Endocrinology Flashcards
what is cushing’s syndrome?
the signs and symptoms of prolonged abnormal elevated cortisol levels
what is cushing’s disease?
- where a pituitary adenoma is producing excess ACTH
- a cause of cushing’s syndrome
presentation of cushing’s syndrome? (hint: there’s a LOT)
- “lemon on matchsticks” (truncal obesity with proximal limb muscle wasting)
- abdo striae
- “moon face” (rounded)
- “buffalo hump” (fat pad on back)
- HTN
- T2DM or hyperglycaemia
- depression
- insomnia
- osteoporosis
- easy bruising
- poor skin healing
causes of cushing’s syndrome?
- exogenous steroids
- cushing’s disease
- adrenal adenoma
- paraneoplastic cushing’s
what is paraneoplastic cushing’s? commonest cause of this?
- when a tumour releases ACTH but it is NOT in the pituitary
- SCLC is commonest cause
what is ectopic ACTH?
ACTH released from anywhere other than the pituitary
diagnostic investigation for cushing’s syndrome?
dexamethasone suppression test
how is a dexamethasone suppression test carried out?
- patient takes a dose of dexamethasone at night
- cortisol and ACTH measured in the morning
how is the result of a dexamethasone suppression test interpreted?
- normal cortisol and ACTH suggest cushing’s syndrome
- if result is abnormal for a low dose test, do a high dose test next
results of dexamethasone suppression testing in adrenal adenoma?
- ACTH suppressed but cortisol NOT supressed
- this is independent of the pituitary (which produces cortisol)
results of dexamethasone suppression testing in pituitary adenoma?
- cortisol and ACTH both suppressed
- pituitary still functioning somewhat normally
- this is cushing’s disease
results of dexamethasone suppression testing in ectopic ACTH production?
- neither cortisol nor ACTH suppressed
- it’s from an external source
investigations in cushing’s syndrome? hint: don’t forget ectopic causes
- dex suppression test
- 24h urinary free cortisol (high)
- FBC (raised WCC)
- UEs (K+ low if aldosterone also being secreted)
- MRI brain (pit adenoma)
- CT chest (SCLC)
- CT abdo (adrenal adenomas)
management of cushing’s syndrome? hint: underlying cause
- trans-sphenoidal removal of pituitary adenoma
- surgery for adrenal tumour
- surgery for source of ectopic ACTH
what can be done about adrenal tumours which cannot be removed?
remove both adrenal glands and give lifelong replacement steroid hormones instead
which 2 steroids are deficient in adrenal insufficiency?
- cortisol
- aldosterone
what is addison’s disease? commonest cause?
- primary adrenal insufficiency
- autoimmune is commonest cause
what is tertiary adrenal insufficiency? commonest cause?
- reduced CRH release from the hypothalamus
- long-term steroid use
how can tertiary adrenal insufficiency be prevented?
taper down long-term steroids slowly
presentation of adrenal insufficiency?
- fatigue and weakness (most common)
- nausea
- cramps
- abdo pain
- reduced libido
signs O/E of adrenal insufficiency?
- bronze hyperpigmentation (addison’s), seen especially in palmar creases
- (postural) hypotension
what causes bronze skin in addison’s disease?
- increased circulating ACTH
- ACTH stimulates melanocytes
- increased melanin production
investigations and findings in adrenal insufficiency? hint: most are on bloods
- UEs (low Na+, high K+)
- early morning cortisol
- short synacthen test (diagnostic)
- ACTH levels (high in addison’s, low in secondary insufficiency)
- adrenal cortex antibodies (autoimmune)
- 21-hydroxylase antibodies (autoimmune)
- CT / MRI adrenals
diagnostic test for adrenal insufficiency?
short synacthen test
what is synacthen?
synthetic ACTH
how is the short synacthen test carried out?
- give synacthen at 8am
- measure cortisol at baseline
- then after 30 mins
- then after 60 mins
what is the result of the short synacthen test in a healthy person?
cortisol should at least double
if cortisol fails to double on the short synacthen test, what does this indicate?
primary adrenal insufficiency (addison’s)
management of adrenal insufficiency?
