s disease
TSH receptor antibody (TRAb)
MOA carbimazole and propylthiouracil
TPO
What does adrenal gland secrete
adrenaline, aldosterone, cortisol
electrolyte disturbance caused by addisons?
hyponatremia
hyperkalemia
Another name for sub acute thyroiditis =
de quervain
sick euthyroid is common in which patient demographic
hopsital inpatients
treatment for sick euthyroid syndrome
no treatment- Changes are reversible upon recovery from the systemic illness and no treatment is usually needed
TSH and free T3 in sick euthyroid syndrome
low TSH low T3
Sub clinical hypothyroidism TSH and T3 levels
High TSH,
normal T3
Poor compliance with thyroxinE patients: TSH and T3 levels
Hight TSH
normal t3
Polydipsia ivestigation test
water deprivation test
water deprivation test: positive for primary POLYDIPSIA:
starting plasma osmolality
urine osmolality after fluid deprivation
-urine osmolality after desmopressin
starting plasma osmolality LOW
urine osmolality after fluid deprivation: HIGH
urine osmolality after desmopressin: HIGH
Water deprivation test: nephrogenic DI
urine osmolality after fluid deprivation: low
urine osmolality after desmopressin: low
where is ADH secreted
hypothalumus
cranial DI water deprivation test
starting plasma osmolality:High
urine osmolality after fluid deprivation:low
urine osmolality after desmopressin: high
which medication deiabetes med can cause DKA
Dapagliflozin/SGLT2 inhibitors
Klinefelter’s syndrome chromosome abnormality
CFs
47XXY
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone HIGH LH, HIGH FHS
HYPOCALCAEMIA ECG
LONG QTC
Which syndrome causes LH & FSH low-normal and testosterone is low
Kallmans syndrome
Also, cleft palate, small testes, X LINKED recessive INHERITED
Sjogrens syndrome can cause ?type of renal tubular acidosis
type 1- distal
treatment for severe hyponatremia
3% nacl
Familial hypercholesterolaemia (FH) - inheritance
is an autosomal dominant c
bilateral adrenal hyperplasia causes hyper????????
HYPERALDOSTEROINISM
most common cause primary hyperparathyroidism
Primary hyperparathyroidism: solitary adenoma
in pregnancy- increase in which thyroid antibody
TBG- thyroxine binding globulin
Exenatide = MOA
Exenatide = Glucagon-like peptide-1 (GLP-1) mimetic
Deafness and hypothyroidism== what condition
pendred disease
MODY inheritance patter
auto dominant
is urinary sodium high or low in SIADH
high
which diabetes med can cause pancreatitis and severe renal impairment
exenatide
long term corticosteroid use can cause
avascular necrosis
acromegaly patients high risk for which type of cancer
colorectal
Meglitinides - moa
bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells
MEN 1, 2a and 2b associated conditions
see screenshot
MEN 1
PPP
Parathyroid, pituitary, pancreas
MEN 2a
PP
Parathyroid
Phaechromocytoma
MEN 2b
P
Phaeochromocytoma
Marfanoid body
medullary throid
hypercalcaemia is most common in which MEN type
MEN 1
acetozolamide - electrolyte hypo or hyperkalemia
hypokalemia
thiazide- electrolyte hypo or hyperkalemia
hypokalemia
sick euthyroid syndrome- TSH and T4 level
BOTH LOW
VBG of (all) renal tubular acidosis
hyperchloraemic metabolic acidosis
(normal anion gap)
carbimazole MOA
Blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin –> reducing thyroid hormone production + no action on 5’-deiodinase
carbimazole
== NO ACTION ON 5 deiodinase
propylthiouracil moa
Blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin –> reducing thyroid hormone production + inhibits 5’-deiodinase which reduces peripheral conversion of T4 to T3
incontinence in elderly—give?
give mirabegron
NOT oxybutynin (bc elderly == confusion)
MOA mirabegron
mirabegron- beta3 agonist
definitive mangement hyperparathyroidism
total parathyroidectomy
anti thyroid medications in pregnancy
1st trimester
2nd trimester
1st trimester- propylthiouracil
2nd trimester onwards- switch back to carbimazole
primary hyperparathyroidism symptoms
bones groans stones psychic moans
MEN 1 and 2
electrolyes in primary hyperparathyroidism
high calcium
low phosphate
normal-high PTH
In a patient with T2DM (poorly controlled) and CVD:
add metformin first
if still not helping:
add ???
