Endocrinology AS Flashcards
Diabetes Mellitus definition
Multisystem disorder due to an absolute or relative lack of endogenous insulin –> Metabolic and vascular complications
Type 1 DM
T1DM
- Pathology: autoimmune destruction of B-cells –> absolute insulin deficiency
- Age: usually starts before puberty
- Presentation: Polyuria, polydipsia, decreased weight, DKA.
- Genetics: concordance only 30% in MZ
- Association: HLA-D3 and D4, other AI disease
- Abs: Anti-islet, anti-GAD
T2DM?
Pathology: Insulin resistance and B-cell dysfunction –> relative insulin deficiency
Age: Usually older patients
Presentation: polyuria, polydipsia, complications
Genetics: concordance 80% in MZs
Associated: Obesity, decreased exercise, calorie and ETOH excess
Diagnosis of symptomatic diabetes?
Symptomatic - Polyuria, polydipsia, decreased weight, lethargy.
Need 1 test
- Increased plasma venous glucose detected once!
- Fasting >7mm
- Random >11.1
- 2 hr Plasma glucose >11.1 2hr after ingestion of glucose during OGTT (need to check with blood)
- HbA1c >48 mmol/ >6.5
Beware that sickle cell anaemia and other haemoglobinopathies can give falsely low HbA1c readings due to decreased lifespan of RBCs.
Sickle cell, G6PD, hereditary is low.
Vit B12, folic acid and iron deficiency anaemia, splenectomy give higher readings due to higher red blood cell lifespan.
Consider measuring C-peptide after initial presentation if there is difficuly distinguishing type 1 from others. C-peptide is low in T1DM. Normal or high in Type 2
Diagnosis of Asymptomatic diabetes?
in an asymptomatic person, the diagnosis of diabetes should never be based on a single abnormal HbA1c or fasting plasma glucose level; at least one additional abnormal HbA1c or plasma glucose level is essential. If the second test results are normal, it is prudent to arrange regular review of the person.
- Increased venous glucose on 2 separate occasions.
- Or 2h OGTT >11.1 mM
- 2 Separate HbA1c readings.
What is a OGTT?
- Only needed if borderline fasting or random glucose measurements
What is normal fasting glucose?
<6.1 (<41)
What is impaired fasting glucose defined as?
- 1-6.9 fasting (42-47)
- These patients should be recommended diet and exercise.
What is diabetes defined as on fasting glucose?
> 7 (>48)
What is normal in a 75g OGTT?
<7.8
What is impaired glucose tolerance
7.8-11
What is diabetes on OGTT?
> 11.1
What are secondary drug causes of DM?
Drugs: Steroids, anti-HIV, atypical neuroleptics, thiazides
what are secondary pancreatic causes of DM?
CF, chronic pancreatitis, HH, pancreatic Ca
What are secondary endo causes of DM?
Phaeo, Cushings (increases blood sugar), Acromegaly, hyperthyroidism
Other: glycogen storage
What is metabolic syndrome?
- Central obesity (increased weight circumference >102 in men, 88 women
- Triglycerides 150mg/dl
- HDL-cholesterol <40mg/dL in men and <50 mg/dl in women
- HTN: BP 130/85
- DM, IGT, IFG
Conservative management of diabetes?
- MDT
GP, endorinologist, surgeons, specialist nurses, dieticians, chiropodists, fellow patients (education groups)
The 4Cs of diabetes monitoring?
Control - glycaemic - Record of coplications: DKA, HONK, Hypos - Capillary blood glucose Fasting: 4.5-6.5mM 2h post prandial: 4.5-9mM
- HbA1C
Reflects exposure over last 6-8 weeks
Aim <45-50mM (7.5-8%)
BP, lipids
Complications - Macro Pulses, BP, cardiac auscultation - Micro Fundoscopy, ACR+U&Es, Sensory testing plus foot inspection
Competency
- With insulin injections
- Checking injection sites
- BM monitoring
Coping
- Psychosocial e.g depression
- Occupation
- Domestic
Lifestyle modifications for Diabetes Mellitus?
DELAYS - Diet Same as that considered healthy for everyone Decreased total calorie intake decreased refined CHO, increased complex CHO Increased soluble fibre decreased fat (especially saturated) decreased salt Avoid binge drinking
- Exercise
- Lipids
Risk of hyperlipidaemia
Primary prevention with statins if over >40 yrs - ABP
decreased Na intake and ETOH
Keep BP <130/80
ACEi best (B-B: mask hypos, thiazides: increased glucose) - Aspirin
Primary prevention if >50yrs or <50 with other CVD RFs.
Yearly/ 6-monthly check:
Smoking cessation
HTN - HbA1c checked every 3-6 months until stable, then 6 monthly. Target on lifestyle or with metformin = 48. Inclusion of a sulphonylurea = 53.
BP and Diabetes - No end organ damage: <140/80
End organ damage: <130/80
Management of diabetes - Oral hypoglycaemics - first line after lifestyle modification?
Aim HbA1c <6.5% / 48mmol
- Lifestyle Modification: delays
- Start Metformin (if HBA1c >target after lifestyle changes to reduce micro and macrovascular complications)
SE: Nausea, diarrhoea, abdo pain, lactic acidosis
CI: GFR<30, tissue hypoxia (sepsis, MI), morning before GA, iodinated contrast media, CKD (increase risk of lactic acidosis)
500mg after evening meal, increasing to 2g max.
