Endocrine Flashcards
What is diabetes insipidus
excess dilute urine = extreme thirst due to too little ADH
hormones in the urine process in a normal person
- hypothalamus produces vasopressin (ADH) - stored in pituitary gland
- ADH released when water in body too low
- ADH retains water in body by reducing amount of water lost through kidneys
= more concentrated urine
hormones in the urine process in diabetes insipidus
- reduced vasopressin so reduced ADH
- kidneys don’t retain as much water
- too much water passed from body = extreme thirst/polyuria
= more dilute urine
Two types of diabetes insipidus
- pituitary (cranial)
- nephrogenic (partial)
What is pituitary (cranial) diabetes insipidus
- lack of vasopressin (ADH) production
- most common type
- Tx = vasopressin or desmopressin
What is nephrogenic (partial) diabetes insipidus
- you have ADH but kidneys don’t respond to it
- Tx = thiazide like diuretic (paradoxical effect)
Desmopressin information
- more potent and longer duration of action than vasopressin
- no vasoconstrictor effect
- side effects = hyponatraemia, nausea
What does too much ADH cause
- body stores too much water = dilutes the salt conc in blood = hyponatraemia
Too much ADH treatment
- fluid restriction
- demeclocycline (blocks renal tubular effect of ADH)
- tolvaptan (vasopressin antagonist)
- avoid rapid correction of hyponatraemia with tolvaptan as it causes osmotic demyelination = serious neurological events
What is diabetes mellitus
- persistent hyperglycaemia
- type 1 = deficient insulin secretion
- type 2 = resistance to action of insulin
- gestational = pregnant
- secondary to medications
Diabetes and fitness to drive
- treatment with insulin = notify DVLA
- assess on awareness of hypoglycaemia - capability of bringing vehicle to a safe stop
Diabetes and group 1 driver rules
- ‘normal’ drivers
-adequate awareness of hypoglycaemia - no more that 1 episode of severe hypo while awake in last 12 months
Diabetes and group 2 driver rules
- HGV/lorry/bus drivers
- report all episodes of severe hypo including in sleep
- full awareness of hypo
- no episodes of severe hypo in last 12 months
- must use glucose meter with sufficient memory to store 3 months of readings
- visual complications = notify DVLA and don’t drive
DVLA advice for diabetics
- tx with insulin = always carry glucose meter and strips
- check glucose 2 hours before and every 2 hours during driving
- glucose always > 5, if < 5 have a snack
- ensure supply of fast-acting carbohydrate in vehicle e.g. glucose tablets, glucose drinks, full sugar soft drinks, sweets, biscuits
Hypoglycaemia whilst driving rules
- considered as < 4mmol/L
1. stop vehicle
2. engine off, remove keys, move from drivers seat
3. eat/drink suitable source of sugar
4. wait 45 minutes after blood glucose back to normal - DONT drive if hypo awareness lost - notify DVLA
what is type 1 diabetes
- insulin deficiency - destroyed b-cells in islets of langerhans
- commonly before adulthood
Features of type 1 diabetes
- hyperglycaemia (>11mmol/L)
- ketosis
- rapid weight loss
- BMI<25
- age < 50
- family history of autoimmune disease
Type 1 diabetes blood glucose monitoring frequency and targets
- at least QDS including before meals and bed
- on waking = 5-7
- fasting before meals/other times of day = 4-7
- 90 mins after eating = 5-9
- when driving = > 5
Type 1 diabetes insulin regimen
- basal-bolus regimen
- basal = long/intermediate
- bolus = short/rapid - before meals
name the long acting insulins
- detemir - BD
- glargine - OD
- degludec - OD
name the rapid acting insulins
- asparte
- lispro
- glulisine
Name intemediate acting insulin
- biphasic isophane
- biphasic asparte/lispro (isophane + short acting)
what is biphasic insulin
