Endocrinology 1/6/20 Flashcards
causes of hyponatraemia (with urine Na osmolarity >20mmol/L)
euvolaemic patient
- SIADH
- hypothyroidism
hypovolaemic patient
> Addison’s disease
> renal failure
> diuretics (thiazides/loop diuretics)
causes of hyponatraemia (with urine Na osmolarity <20mmol/L)
hypovolaemic patient
> diarrhoea, vomiting
> burns
oedematous patient
> secondary hyperaldosteronism (heart failure, liver cirrhosis, renal artery stenosis)
> nephrotic syndrome
> IV dextrose
> psychogenic polydipsia
mild, mod, sev hyponatraemia serum Na values
normal blood sodium = 135-145mmol/L
mild = 130-134 mmol/l mod = 120-129 mmol/l sev = <120 mmol/l
symptoms of hyponatraemia
mild + mod:
Non-specific symptoms such as headache, lethargy, nausea, vomiting, dizziness, confusion, and muscle cramps
sev:
- seizures
- coma
- respiratory arrest
management of mild hyponatraemia (130-134 mmol/L)
- fluid restriction (<800ml/day)
- loop diuretics (eg. furosemide)
management of moderate hyponatraemia (120-129mmol/L)
- hypertonic saline in first 4 hrs (to raise Na)
- fluid restriction (<800ml/day)
- loop diuretics (eg. furosemide)
management of severe hyponatraemia (<120mmol/L)
- bolus of hypertonic saline until symptom resolution
- may add conivaptan/tolvaptan to inhibit ADH (can be hepatotoxic)
other management concerns for hyponatraemia
Fluids restriction in the following patients:
- Oedematous states like heart failure and cirrhosis
- SIADH
- Renal failure
- Psychogenic polydipsia
Central pontine myelinolysis is a risk in correcting severe hyponatraemia too quickly - leads to irreversible neuro damage, can lead to locked in syndrome
causes of hypernatraemia
- dehydration
- osmolar diuresis eg. hyperosmolar hyperglycaemic state (HHS)
- diabetes insipidus
- excess IV saline
hyperosmolar hyperglycaemic state (HHS) features
Often confused with DKA - check ketones/pH (HHS more common in DM2, while DKA usually DM1)
General Nervousness Harms Hearts
General:
polyuria, 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
diagnosis of hyperosmolar hyperglycaemic state (HHS)
- hypovolaemia
- marked hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- significantly raised serum osmolarity (> 320 mmol/kg) gives features of hyperviscosity
management of hyperosmolar hyperglycaemic state (HHS)
treat underlying cause
- Normalise the osmolality (gradually)
- Replace fluid (normal saline or 0.45% saline if not reducing in osmolarity sufficiently as is more hypotonic) and electrolyte losses
- Normalise blood glucose (gradually)
prophylactic anticoagulation
iatrogenic causes of siADH
- carbamazepine
- thiazides
- SSRIs and tricyclics
- vincristine and cyclophosphamide
- oxytocin and vasopressin
management of siADH
correction must be done slowly to avoid precipitating central pontine myelinolysis
- fluid restriction
- demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH (can cause photosensitive rash)
- ADH receptor antagonist eg. conivaptan/tolvaptan
non-drug causes of siADH
- malignancy - particularly SCLC but also pancreatic and prostate
- neurological - stroke/SA or SD haemorrhage/meningitis or encephalitis or abscess
- infections - TB or pneumonia
diagnosis of siADH
diagnosis of exclusion, must fill the folowing criteria:
- low plasma sodium concentration <135 mmol/l
- high urinary sodium concentration >30mmol/L
- patient euvolaemic
- absence of adrenal and thyroid dysfunction
- no diuretic use (recent or past)
causes of hypercalcaemia
- primary hyperparathyroidism (PHPT): commonest cause in non-hospitalised patients
- malignancy: the commonest cause in hospitalised patients, may be due to a number of processes, including bone metastases, myeloma, PTHrP from squamous cell lung cancer
- other (<10% cases):
> vit D intoxication
> granulomas eg. sarcoidosis/TB
> drugs (thiazides, calcium antacids, lithium, dietary calcium)
> Addison's
> thyrotoxicosis
features of hypercalcaemia
- bones, stones, thrones (polyuria + constipation), abdo groans (stones, peptic ulcer, constipation, nausea) and psychiatric moans (confusion, mood change)
- polyuria + polydipsia
- anorexia/weight loss
- corneal calcification
- shortened QT interval
normal adjusted calcium
Adjusted calcium range = 2.20-2.60 mmol/L
management of hypercalcaemia
generally correct underlying cause and do an ECG and urine calcium (consider BMD scan)
- give saline IV
- bisphosphonate IV
- surgery in mets/PHPT
primary adrenal insufficiency (Addisons) site of disease
adrenal cortex dysfunction
secondary adrenal insufficiency site of disease
pituitary or hypothalamus dysfunction
tertiary adrenal insufficiency site of disease
chronic glucocorticoid administration
causes of primary adrenal insufficiency
- autoimmune “Addison’s” (destruction of adrenal glands)
- trauma
- TB
- malignancy (eg. bronchial carcinoma)
- meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
causes of secondary adrenal insufficiency
pituitary or hypothalamus disorders (e.g. tumours, irradiation, infiltration)
causes of tertiary adrenal insufficiency
- glucocorticoid suppression
- post treatment of Cushing’s
features of adrenal insufficiency
- lethargy, weakness, anorexia, nausea & vomiting, weight loss, hypotension, ‘salt-craving’
- skin/gum changes (in primary addison’s - hyperpigmentation (especially palmar creases), vitiligo, loss of pubic hair in women (due to reduced androgens)
- hypoglycaemia, hyponatraemia and hyperkalaemiac metabolic acidosis may be seen
investigations for adrenal insufficiency
ACTH stimulation test (short synacthen test)
- plasma cortisol is measured before and 30 minutes after giving synacthen 250ug IM
- adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated in Addison’s
if not readily available eg. general practice, can use a 9am serum cortisol blood test
history and examination can rule out secondary/tertiary
management of Addison’s
glucocorticoid and mineralocorticoid replacement therapy (double in illness to prevent crisis)
- hydrocortisone
- fludrocortisone
patient education
management of Addisonian crisis
- hydrocortisone 100 mg IM or IV
- 1000ml normal saline IV (with dextrose if hypoglycaemic)
- continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
- oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
role of PTH
increases:
- Ca2+ reabsortion in kidney
- hydroxylation of 25 OH vit D in kidney
- Ca2+ release from bone remodelling
- Ca2+ gut absorption via 25 OH vit D
decreases:
- phosphate reabsorption by kidney
hypoparathyroidism features (symptoms of hypocalcaemia)
symptoms due to hypocalcaemia:
- tetany: muscle twitching, cramping and spasm
- perioral paraesthesia
- Trousseau’s sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
- Chvostek’s sign: tapping over parotid causes facial muscles to twitch
- if chronic: depression, cataracts
- ECG: prolonged QT interval
pseudohypoparathyroidism
- chromosomal abnormality leading to PTH target G proteins being ineffective, so PTH less potent
- association with low IQ, short stature and short 4th and 5th metacarpals
- low calcium, high phosphate, high PTH
pseudopseudo hypoparathyroid = similar phenotype to pseudohypoparathyroidism but normal biochemistry
Cushing’s syndrome causes
exogenous
- chronic steroid use
endogenous
- pituitary adenoma (Cushing’s disease)
- adrenal adenoma/carcinoma
- ectopic ACTH production (eg. SCLC)
Cushing’s syndrome symptoms
due to cortisol's effect on different tissues
- muscle wasting
- central obesity
- moon face
- buffalo hump
- abdominal striae
- osteoporosis - fractures
- thin skin/easy bruising
- hyperglycaemia
> diabetes
> hypertension
> amenorrhoea
> infection susceptibilitydiagnosis of Cushing’s disease
measure free cortisol
- overnight dexamethasone suppression test
- 24hr urinary cortisol
dexamethasone suppression test results meaning
low dose dexamethasone
- suppressed cortisol = normal
- cortisol not suppressed = endogenous cortisol Cushing’s
high dose dexamethasone
- suppressed by high dose but not low = cushing's DISEASE (pituitary adenoma)
- not suppressed by low or high
> ACTH = low = adrenal Cushing's
> ACTH = high = ectopic ACTH
causes of hypokalaemia
- primary hyperaldosteronism (Conn’s)
- loop/thiazide diuretics
- metabolic alkalosis (eg. D+V)
- Cushing’s syndrome (high cortisol causes low potassium)
- insulin overdose
- magnesium deficiency
- renal tubular acidosis types 1 and 2
features of hypokalaemia
- muscle weakness
> skeletal = weakness, flaccid paralysis, cramps
> smooth = constipation, respiratory distress
> cardiac = arrhythmias
- hypotonia
- increased risk of digoxin toxicity
ECG:
- U waves
- small or absent T waves
- prolonged PR interval
- ST depressioncauses of hyperkalaemia
- acute kidney injury
- drugs: potassium-sparing diuretics, antihypertensives, ciclosporin, heparin
- metabolic acidosis/renal tubular acidosis type 4
- insulin deficiency
- Addison’s disease (due to low aldosterone)
- cell lysis eg. rhabdomyolysis/tumour lysis/burns
- massive blood transfusion
features of hyperkalaemia
- ascending muscle weakness
- flaccid paralysis
- arrhythmias
ECG: - tall-tented T waves
- loss of P waves
- broad QRS complexes
management of kyperkalaemia
- calcium gluconate protects against cardiac arrhythmias
- calcium resonium (resin that aids secretion of K+)
- insulin + dextrose infusion
- nebulised salbutamol
- dialysis
features of pituitary apoplexy
- headache (often sudden and severe)
- nausea and vomiting
- diplopia
- tunnel vision
- ptosis
causes of thyroid storm
- thyroid or non-thyroidal surgery
- trauma
- infection
- acute iodine load e.g. CT contrast media
thyroid storm features
- fever > 38.5ºC
- tachycardia
- confusion and agitation
- nausea and vomiting
- hypertension
- heart failure
- abnormal liver function test - may be jaundiced
management of thyroid storm
- treatment of underlying precipitating event
- symptomatic treatment e.g. paracetamol for fever
- Lugol’s iodine
- anti-thyroid drugs: e.g. propylthiouracil
- beta-blockers: typically IV propranolol
- dexamethasone - blocks the conversion of T4 to T3
posterior pituitary hormones
oxytocin and ADH
causes of hypothyroidism
- Hashimoto’s thyroiditis (autoimmune)
- iodine deficiency
- iatrogenic - amiodarone, lithium
- postpartum thyroiditis
- subacute thyroiditis (viral) - painful goitre and raised ESR
- Riedel thyroiditis - painless fibrous goitre
causes of thyrotoxicosis
- Graves’ disease (autoimmune)
- toxic multinodular goitre
- iatrogenic - amiodarone
autoantibodies for autoimmune thyroid disease
- anti-thyroid peroxidase (anti-TPO) antibodies - mostly Hashimoto’s
- TSH receptor antibodies - mostly Graves’
- thyroglobulin antibodies
types of hyperparathyroidism
primary - due to tumour - high PTH - high Ca2+ secondary - due to vit D deficiency/CKD - high PTH - low Ca2+ tertiary - due to chronic secondary HPT, hyperplasia of glands cause irreversile high PTH secretion - high Ca2+ if vit D/CKD treated - treated by excision of surplus cells
treatment for primary hypoparathyroidism
alfacalcidol
features of myxoedema coma
severely hypothyroid
- hypothermia
- confusion/reduced GCS
- symptoms of hypothyroidism
management of myxoedema coma
medical emergency
- IV liothyronine
- IV fluid
- IV corticosteroids (until the possibility of coexisting adrenal insufficiency has been excluded)
- electrolyte imbalance correction
- may need rewarming
where is tumour in phaeochromocytoma?
