Endocrinology Peer Teaching Flashcards
cushings is too much/too little _______
cushing’s is too much cortisol
conn’s syndrome is too much/too little _______
conn’s syndrome is too much aldosterone
addison’s syndrom is too much/too little ________
addison’s sundrome is too little cortisol and too little aldosterone
diabetes insipidus is too muc/too little _______
diabetes insipidus is not enough ADH
siADH is too much/too little _______
siADH is too much ADH
describe the anatomy of the pituitary gland
it lies just inferior to the optic chiasm. it is connected to the hypothalamus via the pituitary stak (infundibulum)
draw the flow chart for anterior pituitary hormones and their target organs and effects
are men or women more affected by thyroid conditions?
F>M
when does hyperthyroidism mainly present
20-40yrs
what is most hyperthyroidism caused by
2/3 is graves disease
what are some non-graves causes of hyperthyroidism
toxic multinodular goitre
toxic thyroid adenoma
iodene excess
8 symptoms of hyperthyroidism
diarrhoea
weight loss
heat intolerance
palpitations
tremor
anxiety
menstrual disturbances
hyperthyroidism signs
tachycardia
lid lag
lid retraction
bilateral exopthalmos
onycholysis - when nail detatches from skin underneith
investigations for hyperthyroidism - primary and secondary results
primary = low TSH, high T3/T4
secondary = high TSH, high T3/T4
thyroid autoantibodies (TPO, thyroglobulin and TSH receptor antibody)
radioactive iodine isotope uptake scan
hyperthyroidism treatment
beta blockers for rapid symptom control during attacks
carbimazole - antithyroid drugs
radioiodine therapy
thyroidectomy
what happens in graves disease
it is autoimmune induced excess production of TH
it is associated with other autoimmune conditions such as T1D and addison’s
there are increased levels of TSH receptor stimulating antibody (TRAb) - this causes excess TH secretion from the thyroid
what are the clinical features of graves disease
it includes all of the clinical features of hyperthyroidism
thyroid achropachy (digital clubbing and finger and toe swelling)
treatment for graves disease
beta blockers
carbimazole
what are the causes of hypothyroidism?
hashimoto’s thyroiditis
iodine deficiency
radiotherapy
over-treatment of hyperthyroidism
hypothyroidism symptoms
fatigue
cold intolerance
weight gain
constipation
menorrhagia
oedema
myalgia
signs of hypothyroidism
BRADYCARDIC
bradycardia
reflexes relax slowly
ataxia
dry thin hair
yawning
cold hands
ascites
round puffy face
defeated demeanour
immobile
congestive heart failure
what is the difference between acromegaly and gigantism
both are increased production of growth hormone but acromegaly is after the fusion of the epiphyseal plates and gigantism is after
what is the incidence of acromegaly
3/m/year
what is the mean age at diagnosis of acromegaly
40
are men or women more affected by acromegaly
M=F
symptoms of acromegaly
acroparaesthesia
sweating
decreased libido
arthralgia
headache
6 signs of acromegaly
massive growth of the hands, feet and jaw
big tongue with widely spaced teeth
puffy lips, eyelids and skin
darkening skin
deep voice
obstructive sleep apnoea
what are the best investigations for acromegaly
- not a random growth hormone test cause these vary throughout the day
- glucose tolerance test
- normally a rise in glucose will suppress GH
- if they’re still high after glucose then this is diagnostic of acromegaly
- follow up with MRI the pituitary fossa to look for adenomas
treatment for acromegaly
transphenoidal surgery to remove the adenoma
give a GH antagonist like pegvisomant
what is the definition of Conn’s syndrome
it refers to high aldosterone independant of the RAAS system which leads to low renin caused by solitary aldosterone producing adenoma
2/3 cases of hyperaldosteronism is conn’s syndrome
1/3 is bilateral adrenocortical hyperplasia
what does excess aldosterone cause
aldosterone works in the kidney to cause potassium loss
therefore excess aldosterone leads to hypokalaemia and sodium and water retention
what are the clinical features of hyperaldosteronism
- they are those of hypokalaemia
- constipation
- weakness and cramps
- parasthaesia
- polyuria and polydipsia
- hypertension due to increased blood flow
investigation for hyperaldosteronism
U&E
decreased renin
increased aldosterone
ECG: flat T wave, long PR interval and Long Qt, U waves
Adrenal CT
in which condition do you have a short 4th metacarpal
Pseudohyperparathyroidism
what is the treatment for hyperaldosteronism
laperoscopic adrenalectomy
spironolactone (potassium sparing diuretic since it is an aldosterone antagonist)
parathyroid hormone is secreted from the parathyroid glands in response to:
a drop in serum calcium levels
what is the action of parathyroid hormone
increased bone resorption by osteoclasts
increased intestinal absorption of calcium
activates calcidiol to calcitriol in the kidney
increased calcium reabsorption and phosphate excretion in the kidney
what are the causes of hyperparathyroidism?