- short acting mixed with intermediate - 1-3x a day
Long acting insulin onset and duration
- onset = 2-4 days to reach steady state
- duration = 36 hours
Name soluble insulins
- human + bovine/porcine
Soluble insulin details
- 15-30 minutes before meals
- onset = 30 to 60 minutes
- peak action = 1-4 hours
- duration = up to 9 hours
Rapid insulin details
- immediately before meals
- onset < 15 minutes
- duration = 2-5 hours
Intermediate insulin details
- onset = 1-2 hours
- peak affect = 3-12 hours
- duration = 11-24 hours
What is used for disabling/uncontrolled hyperglycaemia
continuous subcutaneous insulin infusion (insulin pump)
When to increase/decrease insulin
- increase insulin when - infection, stress, trauma
- reduce insulin when - physical activity, intercurrent illness, reduced food, reduced renal function, thyroid disease, addisons, coeliacs
Insulin administration
- inactivated by GI enzymes - give subcut into fat e.g. abdo (fastest absorption), outer thigh, buttocks (slower absorption)
- rotate site - lipohypertrophy = erratic absorption of insulin
What is type 2 diabetes
- insulin resistance later in life
- pre diabetes = HbA1c: 42-47
- diabetes = 48 mol/mol
- offer lifestyle advice 1st line
Type 2 diabetes treatment (low CVD risk)
- assess HbA1c, kidney function and CVD risk
1. Metformin
2. + DPP-41 (gliptin), pioglitazone, sulfonylurea or SGLT2i (flozin)
3. triple therapy (add/swap)
4. specialised e.g. insulin, GLP1 agonist
Type 2 diabetes treatment (high CVD risk)
- assess HbA1c, kidney function, CVD risk (high risk = established attherosclerotic CVD/HF or QRISK > 10%)
1. metformin
2. SGLTi (flozin)
3. +DPP-4i (gliptin), pioglitazone or sulfonylurea
4. triple therapy (add/swap) - if at any point develops high risk - consider SGLT2i
Type 2 diabetes metformin resistant treatment
- if due to GI side effects - use MR prep
- assess HbA1c, kidney function, CVD risk
1. DPP-4i (gliptin), pioglitazone, sulfonylurea OR SGLT2i (flozin - in high CVD risk)
2. DPP-4i + pioglitazone OR DPP-41 + sulfonylurea OR pioglitazone + sulfonylurea
3. insulin - aim for individually agree threshold for HbA1c through tx
Diabetic complications - CVD treatment
- low dose statin (T1DM, age > 40, diabetes > 10 yrs, nephropathy, other CVD)
- ACEi to reduce CVD risk
Diabetic complications - diabetic nephropathy
- nephropathy causing proteinurea = ACEi (including black and >55)/ARB
- ACEi/ARB potentiate hypoglycaemic effect of anti diabetic drugs/insulin
Diabetic complications - diabetic neuropathy
- painful peripheral neuropathy
- anti-depressant, gabapentin, pregabalin
Diabetic complications - diabetic foot
- treat pain
- manage infection
Diabetic complications - autonomic neuropathy
- treat diarrhoea with codeine or tetracyclines
Diabetic complications - neuropathic postural hypotension
- increase salt intake
- OR fludrocortisone
Diabetic complications - gustatory sweating
- antimuscarinic (propantheline bromide)
Diabetic complications - erectile dysfunction
- sildenafil
Diabetic complications - visual impairment
- annual eyes test - free
Metformin (biguanide) MoA
reduces gluconeogenesis and increases peripheral utilisation of glucose
Metformin side effects
- lactic acidosis (DONT use if eGFR < 30)
- GI effects (increase dose slowly/MR)
- reduces vitamin B12
- hold if AKI
Sulphonylureas MoA
augments insulin secretion
Name short acting and long acting sulphonylureas
- short-acting: gliclazide, tolbutamide
- long-acting: glibenclamide, glimepiride
Sulphonylureas side effects
- prolonged/fatal hypoglycaemia (avoid elderly) (target - 7%)
- avoid in acute porphyrias
- avoid in hepatic and renal failure
Pioglitazone MoA
reduces peripheral insulin resistance
Pioglitazone side effects
- avoid in history of heart failure