Advise is to stop if patient is ill due to renal impairment.
If Metformin is contraindicated offer a DPP4 (gliptins), pioglitazone, sulfonylurea, SGLT-2 inhibitor)
Management of diabetes - Oral hypoglycaemics - after metformin?
If HbA1c >58 mmols (7.5%)
For non-obese patients
Metformin + Sulphonylureas (if HBA1c >target) such as gliclazide. Major hypoglycaemia concern with unpredictable eating/exercise habits).
OR
Metformin + SGLT2 inhibitor (empagliflozin) 10mg OD. (reduce CVS risk and renal benefits).
OR
Metformin + pioglitazone (contraindicated in patients with heart failure due to fluid retention).
OR
Metformin + DPP4 (gliptin) - sitagliptin (do not offer cardiovascular benefits, but few identified side effects). No weight gain, oral preparation. Therefore for obese patients.
What dual therapy do you use if metformin is not suitable?
- Gliptin plus pioglitazone (contraindicated if bladder cancer)
- Gliptin (DPP4 inhibitor) plus sulphonylurea (gliclizide)
- Pioglitazone + sulphonylurea
Gliptins = DPP4 = Inactivating GLP1 therefore block this to increase action of GLP1
Pioglitazone = PPAR - modifies transcription of insulin. Class is the Thiazolidinedione
Gliclazide = Sulphonylureas.
What is 3rd line treatment for diabetes mellitus
HBA1c >58
Triple therapy
- Metformin, gliptin and a sulphonylurea
- Metformin, pioglitazone (thiazolidinedione), sulphonylurea
- Metformin, pioglitazone or sulphonylurea and an SGLT-2 (pee out glucose)
Sensitise your body to insulin (metformin)
Starting insulin treatment - safe starting dose 0.1-0.3 U/kg
- Neutral Protamine Hagedorn (1-2 daily) + short-acting insulin
- Insulin determir or glargine alternative to NPH.
What if third-line is ineffective for DM?
- Consider Metformin, sulphonylurea and GLP-1 (exenatide) for those with BMI >35 or those with BMI <35 who would have occupational problems with insulin.
Exenatide leads to increased insulin secretion + inhibits glucagon secretions. Leads to weight loss. Within 60 mins before the morning and evening meals.
Consider adding exenatide to metformin and a sulfonylurea if:
BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight, or
BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.
- Consider acarbose if unable to use other glucose-lowering drugs.
What are the principles of insulin?
Ensure pt education about
- Self-adjustment with exercise and calories
- Titrate dose
- Family member can abort hypo with sugary drink or GlucoGel
- Fasting BM before meals informs re long-acting insulin dose.
Type 1: 5-7 mmol on waking and 4-7 before meals at other times of the day.
- Finger-prick BM after meals informs re shorting-acting insulin dose (for that last meal)
What are the common insulin regimes?
HbA1c - monitored every 3-6 months.
Adults should have a target of HbA1c level of 48.
Monitor 4 times a day.
1 ml = 100 units.
10ml = 1000 units.
1) Basal-bolus insulin regimen
- Bedtime long-acting (glargine) + short acting before each meal (lispro)
Adjust dose according to meal size
~50% of insulin given as long-acting
Allows flexible lifestyle for T1DM
Best outcome
2) 1,2 or 3 insulin injections per day (biphasic)
- Usually short-acting insulin or rapid-acting mixed with intermediate-acting insulin (Biphasic regimen)
- 30 mins before breakfast and dinner
Rapid: actrapid
Intermediate/long-acting: insulatard
- Associated with fasting hyperglycaemia
- Suitable for children, older patients (regular lifestyle).
3) Continuous subcutaneous insulin infusion (insulin pump) - this is a programmable pump that offers regular insulin in the form of rapid acting) by subcut/cannula.
Rapid insulin = 5 mins - peak 1 hr (Novorapid)
Short acting = 30 mins onset, 3 horus peak, last 6-8hrs (Actrapid)
Intermediate-acting insulin = 2hr peak 5-8hrs, duration 12-18hrs. (isophane insulin)
Long-acting insulin analogues = 1-2 hrs, flat profile uper to 24hrs. (Insulin Determir, insulin glargine).
Management of insulin during illness?
- Insulin requirements usually increased (even if food intake decreases)
- Maintain calories (e.g with milk)
- Check BMs >4hrly and test for ketonuria.
- Increased insulin dose if glucose rising
Side effects of insulin?
Hypoglycaemia
- At risk: ETOH binge, B-B (mask symptoms), elderly
- Need to admit sulphonylurea-induced hypo
Lipohypertrophy
- rotate injection sites: abdomen, thighs
Weight gain in T2DM
- increased weight gain if insulin given with metformin
What are the complications of diabetes?
Hyperglycaemia: DKA, HONK Hypoglycaemia Infection Macrovascular: MI, CVA Microvascular
Macrovascular complications of diabetes?
MI: may be silent due to autonomic neuropathy
PVD: Claudication, foot ulcers
CVA: Strokes
Management of Macrovascular complications?
CV risk factors
- BP (aim <130/80) if end-organ damage otherwise 140/80. ACEi have renoprotective effect in diabetes give as 1st line. Otherwise for African/Caribbean give ACEi + thiazide/CCB.
- Smoking
- Lipids
- HBA1c
Prevention
- Good glycaemic control prevents both macro- and micro-vascular complications
- Regular screening: fundoscopy, ACR, foot checks.