- adrenal medulla - Chromaffin cells
tumour secretes catecholamines
sometimes affects neural tissue on abdominal aorta
features of phaeochromocytoma
- hypertension
- pounding headache
- palpitations/tachycardia
- diaphoresis (extreme sweating)
diagnosis of phaeochromocytoma
24 hr urinary collection of metanephrines
management of phaeochromocytoma
surgery required,
until then:
- alpha adrenergic blockade (phenoxybenzamine)
- THEN beta adrenergic blockade (propranolol)
effects of digoxin
- increased inotrophic effect
- reduced heart rate (vagus parasymp stim)
takes ~7-10 days to reach steady state, important due to narrow therapeutic window (0.5-0.9ng/mL)
drug interactions with digoxin
- amiodarone, verapamil - both increase arrhythmia risk
- PPIs - increase digoxin effect
- antacids - decrease digoxin effect
electrolyte changes in refeeding syndrome
- hypophosphataemia
- hypokalaemia
- hypomagnesaemia: may predispose to torsades de pointes
- abnormal fluid balance
causes of hypomagnesaemia
- drugs: diuretics, proton pump inhibitors
- total parenteral nutrition
- diarrhoea
- alcohol
- hypokalaemia, hypocalcaemia
pathophysiology of diabetes insipidus
Diabetes insipidus is due to either:
- deficiency of ADH (cranial DI)
- insensitivity to ADH (nephrogenic DI)
causes of nephrogenic diabetes insipidus
- lithium/tetracycline
- genetic
- CKD
- hypokalaemia/hypercalcaemia
features of diabetes insipidus
- polyuria
- polydipsia
- hypernatraemia
- dehydration
management of diabetes insipidus
cranial = desmopressin nephrogenic = find cause, thiazides, low salt/protein diet
features of prolactinoma
men - impotence - loss of libido - galactorrhoea women - amenorrhoea - infertility - galactorrhoea - osteoporosis
drugs that can cause increased prolactin
- metoclopramide, domperidone, prochlorperazine
- haloperidol
management of prolactinoma
- medical = dopamine agonists (e.g. cabergoline, bromocriptine)
- surgical removal
causes of hirsutism
Ovarian - PCOS - androgen secreting ovarian tumour Adrenal - Cushing's syndrome - congenital adrenal hyperplasia - androgen therapy - adrenal tumour Other - obesity: thought to be due to insulin resistance - drugs: phenytoin, corticosteroids
investigation for acromegaly
Serum IGF-1 level
investigations for hypocalcaemia
- magnesium (if low can cause reduced PTH)
- vitamin D (deficiency will usually only cause mild hypocal)
- PTH
management of hypocalcaemia
- ECG (long QTc)
- IV calcium gluconate (10ml 10% 10 mins, then infusion)
Complications of hypothyroidism:
- high cholesterol/dyslipidaemia
- metabolic syndrome
- coronary heart disease and stroke, heart failure
- neurological and cognitive impairments
- adverse maternal and fetal outcomes in pregnancy
target rate of Na+ rise when treating hyponatraemia
- no more than 4 to 6 mmol/l increase in a 24-hour period due to risk of central pontine myelinolysis
estimation of serum osmolarity
osmolarity can be estimated with 2Na + glucose + urea
autoantibodies in Addison’s disease
anti-21-hydroxylase
features of Addisonian crisis
Follows a stressor that should increase cortisol eg. infection, illness, stress, etc
- hypotension
- hypoglycaemia
- hyperkalaemia
management of hypernatraemia
treat underlying cause eg. dehydration/diarrhoea/HHS
- acute = dextrose 5%
- chronic = half-normal saline (0.45%)
antibodies present in thyroid disease
Graves:
- TSH receptor stimulating antibodies (90%)
- anti-thyroid peroxidase (TPO) (75%)
Hashimoto’s:
- anti-thyroid peroxidase (TPO)
- anti-thyroglobulin (Tg) antibodies