- increase risk of bladder cancer - review in 3-6 months, report haematuria, dysuria, urinary urgency
- increased risk of bone fractures and liver toxicity - report NV, abdo pain, fatigue, dark urine
Dipeptidylpeptidase-4 inhibitors MoA
- alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliption (new hepatotoxic)
- inhibits DPP-4 to increase insulin secretion and lower glucagon secretion
DPP-4i side effects
cause pancreatitis - stop if persistent, severe abdo pain
Sodium Glucose Co-transporter 2 inhibitors MoA
- canagliflozin, dapagliflozin, empagliflozin
- inhibits SGLT2 in renal proximal convoluted tubule
SGLT2i MHRA warnings
- life threatening/fatal DKA - monitor ketones
- fourniers gangrene (necrotising fasciatis of genitalia/perineum)
- canagliflozin: lower limb amputation (mainly toes)
SGLT2i side effects
- volume depletion - correct hypovolaemia, monitor renal function
GLP1 Agonist MoA
- dulaglutide, eventide, liraglutide, lixisenatide
- increase insulin secretion, suppresses glucagon secretion, slows gastric emptying
GLP1 agonist MHRA warning
- DKA with concomitant insulin rapidly reduced
GLP1 agonist side effects
- acute pancreatitis - persistent, severe abdo pain
- dehydration - GI side effects
Acarbose MoA and side effects
- delays digestion and absorption of starch and sucrose
- GI effects = reduce dose
Meglitides (nateglinide or repaglinide) MoA and side effects
- stimulates insulin secretion
- stress exposure = tx interruption and replacement with insulin to maintain glycemic control
Diabetes medications affecting weight
- gain: pioglitazone, sulphonylureas
- neutral: DPP-4i
- loss: metformin, GLP1 agonist, SGLT2i
what is diabetic ketoacidosis
- severe hyperglycaemia
DKA symptoms
- polyurea
- thirsty
- pear drop breath (ketones)
- deep/fast breathing
- 4Ts: thin, thirst, toilet, tired
DKA monitoring
- check blood sugar if > 11mmol/L, check ketones (urine/blood) if:
= 0.6 - 1.5 mmol = slight risk (retest 2 hours)
= 1.6 - 2.9 mmol = increased risk (GP)
= 3 mmol + = medical emergency (hospital)
DKA treatment
- If BP < 90, restore volume with 500mL IV NaCl 0.9%
- Once BP > 90 = maintenance IV NaCl 0.9%
- IV insulin with NaCl at rate so ketones fall at 0.5 mmol/L/hr and blood glucose falls at 3 mmol/L/hr
- when BG < 14 mmol/L give IV glucose 10%
- continue insulin until ketone < 0.3 mmol/L and pH > 7.3
- when able to eat, give fast acting insulin with meal
- stop tx 1 hour after food
Insulin adjustment for elective & minor surgery
- reduce OD basal by 20% day before surgery
Insulin adjustment for elective and major surgery
- reduce OD basal by 20% day before surgery
- on the day = reduce OD basal by 20% - stop other insulin until eating, IV infusion of KCl + glucose + NaCl, variable rate IV insulin (soluble human) in NaCl via pump, hourly blood glucose measurements for first 12 hours, IV glucose 20% if drops under 6 mmol/L
Insulin requirements post surgery
- back to subcut when pt can eat/drink w/o vomiting
- basal-bolus - restarted with first meal - infusions until 30-60 minutes after first meal that includes the short acting glucose administration
- long-acting - continue at reduced by 20% until leaves hospital
- BD regimen = restart at breakfast or evening meal - infusions until 30-60 minutes after first meal
Sick day rules
- Sugar levels - check BG regularly
- Insulin - continue taking
- Carbohydrates - keep eating, stay hydrated
- Ketones - check ketones regularly
Diabetes in pregnancy and breast feeding
- diabetes in pregnancy = increase risks to mum and foetus - effective glucose control to reduce risk
- before preg = if HbA1c > 48 mmol/mol, take folic acid 5mg
Diabetes medication in pregnancy
- stop all oral anti diabetic meds except metformin and replace with insulin
- isophane is first choice as basal in preg
- if taking statin/ACEi/ARBs - discontinue
- aware of hypoglycaemia risk and always carry fast acting glucose
What is gestational diabetes
developed during preg, stop treatment after birth as it is due to pregnancy
Gestational diabetes treatment if FBG < 7 mmol/L
- diet & exercise
- metformin
- insulin
- move to next step if requirement not met in 1-2 weeks
Gestational diabetes treatment if FBG > 7mmol/L
- diet and exercise + insulin +/- metformin
Gestational diabetes treatment if FBG 6 - 6.9 mmol/L with complication
- insulin +/- metformin
Hypoglycaemia (< 4 mmol/L) symptoms
- sweating
- lethargic
- dizziness
- hunger
- tremor
- tingling lips
- palpitation
- extreme moods
- pale
Hypoglycaemia treatment if conscious and able to swallow
- fast acting carbohydrate by mouth e.g.:
- 4-5 glucose tabs
- 3-4 heaped teaspoons of sugar
- 150-200mL fruit juice
- repeat every 15 minutes for 3 cycles
Hypoglycaemia treatment if patient unconscious/oral doesn’t work
- IM glucagon
- then if unresponsive after 10 minutes, IV glucose
Hypoglycaemia awareness
awareness of hypoglycaemia can become blunted preventing early recognition - can happen through increases numbers of hypos or taking b-blockers
What is osteoporosis
progressive bone disease causing reduced bone mass and density = increased risk of fractures
osteoporosis risk factors
- postmenopausal
- men over 50
- long term glucocorticoids
- age increase
- vitamin D and calcium deficiency
- reduced exercise
- low BMI
- smoking, drinking
- history of fractures
- early menopause
osteoporosis life style advice
- increase exercise
- stop smoking
- reduce alcohol intake
- maintain ideal BMI
- increase vitamin D and calcium inake
Osteoporosis treatment
- oral bisphosphonates (alendronic/risedronate)
- review after 5 years (3 years for zoledronic)
Oral bisphosphonates alternatives for treatment of osteoporosis in different patient groups
- postmenopausal = ibandronic, denosumab, raloxifene, strontium
- younger menopausal = HRT or tibolone
- severe osteoporosis = teriparatide
- men = zoledronic, denosumab, teriparatide, strontium
- glucocorticoid induced = zoledronic, denosumab, teriparatide
Glucocorticoid induced osteoporosis prophylaxis
- for women 70 yrs+, previous fragility fracture, pred > >7.5mg daily or equivalent
- for men > >70 yrs AND previous fragility fracture or pred > >7.5mg daily or equivalent
- large doses of corticosteroids for > 3 months
Bisphosphonates MHRA warnings
- atypical femoral fractures - report thigh, hip, groin pain
- osteonecrosis of jaw - report dental pain, swelling, non-healing sores, discharge
- osteonecrosis of external auditory canal - report ear pain, discharge, infection
Bisphosphonates side effects
- oesophageal reactions - take with full glass of water whilst standing and remain upright for 30 minutes after
- alendronic = 30 mins before breakfast/other meds
- risedronate = 30 minutes before breakfast or leave 2 hours before and after food/drink if at other time in the day
Mineral corticosteroids MoA
- high fluid retention, low anti-inflammatory effect
- highest mineral corticosteroids activity = fludrocortisone
- hydrocortisone also mineral corticosteroid activity
fludrocortisone indication
hypotension
mineral corticosteroids side effects
- sodium and water retention (oedema)
- hypokalaemia
- hypocalcaemia
- these effects negligible with high potency glucocorticoids (betamethasone & dexamethasone)
Glucocorticoids MoA
- high anti-inflammatory effect, low fluid retention
- highest glucocorticoid activity = dexamethasone/betamethasone
- also prednisolone, prednisone, deflazacort
glucocorticoids side effects
- diabetes
- osteoporosis -> fractures
