Endocrine Flashcards
What is T1 diabetes
A progressive destruction of islet B cells
Onset usually <40 years
Autoantibodies may be detected
Tendency to ketosis
Treated with exogenous insulin combined with a healthy diet and exercise
What are the different types of insulin preparations
Short acting:
- soluble
- analogues (rapid-acting: lispro, aspart)
Intermediate acting:
- isophane (complexed with protamine)
Long acting:
- insulin zinc suspension
- analogues (glargine, detemir)
Biphasic:
- mix of short and intermediate acting insulins
What is DAFNE
Dose adjustment for normal eating
- adjusting insulin regimens to suit the individual lifestyle
What can increase insulin requirements
Stress
Infection
Puberty (GH)
Accidental or surgical trauma
Pregnancy post 1st trimester
Why does insulin injection site need to be rotated
To limit Lipodystrophy
What is T2 diabetes
Relative insulin deficiency (impaired B cell function) and / or insulin resistance
- impaired insulin signalling pathways
- nutrient oversupply, cellular stress and inflammation
How is T2DM managed
Diet and lifestyle changes
Agree on a glycaemic target (HbA1c)
Cardiovascular risk management
Management of CKD
Pharmacotherapy
How should people with T2DM adjust their lifestyle
Exercise
Smoking cessation
When should metformin be cautioned
Patients with renal impairment
What should be given first line if metformin is inappropriate in T2DM
DPP-4 inhibitor
Pioglitazone
Sylphonlyurea
SGLT2 inhibitor
When is an SGLT2 inhibitor given with metformin
If the CVD/ CHF/ QRISK2 is >10%
When is insulin given in T2DM
After triple therapy has not been effective
What is metformin
MoA not clear, described as an insulin sensitiser
May activate AMP kinase
- reduces hepatic glucose production, reduces lipid stores, increases liver sensitivity to insulin
- increases peripheral glucose uptake and utilisation
What are sulphonylureas
Inhibit islet B cell ATP sensitive potassium channels - increase insulin secretion
Cause weight gain as a side effect, hypoglycaemia especially with long acting
What is pioglitazone
Activates nuclear peroxisome proliferator activated receptors
An insulin sensitiser - enhances glucose utilisation in tissues and reduces insulin resistance
Reduces hepatic glucose output
Increases glucose uptake and utilisation in skeletal muscle
Increases fatty acid uptake into adipose cells
Adverse effects of pioglitazone
Liver toxicity (monitor)
Avoid in heart failure
Increased risk of bladder cancer and bone fractures
What do incretins (GLP-1) do
Stimulate glucose induced insulin release
And inhibit glucagon release
What are some benefits of incretin based therapies
Reduce gastric emptying
Promote satiety
Reduce hepatic glucose production
What do SGLT2 inhibitors do
Inhibit renal glucose reabsorption and increase urinary glucose excretion which reduces blood glucose
Cardiovascular and renal benefits
Side effects of SGLT2 inhibitors (flozins)
Genitourinary infections
Increased urination, thirst
Hypovolaemia, hypotension
DKA
What are complications of diabetes treatment
Hypoglycaemia (insulin SUs)
Diabetic ketoacidosis: lack of insulin; SGLT2 inhibitors
Hyperosmolar hyperglycaemic state (HHS, T2DM)
What are Microvascular complications
Damage of the small vessels
1. Retinopathy (eye)
2. Nephropathy (kidney disease)
3. Neuropathy (nerve damage)
What are Macrovascular complications
- CVD
- Stroke
- Peripheral vascular disease
What are the individual HbA1c targets
T1DM: 40mmol/mol (adults)
T2DM: 40mmol/mol when using diet/lifestyle and 1 drug and not hypoglycaemic
T2DM: 53mmol/mol when using drugs that can cause hypoglycaemia
Ways of reducing CV risk in T2DM
Glycaemic control (HbA1c)
Lifestyle: diet, exercise, weight management, alcohol, smoking cessation
BP control
Use of statins for primary prevention (atorvastatin 20mg with QRISK>10%)
What are the target BP for T1DM
135/85
But 130/80 is presenting with albuminuria or 2 more more features of metabolic syndrome
Use a first line ACEi or an angiotensin receptor blocker
What is the target BP for T2DM
140/90
130/80 if CKD is present
Use a first line ACEi or angiotensin receptor blocker
How to prevent Microvascular complications
Good glycaemic control
Control of hypertension (ACEi, ARB, CCB)
How to manage macrovascular risk factors
Good glycaemic control
Control hypertension
Control dyslipidaemia
Use of anti platelet drugs in CVD
Metabolic Signs and symptoms of hypothyroidism
Cold intolerance
Weight gain
Constipation
Reduced appetite
Reduced BMR
Reduced sweating
Reduced body core temp
CNS signs and symptoms of hypothyroidism
Depression
Confusion
Poor memory
Difficulty concentrating
Cretinism (perinatal) - mental retardation and dwarfism
Resting CVS signs and symptoms of hypothyroidism
Decreased heart rate
Decreased arterial BP