Diabetic Foot
Due to Ischaemia - Critical toes - Absent pulses (do ABPI) - Ulcers: painful, punched-out, foot margins, pressure points
Neuropathy
- Loss of protective sensations
- Deformity: Charcot’s joints (weakening of foot and breaking of bones but can’t feel due to neuropathy), pes cavus, claw toes (extension of MTPJ and flexion of IPJ due to diabetic foot)
- Injury or infection over pressure points
- Ulcers: painless, punched-out, metatarsal heads, calcaenium
Charcot’s is a localised inflammatory condition leading to varying degrees and pattern of bone destruction, subluxation, dislocation and deformity.
Management of diabetic foot?
Prevention
- Education about foot care is fundamental in the prevention of gangrene.
- Good glycaemic control prevents both macro- and micro-vascular complications
- Regular screening: fundoscopy, ACR, foot checks.
Conservative - Daily foot inspection (e.g with mirror) - Comfortable/therapeutic shoes - Regular chiropody (remove callus) - Wound care Medical - Management of infection: benpen + fluclox ± metronidazole Surgical - Abscess or deep infection - Spreading cellulitis - Gangrene - Suppurative arthritis
Screen for ischaemia and neuropathy.
All those with moderate to high risk should be followed up regularly by local diabetic foot centre.
Therefore any patient that has a problem other than simple calluses should be followed up in local diabetic foot centres.
Microvascular complications of diabetes
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy
Diabetes complications - Diabetic nephropathy
Pathophysiology
- Hyperglycaemia –> nephron loss and glomerulosclerosis
Features of diabetic nephropathy?
Microalbuminuria
- urine albumin:Cr (ACr) >30 mg/Mm
- If present –> ACEi/ARA
- Refer if UCR >70
Diabetic Retinopathy
- Microvascular disease –> Retinal ischaemia –> increased VEGF
- Increased VEGF –> new vessel formation
Presentation of diabetic retinopathy?
- Retinopathy and maculopathy
- Cataract
- Rubeosis iris: new vessels on iris –> glaucoma
- CN palsies
Diabetic retinopathy and maculopathy?
- Commonest cause of blindness up to 60yrs
- Refer if pre-proliferative retinopathy/maculopthy
- Ix: fluorescein angiography (for macula) /imaging of fundus
- Rx: laser photocoagulation
Management - Intravitreal anti-VEGF and consider macular laser laser therapy.
- Also urgent pan-retinal photocoagulation of high risk proliferate
Stages of diabetic retinopathy?
Background Retinopathy
- Dots: Microaneurysms
- Blot haemorrhages
- Hard exudates: yellow lipid patches (hard)
Pre-proliferative retinopathy
- Cotton-wool spots (retinal infarcts - white fluffy)
- Venous beading
- Haemorrhages
Proliferative
- New vessels
- Pre-retinal or vitreous haemorrhage
Maculopathy
- Decreased acuity may be only sign
- Hard exudates within one disc width of macula (where fovea sits)
Management
- Intravitreal anti-VEGF and consider macular laser laser therapy.
- Also urgent pan-retinal photocoagulation of high risk proliferate
Diabetic Neuropathy pathophysiology?
Pathophysiology
- Metabolic: glycosylation, ROS, sorbitol accumulation
- Ischaemic: loss of vasa nervorum
Types of diabetic neuropathy?
- Symmetrical sensory polyneuropathy
- Mononeuropathy/Mononeuritis multiplex (isolated cranial or peripheral nerve)
- Femoral neuropathy/amyotrophy(radiculopathy)
- Autonomic neuropathy
Diabetic Neuropathy - Symmetric sensory polyneuropathy?
Glove and stocking: length-dependent (therefore feet 1st)
- Loss of all modalities
Absent ankle jerk
Absent ankle jerk
Numbness, tingling, pain (worse at night)
Management
- Paractamol
- Amitriptyline, Gabapentin, SSRI, pregabalin or duloxetine.
Use Tramadol as rescue therapy for exacerbation of neuropathic pain.
Amitriptylline is normally first choice but given history of BPH better to avoid amitriptylline due to risk of urinary retention. Anti-muscarinic effects.
- Capsaicin cream
- Baclofen
Diabetic Neuropathy - Mononeuropathy/Mononeuritis multiplex
- Progressive motor and sensory deficit in the distribution of specific peripheral nerves.
- Numbness and weakness
- Pain
Eg of CN3/6 palsies
Diabetic Neuropathy - Femoral neuropathy/amyotrophy
Painful asymmetric weakness and wasting of quads with loss of knee jerks
Dx: nerve conduction and electromyography
Diabetic Neuropathy - Autonomic neuropathy?
- Postural hypotension - Rx: fludrocortisone
- Gastroparesis –> Early satiety, GORD, bloating
- Diarrhoea: Rx with codeine phosphate
- Urinary retention
What is the pathogenesis of DKA?
Hyperglycaemia
Ketogenesis
- decreased insulin –> increased stress hormone and glucagon
- decreased glucose utilisation in tissues+ increased fat B-oxidation
- Increased fatty acids from tissues –> increased ATP + generation of ketone bodies
Dehydration
- Decreased insulin –> decreased glucose utilisation + increased gluconeogenesis –> severe hyperglycaemia
- Osmotic diuresis –> dehydration
- Also, increased ketones –> vomiting
Acidosis
- Dehydration –> renal perfusion
- Hyperkalaemia
- Ketones
Precipitants of DKA?