- avascular necrosis of the femoral head and muscle wasting
- gastric ulceration and perforation
All corticosteroids MHRA warning
central serous chorioretinopathy - report blurred vision/disturbances
All corticosteroids side effects
- psychiatric reactions = insomnia, irritability, mood change, suicidal thoughts, behavioural disturbances
- adrenal suppression = prolonged use = adrenal atrophy. abrupt withdrawal = adrenal insufficiency, hypotension, death. illness, trauma, surgical procedure = increase dose
- infection - immunosuppressed
- chickenpox - vaccinate
- measles - prophylactic AM normal immunoglobulin
- insomnia - morning dose - when cortisol produced
- children - stunted growth (incl. ICS), skin thinning (topical)
- prolonged use = Cushing’s syndrome = moon face, striae, hirsutism, acne, managed with metyrapone, tx with ketoconazole
CORTICOSTEROID USE acronym
- Cushing’s
- Osteoporosis
- Retardation of growth
- Thin skin
- Immunosppressed, Insomnia
- Chlorioretinopathy
- Oedema (water retention)
- STriae
- Emotional disturbance
- Rise in BP
- Obesity (truncal)
- Increased hair growth (hirsutism)
- Diabetes (hyperglycaemia)
- Ulcers (peptic)
- Suppression (adrenal)
- Electrolyte imbalance (reduced K+)
Managing corticosteroid side effects
- lowest effective dose for minimum period
- single dose in morning
- total dose for 2 days can be taken as single dose on alternate days
- intermittent therapy with short courses
- local tx rather than systemic e.g. cream, intra-articular injections, inhalations, eye drops, enemas
Gradually withdraw steroids if
- > 40mg pred (or equiv) daily for >1 weeks
- repeat evening doses
- > 3 weeks treatment
- recently received repeated courses
- taken short course within 1 year of stopping long-term therapy
- other possible causes of adrenal suppression
- all patients to be given steroid card
Topical steroid potencies
- mild: hydrocortisone
- moderate: clobetasone
- potent: betamethasone
- very potent: clobetasol
What is adrenal insufficiency
- medical emergency
- caused by addison’s or congenital adrenal hyperplasia
- can lead to adrenal crisis = severe dehydration, hypovolaemic shock, altered consciousness, seizures, stroke, cardiac arrest = death if untreated
adrenal insufficiency treatment
- hydrocortisone mainly
- fludrocortison as well if primary adrenal insufficiency
Name natural oestrogens
- estradiol
- estrone
- estriol
Name synthetic oestrogens
- ethinylestradiol
- mestranol
Name progestogens
- norethisterone
- levenorgestrel
- desogestrel
Tibolone
= oestrogen, progestognenic, and weekly androgenic
HRT treatments
- oestrogens (+ progestogen if uterus) alleviates menopausal symptoms e.g. vaginal atrophy (topical), vasomotor instability (systemic), reduces postmenopausal osteoporosis
- clonidine for vasomotor symptoms, but large side effects profile
HRT risks
- benefits > risks especially age < 60
- breast cancer - increased in combined over oestrogen only
- endometrial cancer with tibolone - if uterus - reduced risk with combined over oestrogen only
- ovarian - small risk, disappears after stopping
- DVT
- stroke - slight increase, tibolone increased by 2.2x in first year of tx
- coronary heart disease - increased risk with combined if started more than 10 years after menopause
Choosing HRT if have uterus
- oestrogen throughout with cyclical progestogen for last 12-14 days of cycle
- continuous oestrogen and a progestogen
- avoid continuous combined and tibolone in perimenopausal or if within 12 months of last menstrual period
Choosing HRT if dont have uterus
- continuous oestrogen use
- if endometriosis = + progesterone
HRT and surgery
- elective = stop HRT 4-6wks before surgery, reinitiate when fully mobile
- non-elective = prophylactic heparin, graduated compression stockings
Reasons to stop HRT
- sudden severe chest pain/SOB - PE
- swelling/severe pain in calf of one leg - DVT
- severe stomach pain - hepatotoxicity
- serious neurological effects - unusual, severe, prolonged headache, fainting, epileptic seizure, motor disturbances, numbness
- hepatitis/jaundice
- BP > 160 systolic of 95 diastolic
- prolonge immobility - risk of VTE
Thyroid disorders MoA
- circulated thyroid hormone regulated by negative feedback loop
- increased T3/T4 = suppression of TSH or TRH produced by hypothalamus = inhibits their own production
hyperthyroidism signs and symptoms
- high T3/T4, low TSH
- increased metabolism/activity
- hyperactive
- insomnia
- heat intolerance
- increased appetite
- weight loss
- diarrhoea
- goitre
Hyperthyroidism treatment
- carbimazole
- propylthiouracil
- b-blockers - symptomatic relief
carbimazole MHRA warnings
- neutropenia & agrunolocytosis - sore throat, malaise, fever, bleeding gums
- congenital malformations - use contraception
- acute pancreatitis - report and stop if severe abdo pain
propylthiouracil side effects
cautions of liver disorder - jaundice, dark urine, nausea
Graves disease treatment (severe hyperthyroidism)
- radioactive iodine
- if remission likely with anti-thyroids, consider carbimazole - carbimazole if iodine or surgery not suitable - block and replace regimen in combo with levothyroxine for 12-18 months
hyperthyroidism treatment in pregnancy
- 1st trimester = propylthiouracil (carbimazole = congenital defects)
- 2nd and 3rd trimester = carbimazole (propylthiouracil = hepatotoxicity)
Hypothyroidism signs and symptoms
- low T3/T4, high TSH
- reduced metabolise/activity
- fatigue
- weight gain
- constipation
- depression
- dry skin
- cold intolerance
- menstrual irregularities
Hypothyroidism treatment
- levothyroxine
- liothyronine
Levothyroxine details
- monitor TSH every 3 months until stable, then annually
- OM 30 minutes before breakfast/caffeinated drinks
- MHRA - potentially feel symptoms if alternating brands
Liothyronine details
- more rapid and potent output than levo (20-25mcg = 100mcg of levo)
- non-UK brands may not be bioequivalent
Which statin and dose is used in T2DM and established CVD
atorvastatin 80mg
How often should HbA1c be monitored if the patient is stable
every 6 months
What should the HbA1c be before another anti diabetic medication is added
58mmol/mol
Which anti diabetic medication causes vaginal thrush
SGLT2 inhibitors
which anti diabetic medication causes UTIs
dapagliflozin
T2DM and HTN - HTN target
- 140/90
- if > 80 years old then 145/95
When should a GLP-1agonist be continued
if at least 3% reduction in initial body weight and 1% reduction of HbA1c within 6 months
AKI symptoms
- oedema
- SOB
- confusion
- nausea
- seizures
- chest pain
- oliguria (abnormally small amounts of urine)
which anti diabetic medications cause hypotension
sulfonylureas
which anti diabetic medication has a risk of bladder cancer
pioglitazone
why is ramipril cautioned in diabetes
it may lower blood glucose
Insulin aspart administration directions
TDS before meals
eGFR range that indicates severe renal impairment
- 15-29
- also indicates stage 4 CKD
Reasons to stop HRT
- PE (chest pain, SOB)
- DVT (calf swelling, red, hot)
- severe stomach pain (pancreatitis)
- neurological affects
- hepatitis/jaundice/liver enlargement
- BP > 160/95
- prolonged immobility
Recommended blood glucose levels if fasting and if not fasting
- fasting < 5.5
- non-fasting < 11.1
What is the recommended HbA1c when T2DM is managed by diet alone or with a single anti diabetic drug not associated with hypoglycaemia
48 mmol/mol (6.5%)
Rapid insulin administration directions post op
- PRN
- can be adjusted according to glucose levels
