Endocrine Flashcards
Causes of hyponatraemia - give 3 per fluid status (hypo, eu and hypervolaemic)
hypovolaemic:
- fluid loss (especially diarrhoea and vomiting)
- diuretics
- Addison’s disease
euvolaemic:
- Sydrome of inappropriate anti-diuretic hormone (SIADH)
- psychogenic polydipsia
- hypothyroidism
hypervolaemic:
- heart failure
- renal failure
- liver failure (causing hypoalbuminaemia)
- nutritional failure (causing hypoalbuminaemia)
- thyroid failure (hypothyroidism; can be euvolaemic too)
Causes of hypernatraemia
Causes all start with ‘D’
- dehydration
- drips (i.e. too much IV saline)
- drugs (e.g. effervescent tablet preparations or intravenous preparations with a high sodium content)
- diabetes insipidus
Causes of Hypokalaemia
DIRE -
- drugs (loop and thiazide diuretics)
- Inadequate intake or intestinal loss (diarrhoea/vomiting)
- Renal tubular acidosis
- Endocrine (Cushing’s syndrome, Conn’s syndrome)
Causes of hyperkalaemia
DREAD -
- Drugs (potassium-sparing diuretics and ACE-inhibitors)
- Renal failure
- Endocrine (Addison’s disease)
- Artefact (very common, due to clotted sample)
- DKA (note that when insulin is given to treat DKA the potassium drops, requiring regular (hourly) monitoring +/− replacement)
typical presentation of Hyperglycaemic hyperosmolar state
seen in unwell pts with T2DM
history is longer (eg 1 week)
there is marked dehydration.
clinical features 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
diagnosis of HHS
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- Significantly raised serum osmolarity (> 320 mosmol/kg)
Note: A precise definition of HHS does not exist, however the above 3 criteria are helpful in distinguishing between HHS and DKA. It is also important to remember that a mixed HHS / DKA picture can occur.
management of HHS
The first 24 hours of treatment is very labour intensive so these patients are best managed in either a medical high dependency unit.
- Occlusive events are a danger to life - give LMWH prophylaxis unless CI
- rehydrate slowly with 0.9% NaCl IVI over 48hrs. typical deficits are 110-220 mL/Kg.
- monitor serum osmolarity, sodium and glucose levels closely
(If not available then a calculated osmolarity can be estimated with 2Na + glucose + urea). The rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours. A safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. also measure ketones to check for development of ketonaemia/ketosis. - insulin should NOT be used in the first instance unless there is significant ketonaemia or blood glucose not falling sufficiently with rehydration as use of insulin before adequate fluid replacement may result in cardiovascular collapse. If using insulin start slowly 0.05u/kg/hr. Keep blood glucose atleast 10-15 mmol/L for 1st 24 hrs to avoid cerebral oedema.
- Potassium should be replaced or omitted as required. Only replace K+ if urine is flowing.
- search for and treat cause eg MI, drugs, sepsis, bowel infarction, etc.
risk factors for T2DM
increased age
black/south asian/chinese ethnicity
obesity
high (particularly refined) carbohydrate diet
family history
sedentary lifestyle
presentation of t2dm
asymptomatic with RFs
Fatigue
Polydipsia and polyuria (thirsty and urinating a lot)
Unintentional weight loss
Opportunistic infections
Slow healing
Glucose in urine (on dipstick)
prediabetes diagnosis
Pre-diabetes can be diagnosed with a HbA1c or by “impaired fasting glucose” or “impaired glucose tolerance”. Impaired fasting glucose means that their body struggles to get their blood glucose levels in to normal range, even after a prolonged period without eating carbohydrates. Impaired glucose tolerance means their body struggles to cope with processing a carbohydrate meal.