80% are due to a solitary adenoma
20% are due to parathyroid hyperplasia
rarely it’s parathyroid cancer
can also be secondary to hypocalcaemia i.e. that caused by GI diseases/CKD
clinical features of hyperparathyroidism
- those associated with hypercalcaemia:
- weakness
- fatigue
- depression
- polydipsia
- renal calculi
- bone resorption
- pain
- fractures
- osteoporosis
why do you get high calcium PTH in kidney disease
if the kidneys aren’t filtering phosphate into the urine properly then all the free calcium in the blood binds to the phosphate and the PTH thinks there’s hypocalcaemia
the kidneys also aren’t producing enough calcitriol which is responsible for increasing the absorption of calcium in the gut
what is tertiaty hyperparathyroidism
it’s where patients who have had secondary hyperparathyroidism for years develop primary hyper parathyroidism
PTH, Ca and Phosphate levels in primary, secondary and tertiary hyperparathyroidism
primary: high PTH, high Ca and low phosphate (PTH makes kidney excrete phosphate)
secondary: high PTH, low Ca and high phosphate (likely caused by dodgy kidney not filtering phosphate into urine properly)
tertiary: everything’s high as it’s a progression of 2ndary (phosphate will be low if they have a new kidney)
investigations for hyperparathyroidism
bloods for PTH, Ca, and phosphate
dexa scan for osteoporosis
24h urinary calcium excretion
treatment for hyperparathyroidism
fluids
surgically treat underlying cause
bisphosphinates
causes of hypoparathyroidism
autoimmune destruction of PT glands
congenital abnormalities
surgical removal (secondary)
what are the signs and symptoms of hypoparathyroidism
- the same as hypocalcaemia: CATS
- convulsion
- arrhythmias
- tetany
- spasm and stridor
treatment for hypoparathyroidism
calcium supplementation
calcitriol
synthetic PTH
what is pseudohypoparathyroidism
decreased bone response to pth
bloodwork: low ca, high PTH
treat as you would normal hypoparathyroid
what is hypokalaemia
[K+] <3.5mmol/L
low K+ in the blood draws K+ out of cells
this causes hyperpolarisation of the myocycte membrane causing decreased myocyte excitability
what is hypokalaemia Ix
ECG
U have No Pot and No T but a long PR and a long QT
U waves
no T wave
long PR
long QT
treatment for mild and severe hypokalaemia
oral K+
IV K+
hyperkalaemia ECG
tall tented T waves
small P waves
wide QRS
non-urgent treatment of hyperkalaemia
polystyrene sulphonate resin = binds K+ in the gut decreasing uptake
urgent treatment for hyperkalaemia
calcium gluconate (decreases risk of VF)
insulin with dextrose
causes of lowered potassium intake
anorexia
fasting
causes of excess potassium intake
excessive consuption at a fast rate - IV fluids
which hormone stimulates the secretion of K+ in the kidneys?