- Infection/stress ± Stopping insulin
- New T1DM
Presentation of DKA?
- Abdo pain + vomiting
- Gradual drowsiness
- Sighing Kussmaul hyperventilation
- Dehydration (sunken eyes, poor skin turgor)
- Ketotic breath
Signs of diabetes
- Polyuria
- Polydipsia
Diagnosis of DKA?
- Acidosis (increased AG): ph <7.3 (± HCO3 <15mM)
- Hyperglycaemia: >11.1 mM (or known DM)
- Ketonaemia: >3mM (>++ on dipstick)
Investigations for DKA?
Urine: ketones and glucose, MCS
Cap glucose and ketones
VBG: acidosis + increased K (due to extracellular shift of potassium due to insulin insufficiency, acidiaemia). Na is low due to osmotic reflux from intracellular to extracellular space due to hyperglycaemia
Total body potassium conc is low due to diuresis.
Bloods: U+E, FBC, Glucose, Cultures, Magnesium, elevated anion gap, serum osmolality.
CXR: Evidence of infection
Why Hyponatraemia in DKA?
- Osmolar compensation for hyperglycaemia - water moving into where sugar is, leading to a dilutional hyponatraemia.
If there is little water, means hypernatraemia. - Increased or normal Na indicates severe dehydration
Why should you avoid rapid decreased in insulin once glucose normalised in DKA?
Glucose decreases faster than ketones and insulin is necessary to get rid of ketones
Why is amylase up in DKA?
Amylase is up due to extrapancreatic sources or pancreas itself.
Why do you get hyperchloraemic metabolic acidosis after management of DKA?
Excretion of ketones –> loss of potential bicarbonate
Management of DKA?1st step
In HDU
- Rehydrate
- Insulin infusion
- Potassium replacement
Fluid
- 0.9% saline infusion via large bore cannula
SBP <90 –> 1L stat + more until SBP >90
SBP >90 –> 1L over 1h
Then: 1L over next 2hrs (1L with potassium chloride) 1L/2h, (with potassium chloride) 1L/4h, (with potassium chloride) 1L/4h, (with potassium chloride) 1L/6h (with potassium chloride)
- Switch to 5% dex 1L/8hr with 0.45% saline when glucose <11.1mM, to avoid hypoglycaemia
Management of DKA?2nd step?
- Insulin therapy corrects hyperosmolarity + acidaemia decreased plasma conc of potassium by driving it into cells.
- Potassium chloride/phosphate
20-30 mEq/L/hour IV infusion.
-Please start this on the 2nd bag of fluid.
>5.5 –> nil
3.5-5.5mM –> 40mmol/L
<3.5 –> consult senior for review
Management of DKA? 3rd step?
Insulin infusion
- Actrapid 0.1u/kg/h (6u if no weight, max 15u)
Management of DKA? 4th step
Assessment
- Hx + full examination
- Capillary, urine, blood, imaging
Additional measures
- Urinary catheter (aim: 0.5ml/kg/hr
- NGT if vomiting or decreased GCS
- Thromboprophylaxis with LMWH
- Refer to specialist diabetes team
- Find + treat precipitating factors
Monitoring required for DKA?
- Hrly capillary glucose and ketones
- VBG @ 60 mins, 2hr, and then 2hrly
- Plasma electrolytes 4hrly
Aims
- decreased ketones by >0.5 mM/h or increased HCO3 by >3mM/h
- decrease plasma glucose by <3mM/h
- Maintain K in normal range. Normally DKA will lead to hyperkalaemia due to H+ being pushed in cells to normalise acidaemia. Following on from this, when insulin in administered, K+ is driven into cells, so hypokalaemia.
- Avoid hypoglycaemia
Resolution of DKA?
- Ketones <0.3 mM + venous pH >7.3
- transfer to sliding scale if not eating
- Transfer to SC insulin when eating and drinking
When converting - see how much they use in 24hr, 2/3 given, then 10 units split in morning, afternoon, evening.
Transfer to SC insulin + provide education?
- When biochemically resolved and eating
- Start long-acting insulin the night before
- Give short-acting insulin before breakfast
- Stop IVI 30 mins after short acting
Education
- ID precipitating factors and provide action plan
- provision of ketone meter with education on use.
Complications of DKA?
- Cerebral oedema: excess fluid administration
Commonest cause or mortality - Aspiration pneumonia
- Hypokalaemia
- Hypoglycaemia
- Hypophoshataemia –> resp and skeletal muscle weakness/ ARDS
- Thromboembolism
- hyperchloraemic acidosis - loss of ketoanions needed for bicarb regen, increased reabsorption of chloride secondary to intensive admi of chloride fluids.
What is a hyperosmolar non-ketotic coma?
HHS - characterised by
- profound hyperglycaemia,
- hyperosmolality
- volume depletion in the absence of significant ketoacidosis.
Severe hyperglycaemia, dehydration and renal failure, mild/absent ketonuria.
The insulin conc in these patients is sufficient to suppress lipolysis and ketogenesis.
Cause- Infection, non-adherence, corticosteroids, thiazide diuretics, beta-blockers
The patient
- usually T2DM, often new presentation
- Usually older
- Long hx (e.g 1 week)
Metabolic derangement in HONK?
Marked dehydration and glucose >30mM (hypovolaemia).
No acidosis (no ketogeneisis) Osmolality >320mosmol/kg.
Ketones can be high but normally. No acidosis.
Complications of HONK?
Occlusive events are common: DVT, Stroke
Give LWMH
Management of HONK?
Rehydrate with 0.9% NS over 48hr 0
- May need ~9L
- Wait 1hr before starting insulin (sliding scale) - variable rate for uncontrolled diabetes.
May not be needed
Start low to avoid rapid changes in osmolality 1-3u/hr
Consider potassium therapy
- Look for precipitant
MI, infection, bowel infarct.
Define Hypoglycaemia: Whipple’s Triad?
- Low plasma glucose <3mM
- Symptoms consistent with hypoglycaemia
- Relief of symptoms by glucose administration
Insulin produced in beta cells of pancreas. Central to regulating carbs and fat metabolism.
Pro-insulin is formed and cleaved to form insulin and c-peptide.
How to you classify symptoms of hypoglycaemia?
- Autonomic: 2.5-3
- Neuroglycopenic: <2.5
What are the autonomic symptoms of hypoglycaemia?
- Sweating
- Anxiety
- Hunger
- Tremor
- Palpitations
What are the neuroglycopenic symptoms of hypoglycaemia ?
- Confusion
- Drowsiness
- Seizures
- Personality change
- Focal neurology
- Coma (<2.2)
Causes of a fasting hypoglycemia?
EXPLAIN
- usually insulin or sulfonylurea management in a known diabetic (exercise, missed meal, OD)
- Exogenous drugs (quinine sulphate, aspirin pentamidine, quinine sulphate, ACEi).
- Pituitary insufficiency (failure of cortisol)
- Liver failure
- Addison’s
- Islet cell tumours (insulinomas - neuroendocrine tumours)
- Immune (insulin receptor Abs: Hodgkin’s)
- Non-pancreatic neoplasm: fibrosarcoma
Investigations of hypoglycaemia?
72hr fast with monitoring
Bloods
- Glucose, (at conclusion of 72hrs -every 6 hours with finger stick blood sugar).
- insulin (measure when glucose <3.3 or end of 72hr fast. Should be undetectable. Elevated value = factitious
hypoglycaemia or insulinoma. - C-peptide = elevated if insulin is endogenous. INappropriate elevation of c-peptide suggests either insulinoma or sulfonylurea.
- If insulin in raised when you have glycaemia this is not a physiological reaction, should have very low insulin to put glucose back into the blood.
- Therefore if high insulin and high c-peptide, endogenous insulin is coming from somewhere, either gliclazide (sulfonylurea). Cannot be exogenous insulin as this doesnt raise C-peptide.
On administration of insulin
Diagnosis of hypoglycaemia: a hyperinsulinaemic hypoglycaemia?
Drugs
- Increased C-pep: Sulfonylurea. Increasing the endogenous levels on insulin with C-peptide.
- Normal C-pep: insulin
Insulinoma.
C-peptide does not fall on admin of insulin if the patient has an insulinoma as endogenous levels are not reduced.
C-peptide levels fall on admin of insulin if self-medication. This is because on administration of insulin, his endogenous insulin drops, therefore C-peptide also drops.
Diagnosis of hypoglycaemia: a decreased insulin with no ketones?
- Non-pancreatic neoplasms (secrete IGF-II which is like insulin)
- Insulin receptor antibodies
Diagnosis of hypoglycaemia: a decreased insulin, increased ketones?
- Alcohol binge with no food
- Pituitary insufficiency/ Addison’s due to a failure to respond to hypoglycaemia.
What is an insulinoma?
Path: 95% benign B-cell tumour usually seen with MEN1
Pres: fasting/exercise induced hypoglycaemia
Ix:
- Hypoglycaemia + increased insulin
- Exogenous insulin doesn’t suppress C-pep
- MRI, EUS pancreas
Manangement
- Excision
Causes of a post-prandial hypoglycaemia?
Dumping post-gastric bypass
Management of hypoglycaemia if alert and orientated?
Rapid acting: Lucozade
Long acting: toast, sandwich
Management of hypoglycaemia if drowsy/confused but swallow intact: Buccal Carb?
Hypostop/Glucogel
Consider IV access.
IF IV access give 100ml 20% glucose IV .
Management of hypoglycaemia if unconscious or concerned with swallow: IV dextrose
100ml 20% glucose IV
Management of hypoglycaemia if deteriorating/refractory/insulin-induced/no access?
- 1mg glucagon IM/SC
Won’t work in drunks + short duration of effect (20 mins). - May get rebound hypoglycaemia (insulin release may)
Define thyrotoxicosis?
The clinical effect of increased T4, usually from gland hyperfunction.
Symptoms of hyperthyroidism
- Diarrhoea
- Increased appetite but
decreased weight - Sweats, heat intolerance
- Palpitations
- Tremor
- Irritability
- Oligomenorrhoea ± infertility
Signs in the hands of hyperthyroidism
- Fine tremor
- Fast/irregular pulse
- Warm, moist skin
- Palmer erythema
- Bruit in thyroid (TSH)
Signs in the face of hyperthyroidism?
Thin hair
Lid lag
Lid retraction
Signs in the neck of hyperthyroidism?
Goitre or nodules
Specific hyperthyroidism signs in the eyes for Graves? Ophthalmopathy?
Autoimmune response against the autoantigen (TSH receptor) –> retro-orbital inflammation. Inflammation results in glycosaminoglycan and collagen deposition in the muscles.
