Endocrinology Flashcards
What is Cushing’s syndrome?
- refers to signs and symptoms
- after prolonged abnormal elevation of cortisol
What is Cushing’s disease?
- refers to specific condition
- where pituitary adenoma
- secretes excessive ACTH
5 things that high levels of stress hormone can cause?
- hypertension
- cardiac hypertrophy
- hyperglycaemia (t2dm)
- depression
- Insomnia
5 key characteristics of a patient with Cushing’s disease?
- round moon face
- central obesity
- abdominal striae
- buffalo hump
- proximal limb muscle wasting
state 4 causes of Cushing’s syndrome?
- patients on long term high dose steroids
- Pituitary adenoma releasing excessive ACTH (Cushing’s disease)
- Adrenal adenoma (hormone secreting adrenal tumour)
- paraneoplastic Cushing’s
What is paraneoplastic Cushing’s?
- excess ACTH
- released from a cancer (not of the pituitary)
- stimulates excessive cortisol release
What is the most common cause of paraneoplastic Cushing’s?
Small cell lung cancer
What tests might you do to test for Cushing’s?
Dexamethasone suppression test
What is a normal response for a low dose dexamethasone suppression test?
1mg
- dexamethasone to suppress
- release of cortisol
- through negative feedback on hypothalamus and pituitary
- hypothalamus responds by reducing CRH
- pituitary responds by reducing ACTH
When the cortisol level is not suppressed, this is the abnormal result seen in Cushing’s Syndrome.
When is the high dose dexamethasone suppression test performed?
8mg
after abnormal result on the low dose test
Describe high dose dexamethasone suppression test in Cushing’s disease?
In Cushing’s disease
- pituitary still shows some response to negative feedback
- 8mg d.methasone enough to suppress cortisol
Describe high dose dexamethasone test in presence of adrenal adenoma?
In Adrenal adenoma
- cortisol production independent from pituitary
- cortisol not suppressed
- ACTH suppressed due to negative feedback
- on hypothalamus and pituitary gland
Where there is ectopic ACTH, describe result of high dose dexamethasone test?
In Ectopic ACTH (e.g. from small cell lung cancer)
- neither cortisol nor ACTH suppressed
- ACTH production independent of hypothalamus of pituitary
Describe 6 other investigations for Cushing’s?
Give an example of what might be found in these 6 investigations
- 24 hr urinary free cortisol
- FBC (raised white cells)
- U&Es (K+ low if aldosterone also secreted by adrenal adenoma)
- MRI (pituitary adenoma)
- Chest CT (small cell lung cancer)
- Abdominal CT (adrenal tumours)
3 main treatment options for Cushings?
Surgically remove tumour
- Tran sphenoidal (removal of pituitary adenoma)
- surgical removal of adrenal tumour
- surgical removal of tumour producing ectopic ACTH
If surgical removal of the underlying cause of Cushing’s is not possible, what else might be done?
- remove adrenals
- give patient steroid hormone replacement for life
What is Adrenal Insufficiency?
- where adrenal glands don’t produce enough steroid hormones
- mainly cortisol and aldosterone
What is Addison’s disease?
- adrenals damaged
- reduction in secretion of cortisol and aldosterone
- aka primary adrenal insufficiency
- autoimmune
Addisons disease is also called…
primary adrenal insufficiency
Secondary adrenal insufficiency results from:
- inadequate ACTH stimulating adrenals
- results in low cortisol release
- aar of loss of damage to pituitary
Sheehan’s syndrome
- massive blood loss during child birth
- leads to pituitary gland necrosis
What is tertiary adrenal insufficiency?
- result of inadequate CRH by hypothalamus
- aar of patients being on long term oral steroids
- causing suppression of hypothalamus
5 main symptoms of adrenal insufficiency
- fatigue
- nausea
- cramps
- abdominal pain
- reduced libido
2 main signs of adrenal insufficiency
- bronze hyperpigmentation
2. hypotension (particularly postural hypotension)
Why does bronze hyperpigmentation occur in adrenal insufficiency?
ACTH stimulates melanocytes
to produce melanin
hyperpigmentation found particularly in skin creases
Describe ACTH levels in primary adrenal failure?