- steroid replacements
- hydrocortisone for cortisol
- fludrocortisone for aldosterone
- double doses in acute illness
signs of addisonian crisis?
everything low but K+ high
- reduced consciousness
- hypotension
- hypoglycaemia
- hyponatraemia
- hyperkalaemia
- patient looks very unwell
triggers of addisonian crisis?
- could be first presentation of addison’s disease
- infection
- trauma
- other acute illness
management of addisonian crisis?
- IV hydrocortisone 100mg stat
- repeat 6 hourly
- IV fluid resus
- correct hypoglycaemia
- monitor electrolytes and fluid closely
TFT findings in hyperthyroidism? hint: different if pituitary source
- low TSH, high if pituitary adenoma
- high T3 and T4
TFT findings in hypothyroidism? hint: different if pituitary / hypothalamic source
- high TSH
- low TSH if pituitary / hypothalamic cause (secondary hypothyroidism)
- low T3 and T4
in which conditions are anti-TPO antibodies present?
- grave’s disease
- hashimoto’s thyroiditis
in which conditions are antithyroglobulin antibodies present?
- grave’s disease
- hashimoto’s thyroiditis
- thyroid cancer
in which conditions are TSH receptor antibodies present?
grave’s disease
what is the difference between hyperthyroidism and thyrotoxicosis?
- hyperthyroidism describes excessive thyroid hormone production by the thyroid
- thyrotoxicosis means excess of thyroid hormone in the body
what is grave’s disease? describe the pathophysiology
- autoimmune primary hyperthyroidism
- TSH receptor antibodies mimic TSH and stimulate the thyroid TSH receptors
commonest cause of hyperthyroidism?
grave’s disease
describe toxic multinodular goitre
nodules develop on the thyroid which keep producing thyroid hormone, independent to the feedback loop
what is exophthalmos? which condition is it seen in? what causes it?
- eyeball bulging from socket
- seen in grave’s disease
- is a direct reaction to TSH receptor antibodies
describe pretibial myxoedema. which condition is it seen in? what causes it?
- discoloured, waxy oedematous skin over shins
- grave’s disease
- is a direct reaction to TSH receptor antibodies
presentation of hyperthyroidism?
- anxious, irritable
- heat intol, sweating
- tachycardia
- weight loss
- fatigue
- diarrhoea
- sexual dysfunction
which features in presentation are unique to grave’s disease?
- diffuse goitre without nodules
- bilateral exophthalmos
- pretibial myxoedema
which features in presentation are suggestive of toxic mulitnodular goitre?
- goitre with firm nodules felt in neck
- usually aged 50+
describe the presentation in de quervain’s thyroiditis?
- viral infection with fever
- neck pain / tenderness
- dysphagia
- hyperthyroidism followed by hypothyroidism
prognosis and management of de quervain’s thyroiditis?
- self-limiting condition
- supportive treatment, e.g. NSAIDs, BBs
what is the other name for a thyroid storm? describe the presentation of this
- thyrotoxic crisis
- pyrexia
- tachycardia
- delirium
management of a thyrotoxic storm?
- fluid resus if needed
- BBs
- propylthiouracil
- hydrocortisone
management of hyperthyroidism?
- 1st line: carbimazole
- 2nd: propylthiouracil
- radioactive iodine (drink)
- BB (e.g. propanolol)
- surgery
causes of hypothyroidism?
- hashimoto’s thyroiditis
- iodine deficiency
- overtreatment of hyperthyroidism
- drugs
- tumours
- infections
- sheehan syndrome
- radiation
presentation of hypothyroidism?
- depressed
- weight gain
- fatigue
- dry skin
- coarse hair, hair loss
- fluid retention (oedema, pleural effusions, ascites)
- amenorrhoea
- constipation
TFT findings in primary hypothyroidism?
- TSH high
- T3 and T4 low
TFT findings in secondary hypothyroidism?