- Exophthalmos
- Ophthalmoplegia: Esp up-gaze palsy (failure)
- Eye discomfort and grittiness
- Loss of the colour red
- Photophobia and decreased acuity (dangerous)
- Chemosis
- Most worrying is corneal involvement.
Other worrying signs are proptosis, corneal involvement, sight loss due to optic nerve involvement.
Dangerous - inability to close the eyes.
Loss of visual acuity
Smoking is the most important modifiable risk factor for development of thyroid eye disease.
Can use radiotherapy, steroids or surgery.
Other Grave’s specific signs apart from ophthalmopathy?
- Dermopathy: pre-tibial myxoedema - excess glycosaminoglycans in tissue of legs, with plaques or scaly nodules. Overlying discoloured skin.
- Thyroid acropachy (digital clubbing, soft tissue swelling of hands and feet, periostitis)
Only lid retraction
odt tissue involvement
Proptosis
Extra-ocular involvemnt
Investigations of thyrotoxicosis?
- TFT: Decreased TSH, increased T4/T3
- Abs: TSH receptor (diagnostic), TPO (less specific to Graves, also in Hashimoto’s).
- Increase Ca due to thyroid hormone mediated increase in bone resorption, increased LFTs
- Isotope scan
Increased in Graves
Hot+cold thyroiditis - Ophthalmopathy: acuity, fields, movements
Most common cause of thyrotoxicosis?
Graves 60% of cases of thyrotoxicosis Prev: 0.5% Sex: F>>M= 9:1 Age: 40-60 yrs.
Features of Graves’?
- Ophthalmopathy and dermopathy and thyroid acropachy
Triggers for Graves?
Stress, infection, child-birth
Disease associations with Graves?
- T1DM
- Vitiligo
- Addison’s
Name some other causes (apart from Graves) of thyrotoxicosis?
Toxic multinodular goitre = Plummer’s disease
- Autonomous nodules develop on background multinodular goitre
- Elderly and iodine-deficient areas
- Iodine scan shows hot nodules
Manage with radioactive iodine.
Toxic adenoma
- solitary hot nodules ± producing T3/T4
- Most nodules are non-functional
Thyrotoxic phase of Thyroiditis
- de Quervain’s
- Hashimoto’s
- Subacute lymphocytic
Drugs
- Thyroxine
- Amiodarone
Management of hyperthyroidism - Medical
Medical management of symptoms - B-B (propranolol 40mg/6h)
- Anti-thyroid: carbimazole/(inhibits TPO) or
Titrate according to TFTs or block and replace.
In Graves’ Rx for 12-18 mo then withdraw - 50% relapse then move to surgery or radioiodine
Big side-effect of carbimazole?
Agranulocytosis (1/2000), Rash (1/200). Must warn patients
Radiological treatments of hyperthyroidism?
Most become hypothyroid
CI: pregnancy, lactation
Surgical treatment of hyperthyroidism?
Treat prior to surgery with antithyroid drugs until euthyroidism is achieved
Thyroidectomy
- May be preferred in woman planning pregnancy
- Complications
Recurrent laryngeal N.damage –> hoarseness
Hypoparathyroidism
Hypothyroidism
What are the features of a thyroid storm?
Develops in untreated or partially treated patient. Caused by a precipitate
- Recent thyroid surgery or radio-iodine
- Infection
- MI
- Trauma
Management of a thyroid storm?
- Fluid resuscitation + NGT
- Bloods: TFTs + cultures if infection suspected
- Propranolol PO/IV
- Carbimazole/methimazole or propylthiouracil then
Lugol’s Iodine 4hr later to inhibit thyroid (escape from Wolff-Chaikoff effect)
5. Hydrocortisone - blocks conversion of T4 to T3
- Manage cause
Epidemiology of hypothyroidism?
Incidence 4/1000 / yr
Sex: F>M = 6:1
Age >40yrs.
Symptoms of hypothyroidism?
Lethargy Cold intolerance decreased appetite but increased weight Constipation Menorrhagia Decreased mood
Signs of hypothyroidism?
Cold hands Bradycardia Slow-relaxing reflexes Dry hair and skin Puffy face Goitre Myopathy, neuropathy Ascites Myxoedema - SC tissue swelling in severe hypothyroidism Typically around eyes and dorsum of hand
Causes of primary hypothyroidism?
Primary?
- Atrophic thyroiditis
- Hashimoto’s thyroiditis
- Subacute thyroiditis (post-partum)
- Post de Quervain’s thyroiditis
- Iodine deficiency (commonest worldwide)
- Drugs: Carbimazole, amiodarone (contains iodine), lithium (stop drug entirely)
- Congenital: thyroid agenesis
Causes of post-surgical hypothyroidism?
Thyroidectomy
Radioiodine
Causes of secondary hypothyroidism?
Hypopituitarism.
Replacement steroid therapy is required prior to thyroxine.
What is atrophic thyroiditis? (part of Hashimotos, but without Goitre)
Thyroid antibodies +ve: anti-TPO, anti-TSH.
Lymphocytic infiltrate –> atrophy (no goitre)
Associations
- Pernicious anaemia
- Vitiligo
- Endocrinopathies
What is hashimoto’s thyroiditis?
- TPO +ve
- Atrophy + regeneration –> goitre
- May go through initial thyrotoxicosis phase
- May be euthyroid or hypothyroid
Investigations for hypothyroidism?