- primary adrenal failure
- ACTH level is high
- pituitary trying to stimulate adrenals without any negative feedback
Describe ACTH levels in secondary adrenal failure?
- ACTH low
- adrenal glands not stimulated by ACTH
- thus not producing cortisol
Test of choice for adrenal insufficiency?
- short synacthen test
- synthetic acth
- blood cortisol measured at baseline, 30 min then 60 mins post administration
- failure of cortisol to rise, less than double, indicates primary adrenal insufficiency
Treatment of adrenal insufficiency?
- steroid replacement
- hydrocortisone (glucocorticoid, used to replace cortisol)
- fludrocortisone (mineralocorticoid, used to replace aldosterone(
During acute illness in a patient with adrenal insufficiency what happens to steroid dose?
- steroid dose doubled
- until patient has recovered
- to match normal steroid response to illness
4 main presentations of patient in an Addisonian Crisis?
- reduced consciousness
- hypotension
- hypoglycaemia, hyponatraemia, hyperkalaemia
- VERY UNWELL
management of Addisonian Crisis
- Parenteral steroids (IV hydrocortisone 100mg stat, then 100mg every 6hrs)
- IV fluid resus
- correct hypoglycaemia
- monitor electrolytes and fluid balance
Low TSH
High T3 & T4
Hyperthyroidism
High TSH
Low T3 & T4
Primary hypothyroidism
Low TSH
Low T3 and T4
Secondary hypothyroidism
In which two conditions are antithyroid peroxidase antibodies found?
anti-TPO
- usually present in Grave’s disease
- and Hashimoto’s thyroiditis
In which three conditions are anti-thyroglobulin antibodies present?
- graves disease
- hashimoto’s thyroiditis
- thyroid cancer
in which condition are TSH receptor antibodies found?
- autoantibodies
- mimic TSH
- bind to TSH receptor
- stimulate thyroid hormone release
Diffuse high uptake in radioisotope scan is found in which condition?
Grave’s disease
Focal, high uptake in radioisotope scans are found in which two conditions?
- toxic multinodular goitre
2. adenomas
cold areas on radioisotope scan may indicate
- low uptake
- thyroid cancer
Describe primary hyperthyroidism
- due to thyroid pathology
- thyroid itself is misbehaving
- and producing excess thyroid hormone
What is secondary hyperthyroidism
- thyroid produces excess thyroid hormone
- as a result of overstimulation by thyroid stimulating hormone
- pathology either hypothalamus or pituitary
Condition where nodules develop on thyroid gland that act independently of the normal feedback system
and continuously produce excessive thyroid hormone
toxic multinodular goitre
What is key features are caused by Grave’s disease?
Exophthalmos
Pretibial myxoedema
What causes pretibial myoxoedema?
- deposits of mucin under skin
- of anterior leg
- gives discoloured, waxy, oedematous appearance to skin
- due to reaction to the TSH receptor antibodies
Summarise four main causes of hyperthyroidism?
- Grave’s disease
- Toxic multinodular goitre
- Solitary toxic thyroid nodule
- Thyroiditis
7 universal features of hyperthyroidism
- anxiety and irritability
- sweating and heat intolerance
- tachycardia
- weight loss
- fatigue
- frequent loose stools
- sexual dysfunction
what is De Quervain’s thyroiditis?
- presentation of a viral infection
- fever, neck pain, tenderness, dysphagia
- and features f hyperthyroidism
Treatment for De Quervain’s thyroiditis
supportive
NSAIDS for pain and inflammation
beta blockers for symptomatic relief of hyperthyroidism
Describe presentation of patient with a thyrotoxic crisis
- pyrexia
- tachycardia
- delerium
Management of a thyrotoxic crisis?
- admission for monitoring
- fluid resus
- anti-arrhytmic medicatication
- beta blockers
first line treatment for hyperthyroidism management
- carbimazole
second line treatment for hyperthyroidism
propylthiouracil
summarise 5 management options for hyperthyroidism
- caribimazole
- propylthiouracil
- radioactive iodine
- beta blockers to block adrenalin symptoms
- thyroid surgery
Four main causes of Hypothyroidism?
- Hashimoto’s thyroiditis
- iodine deficiency
- secondary to treatment of hyperthyroidism
- medications: lithium, amiodarone
Two medications with may cause hypothyroidism?