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
diagnosis of diabetes
HbA1c > 48 mmol/mol
Random Glucose > 11 mmol/l
Fasting Glucose > 7 mmol/l
OGTT 2 hour result > 11 mmol/l
either on 2 occassions or on 1 occasion with symptoms
management of t2dm
- Patient education about their condition and the lifestyle changes they need to make is essential. It is important to advise the patient that it is possible to cure type 2 diabetes
- Dietary Modification
Vegetables and oily fish
Typical advice is low glycaemic, high fibre diet
A low carbohydrate may in fact be more effective in treating and preventing diabetes but is not yet mainstream advice - Optimise Other Risk Factors
Exercise and weight loss
Stop smoking
Optimise treatment for other illnesses, for example hypertension, hyperlipidaemia and cardiovascular disease - Monitoring for Complications
Diabetic retinopathy
Kidney disease
Diabetic foot - medical management - if lifestyle changes alone are insufficient
treatment targets for t2dm
SIGN Guidelines 2017 and NICE Guideline 2015 recommend the following HbA1c treatment targets:
48 mmol/mol for new type 2 diabetics
For adults on a drug associated with hypoglycaemia, support the person to aim for an HbA1c level of 53 mmol/mol (7.0%)
medical management of t2dm
2 pathways -
1.IF metformin tolerated or not CI -
First line: standard release metformin titrated from initially 500mg once daily as tolerated. if standard release metformin not tolerated due to GI side effects, then trial modified release metformin.
second drug to be added only if the HbA1c rises to 58 mmol/mol (7.5%).
Second line add: sulfonylurea, pioglitazone or DPP-4 inhibitor or SGLT-2 inhibitor.
Third line: Triple therapy with metformin and two of the second line drugs combined, or;
starting insulin based treatment (metformin shd be continued, others - need to be reviewed). NICE recommend starting with human NPH insulin (isophane, intermediate-acting) once or twice daily according to need
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)
if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagon-like peptide1 (GLP1) mimetic if:
BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
- IF metformin not tolerated or CI and HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions, consider one of the following:
sulfonylurea
gliptin
pioglitazone
if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
gliptin + pioglitazone
gliptin + sulfonylurea
pioglitazone + sulfonylurea
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy.
SEs of metformin
Diarrhoea and abdominal pain(GI upset). This is dose dependent and reducing the dose often resolves the symptoms
Lactic acidosis
SEs of pioglitazone
Weight gain
Fluid retention
Anaemia
Heart failure
Extended use may increase the risk of bladder cancer
sulfonylurea SEs
eg of a SU - gliclazide
SEs-
Weight gain
Hypoglycaemia
Increased risk of cardiovascular disease and myocardial infarction when used as monotherapy
what are incretins and what is DPP4?
ncretins are hormones produced by the GI tract. They are secreted in response to large meals and act to reduce blood sugar. They:
Increase insulin secretions
Inhibit glucagon production
Slow absorption by the GI tract
The main incretin is “glucagon-like peptide-1” (GLP-1). Incretins are inhibited by an enzyme called “dipeptidyl peptidase-4” (DPP-4).
**A recent meta-analysis (JAMA 2018) showed that GLP-1 mimetics were associated with a reduction in all cause mortality whereas DPP-4 inhibitors were not.
eg of DPP4 inhibitor and SEs
The most common DPP-4 inhibitor is “sitagliptin”.
Notable Side Effects:
GI tract upset
Symptoms of upper respiratory tract infection
Pancreatitis
GLP-1 mimetics eg and SEs
A common GLP-1 mimetic is “exenatide”. Exenatide is given as a subcutaneous injection either twice daily by the patient or once weekly in a modifiable-release form. Another GLP-1 mimetic is liraglutide, which is given daily as a subcutaneous injection. They are sometimes used in combination with metformin and a sulfonylurea in overweight patients.
Notable Side Effects:
GI tract upset
Weight loss
Dizziness
SGLT-2 inhibitors eg and mechanism of action
SGLT-2 inhibitors end with the suffix “-gliflozin”, such as empagliflozin, canagliflozin and dapagliflozin. The SGLT-2 protein is responsible for reabsorbing glucose from the urine in to the blood in the proximal tubules of the kidneys. SGLT-2 inhibitors block the action of this protein and cause glucose to be excreted in the urine.
Empagliflozin has been shown to reduce the risk of cardiovascular disease, hospitalisation with heart failure and all cause mortality in type 2 diabetes (EMPA-REG study). Canagliflozin has been shown to reduce the risk of cardiovascular events such as MI, stroke and death and hospitalisation with heart failure in type 2 diabetes (CANVAS trial). These reduced risks are likely related to the class rather than the individual medications but have not been proven for all SGLT-2 inhibitors.
SEs of SGLT-2 inhibitors
increased rate of urinary tract infections
Weight loss
Diabetic ketoacidosis, notably with only moderately raised glucose or euglycaemia. This is a rare complication
Lower limb amputation appears to be more common in patients on canagliflozin. It is not clear if this applies to other SGLT-2 inhibitors
how often shd HbA1c be checked in pts with T2DM?
once every 3-6 months until it is stable and then every 6 monthly