Add SGLT2 inhibitor
eg piglitazone
what type of anti diabetic med good for CVD
SGLT 2 inhibitor eg dapagliflozin
how often check hba1c in t2dm
every 3-6 months until stable , then 6 monthly
HBA1C targets in T2DM
lifestyle only
lifestyle + metformin
lifestyle +drug can cause hypos
lifestyle only 48
lifestyle + metformin 48
lifestyle +drug can cause hypos 52
Causes of HTN and hypokalemia (plus mneumonic)
Liddle Cushing Conned 11 people
Liddle’s syndrome
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
11-beta hydroxylase deficiency
Causes of hypokalemia WITHOUT HTN
diuretics
GI loss (e.g. Diarrhoea, vomiting)
renal tubular acidosis (type 1 and 2**)
Bartter’s syndrome (furosemide ascLOH)
Gitelman syndrome
which antidiabetic med causes glycosria
dapagliflozin
which antidiabetic med CI in heart failure
Thiazolidinediones- eg pioglitazone
cinacalcet==? and when to give
in primary hyperparathyroidism
= calcium mimetic
familial hypercholesterolaemia inheritance
aut dom (exception to rule)
addisons disease investigation
ACTH stimulation test- synacthen test
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM
if this not possible:
9am cortisol
electrolytes in addisons
addisons- primary hypoaldosteronism
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
investigations cushing disease
confirm and localise
confirm:
overnight dexamethasone suppression test
IF positive for cushings disease:
NO suppression of morning cortisol
Localise:
high-dose dexamethasone suppression test
VBG in cushings sydnrome
met alk and kypokalemic
interpretation of high dose dexamethasone suppression test to localise cushings
Cushings syndrome (eg adrenal adenoma)
Cortisol- NOT supp
ACTH : +SUPpressed
Cushing disease (pit adenoma)
Cortisol: suppressed
ACTH: suppressed
Ectopic ACTH syndrome:
Cortisol: not suppressed
ACTH: not suppressed
how does osteomalacia affect calcium and phosphate
LOW CALCIUM
and LOW PHOSPHATE
impaired fasting glucose range
6.1-7.0
impaired glucose tolerance rang
fasting <7.0
AND
OGTT 2 hr 7.8-11.0
gitelmans syndrome
cause
how it affects electrolytes
Gitelman’s syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
Features
normotension
hypokalaemia
hypocalciuria
hypomagnesaemia
metabolic alkalosis
what type of cancer ass’d with MODY
HCC
what type of med is dapagliflozin, canagliflozin, GLIFLOZINS and their
MOA
gliflozins
MOA: SGLT2 inhibitor
Increase urinary glucose
excretion
reduce glucose reabsorption`
gliflozins can cause forniers gangrene
in toxic multinodular goitre– nuclear scintigraphy == ?
patchy uptake-
Second-line treatments T2DM:
Sulphonylureas e.g. gliclazide.
Gliptin’s e.g. sitagliptin.
Thiazolidinedione e.g. pioglitazone
Sodium/glucose cotransporter 2 (SGLT-2) inhibitors e.g. canagliflozin
Second-line treatments for type 2 diabetes range from:
Sulphonylureas e.g. gliclazide. Side effects include weight gain and hypoglycaemia.
Gliptin’s e.g. sitagliptin. Side effects include headaches, but are generally well tolerated.
Thiazolidinedione e.g. pioglitazone. Side effects include fluid retention and weight gain.
Sodium/glucose cotransporter 2 (SGLT-2) inhibitors e.g. canagliflozin. Side effects include urinary tract infections and increased risk of foot amputations (mainly with canagliflozin, but no evidence of a link with empagliflozin and dapagliflozin).
