Endocrinology Flashcards
what does the anterior pituitary gland release?
TSH
ACTH
LH
GH
prolactin
what does the posterior pituitary release?
oxytocin
ADH
how is T3 and T4 released?
hypothalamus releases TRH which stimulates ant pit to release TSH which stimulates the thyroid glands to release T3 and T4, neg feedback of TRH and TSH
when is cortisol highest and how is it released?
peaks in the morning
hypothalamus ->CRH-> ant pit-> ACTH->adrenal gland->cortisol
cortisol suppresses CRH and ACTH
what are the actions of cortisol?
Inhibits the immune system
Inhibits bone formation
Raises blood glucose
Increases metabolism
Increases alertness
how is IGF-1 released?
GnRH from hypothalamus -> ant pit-> GH ->liver -> IGF-1
what are the actions of IGF 1?
Stimulates muscle growth
Increases bone density and strength
Stimulates cell regeneration and reproduction
Stimulates growth of internal organs
what are the actions of PTH?
increases no and activity of osteoclasts-> serum calcium increases
increase in calcium reabsoprtion in kidneys -> serum calcium increases
stimulates kidneys to convert vit D3-> calitriol -> calcium reabsorption from food in small intestines
define RAAS system
Renin is a hormone secreted by the juxtaglomerular cells that sit in the afferent (and some in the efferent) arterioles in the kidney. They sense the blood pressure in these vessels. They secrete more renin in response to low blood pressure and secrete less renin in response to high blood pressure. Renin is an enzyme that acts to convert angiotensinogen (released by the liver) into angiotensin I. Angiotensin I converts to angiotensin II in the lungs with the help of an enzyme called angiotensin-converting enzyme (ACE).
Angiotensin II acts on blood vessels to cause vasoconstriction. This results in an increase in blood pressure. Angiotensin II also stimulates the release of aldosterone from the adrenal glands.
Aldosterone is a mineralocorticoid steroid hormone. It acts on the nephrons in the kidneys to:
Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts
When sodium is reabsorbed in the kidneys water follows it by osmosis. This leads to an increase in intravascular volume and subsequently blood pressure.
define cushing’s syndrome and disease
syndrome - prolonged abnormal elevation of cortisol
disease - pituitary adenoma secretes ACTH
what are the features of cushing’s syndrome?
Round “moon” face
Central Obesity
Abdominal striae
Buffalo Hump (fat pad on upper back)
Proximal limb muscle wasting
Hypertension
Cardiac hypertrophy
Hyperglycaemia (Type 2 Diabetes)
Depression
Insomnia
osteoporosis
easy bruising and poor skin healing
what are the causes of cushing’s syndrome?
Exogenous steroids (in patients on long term high dose steroid medications)
Cushing’s Disease (a pituitary adenoma releasing excessive ACTH)
Adrenal Adenoma (a hormone secreting adrenal tumour)
Paraneoplastic Cushing’s - excess ACTH is released from a cancer (not of the pituitary) and stimulates excessive cortisol release, usually small cell lung cancer
what is the first line investigation for cushing’s?
dexamethasone suppression test - If the low dose test is normal, Cushing’s can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes…see if dexamethasone suppresses normal morning spike of cortisol..if doesnt ->high dose, in cushing’s disease this suppresses cortisol,if adrenal adenoma - cortisol is produced independent of the pituitary so does not suppress it, however ACTH will be supressed as neg feedback on hypothalamus, if ectopic ACTH - neither cortisol or ACTH will be suppressed as independent of hypothalamus AND pituitary
what other investigations are used for cushing’s?
24 hour urinary free cortisol
FBC - raised white cell, potassium low, MRI brain for pituiary adenoma, chest CT for small cell lung cancer, abdo CT for adrenal tumours
how is cushing’s treated?
Trans-sphenoidal (through the nose) removal of pituitary adenoma
Surgical removal of adrenal tumour
Surgical removal of tumour producing ectopic ACTH
define addison’s disease
primary adrenal insuffiency - reduces cortisol and aldosterone
most common cause - autoimmune
secondary adrenal insufficiency - inadequate ACTH stimulates adrenal gland so less cortisol due to damage to pituitary gland - due to surgery to remove a tumour, infection, loss of blood flow or radiotherapy or sheehan’s syndrome
tertiary adrenal insufficiency - inadequate CRH, usually due to long term steroids causing suppression of hypothalamus, steroids should be tapered
what are the sx of addison’s?
Fatigue
Nausea
Cramps
Abdominal pain
Reduced libido
what are the signs of addisons?
Bronze hyperpigmentation to skin (ACTH stimulates melanocytes to produce melanin)
Hypotension (particularly postural hypotension)
which investigations are required for addisons?
electrolytes - hyponatraemia, hyperkalaemia
early morning cortisol levels - but sometimes falsely nromal
short synacthen test is test of choice
ACTH levels - high if primary, low if secondary,
adrenal autoantibodies - adrenal cortex antibdoies, 21-hydroxylase antibodies
CT/MRI adrenls
MRI pituitary
how does ACTH stimulation test work?
short test - giving synacthen - which is synthetic ACTH, measure cortisol at baseline, 30 and 60 mins after administered, should have at least doubled…failure to do so = primary (addisons disease)
long test - primary = no cortisol response, in secondary = cortisol will rise
…nowadays simply measure ACTH
how is addison’s disease treated?
replacement steroids - hydrocortisone for cortisol and fludrocortisone to replace aldosterone
pts given steroids card and emergency ID tag to alert emergency services
doses of steroids are doubled in acute illness
define addisonian crisis
an acute presentation of severe Addisons, where the absence of steroid hormones leads to a life threatening presentation
what are the sx of addisonian crisis?
Reduced consciousness
Hypotension
Hypoglycaemia, hyponatraemia, hyperkaemia
Patients can be very unwell
what can trigger addisonian crisis?
sudden withdrawal of steroids
infection
trauma
illness
how is addisonian crisis managed?
Intensive monitoring if unwell
Parenteral steroids (i.e. IV hydrocortisone 100mg stat then 100mg every 6 hours)
IV fluid resuscitation
Correct hypoglycaemia
Careful monitoring of electrolytes and fluid balance
what are the biochemical results of hyperthyroidism?
TSH low, except if pituitary adenoma which TSH will be high,high T3 and T4
what are the biochemical results of primary hypothyroidism?
high TSH, low T3 and T4
what are the biochemical results of secondary hypothyroidism?
low TSH, low T3, T4 - pituitary or hypothalamic cause
what are the antibodies involved in thyroid diseases?
anti-TPO antibodies - grave’s and hashimoto thyroiditis
antithyroglobulin antibodies - grave’s, hashimotos thyroditis, and thyroid cancer
TSH receptor antibodies - autoantibodes that mimic TSH - grave’s disease
which imaging is used in thyroid disease?
thyroid USS - thyroid nodules - cystic and solid nodules
radioisotope scans - The more gamma rays that are emitted from an area the more radioactive iodine has been taken up. Diffuse high uptake is found in Grave’s Disease, Focal high uptake is found in toxic multinodular goitre and adenomas, “Cold” areas (i.e. abnormally low uptake) can indicate thyroid cancer-
define grave’s disease
autoimmune conditions …primary hyperthyroidism. TSH receptor antibodies are abnormal antibodies produced by the immune system that mimic TSH and stimulate the TSH receptors on the thyroid.
define plummer’s disease
toxic multinodular goitre…nodules develop on thyroid gland and continuously produce excessive thyroid hormones
what are the sx of grave’s disease and their cause?
exopthalmos - inflammation and hypertrophy of tissues behind eyeball
pretibial mxoedema - deposits of mucin under skin in pre tibial area
diffuse goitre
geave’s eye disease
what are the causes of hyperthyroidism?
Grave’s disease
Toxic multinodular goitre
Solitary toxic thyroid nodule
Thyroiditis (e.g. De Quervain’s, Hashimoto’s, postpartum and drug-induced thyroiditis)
what are the universal features of hyperthyroidism?
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue
Frequent loose stools
Sexual dysfunction
what are the unique features of plummer’s disease?
Goitre with firm nodules
Most patients are aged over 50
Second most common cause of thyrotoxicosis (after Grave’s)
define solitary toxic thyroid nodules and how it is treated?
single abnormal thyroid nodules relasing thyroid hormone
usually benign adenomas
surgical removal of nodule
define de quervain’t thyroiditis, how it presents and how it is treated?
viral infection with fever, neck pain and tenderness, dysphagia and fx of hyperthyroidism
There is a hyperthyroid phase followed by a hypothyroid phase as the TSH level falls due to negative feedback. It is a self-limiting condition and supportive treatment with NSAIDs for pain and inflammation and beta-blockers for symptomatic relief
define thyroid storm
rare presentation of hyperthyroidism - thyrotoxic crisis
severe - pyrexic, tachycardic, delirium
admission for monitor
fluid resus, anti arrhytmic meds, beta blockers
how is hyperthyroid managed?
carbimazole - first line
propylthiouracil - second line (hepatic reactions, death)
radiactive iodine destroys thyroid cells (must no be preg or be in contact with children or preg women)
beta blockers - block adrenaline related sx
surgery - remove whole thyroid or toxic nodules, require levothyroxine replacement for life
what are the causes of hypothyroidism?
hashmito’s thyroiditis = anti-TPO antibodies and antithyroglobulin antibodies…goitre then atrophy of thyroid gland
iodine deficiency
secondary to tx of hyperthyroidism - carbimazole etc
medications - lithium inhibits production of thyroid hormones as well as amiodarone
hypopituitarism - caused by tumours, infection, vascular causes or radiation
how does hypothyroisim present?
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (oedema, pleural effusions, ascites)
Heavy or irregular periods
Constipation
which investigations are required to diagnose hypothyroidism?
TSH, T3, T4 levels - see previous flashcard
how is hypothyroidism managed?
Replacement of thyroid hormone with oral levothyroxine - synthetic T4, and metabolises to T3 in the body. have to measure TSH leevls months until stable
if too high - dose is too low , if tsh low, dose is too high
define ketogenesis
insufficient glucose supply and glycogen - fatty acids are converted to ketones which can cross BBB
can be measured in urine dipstick and in blood using ketone meter
acetone breath
if diabetic - can not buffer the acidity…DKA which is lifethreatening
define the pathophysiology of type 1 DM
pancreas stops producing insulin
genetic or triggered by virus such as enterovirus
when does DKA occur/
not enough insulin to process glucose
what occurs as a result of DKA?
acidosis of blood due to ketogenesis
dehydration - due to osmotic diuresis caused by hyperglycaemia…polyuria and polydipsia
potassium imbalance - without insulin, potassium is not added to and stored in cells, so hypokalaemia…arrhythmias
how does DKA present?
life threatening!
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)
how is DKA diagnosed?
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
Ketosis (i.e. blood ketones > 3 mmol/l)
Acidosis (i.e. pH < 7.3)
how is DKA treated?
F – Fluids – IV fluid resuscitation with normal saline (e.g. 1 litre stat, then 4 litres with added potassium over the next 12 hours)
I – Insulin – Add an insulin infusion (e.g. Actrapid at 0.1 Unit/kg/hour)
G – Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level (e.g. 14 mmol/l)
P – Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required
I – Infection – Treat underlying triggers such as infection
C – Chart fluid balance
K – Ketones – Monitor blood ketones (or bicarbonate if ketone monitoring is unavailable)
how is type 1 DM managed long term?
education
monitor
subcut insulin regimes - background, long acting insulin given once a day and a short acting insulin injected 30 minutes before intake of carbohydrate
monitor carb intake
monitor blood sugar
monitor for and manage complications
cycle their injection sites - lipodystrophy stops absorption
what are the short term complications of incorrect insulin management?
hypoglycaemia - tremor, sweat, irritable, dizzy, pallor, reduced consciousness, coma and death
….treated with rapid acting glucose and slower acting carbs such as biscuits for when rapid acting glucose is used by, if severe - IV dextrose and IM glucagon
hyperglycaemia - insulin is required
what are the long term complications of chronic exposure to hyperglycaemia?
Macrovascular Complications-
Coronary artery disease
Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
Stroke
Hypertension
Microvascular Complications-
Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis
Infection Related Complications-
Urinary Tract Infections
Pneumonia
Skin and soft tissue infections, particularly in the feet
Fungal infections, particularly oral and vaginal candidiasis
how is DM monitored?
HbA1c - glycated Hb, measured every 3-6 months as red cells last 3-4 months
capillary blood glucose
flash glucose monitoring - sensor on skin that measures glucose level of interstitial fluid
what is the pathophysiology of type 2 DM?
Repeated exposure to glucose and insulin makes the cells in the body become resistant to the effects of insulin. It therefore requires more and more insulin to produce a response from the cells and get them to take up and use glucose. Over time, the pancreas (specifically the beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less
what are the risk factors for type DM?
Non-Modifiable-
Older age
Ethnicity (Black, Chinese, South Asian)
Family history
Modifiable-
Obesity
Sedentary lifestyles
High carbohydrate (particularly refined carbohydrate) diet
how does type 2 DM present?
Fatigue
Polydipsia and polyuria (thirsty and urinating a lot)
Unintentional weight loss
Opportunistic infections
Slow healing
Glucose in urine
how is type 2 DM diagnosed?
oral glucose tolerance test - baseline fasting plasma glucose then giving a glucose drink and measure 2 hours later
HbA1c
how is prediabetes diagnosed?
pre diabetes
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 is the criteria for diabetes to be diagnosed?
HbA1c > 48 mmol/mol
Random Glucose > 11 mmol/l
Fasting Glucose > 7 mmol/l
OGTT 2 hour result > 11 mmol/l
how is type 2 DM managed?
dietary = veg and oily fish, low glycaemic and high fibre diet, low carb diet
optimise risk fx = exercise and weight loss, stop smoking, tx for hypertension, hyperlipidaemia, CVD
monitor for complications = retinopathy, kidney disease, diabetic foot
what are the treatment targets for type 2 DM?
48 mmol/mol for new type 2 diabetics
53 mmol/mol for diabetics that have moved beyond metformin alone