aldosterone
why might ACEis and ARBs cause hyperkalaemia
they reduce the production of aldosterone which is responsible for the secretuion of K+ into the urine
three things that can cause low secretion of K+ and therefore hyperkalaemia
ARBs and ACE inhibitors
AKI - less secretion of K+ into urine since less flow through kidneys
low aldosterone due to adrenal insufficiency
how does insulin affect K+ balance
it causes K+ to nter cells so high insulin can cause hypo and low insulin can cause hyper
how does pH affect K+ balance
acidic pH causes k+ to flow out of cells in exchange for H+ so acidic pH can lead to hyperkalaemia
alkaline pH causes K+ to flow into cells in exchange for H+ so alkaline pH can cause hypokalaemia
how can Beta 2 receptors affect K+ balance
beta blockers: inhibit pumping of K+ into cell so can lead to hyperkalaemia
B 2 agonists (SABA/LABA) increase B2 pumping of K+ into cells so can lead to hypokalaemia
how can severe burns affect K+ balance
cell lysis leads to release of K+
hypokalaemia symptoms
everything slows down
smooth muscle: constipation
skeletal muscle: weakness/cramps
Cardiac muscle: arrhythmias and palpitations
hyperkalaemia symptoms
everything speeds up
smooth muscle: cramping
skeletal muscle: flaccid paralysis (overcontraction causes exhaustion of muscles)
cardiac muscle: arrythmias and arrest
what is calcium stored as in bone
calcium phosphate
what two things does calcitonin do to control serum calcium level
it decreases calcium absorption in the gut
it increases osteoblast activity
the overall effect is to reduce serum calcium
causes of hypocalcaemia
- HAVOC
- hypoparathyroidism
- acute pancreatitis
- vitamin D deficiency
- osteomalacia
- chronic kidney disease
symptoms of hypocalcaemia
- CATS
- convulsions
- arrhythmias
- tone
- spasm and stridor
what will the ECG show if there’s hypocalcaemia
there will be a long QT interval
treatment for mild and severe hypocalcaemia
mild: adcal
severe: calcium gluconate
what is the cause of most hypercalcaemia
90% is caused by primary hyperparathyroidism or cancer
symptoms of hypercalcaemia
- painful bones
- renal stones
- abdominal groans
- nausea, vomiting, constipation, indigestion
- psychiatric moans
- fatigue, memory loss, depression, psychosis
investigations for hypercalcaemia
- find out the cause:
- corrected calcium levels: will be very high in cancer and only mildly increased in hyperparathyroidism
- PTH level: will be low in cancer and high in hyperparathyroidism
- identify the damage
- U&E to identigy the renal damage
- X-Ray for cancer
treatments for hypercalcaemia
bisphosphinates for bone damage
Saline (NaCl)
what is hypercalcaemia of malignancy and what are the investigations
it is where cancers (most commonly myeloma) cause increase in osteoclast activity and inhibit osteoblast precursors. this leads to bone breakdown
bloodwork will show high PO43- and high calcium
do a CXR
what is the most important cause of cushing’s syndrome that isn’t cushing’s disease
oral steroids so iatrogenic
what is cushing’s syndrome
it is excess cortisol with loss of the HPA axis feedback and loss of circadian rhythms
what is cushing’s disease
it is cushing’s syndrome that has been caused by a pituitary adenoma
there is bilateral adrenal hyperplasia due to the ACTH hypersecretion by the pituitary
cushing’s syndrome symptoms
- CUSHING
- cateracts
- ulcers
- skin striae
- hypertension
- infections
- necrosis
- glucosuria
- aesthetic things
- truncal obesity
- moon face
- buffalo hump
- acne
cushing’s investigations
NOT a random plasma cortisol test as these change with stress, time of day, illness etc.
use a dexamethasone suppression test - dexamethasone usually suppresses cortisol level - failure to suppress over 24hr period is diagnostic of cushing’s
24hr urinary free cortisol measurement - normal levels mean cushings is unlikely
treatment for cushings
if iatrogenic stop steroids
transphenoidal removal of pituitary tumour for cushing’s disease
adrenalectomy and radiotherapy for an adrenal adenoma
what may adrenalectomy cause
nelson’s syndrome
Nelson’s syndrome is a rare disorder that occurs in some patients with Cushing’s disease patients as a result of removing both adrenal glands. In Nelson’s syndrome, the pituitary tumor continues to grow and release the hormone ACTH.
This invasive tumor enlarges, often causing visual loss, pituitary failure and headaches. One key characteristic of Nelson’s disease is dark skin pigmentation, resulting from the skin pigment cells responding to the release of ACTH.