What can lithium cause- cranial or nephrogenic DI
nephrogenic DI
Dapagliflozin MOA and where it acts
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule
gestational diabetes diagnosis range
Diagnostic thresholds for gestational diabetes
gestational diabetes is diagnosed if either:
fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L
5678
what to give in gestational diabetes if metformin not tolerated
glibenclamide
or give if BM targets not met on metformin but pt declines insulin
management of pre existing diabetes in pregnancy
BMI <27
stop meds apart from metformin and start insulin
folic acid 5mg od
Targets for self monitoring of pregnant women (pre-existing and gestational diabetes)
537864
fasting 5.3
1 hr post meal 7.8
2 hr post meal 6.4`
what is hungry bone syndrome and how does it affect calcium levels
hungry bone syndrome = sudden drop in previously high parathyroid hormone levels
causes hypocalcaemia
Bartter’s syndrome : where does it act
CFs
loop of henle , inhibits Na-K-2Cl
acts like furosemide
CFs
normotension
polyuria, polydipsia
hypokalemia
FTT in childhood
Liddles syndrome
inheritance
CFs
treatment
where does it act
aut dominant
HTN
hypokalemia
met alkalosis
Tx= amiloride or triamtrelene
acts in distal tubules
incr sodium absorption
graves disease- antibodies most common
anti TSH
GLP 1 mimetic - egs
MOA
major pro with GLP 1 mimetics
eg exenatide, liraglutide
MOA= increase insulin secretion
inhibit glucagon secretion
weight lose
Hashimotos thyroiditis associated with which type of cancer
thyroid lymphoma
orlistat MOA
lipase inhibitor
drug induced gynaecomastia
spironolactone
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
insulin and c peptide levels
sulfonylurea-induced hypoglycemia: Insulin and C-peptide Rise
Insulin - Induced Hypoglycemia: Insulin Rise but C-peptide Low
is MGUS associated with hyper or hypo calcaemia or normal calcium
NO HYPERCALCAEMIA
RET oncogene thyroid cancers (2)
papillary and medullary
what is monoclonal gammopathy of uncertain significance (MGUS)
the absence of complications such as immune paresis, hypercalcaemia and bone pain
gestational diabetes - patient previously had in prev pregnancy- when to do OGTT in next pregnancy?
ASAP
which antibody most likely to be found in hashimotos
anti tpo + goitre
Gitelman = Thiazide diuretic
Bartter = Loop diuretic
Gitelman = Thiazide diuretic in DCT
Bartter = Loop diuretic
GITELMAN WAS A Normal man (normotension)
tender goitre, hyperthyroidism and raised ESR. ==?
subacute thyroiditis
Sick euthyroid:
T4 + T3 low, TSH normal or low
Subclinical hyperthyroidism:
T4 + T3 normal, TSH low (high if subclinical hypo)
Sick euthyroid:
T4 + T3 low, TSH normal or low
Subclinical hyperthyroidism:
T4 + T3 normal, TSH low (high if subclinical hypo)
haemochromatosis
general population testing
genetic family testing
general population: transferrin saturation > ferritin
family members: HFE genetic testing
Mx urge incontinence
- lifestyle
- if still not improved- musicarinic antagonists eg oxybutynin
IF ELDERLY AND FRAIL
mirabegron (a beta-3 agonist)
androgen insensitivity syndrome
46XY
Features
‘primary amenorrhoea’
little or no axillary and pubic hair
undescended testes causing groin swellings
breast development may occur as a result of the conversion of testosterone to oestradiol
Management
counselling - raise the child as female
bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
oestrogen therapy
conns anti HTN of choise
spironolactone
phaeochromoctyoma Tx anti htn
phenoxybenzamine = non selective alpha antagonist
presents as adrenal mass
which pit hormone is constantly under inhibition
prolactin
cushings electrolyte and VBD
hypokalemic met alk
causes of pseudohyponatremia
hyperlipidaemia
or taking blood from arm with IV in
hyper thyroid and hypo thyroid
which cause galatorrhoea and gynaecomastia
Hyperthyroidism - Gynaecomastia
Hypothyroidism - Galactorrhoea
low=cry=leak
pegvisomant moa AND WHAT IS IT used ofr