- Increased TSH, decreased T3/T4
- Increased MCV ± normochromic anaemia
- Increased triglyceride + increased cholesterol
- Check prolactin levels (PRL- secreting pituitary adenoma)
- Hyponatraemia (SIADH)
- Increased CK if associated with myopathy
- Abs: Anti-TPO and TSH
MUST Do a Short synACTHen test.
Management for hypothyroidism?
Short synACTHen test for addison’s/
- Levothyroxine - must take early in the morning at 6am.
1.7 microgram/kg/day.
30 mins before food as it’s absorption may affect food.
Titrate to normalise TSH
Enzyme inducers increase thyroxine metabolism
Clinical improvement takes ~2 weeks.
Check for other AI disease: E.g Addison’s, PA
For older patients or those with cardiac disease, severe hypothyroidism or patients over 50 the initial starting dose should be 25mcg od.
Other patients should start at 50-100mcg.
Check after 8-12 weeks.
Increased dose if pregnant.
May cause hyperthyroidism, reduced bone mineral density, worsening of angina, AF.
Management is aiming to normalise the TSH.
What is a myxoedema coma?
- Looks like hypothyroidism
- Hypothermia
- Hypoglycaemia
- Heart failure: bradycardia and decreased BP
- Coma and seizures
Precipitants of Myxoedema coma?
Radioiodine
Thyroidectomy
Pituitary surgery
Infection, trauma, MI, stroke
Management of myxoedema coma?
- Blood: TFTs, FBC, U+E, Glucose, cortisol
- Correct any hypoglycaemia
- T3/T4 IV slowly (may ppt myocardial ischaemia
- Hydrocortisone 100mg IV
- Rx hypothermia and heart failure
Benign thyroid disease - Simple goitre features and management?
Diffuse painless goitre Mass effect: - dysphagia - Stridor - SVC obstruction
Usually euthyroid, may –> hypothyroidism
Causes: iodine deficinecy, autoimmune, (goitrogens (sulphonylureas) or hereditary.
Manage - thyroxine and/or thyroidectomy if pressure symptoms.
Benign thyroid disease - Multinodular goitre features and signs?
- Evolves from long-standing simple goitre.
- Mass effects
- Euthyroid or subclinical hyperthyroidism
As for simple goitre
Treat with thyroxine, total or subtotal thyroidectomy if pressure symptoms.
Mainly concerned about thyroid pressure symptoms.
Benign thyroid disease - Plummer’s Disease - Toxic multinodular goitre signs and features?
- Multinodular goitre
- Thyrotoxicosis
- Uneven iodine uptake with hot nodule
Caused by an autonomous nodule developing on a background of a multinodular goitre
Management is with anti-thyroid drugs such as carbimazole, then surgical treatment such as total or subtotal thyroidectomy.
Benign thyroid disease - Graves’ disease features and signs
DIFFUSE goitre with bruit Ophthalmopathy Dermopathy Thyrotoxicosis Assoc with other AI disease (TiDM, PA) Increased uptake on radionucleotide scan
Caused by autoimmune (T2 hypersensitivity)
- Anti-TSH receptor
Management of Graves
- Propanolol
- Carbimazole
- Radioiodine
- Thyroidectomy
Benign thyroid disease - Hashimoto’s thyroiditis signs and features?
- Diffuse PAINLESS goitre
- May have transient thyrotoxicosis, then hypothyroidism
- Associated with AI disease (TIDM, PA)
Caused by autoimmune (T2+T4) - anti-TPO, -Tg.
Management with levothyroxine.
Benign thyroid disease - de Quervain’s thyroiditis signs and features
- Diffuse PAINFUL goitre
- Preceding viral URTI common
- Thyrotoxicosis –> hypo –> eu
- Decreased iodine uptake on thyroid scintigraphy.
Caused by a viral Coxsackie or autoimmune
Management is usually self-limiting. Thyroid pain managed with aspirin or other NSAIDs.
In more severe cases steroids are used.
Benign thyroid disease - Subacute lymphocytic signs and features?
Diffuse painless goitre
May occur post-partum
Thyrotoxicosis –> hypo –> eu
Normally autoimmune in origin
Self-limiting management.
Benign thyroid disease - Follicular adenoma signs and features?
Single thyroid nodule ± thyrotoxicosis (majority are cold)
May get pressure symptoms
Management is with a hemithyroidectomy
Benign thyroid disease - Thyroid cysts signs and features?
Solitary thyroid nodule
Asymptomatic or pressure symptoms
Can –> localised pain due to cyst bleed.
Management with aspiration or excision.
Malignant Thyroid disease - What is Papillary carcinoma?
- 80% frequency total thyroid malignancy
- associated with irradiation
- Normally young (20-40yrs old)
- Origin from follicular cells
- Thyroglobulin tumour marker
Associated with lymphadenopathy.
Spreads nodes and lung
- JDG node = lateral aberrant thyroid.
Marker = Antibodies to thyroglobulin.
Management of papillary thyroid carcinoma?
Total thyroidectomy
± node excision
± radioiodine
T4 to suppress TSH
> 95% 10yrs.
What is follicular thyroid carcinoma + management?
10% frequency
- F>M = 3:1
- Age 40-60
- Cell origin is the follicular cells and Thyroglobulin is the tumour marker.
Spread is from the blood –> bones and lungs
Management is through total thyroidectomy + T4 suppression +radioiodine
> 95% 10yrs.