what is the definition of diabetes mellitus
syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance or both
microvascular complications of hyperglycaemia
retinopathy
nephropathy
neuropathy
macrovascular complications of hyperglycaemia
strokes
renovascular disease
limb ischaemia
blood glucose levels should be between what
3.5-8.0mmol/L
diabetes is usually primary but can be secondary to other conditions including:
- pancreatic pathology e.g. total pancratectomy, chronic pancreatitis, haemochromatosis
- maturity onset diabetes of youth (MODY)
- AD form of T2 diabetes - single gene defect altering B cell function
- presents <25 yrs old with +ve FH
which populations have increased incidences of T1D
northern european - especially finland
what is latent autoimmune diabetes in adults
LADA
- slow burning variant with slower progression to insulin deficiency and occurs later in life
- difficult to differentiate from type 2 diabetes but clues are:
- leaner build
- rapid progression to insulin therapy following initial response to other therapies
- presence of circulating islet autoantibodies
what are two HLA haplotypes associated with T1DM
HLA-DR3-DQ2
HLA-DR4-DQ8
one or the other present in >90% cases
what other autoimmune diseases is T1DM associated with
coeliac
addison’s
autoimmune thyroid
pernicious anaemia
why do people get DKA
because they have a reduced supply of glucose since there is significant decline in circulating inslin and an increase in fatty acid oxidation due to high glucagon
the production of ketone bodies exceeds the ability of peripheral tissues to oxidise them
they lower the blood pH
how can you tell if a diabetic patient has complete Beta cell destruction
there is absence of serum C-peptide
this is the thing that joins the two insulin chains
patients with which three types of ancestry have increased risk of type 2 diabetes mellitus
south asian
african
caribbean
is there a stronger genetic link in type 1 or type 2 diabetes
type 2 but there is no HLA association
is type 2 diabetes more common in males or females
males
what is type two diabetes
it is insulin resistance and/or decreased insulin secretion
the insulin resistance is post-receptor
at time of diagnosis B cell mass is usually reduced to 50%
what are the two phases of insulin release
rapid release phase: B cells cense rising glucose and release stored insulin
second phase: if glucose levels remain high then the second phase is initiated and this takes longer since the insulin must also be synthesised
why is blood glucose so high in type 2 DM
there’s lack of uptake of glucose by peripheral tissues
there’s also lack of control of gluconeognesis in the liver (due to low insulin) so liver output of glucose is high
what is the starling curve of the pancreas
this is that at diagnosis the insulin levels of a Type 2 diabetic will characteristically be higher than in healthy controls but still insufficient to control hyperglycaemia
insulin levels rise to a point until they begin to decline and due to secretory failure
they therefore progress towards absolute insulin deficiency at which point they will require insulin therapy
why don’t type 2 diabetics tend to develop DKA
even a small amount of insulin can halt fat and muscle breakdown into ketones
what is impaired glucose tolerance
fasting plasma glucose <7mmol/L
but 2hrs post oral glucose test is >7.8mmol/L but < 11mmol/L
what is impaired fasting glucose
fasting plasma glucose >6.1 mmol/L but < 7mmol/L
what is needed for the diagnosis of T2DM
random plasma glucose > 11.1mmol./L
fasting plasma glucose >7mmol/L
if they have symptoms only one abnormal value is required
if they’re asymptomatic then two are required
what are the reasons you get the classical triad of symptoms in DMT1
Polyuria and nocturia:
- Since glucose draws water into the urine by osmosis - not enough
glucose can be reabsorbed as kidneys have reached the renal
maximum reabsorptive capacity
- This results in high levels of glucose in tubule urine and thus lots
of water resulting in polyuria and nocturia
• Polydipsia (thirst):
- Due to the loss of fluid and electrolytes from excess glucose and
thus water being in the urine
• Weight loss:
- Due to fluid depletion and the accelerated breakdown of fat and
muscle secondary to insulin deficiency
symptoms of DMT2
polyuria
polydipsia
weight loss
visual blurring
(characteristic retinopathy can be DIAGNOSTIC but is only present in established cases of diabetes)
what is the HbA1c that is diagnostic of diabetes
6.5% or 48mmol/mol
what tests should you do with someone who’s just been diagnosed with diabetes.
screen urine for microalbuminuria - to assess for kidney disease
FBC, U&E, liver biochemistry
fasting blood sample for cholesterol and triglycerides
diabetes lifestyle advice
exercise
maintain lean weight
good diet - low sugar high fibre low fat
spread nutrient load throughout the day
what is the first line treatment for DMT2
lifestyle and dietary advice
blood pressure control: ramipril
hyperlipidaemia control: statins
orlistat in cases of obesity
what is orlistat
it is a lipase inhibitor that reduces the absorption of fat from the diet
what is the second line treatment in T2DM
oral metformin
what does oral metformin do? and what are some side effects
reduces rate of gluconeogenesis in the liver
increases the cells insensitivity to insulin
reduces CVS risk
SE: anorexia, diarrhoea, nausea IT DOES NOT CAUSE HYPOGLYCAEMIA
What are the contraindications of metformin
heart failure
liver disease
renal disease
next steps after metformin in T2DM treatment
- at 16 weeks if HbA1c >53mmol/L then add oral gliclazide
- promotes insulin secretion
- effect wears off
- SE: hypoglycaemia and promotes weight gain so avoid in overweight
- at 6 months is HbA1c >57mmol/L then add insulin
- or give SC exanatide which mimics the effect of insulin and promotes the release of insulin from the pancreas
pathophysiology of DKA
- in absence of insulin there is:
- unrestrained hepatic gluconeogenesis
- no uptake of glucose by peripheral tissues
- high serum glucose leads to
- osmotic diuresis
- consequent dehydration and loss of electrolytes
- production of ketone bodies leads to a metabolic acidosis
- acidosis aggravated by dehydration –> impaired renal excretion of H+
- hyperventilation - respiratory compensation
- invariably fatal if untreated
risk factors for DKA
stopping insulin therapy
infection surgry
MI
pancreatitis
undiagnosed T1DM
NB insulin may need adjusting but should never be stopped
clinical presentation of DKA
pear drop smell to breath
profound dehydration due to polydipsia and vomiting
drowsiness
vomiting
deep rapid breathing
5% present with coma
Ix and Dx of DKA
hyperglycaemia (>11mmol/L)
raised plasma ketones
acidaemia pH <7.3
metabolic acidosis (low bicarbonate)
urine dipstick (glucose and ketones)
what will K+ be doing in DKA
total body K+ will be low due to osmotic diuresis
but serum K+ will be raised due to absence of insulin which shifts K+ into cells
treatment of DKA
immediate ABC management
replace fluid loss with saline
restore K+
replace deficient insulin and give with glucose
what is a hyperosmolar hyperglycaemic state
it is where insulin levels aren’t low enough to induce ketogenesis but they are low enough to promote hepatic glucose production
you get very very sugary blood
infection is the most common precipitating cause
it is a life threatening emergency characterised by marked hyperglycaemia, hyperosmolality and mild or no ketosis
hyperosmolality can predispose to stroke, MI or arterial insufficiency of lower limbs
what is the definition of hypoglycaemia
plasma glucose <3mmol/L
what is the commonest endocrine emergency
hypoglycaemia
what are the causes of hypoglycaemia in non-diabetics
- EXPLAIN
- Exogenous drugs (insulin, alcohol binge with no food etc.)
- Pituitary insufficiency
- Liver failure
- Addison’s disease
- Islets cell tumour
- Non-pancreatic neoplasm
clinical presentation of hyperosmolar hyperglycaemic state
severe dehydration
decreased level of consciousness
hyperglycaemia
no ketones in blood or urine
stupor or coma
bicarbonate is not lowered
hyperosmolality
treatment for hyperosmolar hyperglycaemic state
fluid replacement with saline
LMWH to reduce risk of thromboembolism, MI, stroke and arterial thrombosis
restore electrolyte loss
THESE PATIENTS ARE MORE SENSITIVE TO INSULIN SO GIVE A LOWER RATE OF INFUSION
What are the three most common causes of premature death in treated diabetes patients
CVD
CKD
infection
name three macrovascular complications of DM
stroke
ischaemic heart disease
peripheral vascular disease
three important sites for microvascular damage in DM
retina
glomerulus
nerve sheath
why do diabetics get foot ulceration
neuropathy results in silent trauma
neuropathy also causes autonomic features that increase skin dryness making it more susceptible to cracking
ischaemia results in failure of ulcer to heal
can lead to infection and eventually amputation
metformin: what’s the drug class? how does it work? and does it cause weight gain or weightloss:
it is a biguanide
it increases insulin sensitivity and reduces gluconeogenesis in the liver
it causes weight loss
IT DOES NOT CAUSE HYPOGLYCAEMIA
What is sulfonyl-urea? what is an example of a drug of this type? how does it work and what are the side effects?
it is a diabetes drug
an example is glipizide
it stimulates B cells to secrete insulin
it causes hypoglycaemia and weight gain since it stimulates the appetite
what is a DPP4 inhibitor, how does it work? give an example of one
DPP4 inhibitors are used in T2DM since they inhibit DPP4 which is an inhibitor of incretins
aka gliptins
e.g. sitagliptin
incretins are a goup of proteins that augment secretion of insulin after eating
DPP4 inhibitors therefore boost the effect of incretins thereby stimulating insulin secretion
what is a glitazone? give an example of one and say how it works.
stimulates the body to make more fat from glucose and fatty acids and thereby lowers blood glucose
an example is piogiltazone
give 4 classes of diabetes drug, give an example of each and say whether they cause weight gain or weightloss
draw the table for normal, prediabetes, diabetes vs random, fasting and 2hr post prandial glucose
overall treatment for T2DM
fill in this table
fill in this table
in very simple terms what is addison’s disease
it is an autoimmune impairment of the adrenal gland
causing low cortisol and aldosterone
so the opposite of cushing’s
what is the most common cause of primary adrenal insufficiency worldwide and in the uk
worldwide: TB
UK: Addison’s
fill in this table
in very simple terms what is diabetes insipidus
too little ADH from the posterior pituitary gland OR the kidney nit responding to the ADH
fill in this table on diabetes insipidus
do this SIADH table