- TSH low
- T3 and T4 low
management of hypothyroidism?
PO levothyroxine
how is levothyroxine treatment monitored?
- measure TSH levels monthly until stable
- if TSH is high, increase levothyroxine dose
- if TSH is low, decrease levothyroxine dose
what does “diffuse high uptake” on a radioisotope scan of the thyroid suggest?
grave’s disease
what does “focal high uptake” on a radioisotope scan of the thyroid suggest?
- toxic multinodular goitre
- adenoma
what do “cold areas” on a radioisotope scan of the thyroid suggest?
thyroid cancer
which cells produce glucagon? where are these found?
- alpha cells
- islets of langerhans in pancreas
which cells produce insulin? where are these found?
- beta cells
- islets of langerhans in pancreas
how does insulin reduce blood glucose levels? hint: 2 ways
- causes body cells to absorb glucose to use
- causes muscle and liver cells to absorb glucose and store it as glycogen
what is ketogenesis? when is it done?
- liver converting fatty acids into ketones
- done when both glucose and glycogen supplies are low
what is the normal blood glucose range?
4.4 - 6.1 mmol/L
pathophysiology of T1DM?
- pancreas unable to produce enough insulin
- no glucose gets absorbed out of the blood
- causes hyperglycaemia
- autoimmune
what is the body’s initial response to rising blood ketone levels?
kidneys produce bicarbonate to counteract the acidity
how does insulin affect potassium? what happens in DKA? what can happen when DKA is treated?
- insulin causes cells to absorb potassium
- in DKA, serum potassium is high or normal because there’s not enough insulin so none of it is being absorbed, but the kidneys carry on excreting it
- however, total body potassium is low
- treating with insulin can cause a severe hypokalaemia
overall effects of DKA on body?
- hyperglycaemia
- dehydration
- ketosis
- metabolic acidosis (with low bicarbonate)
- potassium imbalance
presentation of DKA?
- polyuria
- polydipsia
- N+V
- acetone smell on breath (peardrops)
- kussmaul breathing (deep, laboured breaths)
- dehydration
- hypotension (caused by dehydration)
- altered consciousness
diagnostic criteria for DKA?
- blood glucose >11mmol/L
- blood ketones >3mmol/L
- pH <7.3
FIG PICK: management of DKA?
- Fluids (IV fluid resus)
- Insulin infusion
- Glucose (monitor closely, consider dextrose)
- Potassium (monitor 4-hourly and correct)
- Infection (treat underlying triggers)
- Chart (check fluid balance)
- Ketones (monitor them)
what is the max rate at which potassium can be infused?
10mmol/L
patient advice given in long term management of T1DM?
- explain subcut insulin regimes
- monitor carb intake and glucose
- monitor complications
- advice on changing injection site
when should blood glucose be checked in T1DM?
- on waking
- after a meal
- before bed
what is a typical insulin regime in T1DM?
- background insulin once daily (long-acting)
- short acting insulin 30 mins before each meal
why does the injection site for insulin need to be changed regularly?
risk of lipodystrophy
what is lipodystrophy?
the subcut fat hardens from being injected in so much
symptoms of hypoglycaemia?
- tremor
- sweating
- irritability
- dizziness
- pallor
management of hypoglycaemia in T1DM? if severe?
- first rapid acting glucose (e.g. lucozade)
- then slower acting carbs (e.g. biscuits, toast)
- if severe: IV dextrose and IM glucagon
how could a patient in DKA end up hypoglycaemic?
overtreatment with insulin
short term complications in T1DM?
- hypoglycaemia
- hyperglycaemia
- DKA
macrovascular complications in diabetes?
- CAD
- peripheral ischaemia (diabetic foot)
- stroke
- HTN
microvascular complications in diabetes?
- peripheral neuropathy
- retinopathy
- glomerulosclerosis (kidney)
nature of neuropathy in diabetes?
- peripheral
- “glove and stocking” distribution
infection-related complications in diabetes?
- UTIs
- pneumonia
- skin infections, esp in feet
- oral / vaginal candida
what 3 things are used to monitor T1DM?
- HbA1c
- capillary blood glucose
- flash glucose monitoring (e.g. freestyle libra)
what does HbA1c tell us? how often is it checked?
- average blood glucose levels over last 3 months
- every 3-6 months
non-modifiable risk factors for T2DM?
- older age
- non-white ethnicity
- FHx
modifiable risk factors for T2DM?
- obesity
- sedentary lifestyle
- high carb diet
how might T2DM present?
- fatigue
- polydipsia
- polyuria
- unintentional weight loss
- opportunistic infections
- slow healing
- glucose in urine (on dipstick)
when is an oral glucose tolerance test (OGTT) performed?
first thing in the morning, before breakfast
what does an OGTT involve?
- take a fasting glucose reading
- then give 75g glucose drink
- then measure glucose again 2 hours later
diagnostic criteria for pre-diabetes?
- HbA1c 42 - 47 mmol/L
- fasting glucose 6.1 - 6.9 mmol/L (impaired)
- OGTT 7.8 - 11 mmol/L (impaired)
diagnostic criteria for diabetes?
- HbA1c >48mmol/L
- random glucose >11mmol/L
- fasting glucose >7mmol/L
- OGTT >11mmol/L
diet advice in T2DM?
- more veg and oily fish
- fewer sugary foods including carbs
- high fibre
lifestyle advice given in T2DM?
- diet changes
- exercise and weight loss
- stop smoking
- optimise comorbid conditions (e.g. HTN)
3 main complications to monitor for in T2DM?
- diabetic retinopathy
- kidney disease
- diabetic foot
what is the target HbA1c for type 2 diabetics on metformin alone?
48mmol/L
what is the target HbA1c for type 2 diabetics on more than just metformin?
53mmol/L
medical management of T2DM?
- 1st line: metformin
- 2nd: add add sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor
- 3rd: metformin + sulfonylurea + GLP-1 mimetic
- 4th: metformin + insulin
actions of metformin?
- increases insulin sensitivity
- decreases liver production of glucose
notable side effects of metformin?
- diarrhoea
- abdo pain
- lactic acidosis
example of sulfonylurea?
gliclazide
MOA of gliclazide?
increases insulin production in pancreas
notable side effects of gliclazide?
- weight gain
- hypoglycaemia
- increases CVD risk
notable side effects of pioglitazone?
- weight gain
- fluid retention
- anaemia
- HF
- bladder cancer
example of DPP-4 inhibitor?
sitagliptin
notable side effects of sitagliptin?
- GI upset
- URTI
- pancreatitis
notable side effects of GLP-1 inhibitors?
- GI upset
- weight loss
- dizziness
- hypoglycaemia (less common)
what are the 5 types of insulin? give an example for each
- rapid-acting (novorapid)
- short-acting (actrapid)
- intermediate-acting (insulatard)
- long-acting (levemir)
- combination (humalog 25, 25:75)
what causes acromegaly?
an excess of GH
where is GH produced in the body?
anterior pituitary gland
commonest cause of acromegaly?
pituitary adenoma
what visual field defect is seen in pituitary adenoma? why?
- bitemporal hemianopia
- it compresses the optic chiasm
presentation of acromegaly?
- headaches
- bitemporal hemianopia
- frontal bossing
- large nose
- macroglossia
- large hands and feet
- prognathism
- arthritis
describe frontal bossing
prominent forehead and brow bone
describe prognathism
large, protruding jaw
organ dysfunction caused by GH?
- hypertrophic heart
- HTN
- T2DM
- colorectal cancer
management of acromegaly?
- trans-sphenoidal removal of pituitary adenoma
- removal of any tumour producing ectopic GH
- meds which block GH
which drugs can block GH?
- pegvisomant
- ocreotide (somatostatin analogue)
- bromocriptine (DA agonist)
which 2 hormones can inhibit GH?
- somatostatin
- dopamine
which cells produce PTH? where are these found?
chief cells on the parathyroid glands
when is PTH secreted?
in response to hypocalcaemia
how does PTH increase blood Ca levels? hint: think bone, gut and kidney
- increases osteoclast activity (reabsorbs Ca from bones)
- increases Ca absorption in gut
- increases Ca reabsorption in kidney
- increases vit D activity
what causes primary hyperparathyroidism?
excessive PTH being secreted by a tumour on the parathyroid glands
management of primary hyperparathyroidism?
surgical tumour removal
PTH and calcium levels in primary hyperparathyroidism?
- PTH is high
- serum calcium is high
what causes secondary hyperparathyroidism?
2 main ways:
- vit D deficiency
- chronic renal / liver / failure (mostly CKD)
- bowel disease
PTH and calcium levels in secondary hyperparathyroidism?
- PTH is high
- serum calcium is low
what causes tertiary hyperparathyroidism?
prolonged secondary hyperparathyroidism, resulting in parathyroid hyperplasia
PTH and calcium levels in tertiary hyperparathyroidism?
- PTH is high
- serum calcium is high
management of tertiary hyperparathyroidism?
surgical removal of some of the excess parathyroid gland
main effects of primary hyperparathyroidism? how do these present?
- excessive Ca resorption from bone (osteopenia, fractures)
- excessive Ca excretion by kidneys (renal calculi)
- hypercalcaemia (lots of features)
where are juxtaglomerular cells found? what do they do?
- afferent arteriole of glomerulus of nephron
- sense BP
- release renin in response to low BP
what is the role of renin?
converts angiotensinogen into angiotensin I
where is ACE found in the body? what does it do?
- lungs
- converts angiotensin I to angiotensin II
what is the role of angiotensin II?
stimulates adrenal glands to secrete aldosterone
actions of aldosterone?
- increases Na resorption in distal tubules
- increases K secretion in distal tubules
- increases H secretion from collecting ducts
what is conn’s syndrome?
primary hyperaldosteronism
causes of conn’s syndrome?
- adrenal adenoma secreting aldosterone (commonest)
- bilateral adrenal hyperplasia
- familial hyperaldosteronism
- adrenal carcinoma (rare)
what causes secondary hyperaldosteronism? key finding?
- excess renin, resulting in excess aldosterone
- high serum renin
causes of secondary hyperaldosteronism? hint: renin goes up when kidneys get less blood
- renal artery stenosis
- renal artery obstruction HF
investigations for renal artery stenosis?
- doppler USS
- CT angiogram
- MRA (angiography)
how is hyperaldosteronism screened for?
work out renin:aldosterone ratio from bloods:
- low:high = primary
- high:high = secondary
investigations for hyperaldosteronism?
- bloods (renin, aldosterone)
- BP (HTN)
- electrolytes (hypokalaemia)
- blood gas (alkalosis)
- CT / MRI (adrenal tumour)
- renal doppler USS (renal artery stenosis)
management of hyperaldosteronism?
- treat underlying cause (tumour removal)
- percutaneous renal artery angioplasty (if RAS found)
- aldosterone antagonists (eplerenone, spironolactone)
types of hyperaldosteronism?
- primary (conn’s syndrome)
- secondary
commonest cause of secondary hypertension?
hyperaldosteronism
where is ADH produced?
hypothalamus
where is ADH secreted?
posterior pituitary
actions of ADH?
water reabsorption in collecting ducts of nephron
how much SIADH occur?
- posterior pituitary secreting too much ADH
- ectopic ADH from a tumour (e.g. SCLC)
how does SIADH affect sodium?
- hyponatraemia
- the excess water dilutes it down
how does SIADH affect urine osmolality (and therefore sodium too)?
- high urine osmolality because less water is being excreted (so more concentrated urine)
- high urine sodium because less water in it
symptoms of SIADH? hint: non-specific
- headache
- fatigue
- muscle aches
- cramps
- confusion
- severe hyponatraemia (seizures, reduced consciousness)
causes of SIADH?