- lithium
- inhibits thyroid hormone production - amiodarone
- interferes with thyroid hormone production
Describe secondary hypothyroidism?
- where pituitary gland failing to produce enough TSH
What four things may cause secondary hypothyroidism?
- tumours
- infection
- vascular (Sheehan syndrome)
- radiation
Presentation and features of hypothyroidism
7
- weight gain
- fatigue
- dry skin
- coarse hair and hair loss
- fluid retention
- heavy or irregular periods
- constipation
management of hypothyroidism
- levothyroxine
- dose titrated until TSH levels become normal
what may trigger T1DM
- certain viruses such as Coxsackie B virus and enterovirus
describe why potassium imbalance occurs in DKA
- insulin normally drives potassium into cells
- serum potassium can be high or normal as kidneys continue to balance K+ through urinary excretion
- total body potassium will be low
- as no potassium is stored incells
5 main presentations of patient with DKA
- hyperglycaemia
- dehydration
- ketosis
- metabolic acidosis with low bicarb
- potassium imbalance
Treating DKA
FIG PICK
- IV fluid
- Insulin
- glucose
- potassium
- infection (treat)
- check fluid balance
- monitor ketones
Injecting into the same spot can cause a condition where the subcutaneous fat hardens and patients do not absorb insulin properly from further injections into this spot.
this is known as
lipodystrophy
long term macrovascular complications of type 1 diabetes
- coronary artery disease
- peripheral ischaemic causes poor healing, ulcers and diabetic foot
- stroke
- hypertension
microvascular complications of type 1 diabetes include
- peripheral neuropathy
- retinopathy
- kidney disease: glomerulosclerosis
infection related complications of T1DM
- UTI
- pneumonia
- skin and soft tissue infections
- fungal infections, particularly oral and vaginal candidiasis
Dietary management for T2DM
- vegetables and oily fish
- low carb diet
- low glycaemic, high fibre diet
HbA1c targets for
- new type 2 diabetics
- patients on metformin alone
48 mmol/mol for new type 2 diabetics
53 mmol/mol for diabetics that have moved beyond metformin alone
Summarise medical management of T2DM
1st line : metformin
2nd line: add, sulfonylurea, pioglitazone, DPP-4 inhibitor, SGLT-2 inhibitor
3rd line: triple therapy, metformin + two second line drugs; or metformin and insulin
Describe action of metformin
- increases insulin sensitivity
- decreases liver production of glucose
- weight neural
notable side effects of metformin
- diarrhoea
- abdominal pain
- lactic acidosis
action of pioglitazone
- increases insulin sensitivity
- decreases liver production of glucose
action of sulfonylureas
- stimulate insulin release from pancreas
notable side effects of sulfonylurea’s
- weight gain
- hypoglycaemia
- increased CVD and MI risk
what are incretins?
- hormones produced by GI tract
- secreted in response to large meals
- reduce blood sugar
how to incretins reduce blood sugar?
- increase insulin secretions
- inhibit glucagon production
- slow absorption by GI tract
main incretin is
glucagon-like-peptide-1
incretins are inhibited by what enzyme
dipeptidylpeptidase-4
DPP4
action of DPP-4 inhibitors
- inhibits DPP-4 enzyme
- thus increases GLP-1 activity
notable side effects of DPP-4 inhibitors
GI tract upset
symptoms of upper respiratory tract infection
pancreatitis
SGLT-2 inhibitors end with the suffix
-glifoxin
describe action of sglt-2 inhibitors?
sglt-2 protein responsible for reabsorbing glucose from urine into the blood in PCT
SGLT-2 blocks this
causes glucose excretion
acromegaly caused by:
excessive growth hormone
what may cause bitemporal hemianopia?