What are the 4 types of thyroid malignancy?
Papillary
Follicular
Medullary
Anaplastic
What is medullary thyroid carcinoma and its management?
- 5% of all thyroid malignancy
- 30% are familial through MEN2 (medullary = MEN)
- Affects MEN: young, and can also be sporadic: 40-50.
- Origin is from the parafollicular C-cells and use CEA and calcitonin markers.
Management of medullary thyroid carcinoma
- Do Phaeo screen pre-op
- Thyroidectomy
- Nodal clearance
- Consider radiotherapy
What is anaplastic malignant thyroid disease?
Rare
F>M = 3:1 (ana)
Age >60 (ana)
Cell origin = Undifferentiated follicular cells
Rapid growth + aggressive: local, LN and blood.
Management of anaplastic thyroid disease?
Usually palliative
May try thyroidectomy + radiotherapy
<1% 10yr survival.
Management of lymphoma of the thyroid?
5%
Lymphocytes cell origin from a MALToma in Hashimoto’s.
Chemo-radiotherapy as management.
What is the presentation for malignant thyroid disease?
- Non-functional (cold)
- Painless neck mass
- Cervical mets
- Compression symptoms
Dysphagia
Stridor
SVC obstruction
What is the presentation for malignant thyroid disease?
- Solitary
- Solid
- younger
- Male
- Cold
- Risk factors: Radiation exposure
Indications for thyroid surgery for a malignant disease?
- Pressure symptoms
- Relapse hyperthyroidism (<1 failed drug management)
- Carcinoma
- Comesis
Practicalities of thyroid surgery?
Render euthyroid pre-op with antithyroid drugs
- Stop 10 days prior to surgery (they increase vascularity)
- Alternatively just give propranalol
Check for phaeo in medullary carcinoma
Laryngoscopy: check vocal cords pre-and post-op.
Complications of thyroid surgery - early?
Early
- Reactionary haemorrhage -> haematoma (<1%)
Can –> airway obstruction
Can anaesthetist and remove wound clips
Evacuate haematoma and re-explore wound.
- Laryngeal oedema
Damage during intubation or surgical manipulation
Can –> increase airway obstruction - Recurrent laryngeal nerve palsy (0.5%)
Right RLN more common (oblique ascent)
Damage to one –> hoarse voice
Damage to both –> obstruction needing tracheostomy - Hypoparathyroidism (2.5%
- -> decreased Ca2+ –> Chvostek’s and Trousseau’s (carpopedeal spasm during BP cuff inflation). Chvostek’s tapping sign.
Complications of thyroid surgery - late?
- Keloid scar
- Hypothyroidism
- Recurrent hyperthyroidism
Physiology of hyperparathyroidism?
PTH secreted in response to decrease Ca and causes
- Increased osteoclast activity
- Increase Ca and decreased PO4 reaborption in kidney
- Increased 1a-hydroxylation of 25OH- Vit D3
What is the presentation of hyperparathyroidism?
Increase Calcium? - Stones Renal stones Polyuria and polydipsia (nephrogenic DI) Nephrocalcinosis - Bones Bone pain Pathological # - Moans Depression - Groans Abdo pain n/v and constipation Pancreatitis PUD (increased fastrin secretion) - Other - Increased BP ( check Ca2_ in all with HTN)
What are the causes of primary hyperparathyroidism?
Solitary adenoma: 80%
Hyperplasia: 20%
PArathyroid Ca: <0.5%
What is the investigations of primary hyperparathyroidism, what will you see?
Bloods: Increased Ca2+ and increased PTH, increased ALP, decreased PO4.
PTH can be inappropriately normal
ECG: Decreased QT –> Bradycardia –> 1st degree block
X-ray: osteitis fibrosa cystica –> Phalangeal erosions.
DEXA: osteoporosis
Management for primary hyperparathyroidism
General
- increase fluid intake
- Avoid dietary Ca2+ and thiazide (increased serum Ca)
First line - Parathyroidectomy if symptomatic. (elevated Ca, hypercalciuria, nephrolithiasis, age <50, T score lower than -2.5).
In urgent cases consider hydration with saline. Bisphosphonates and loop diuretics to increase calcium excretion.
Look for scar which is in the crease of neck.
Surgical: excision of adenoma
- Hypoparathyroidism
- Recurrent laryngeal N. palsy
Causes of secondary hyperparathyroidism?
Vitamin D deficiency
Chronic renal failure
Investigations and signs of 2ndry HyperPTH?
increased PTH, decrease Ca, increase PO4, increased ALP, Decreased Vit D.
Management of secondary hyperparathyroidism?
- Correct cause
- Phosphate binders
With Ca: calcichew
W/O Ca: sevelamer - Vit D: calcitriol, ergocalciferol, cholecalciferol (inactive)
Calcium carbonate - 210/1300 mg/day.
Indication for surgery = bone pain, persistent pruritus, soft tissue calcification.
What is tertiary hyperparathyroidism?
- Prolonged 2 HPT –> autonomous PTH secretion.
Allow 12 months following transplant as many cases will resolve.
Total parathyroidectomy.
- Increased Ca, Increased PTH, decreased PO4, Increased ALP.
What causes hypoparathyroidism?
Decreased PTH due to gland failure
What is the presentation of decreased Ca –> SPASMODIC?
- Spasms (carpopedal = Trousseau’s sign)
- Perioral paraesthesia
- Anxious, irritable
- Seizures
- