Endocrine Flashcards
What is adrenal insufficiency?
the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone.
Steroids are essential for life = life-threatening unless the hormones are replaced.
What is Addison’s disease?
PRIMARY ADRENAL INSUFFICIENCY
specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone
Most common cause of Addison’s disease
autoimmune
what is secondary adrenal insufficiency?
inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release
What is ACTH
Adrenocorticotrophic hormone
secreted by the pituitary gland
causes of secondary adrenal insufficiency
damage to pituitary gland:
- pituitary tumour
- infection
- loss of blood flow
- radiotherapy
- Sheehan’s syndrome = massive blood loss in childbirth that leads to necrosis of the pituitary gland
what is tertiary adrenal insufficiency?
inadequate CRH release by the hypothalamus
what is CRH
Corticotrophin releasing hormone, released by the hypothalamus
Describe the HPA axis
hypothalamic-pituitary-adrenal axis:
- hypothalamus releases corticotrophin releasing hormone
- causing anterior pituitary to release adrenocorticotrophic hormone
- causing the adrenal cortex in the adrenal glands to release cortisol
causes of tertiary adrenal insufficiency
long term oral steroids - suppress the hypothalamus
This is why you shouldn’t suddenly withdraw exogenous steroids - hypothalamus is suppressed so no endogenous steroids will be produced
symptoms of adrenal insufficiency
Fatigue Nausea Cramps Abdominal pain Reduced libido
Signs of adrenal insufficiency
Bronze hyperpigmentation to skin (ACTH stimulates melanocytes to produce melanin)
Hypotension (particularly postural hypotension)
Ix for adrenal insufficiency
Hyponatraemia
Hyperkalaemia
Early morning cortisol - often falsely normal
Short synacthen test = FOR DIAGNOSIS
ACTH
- High in primary adrenal insufficiency
- low in secondary adrenal insufficiency
Adrenal cortex antibodies & 21-hydroxylase antibodies - in autoimmune adrenal insufficiency
CT/MRI adrenals
MRI pituitary
What is the short synacthen test?
For diagnosing adrenal insufficiency
Give synacthen (synthetic ACTH) blood cortisol measured at baseline, 30 mins and 60 mins Synthetic ATCH wil stimulate healthy adrenal glands & the cortisol should at least double
Failure of cortisol to at least double = primary adrenal insufficiency (Addison’s)
tx of adrenal insuffiency
hydrocortisone to replace cortisol
fludrocortisone to replace adolesterone
Patients need: steroid card & double doses on sick days (don’t STOP)
What is an addisonian crisis?
Adrenal crisis
Acute presentation of severe Addison’s disease
The absence of steroid hormones leads to a life threatening presentation
Symptoms of addisonian crisis
Reduced consciousness
Hypotension
Hypoglycaemia, hyponatraemia, hyperkaemia
Patients can be very unwell
what triggers an addisonian crisis
infection
trauma
other acute illness
sudden steroid withdrawal
mx of addisonian crisis
Intensive monitoring IV hydrocortisone IV fluid resuscitation Correct hypoglycaemia Careful monitoring of electrolytes
What is cushings syndrome?
the signs and symptoms that develop after prolonged abnormal elevation of cortisol.
What is Cushings disease?
the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH.
Difference between cushings syndrome and cushings disease
Cushings disease causes cushings syndrome
but cushings syndrome isn’t always caused by cushings disease
symptoms of cushings syndrome
round 'moon' face central obesity abdo striae buffalo hump - fat pad on upper back proximal limb muscle wasting
HTN cardiac hypertrophy hyperglycaemia (T2DM) depression insomnia
osteoporosis
easy bruising
poor skin healing
causes of cushings syndrome
exogenous steroids
cushings disease = pituitary adenoma releasing excessive ACTH
adrenal adenoma
paraneoplastic cushings - ACTH released from small cell lung cancer
ix for cushings syndrome
dexamtheasone suppression test 24 hour urinary free cortisol FBC - raised WCC U&E - hypokalaemia if aldosterone also secreted by adrenal adenoma MRI brain - pituitary adenoma chest CT - SCLC Abdo CT - adrenal tumour
Tx for cushings syndrome
remove underlying cause
- trans-sphenoidal removal of pituitary adenoma (cushings disease)
- surgical removal of adrenal tumour
- surgical removal of tumours producing ectopic ACTH
If you can’t remove the cause - remove the adrenal glands and give replacement steroids for life
what is the dexamethasone suppression test used for?
used to diagnose cushings syndrome and find the cause
- Give dexamethasone at 10pm at night, measure cortisol and ACTH in the morning
- do low dose test first - give 1mg of dexamethasone = used to see if they have a normal HPA axis or if they have cushings syndrome
- do high dose test second if they have an abnormal low dose test to look for the cause of cushings syndrome
how does the low dose dexamethasone test work and what is a normal result/a result showing cushings syndrome?
Give 1mg dexamethasone at 10pm
In the morning measure cortisol and ACTH
In a normal person, the addition of steroids causes negative feedback on the hypothalamus and pituitary = low cortisol and ACTH in the morning
In someone with cushings syndrome, the addition of a small amount of steroids makes no difference as they already have high levels of cortisol. Therefore cortisol will be high/normal in the morning
how does the high dose dexamethasone test work and what do the results show?
high dose test is performed following an abnormal result on the low dose test
give 8mg of dexamethasone at 10pm, measure the cortisol and ACTH the next morning
In cushings disease (pituitary adenoma) = pituitary shows some response to negative feedback. 8mg of dex is enough to suppress cortisol & ACTH
In adrenal adenoma = cortisol production is independent on the pituitary. So cortisol is not suppressed but ACTH is
Ectopic ACTH production (SCLC) = cortisol and ACTh won’t be suppressed because ACTH production is independent of the hypothalamus and pituitary gland
What is diabetes insipidus?
a lack of ADH or lack of response to ADH = prevents the kidneys from concentrating the urine so there’s polyuria and polydipsia
how can diabetes insipidus be classified?
nephrogenic
cranial
what is nephrogenic diabetes insipidus?
when the collecting ducts of the kidneys do not respond to ADH
causes of nephrogenic diabetes insipidus
- lithium
- mutations in AVPR2 gene on X chromsome
- Intrinsic kidney disease
- Hypokalaemia
- Hypercalcaemia
what is cranial diabetes insipidus?
when the hypothalamus does not produce ADH for the pituitary gland to secrete
Causes of cranial diabetes insipidus
idiopathic brain tumours head injury brain malformations brain infections - meningitis, encephalitis, TB Brain surgery/chemotherapy
presentation of diabetes insipidus
Polyuria polydipsia dehydration postural hypotension HYPERNATRAEMIA
ix for diabetes insipidus
low urine osmolality
high serum osmolality
water deprivation test
what is the water deprivation test and how is it done?
used to diagnose diabetes insipidus
1) no fluids for 8 hours = fluid deprivation
2) measure urine osmolality
3) give synthetic ADH (desmopressin)
4) 8 hours later measure urine osmolality again
What do the results of the water deprivation test show?
For cranial diabetes insipidus = urine osmolality starts low as the brain isn’t producing any ADH, then after giving desmopressin the usine osmolality is high because the kidneys can still respond to ADH
For nephrogenic diabetes insipidus = the urine osmolality is low to start and stays low after desmopressin is given as the kidneys can’t respond to ADH
for primary polydipsia = the 8 hours of water deprivation will cause a high urine osmolality even before desmopressin is given
whats another name for the water deprivation test?
desmopressin stimulation test
management of diabetes insipidus
desmopressin in cranial DI
High doses of desmopressin in nephrogenic DI under close monitoring
what are the short synacthen test, dexamethasone suppression test and water deprivation test/desmopressin stimulation test each used for?
short synacthen test = low cortisol/adrenal insufficiency ie Addisons disease
dexamethasone suppression test = high cortisol ie cushings syndrome/disease
water deprivation test = diabetes insipidus (nephrogenic/cranial)
Symptoms/signs of Hypercalcaemia
‘bones, stones, groans and psychic moans’
- abnormal bone remodelling/fracture risk
- kidney stones
- abdo cramps/nausea/ileus/constipation
- lethargy, depression, psychosis
corneal calcification
shortened QT interval on ECG
hypertension
causes of Hypercalcaemia
1) primary hyperparathyroidism (most common in the community)
2) malignancy (most common in hospital) = SCLC, bone mets, myeloma
Other causes: sarcoidosis vitamin D intoxication acromegaly thyrotoxicosis thiazides dehydration Addisons disease
mx for Hypercalcaemia
rehydration with NaCl - 3-4L /day
after rehydration = bisphosphonates (take 2-3 days to work)
calcitonin is quicker than bisphosphonates
steroids in sarcoidosis
symptoms of hypocalcaemia
NEUROMUSCULAR EXCITABILITY
tetany - muscle twitching, cramping and spasm
perioral paraesthesia
chronic hypocalcaemia = depression, cataracts
ECG = prolonged QT interval
Trousseau’s sign
Chvosteks sign
what is trousseau’s sign?
seen in hypocalcaemia
carpal spasm if the brachial artery occulded by inflating BP cuff to a pressure above their systolic BP
what is chvostek’s sign?
seen in hypocalcaemia
tapping over parotid causes facial muscles to twitch
causes of hypocalcaemia
vitamin D deficiency (osteomalacia) CKD hypoparathyroidism pseudohypoparathyroidism rhabdomyolysis magnesium deficiency massive blood transfusion acute pancreatitis
contamination of blood samples with EDTA = falsely low calcium
mx of hypocalcaemia
IV replacement for severe hypocalcaemia - IV calcium gluconate 10ml of 10% solution over 10 mins
ECG monitoring
ECG changes seen in hyperkalaemia
Tall tented T waves
Small/loss of P waves
Widened QRS complex - leads to sinusoidal pattern
Asystole
Causes of hyperkalaemia
AKI Potassium sparing diuretics ACEi ARBs Spironolactone Ciclosporin Heparin Metabolic acidosis Addison's disease (primary adrenal insufficiency) Rhabdomyolysis Massive blood transfusion
Mx of hyperkalaemia
Stabilise cardiac membrane = IV CALCIUM GLUCONATE (this doesn’t lower serum K)
Short term shift of K from extracellular to intracellular space = INSULIN/DEXTROSE INFUSION & NEB SALBUTAMOL
Removal of K from body = CALCIUM RESONIUM (oral/enema), LOOP DIURETICS, DIALYSIS (haemofiltration/haemodialysis for patients with AKI & persistent hyperkalaemia)
Stop any exacerbating drugs
Treat underlying cause
classification of hyperkalaemia
mild = 5.5 to 5.9 moderate = 6.0 to 6.4 severe = >6.5
how should you classify hypokalaemia?
with or without hypertension
causes of hypokalaemia with hypertension
cushings syndrome
conn’s syndrome (primary hyperaldosteronism)
liddle’s syndrome
11-beta hydroxyls deficiency - congenital adrenal hyperplasia
causes of hypokalaemia without hypertension
diuretics GI loss - diarrhoea and vomiting renal tubular acidosis bartter's syndrome - inherited cause of severe hypokalaemia gitelman syndrome
symptoms of hypokalaemia
muscle weakness
hypotonia
predisposes to digoxin toxicity
ECG changes in hypokalaemia
U waves
small/absent t waves
prolonged PR interval
ST depression
causes of hypokalaemia with alkalosis
vomiting
thiazide and loop diuretics
cushings syndrome
conn’s syndrome (primary hyperaldosteronism)
causes of hypokalaemia with acidosis
diarrhoea
renal tubular acidosis
acetazolamide
partially treated DKA
mx of hypokalaemia
Check and replete Magnesium
Treat underlying cause
mild = oral KCl if no acidosis or ora potassium bicarbonate if there’s acidosis
moderate = oral KCl unless can’t have PO or there’s ECG changes
Severe = IV KCl. Do not give more than 20mmol/hr. concentration should not exceed 40mmol/L. Faster transfusion than 20mmol/hr through a central line in ICU. Need continuous cardiac monitoring and check K levels every 2-4 hrs
what are the causes of hyponatraemia?
URINARY SODIUM >20 MMOL/L
- thiazide / loop diuretics
- addison’s disease
- diuretic stage of renal failure
- SIADH
- hypothyroidism
URINARY SODIUM <20 MMOL/L
- diarrhoea
- vomiting
- sweating
- burns
- adenoma of rectum
- HF
- liver cirrhosis
- nephrotic syndrome
- IV dextrose
- psychogenic polydipsia
complication of untreated hyponatraemia
cerebral oedema = brain herniation
symptoms of hyponatraemia
early = headache, lethargy, nausea, vomiting, dizziness, confusion, muscle cramps
late = seizures, coma, respiratory arrest
causes of hyponatraemia by volume status
hypovolemic hyponatraemia/clinically dehydrated: diuretic stage of renal failure, diuretics, Addisonian crisis
euvolemic hyponatraemia: SIADH
heart failure, liver failure, nephrotic syndrome
mx of hyponatraemia
hypovolaemic cause:
- 0.9% NaCl
euvolemic cause:
fluid restrict to 500-1000ml/day.
consider demeclocycline / vaptans
hypervolemic cause:
fluid restrict to 500-1000ml/day.
consider loop diuretic/vaptans
severe hyponatraemia with symptoms (<120mmol/L): HDU & give hypertonic saline (3% NaCl)
complications of mx of hyponatraemia
central pontine myelinolysis (osmotic demyelination syndrome)
don’t correct Na by more than 6-12 mmol/l in a 24 hour period
symptoms = dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
(locked in syndrome)
causes of hypernatraemia
dehydration
osmotic diuresis e.g. hyperosmolar non-ketotic diabetic coma
diabetes insipidus
excess IV saline
mx of hypernatraemia
a rate of no greater than 0.5 mmol/hour correction is appropriate = helps avoid cerebral oedema (seizures, coma and death)
IV 5% dextrose
causes of hyperlipidaemia
Predominantly hypertriglyceridaemia = diabetes mellitus (types 1 and 2) obesity alcohol chronic renal failure drugs: thiazides, non-selective beta-blockers, unopposed oestrogen liver disease
predominantly hypercholesterolaemia = nephrotic syndrome cholestasis hypothyroidism familial hypercholesterolaemia
mx of hyperlipidaemia
for primary prevention:
- give to people with 10 year cardiovascular risk of >10% OR T1DM OR eGFR <60
ATROVASTATIN 20MG OD
(titrate up to 80mg if reduction in non-HDL cholesterol hasn’t fallen by at least 40%)
for secondary prevention:
- give if known IHD OR CVA OR PAD
ATROVASTATIN 80MG OD
How to assess 10 year cardiovascular risk
QRISK2
- age
- gender
- ethnicity
- postcode
- BMI
- smoker
- family hx CAD
- HTN, ?treated
- total cholesterol:HDL cholesterol
- DM
- AF
- Renal disease
- RA
lifestyle advice for hyperlipidaemia
cardioprotective diet - reduce fats, wholegrain starches, 5 portion fruit/veg, 2 portions fish per week, 4-5 portions unsalted nuts/seeds/legumes per week
physical activity - 150 mins cardio per week
weight management
alcohol intake to <14 units per week
smoking cessation
what secretes parathyroid hormone and what is it secreted in response to?
chief cells in the parathyroid glands
PTH secreted in response to hypoclacaemia
What does PTH do?
Increases serum calcium by -
- increasing osteoclast activity
- increasing calcium absorption from gut
- increasing calcium absorption from kidneys
- increasing vitamin D activity = increases calcium absorption from intestines
symptoms of hyperparathyroidism
symptoms of hypercalcaemia = painful bones, kidney stones, abdominal groans and psychiatric moans
causes of primary hyperparathyroidism
tumour of the parathyroid glands = releases uncontrolled amounts of PTH
High PTH & high calcium
causes of secondary hyperparathyroidism
parathyroid gland hyperplasia in response to hypocalcaemia from low vitamin D/chronic renal failure
High PTH & low/normal calcium
causes of tertiary hyperparathyroidism
cause of secondary hyperparathyroidism is treated but the enlarged parathyroid gland continues to produce large amounts of PTH
High PTH and high calcium
mx of primary hyperparathyroidism
surgical removal of parathyroid gland tumour
mx of secondary hyperparathyroidism
correct vitamin D deficiency or renal transplant for renal failure
mx of tertiary hyperparathyroidism
surgically remove part of the parathyroid tissue
cause of hyperthermia
malignant hyperthermia
what is malignant hyperthermia?
condition often seen following administration of anaesthetic agents
characterised by hyperpyrexia and muscle rigidity
cause by excessive release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle
genetics associated with malignant hyperthermia
autosomal dominant inheritance
defects in a gene on chromosome 19 encoding the ryanodine receptor, which controls Ca2+ release from the sarcoplasmic reticulum
causative agents of malignant hyperthermia
halothane
suxamethonium
antipsychotics - neuroleptic malignant syndrome
ix for malignant hyperthermia
CK raised
contracture tests with halothane and caffeine
mx of malignant hyperthermia
dantrolene - prevents Ca2+ release from the sarcoplasmic reticulum
what classifies as hypothermia?
Mild hypothermia: 32-35°C
Moderate or severe hypothermia: < 32°C
causes of hypothermia
Exposure to cold in the environment is the major cause
Inadequate insulation in the operating room
Cardiopulmonary bypass
Newborn babies.
risk factors for hypothermia
General anaesthesia Substance abuse Hypothyroidism Impaired mental status Homelessness Extremes of age
symptoms of hypothermia
shivering
cold and pale skin. Frostbite occurs when the skin and subcutaneous tissue freeze, causing damage to cells.
slurred speech
tachypnoea, tachycardia and hypertension (if mild)
respiratory depression, bradycardia and hypothermia (if moderate)
confusion/ impaired mental state
ix in hypothermia
temperature ECG FBC & U&Es - high hb and haematocrit, platelets & WCC low due to sequestration in the spleen, can be hypokalaemic BMs Arterial blood gas Coagulation factors CXR
ECG changes seen in hypothermia
bradycardia 'J' wave - small hump at the end of the QRS complex first degree heart block long QT interval atrial and ventricular arrhythmias
what not to do when someone if hypothermic
Don’t put the person into a hot bath.
Don’t massage their limbs.
Don’t use heating lamps.
Don’t give them alcohol to drink.
what causes primary hypoparathyroidism?
primary hypoparathyroidism:
- secondary to thyroid surgery
symptoms of hypoparathyroidism and ECG changes
the symptoms of hypocalcaemia
- tetany
- perioral paraesthesia
- Trousseau’s sign
- Chvostek’s sign
ECG - prolonged QT interval
ix for primary hypoparathyroidism
hypocalcaemia
high phosphate
low PTH
mx for primary hypoparathyroidism
alfacalcidol
what is pseudohypoparathyroidism?
the target cells are insensitive to PTH due to abnormality in a G protein
what is pseudohypoparathyroidism associated with?
associated with low IQ, short stature, shortened 4th and 5th metacarpals
ix for pseudohypoparathyroidism
low calcium
high phosphate
high PTH
measure urinary cAMP and phosphate following an infusion of PTH - in hypoparathyroidism this causes an increase in cAMP and phosphate levels, in pseudohypoparathyroidism type I cAMP and phosphate don’t increase, pseudohypoparathyroidism type II cAMP increases but phosphate doesn’t
causes of hypothyroidism
Hashimoto’s thyroiditis - autoimmune
Iodine deficiency
carbimazole
propylthiouracil
radioactive iodine
thyroid surgery
Lithium
Amiodarone
secondary hypothyroidism:
- tumours in pituitary gland
- infection in pituitary gland
- vascular e.g. sheehan syndrome
- radiation to pituitary gland
symptoms of hypothyroidism
Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (oedema, pleural effusions, ascites) Heavy or irregular periods Constipation
symptoms of hypothyroidism
Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (oedema, pleural effusions, ascites) Heavy or irregular periods Constipation Decreased deep tendon reflexes carpal tunnel syndrome occasionally - hoarse voice
Ix for hypothyroidism
primary hypothyroidism = low T3 and T4, high TSH
secondary hypothyroidism = low T3, T4, TSH
mx of hypothyroidism
levothyroxine (synthetic T4 that metabolises to T3 in the body)
titrate up dose until TSH level normal
measure TSH monthly until stable then less frequently
check TSH 8-12 weeks after dose change
when should patients get a lower dose of levothyroxine?
elderly patients
IHD
when should you increase a patients dose of levothyroxine?
in women who get pregnant
SEs of levothyroxine
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
interactions of levothyroxine
iron
calcium carbonate
(they reduce the absorption of levothyroxine so give at least 4 hours apart)
mx of obesity
1 diet / exercise
2 medical:
- orlistat = pancreatic lipase inhibitor (causes faecal urgency/incontinence and flatulence)
3 surgical:
- laparoscopic adjustable gastric banding
- sleeve gastrectomy
- intragastric balloon
- biliopancreatic diversion with duodenal switch
- roux-en-Y gastric bypass surgery
what are the effects of a pituitary tumour?
- large ones can compress the optic chiasm = bitemporal hemianopia (loss of outer half of vision)
- acromegaly (excessive GH)
- hyperprolactinaemia
- cushings disease (high cortisol)
- thyrotoxicosis
Causes of hyperthyroidism
primary hyperthyroidism -
- Grave’s disease (autoimmune condition) - most common cause
- toxic multi nodular goitre
- solitary toxic thyroid nodule
- thyroiditis - e.g. de quervains, hashimotos, postpartum and drug induced
secondary hyperthyroidism -
- TSH secreting pituitary tumour
amiodarone
over treatment with levothyroxine
what is grave’s disease?
Autoimmune condition
TSH receptor antibodies cause a primary hyperthyroidism
the TSH receptor antibodies mimic TSH and stimulate TSH receptors on the thyroid
most common cause of hyperthyroidism
What is toxic multinodular goitre?
Also known as Plummer’s disease
Nodules develop on the thyroid gland - act independently of the normal feedback mechanism & continuously produce excessive thyroid hormone
symptom specific to graves disease
Exophthalmos = bulging of eyeball
Pretibial myxoedema = deposits of mucin on anterior of leg - waxy discoloured oedematous appearance of skin (is a reaction to the TSH antibodies)
Diffuse goitre (without nodules)
symptom specific to graves disease
Exophthalmos = bulging of eyeball
ophthalmoplegia
Pretibial myxoedema = deposits of mucin on anterior of leg - waxy discoloured oedematous appearance of skin (is a reaction to the TSH antibodies)
Diffuse goitre (without nodules)
digital clubbing
symptoms specific to toxic multi nodular goitre
Goitre with firm nodules
Most patients are aged over 50
Second most common cause of thyrotoxicosis (after Grave’s)
what is de quervain’s thyroiditis?
a viral infection with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism
hyperthyroid phase followed by hypothyroid phase
mx of de quervain’s thyroiditis?
self limiting condition
NSAIDs
beta-blockers for symptomatic relief of hyperthyroid
what is thyrotoxic crisis/thyroid storm?
a more severe presentation of hyperthyroidism with pyrexia, tachycardia and delirium
what is Thyrotoxicosis
an abnormal and excessive quantity of thyroid hormone in the body.
mx of thyrotoxic crisis
admit to hospital
monitoring
fluid resuscitation
anti-arrhythmic medication beta blockers
mx of hyperthyroidism
1st = Carbimazole - can do titration block or block and replace (give levothyroxine too)
2nd = propylthiouracil
3rd = radioactive iodine
beta blockers for heart palpitations
thyroidectomy + levothyroxine
how is Carbimazole used?
used in the management of thyrotoxicosis.
It is typically given in high doses for 6 weeks until the patient becomes euthyroid before being reduced.
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
side effects of Carbimazole
agranulocytosis
crosses the placenta, but may be used in low doses during pregnancy
risks associated with propylthiouracil
severe hepatic reaction - including death
strict rules when using radioactive iodine to treat hyperthyroidism
Must not be pregnant and are not allowed to get pregnant within 6 months
Must avoid close contact with children and pregnant women for 3 weeks (depending on the dose)
Limit contact with anyone for several days after receiving the dose
how does radioactive iodine work in hyperthyroidism?
Treatment with radioactive iodine involves drinking a single dose of radioactive iodine.
This is taken up by the thyroid gland and the emitted radiation destroys a proportion of the thyroid cells.
This reduction in functioning cells results in a decrease of thyroid hormone production and thus remission from the hyperthyroidism.
Remission can take 6 months and patients can be left hypothyroid afterwards and require levothyroxine replacement.
what autoantibodies are present in graves disease?
TSH receptor stimulating antibodies (90%)
anti-thyroid peroxidase antibodies (75%)
what is acromegaly?
++ growth hormone
GH is produced by the anterior pituitary gland
cause of acromegaly
pituitary adenoma that secretes unregulated amounts of GH
rarely caused by lung or pancreatic cancers that secrete GH
presentation of acromegaly
Space Occupying Lesion:
- Headaches
- Visual field defect (“bitemporal hemianopia”)
Overgrowth of tissues:
- Prominent forehead and brow (“frontal bossing”)
- Large nose
- Large tongue (“macroglossia”)
- Large hands and feet
- Large protruding jaw (”prognathism”)
- Arthritis from imbalanced growth of joints
GH can cause organ dysfunction:
- Hypertrophic heart
- Hypertension
- Type 2 diabetes
- Colorectal cancer
Symptoms suggesting active raised growth hormone:
- Development of new skin tags
- Profuse sweating
Ix for acromegaly
Insulin like growth factor 1 (IGF-1)
Oral glucose tolerance test while measuring GH - high glucose normally suppress GH
MRI brain - pituitary tumour
Ophthalmology referral for visual field testing
Tx of acromegaly
trans-sphenoidal removal of the pituitary tumour
medications used to block GH:
- pegvisomant
- somatostatin analogues e.g. ocreotide
- dopamine agonist e.g. bromocriptine
how does the renin-angiotensin system work?
juxtaglomerular cells in the afferent arterioles in the kidney sense the BP
if there’s low BP, the kidney secrete renin
the liver then secretes angiotensinogen
renin converts angiotensinogen to angiotensin I
angiotensin I is converted to angiotensin II in the lungs with the help of angiotensin converting enzyme (ACE)
angiotensin II stimulates the release of aldosterone from the adrenal glands
what does aldosterone do?
it is released by the adrenal glands
acts on the kidney to:
- increase Na reabsorption from the distal tubule
- increase potassium secretion from the distal tubule
- increase hydrogen secretion from the collecting ducts
what is primary hyperaldosteronism?
Conn’s syndrome
Adrenal glands are directly responsible for producing too much aldosterone
Low serum renin
causes of primary hyperaldosteronism
Adrenal adenoma - that secretes aldosterone Bilateral adrenal hyperplasia Familial hyperaldosteronism Adrenal carcinoma (rare)
what is secondary hyperaldosteronism
excessive renin stimulates the adrenal glands to produce more aldosterone
serum renin is high
causes of secondary hyperaldosteronism
high renin happens when blood pressure to the kidneys is disproportionately lower than blood pressure to the rest of the body
renal artery stenosis
renal artery occlusion
heart failure
Ix for hyperaldosteronism
do a renin / aldosterone ratio
Low renin and high aldosteronism = conn’s syndrome (primary hyperaldosteronism)
High renin and high aldosterone = secondary hyperaldosteronism
Blood pressure - HTN Hypokalaemia Blood gas - alkalosis CT/MRI for adrenal tumour Renal doppler US, CT angiogram or MRA for renal artery stenosis or obstruction
Mx of hyperaldosteronism
Aldosterone antagonists:
- Eplerenone
- spironolactone
Treat underlying cause:
- surgical removal of adenoma
- Percutaneous renal artery angioplasty via the femoral artery
what is the most common cause of secondary hypertension
hyperaldosteronism
if a patients HTN isn’t responding to antihypertensives, do a renin:aldosterone ratio
what is a pheochromocytoma?
a tumour of chromatin cells in the adrenal medulla that secrete an unregulated amount of adrenaline
the adrenaline tends to be secreted in bursts, giving periods of worse symptoms followed by settled periods
what is the cause of 25% of pheochromocytomas?
multiple endocrine neoplasia type 2 (MEN 2)
what is the 10% rule used to describe pheochromocytoma?
10% bilateral
10% cancerous
10% outside the adrenal gland
how is a pheochromocytoma diagnosed
24 hour urine catecholamines
plasma free metanephrines
why are 24 hour urine catecholamines measured for pheochromocytoma?
adrenaline is a catecholamine
serum catecholamines will naturally fluctuate throughout the day so instead measure them in the urine over 24 hours
can see how much adrenaline the tumour is secreting over the 24 hours
Why are plasma free metanephrines measured for pheochromocytomas?
adrenaline has a short half life in the blood
metanephrines are the breakdown products of adrenaline - have a longer half life
the levels of metanephrines are less prone to dramatic fluctuations
symptoms of pheochromocytoma
Anxiety Sweating Headache Hypertension Palpitations, tachycardia and paroxysmal atrial fibrillation
Mx of pheochromocytoma
Alpha blockers (i.e. phenoxybenzamine) Beta blockers once established on alpha blockers Adrenalectomy to remove tumour is the definitive management - need to have symptoms medically controlled before surgery to reduce anaesthetic risk
What is SiADH
there’s inappropriately large amounts of ADH
What does ADH do and where is it secreted from?
secreted by posterior pituitary gland
stimulates water reabsorption from the collecting ducts in the kidneys
Electrolyte disturbances and urine changes caused by SiADH
hyponatraemia due to excessive ADH causing lots of water reabsorption in the collecting ducts
get a euvolemic hyponatraemia - because the reabsorption is not significant enough to cause fluid overload
urine gets more concentrated by kidneys as more water is reabsorbed - high urine osmolality and high urine sodium
symptoms of SiADH
Headache Fatigue Muscle aches and cramps Confusion Severe hyponatraemia can cause seizures and reduced consciousness
causes of SiADH
Post-operative from major surgery
Infection, particularly atypical pneumonia and lung abscesses
Head injury
Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,)
Malignancy, particularly small cell lung cancer
Meningitis
Diagnosis of SiADH
Diagnosis of exclusion (can’t measure ADH directly)
Euvolaemia on examination
U&Es = hyponatraemia
Urine sodium and osmolality high
Do CXR to look for lung abscess/cancer/pneumonia
Exclude other causes:
- short synacthen test
- no diuretic use
- no diarrhoea, vomiting, burns, fistula, excessive sweating
- no excessive water intake
- no CKD or AKI
Mx of SiADH
treat underlying cause or stop medications causing it
correct sodium slowly by no more than 10mmol/l increase in sodium in 24 hours (reduces risk of central pontine myelinolysis)
Mx of SiADH
treat underlying cause or stop medications causing it
correct sodium slowly by no more than 10mmol/l increase in sodium in 24 hours (reduces risk of central pontine myelinolysis)
fluid restriction (500-1l)
Tolvaptan (a vaptan) - ADH receptor blockers
Demeclocycline - tetracycline abx that inhibits ADH
Where is insulin produced?
beta cells in the islets of langerhans in the pancreas
what is T1DM?
a disease where the pancreas stops being able to produce insulin.
When there is no insulin being produced, the cells of the body cannot take glucose from the blood and use it for fuel. Therefore the cells think the body is being fasted and has no glucose supply. Meanwhile the level of glucose in the blood keeps rising, causing hyperglycaemia.
Causes of T1DM
Unknown cause
Some theories:
- Genetic component
- triggered by a virus: coxsackie B / enterovirus
presentation of DKA
Hyperglycaemia Dehydration Ketosis Metabolic acidosis (with a low bicarbonate) Potassium imbalance
The patient will therefore present with symptoms of these abnormalities:
Polyuria Polydipsia Nausea and vomiting Acetone smell to their breath Dehydration and subsequent hypotension Altered Consciousness They may have symptoms of an underlying trigger (i.e. sepsis)
Pathology of DKA
- Ketoacidosis - ketogenesis to make fuel
- dehydration - hyperglycaemia causes glucose to be filtered into urine so water is drawn into urine too
- potassium imbalance - hyperkalaemia as insulin draws K into cells, when insulin tx starts: sudden hypokalaemia
Diagnosis of DKA
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
Ketosis (i.e. blood ketones > 3 mmol/l)
Acidosis (i.e. pH < 7.3)
Mx of DKA
FIG PICK
F - IV fluids with NaCl
I - INsulin - fixed rate insulin infusion (act rapid 0.1 unit/kg/hour)
G - glucose - add dextrose when BM <14
P - potassium (closely monitor)
I - infection (treat)
C - chart fluid balance
K - ketones (monitor blood ketones / bicarbonate)
Establish patient on normal subcut insulin regime prior to stopping insulin and fluid infusion
Don’t infuse K faster than 10 mmol/hr
Long term management of T1DM
Patient education about:
- Subcutaneous insulin regimes
- Monitoring daily carbohydrate intake
- Monitoring BMs - waking, before each meal and before bed
- Monitoring & managing complications
Insulin:
- Background, long acting insulin once daily + short acting insulin 30 mins before a meal
- rotate injection sites to avoid lipodystrophy
short term complications of T1DM
Hypoglycaemia
Hyperglycaemia (DKA)
Typical symptoms of hypoglycaemia
tremor sweating irritability dizziness pallor
severe: reduced LOC, coma and death
Tx of hypoglycaemia
Rapid acting glucose (10-20g in liquid, gel or tablet form) / glycogen + slow acting carbohydrate if able to swallow
Reduced GCS = IM glucagon / IV dextrose (20% 125ml)
Long term complications of T1DM
Macrovascular Complications:
- Coronary artery disease is a major cause of death in diabetics
- Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
- Stroke
- Hypertension
Microvascular Complications:
- Peripheral neuropathy
- Retinopathy
- Kidney disease, particularly glomerulosclerosis
Infection Related Complications:
- UTIs
- Pneumonia
- Skin and soft tissue infections, particularly in the feet
- Fungal infections, particularly oral and vaginal candidiasis
Monitoring of T1DM
HbA1C (to count glycerinated Hb) - check every 3-6 months
Capillary BMs
Flash glucose monitoring e.g. free style libre
What happens in T2DM?
Repeated exposure to glucose and insulin makes the cells in the body become resistant to the effects of insulin.
It requires more insulin to produce a response from the cells and get them to take up and use glucose. The pancreas (beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less.
A continued onslaught of glucose on the body in light of insulin resistance and pancreatic fatigue leads to chronic hyperglycaemia.
Risk factors for T2DM
Non-Modifiable
Older age
Ethnicity (Black, Chinese, South Asian)
Family history
Modifiable
Obesity
Sedentary lifestyles
High carbohydrate (particularly refined carbohydrate) diet
Presentation of T2DM
Fatigue Polydipsia and polyuria (thirsty and urinating a lot) Unintentional weight loss Opportunistic infections Slow healing Glucose in urine (on dipstick)
Ix for T2DM
HbA1C
Oral glucose tolerance test - test fasting plasma glucose have a 75mg glucose drink then measure plasma glucose 2 hrs later
What is pre-diabetes?
An indication the patient is heading towards diabetes, need education on lifestyle + no medications.
HbA1c – 42-47 mmol/mol
Impaired fasting glucose – fasting glucose 6.1 – 6.9 mmol/l
Impaired glucose tolerance – plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT
What are the criteria for the diagnosis of T2DM?
HbA1c > 48 mmol/mol
Random Glucose > 11 mmol/l
Fasting Glucose > 7 mmol/l
OGTT 2 hour result > 11 mmol/l
Mx for T2DM
Patient education Diet modification Exercise weight loss stop smoking treat HTN/lipids
Medical mx:
- 1st line = metformin
- 2nd line = add sulfonylura / pioglitazone / DPP-4 inhibitor / SGLT-2 inhibitor
- 3rd line = triple therapy with metformin and 2 of the second line drugs
OR metformin + insulin
Treatment targets for T2DM
48 mmol/mol for new type 2 diabetics
53 mmol/mol for diabetics that have moved beyond metformin alone
What is metformin, how does it work and what are its side effects?
A biguanide
Increases insulin sensitivity and decreases liver production of glucose
Side effects:
diarrhoea and abdo pain
lactic acidosis
DOES NOT CAUSE hypoglycaemia
What is pioglitazone, how does it work and what are its side effects?
A thiazolidinedione
Increases insulin sensitivity and decreases liver production of glucose
Side effects: weight gain fluid retention anaemia HF Increased risk of bladder ca
DOES NOT CAUSE hypoglycaemia
Give an example Sulfonylurea, how it works and the side effects
Gliclazide
stimulates insulin release from the pancreas
Side effects
Weight gain
HYPOGLYCAEMIA
increased risk of CVD and MI
Give an example DPP-4 inhibitor, how it works and the side effects
Sitagliptin
Works by increasing GLP-1 activity
Side effects
GI upset
Symptoms of URTI
Pancreatitis
Give an example GLP-1 mimetic, how it works and the side effects
Exenatide (subcutaneous injection)
Increase insulin secretions, inhibit glucagon production and slow absorption in GI tract
Side effects GI upset Weight loss Dizziness Low risk of hypoglycaemia
What are example SGLT-2 inhibitors, how do they work and what are their side effects?
empagliflozin, dapagliflozin
cause glucose to be excreted in the urine
Side effects Glucoseuria Increased UTIs Weight loss DKA
What is a hyperosmolar hyperglycaemic state?
Medical emergency
Hyperglycaemia results in osmotic diuresis, severe dehydration, and electrolyte deficiencies.
Pathology of HHS
Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
Who gets HHS?
elderly with T2DM
ncidence in younger adults is increasing
can be the initial presentation of T2DM.
Symptoms of HHS
General: fatigue, lethargy, nausea and vomiting
Neurological: altered level of consciousness, headaches, papilloedema, weakness
Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
Cardiovascular: dehydration, hypotension, tachycardia
Criteria for diagnosing HHS
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- Significantly raised serum osmolarity (> 320 mosmol/kg)
Mx for HHS
- Normalise the osmolality (gradually with NaCl)
the serum osmolality is the key parameter to monitor
if not available it can be estimated by 2 * Na+ + glucose + urea - Replace fluid and electrolyte losses
- Normalise blood glucose (gradually)