- optic chiasm lies above pituitary gland
- pressure on optic chiasm
- will lead to stereotypical ‘bitemporal hemianopia’
Investigations for Acromegaly
- insulin-like-growth-factor-1
- oral glucose tolerance test
- MRI brain for pituitary tumour
- ophthalmology for visual field testing
three types of medications to block growth hormone in management of acromegaly
- GH antagonist: pegvisomant, subcut daily
- block GH release, somatostatin analogue, ocreotide
- dopamine agonist to block GH release
four ways parathyroid hormone acts to raise blood calcium
- increase osteoclastic activity in bones
- increase calcium absorption from gut
- increasing calcium absorption from kidneys
- increasing vitamin D activity
symptoms of hypercalcaemia
renal stones, painful bones, abdominal groans and pyschic moans
abdominal groans: constipation, nausea, vomiting
psychiatric moans: fatigue, depression and psychosis
primary hyperparathyroidism
- uncontrolled pth release
- aar of tumour of pt glands
- hypercalcaemia!
secondary hyperparathyroidism
- insufficient vitamin D or chronic renal failure
- leads to low absorption of calcium
- from intestines, idneys and bones
- hypocalcaemia
tertiary hyperparathyroidism
- aar of longterm secondary hyperparathyroidism
- leads to hyperplasia of glands
- high levels of pth
- high absorption of calcium in intestines, kidneys and bones
- causes hypercalcaemia
which cells in the afferent arteriole of the kidney sense blood pressure?
juxtaglomerular cells
aldosterone acts of kidney to
- increase sodium reabsorption from distal tubule
- increase potassium secretion from distal tubule
- increase hydrogen secretion from collecting ducts
primary hyperaldosteronism
- adrenal glands
- producing too much aldosterone
secondary hyperaldosteronism
- excessive renin
- stimulating adrenal glands
- to produce more aldosterone
investigation for hyperaldosteronism
- renin/ aldosterone ratio
High aldosterone and low renin indicates primary hyperaldosteronism
High aldosterone and high renin indicates secondary hyperaldosteronism
management of hyperaldosteronism
Aldosterone antagonists
- eplerenone
- spironolactone
management of SIADH
- fluid restriction
- ADH receptor blockers
What is central pontine myelinolysis?
- osmotic demyelination syndrome
- complication of long term severe hyponatraemia
What occurs in central pontine myelinolysis?
- blood sodium levels fall
- water will move via osmosis across BBB
- brain swell
- brain reduces solutes to brain to prevent it becoming oedematous
- when blood sodium levels begin to rise, water rapidly shifts out of brain cells into blood
describe the two phases of symptoms in central pontine myelinolysis?
1st phase
- aar electrolyte imbalance
- patient presents as encephalopathic and confused
2nd phase
- due to demyelination of neurones
- occurs few days after rapid correction of sodium
Diabetes insipidus is a …
- lack of or response to ADH
- prevents kidneys from being able to concentrate urine
- leading to polyuria and polydipsia
two classifications of diabetes mellitus
nephrogenic
cranial
what is nephrogenic diabetes insipidus?
- collecting ducts of kidney
- don’t respond to ADH
- can be caused by, lithium, intrinsic kidney disease, electrolyte disturbance
cranial diabetes insipidus?
- when hypothalamus does not produce ADH
- for pituitary to secrete
- can be caused by brain tumours, head injury. brain malformations, brain infections
investigations for diabetes insipidus?
- low urine osmolality
- high serum osmolality
- water deprivation test
method of water deprivation test?
Initially the patient should avoid taking in any fluids for 8 hours.
This is referred to as fluid deprivation.
Then, urine osmolality is measured and synthetic ADH (desmopressin) is administered. 8 hours later urine osmolality is measured again.
management of diabetes insipidus
- desmopression (synthetic ADH)
Cranial DI to replace ADH
Nephrogenic DI higher doses under close monitoring
adrenaline is produced where
- adrenal medulla
- by chromaffin cells
pheochromocytoma
- tumour of chromaffin cells
- secretes unregulated and excessive amounts of adrenaline
diagnosis of pheochromocytoma made with
- 24 hr urine catecholamines
2. plasma free metanephrines
what are metanephrines ??
breakdown product of catecholamines
five typical signs and symptoms of a patient presenting with pheochromocytoma?
- anxiety
- sweating
- headache
- hypertension
- palpitations, tachycardia and paroxysmal atrial fibrillation
management of pheochromocytomas?
- alpha blockers (i.e. phenoxybenzamine)
- beta blockers once established on alpha blockers
- adrenalectomy to remove tumour = definitive management