- Small cell lung cancer
- Infection
- Abscess
- Drugs (carbamazepine, SSRIs)
- Head injury
drug causes of SIADH?
- thiazide diuretics
- carbamazepine
- antipsychotics
- SSRIs
- NSAIDs
how is SIADH diagnosed?
- cannot test specifically for ADH
- euvolaemic O/E
- urine sodium high
- urine osmolality high
- rule out other causes of hyponatraemia
- establish underlying cause
causes of hyponatraemia?
- adrenal insufficiency
- diuretic use
- D + V
- burns, fistulas
- excessive sweating
- CKD, AKI
investigations in SIADH?
- UEs
- CXR (?pneumonia, lung abscess, cancer)
- CT thorax, abdo, pelvis + MRI brain if suspected cancer
management of SIADH?
- treat underlying cause
- commonly drug cause - stop the drug
- fluid restriction 500ml-1L (correct Na)
- tolvaptan (ADH receptor blocker)
- demeclocycline (ABx which inhibits ADH)
major complication of SIADH? how can it happen?
persistent severe hyponatraemia can lead to central pontine myelinolysis
pathophysiology of nephrogenic diabetes insipidus?
collecting duct of nephron not responsive to ADH
causes of nephrogenic diabetes insipidus?
- drugs, esp lithium
- gene mutation
- intrinsic kidney disease
- hypokalaemia
- hypercalcaemia
pathophysiology of cranial diabetes insipidus?
hypothalamus not producing ADH for pituitary to secrete
causes of cranial diabetes insipidus?
- idiopathic
- brain tumour
- head injury
- brain malformation
- infection (meningitis, encephalitis, TB)
- iatrogenic (brain surgery, radiotherapy)
presentation of diabetes insipidus? hint: low fluid
- polyuria
- polydipsia
- dehydration
- postural hypotension
- hypernatraemia
investigations? hint: findings opp to SIADH
- low urine osmolality
- high serum osmolality
- water deprivation test
explain the water deprivation test
- no fluid intake for 8 hours
- measure urine osmolality
- give desmopressin (ADH)
- measure urine osmolality again
what are the results for the water deprivation test if DI is nephrogenic? what about cranial?
- nephrogenic: urine osmolality initially low and stays low (kidneys not responding to ADH)
- cranial: UO initially low, then high (kidneys can respond to ADH)
findings in water deprivation test if the patient has primary polydipsia / is normal?
urine osmolality is normal before even giving desmopressin
management of diabetes insipidus?
- treat underlying cause
- desmopressin (synthetic ADH)
- give higher dose if nephrogenic and monitor closely
what is a phaeochromocytoma? what does it secrete?
- tumour of chromaffin cells in or out of the adrenal gland
- secretes adrenaline
main association of phaeochromocytoma?
25% are associated with multiple endocrine neoplasia 2 (MEN2)
3 x 10% rule of phaeochromocytoma tumours?
- 10% bilateral
- 10% cancerous
- 10% not in the adrenal gland
diagnostic investigations for phaeochromocytoma?
- 24h urinary catecholamines
- plasma free metanephrines
why are urinary catecholamines checked in phaeochromocytoma instead of blood levels?
- the adrenaline secretion is in bursts
- blood levels will fluctuate
- 24h urinary ones will give a better idea of total secretion
why are plasma metanephrines checked in phaeochromocytoma?
- breakdown product of adrenaline
- it has a longer half life so less likely to fluctuate than adrenaline
presentation of phaeochromocytoma?
- anxiety
- sweating
- headache
- HTN
- tremor
- palpitations
- tachycardia
- paroxysmal AF
management of phaeochromocytoma?
- phenoxybenzamine (alpha blocker)
- BBs once established on alpha blocker
- adrenalectomy for tumour removal
TFT results in sick euthyroid syndrome? where is this commonly seen?
- low TSH
- low T4
- common in hospital inpatients
TFT results in subclinical hypothyroidism?
- high TSH
- NORMAL T4
TFT results in pt with poor thyroxine compliance?
- high TSH
- normal T4