pegvisomant for acromegaly
GH receptor antagonist - prevents dimerization of the GH receptor
hyponatremia–
urinary sodium <20 and >20 causes
Urinary sodium > 20 mmol/l
Sodium depletion, renal loss (patient often hypovolaemic)
diuretics: thiazides, loop diuretics
Addison’s disease
diuretic stage of renal failure
Patient often euvolaemic
SIADH (urine osmolality > 500 mmol/kg)
hypothyroidism
——————————————————
Urinary sodium < 20 mmol/l
Sodium depletion, extra-renal loss
diarrhoea, vomiting, sweating
burns, adenoma of rectum
Water excess (patient often hypervolaemic and oedematous)
secondary hyperaldosteronism: heart failure, liver cirrhosis
nephrotic syndrome
IV dextrose
psychogenic polydipsia
Congenital adrenal hyperplasia
causes
cfs
tx
Congenital adrenal hyperplasia is most commonly due to 21-hydroxylase
autosomal recessive disorders
affect adrenal steroid biosynthesis
in response to resultant low cortisol levels the anterior pituitary secretes high levels of ACTH
ACTH stimulates the production of adrenal androgens that may virilize a female infant
Cause
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
17-hydroxylase deficiency (very rare)
CFs
Early puberty irregular menses, acne, hirsutism, early breast and pubic hair development, clitoromegaly and male-pattern baldness.
which anti diabetic med causes incr flatulence
acarbose
heterozygous or homozyhous familial hypercholesterolaemia
The presence of tendon xanthomata and cholesterol levels meet the diagnostic criteria for familial hypercholesterolaemia. Homozygous familial hypercholesterolaemia is exceedingly rare - most patients die in their teenage years from a myocardial infarction.
liddlye syndrome inheritacne
aut dom
LIDL is dominant in the distant tubes
stress incontinence tx
1 pelvic floor exercises
2 . duloxetine
fibrate MOA
globally decreased uptake on thyroid scan
deceased uptake, painful goitre= subacute de quervain thyroiditis
sulphonylurea MOA
increase peripheral insulin secretion by CLOSING potassium-ATP channels on the beta cells
most common cause of tertiatry hyperparathyroidism
CKD renal disease
pendred syndrome
hypothyroid
painless goitre
deafness
what causes ketone production in DKA
lipolysis
what is fanconi syndrome
Fanconi syndrome describes a generalised reabsorptive disorder of renal tubular transport in the proximal convoluted tubule resulting in:
type 2 (proximal) renal tubular acidosis
polyuria
aminoaciduria
glycosuria
phosphaturia
osteomalacia
insulinoma c peptide level
high c peptide level in insulinoma
siadh Dx urine osmolality
Euvolema + urine osmolality higher than serum osmolality= SIADH
which malignant cell secretes PTH related peptide?
SQUAMOUS– secreted by lung SCC
what causes hypercalcium in sarcoidosis
hypercalcaemia: macrophages inside the granulomas cause an increased conversion of vitamin D to its active form (1,25-dihydroxycholecalciferol)
addisons crisis mx
100mg hydrocortisone IV
IV 0.9 nacl
insulin lispro =?
fast rapid action
myxoedema coma CFs
very low fT3 T4 and high TSH
unconcious
HYPOTHERMIC
heart failure
which pit hormone is constantly under inhibition
prolactin
does wilsons or haemochromatosis cause chorea
WILSONS causes chorea
difference between pit adenoma and pit apoplexy
pit apoplexy =
Pituitary apoplexy is commonly seen in the presence of a pituitary tumour and is caused by bleeding into or impaired blood supply of the pituitary, This generally presents with sudden onset headache, followed by symptoms of non-functioning pituitary.
TYPES OF MODY and their gene mutations
most common = mody 325
MODY 3= HNF alpha
MODY 2= glucokinase
MODY 5 = HNF Beta
how does alcohol affect BMs
Alcohol causes increased insulin secretion
what type of mab is used in familial hypercholesterolaemia
evolucumab
what anti htn is used in marfans
losartan
Tx thyroid eye disease
RITUXIMAB
cushings initial investigation
24hr urinary free cortisol
(not suppressed if + cushings)
adrenal adenoma HTN treatment
spironolactone or eplenerone