Why are newborns tested for TSH and T4
To test for congenital hypothyroidism as can cause dwarfism and mental retardation
How is hypothyroidism diagnosed
Thyroid function test
Primary: reduced T3 and T4; increased TSH
Secondary: reduced T3, T4 and TSH
Management of hypothyroidism
Synthetic thyroid hormones
Levothyroxine - first line
Liothyronine
What is Graves’ disease
Most common cause of hyperthyroidism
90% of cases
Autoimmune condition in which body makes thyroid stimulating immunoglobulins which activate the thyroid gland to produce and release thyroid hormones
Symptoms of Graves’ disease
Nervousness
Palpitations
Weight loss
Tremor
Sweating
Heat intolerance
Goitre
Diagnosis of hyperthyroidism with thyroid function test
Elevated T3 and T4 and decreased TSH (tumour / Graves’ disease)
Radioactive isotope scan - increased uptake in Graves’ disease
Presence of thyroid autoantibodies
Management of hyperthyroidism
Anti thyroid drugs
Radioiodine
Surgery (thyroidectomy)
What are anti thyroid drugs
Carbimazole and propylthiouracil
- decrease production of thyroid hormones by inhibiting iodination and coupling processes
Takes several weeks for a clinical response
How is levothyroxine prescribed (replacement for T4)
Adults aged 18-49 are given a loading dose of 50-100ug/d
Increased by 25-50 ug every 4 weeks until plasma TSH has normalised
Maintenance dose is 100-200ug/d
Adults 50+ or with cardiac disease are given a loading dose of 25ug/d
This is increased by 25ug every 4 weeks until plasma TSH has normalised.
Maintenance dose is 50-200ug/d
What are the cautions with levothyroxine
May worsen or uncover angina.
If angina, a B blocker may be prescribed
How is liothyronine prescribed (replacement for T3)
Maximum effect is 24h, disappears at 24-48h
Not used routinely, rapid onset can induce heart failure
Used in severe hypothyroid states when rapid response is desired
What are some counselling points for levothyroxine
Life long condition therefore life long treatment
Take daily dose at least 30min before breakfast, caffeine containing drinks or other medications
Consult GP if experiencing angina or pre existing angina gets worse
Report symptoms such as diarrhoea, nervousness, tremors or insomnia as can indicate overdose
Requirements may change during pregnancy
TSH levels need measuring every 3 months until stabilised, then yearly thereafter
Why are non selective B blockers given alongside anti thyroid drugs
Propranolol, nadolol, metoprolol
These reduce the actions of catecholamines and provide rapid symptomatic relief of tremor, palpitations and anxiety and have no effect on thyroid hormone release
CCI can be used is B blockers are contraindicated
Explain the dose titration approach that is used with anti thyroid drugs
- only anti thyroid drugs are used
- doses are adjusted to achieve normalisation of thyroid hormone production
Explain the block and replace approach used with anti thyroid drugs
Where anti thyroid drugs are given with thyroxine replacement
How is carbimazole prescribed in a dose titration approach
Initial dose - 15-40mg daily until euthyroid - 4-8 weeks
Gradually reduce to maintenance dose 5-15mg daily
How is carbimazole prescribed in a block and replace approach
40-60mg daily
Plus levothyroxine 50-150ug daily
Side effects of carbimazole
Rashes and pruritus are common
Rare complication - neutropenia and agranulocytosis (bone marrow suppression)
Patients are counselled to report signs and symptoms suggestive of infections eg sore throat
WBC count performed if clinical evidence of infection
Increased risk of congenital malformations - effective contraception
Risk of acute pancreatitis
Who should not be prescribed carbimazole
Patients with a history of acute pancreatitis
What is the second line choice if carbimazole is inappropriate
Propylthiouracil
- initial dose 200-400mg daily until euthyroid roughly 4-8 weeks
- gradually reduce to maintenance dose 50-150mg daily
When switching from carbimazole to propylthiouracil what is the equivalent dose
Carbimazole 1mg is considered equivalent to propylthiouracil 10mg but the dose may need adjusting according to the response
What is the recommendation for use of anti thyroid drugs in pregnancy
Can be used but at lowest dose to control hyperthyroid state
High doses can cause foetal goitre and hypothyroidism
Pros and cons of radioactive iodine as a treatment
Pros:
- Safe, effective and cost effective treatment for Graves’ disease
Reduced rate of recurrence of hyperthyroidism
Cons:
- not for use in a patient trying for a family in the next 4-6 months
- not for use in patients with a suspected malignancy
When is surgery used to treat hyperthyroidism
If radioactive iodine and anti thyroid drugs are unsuitable
Indicated if malignancy is suspected or there are obstructive symptoms
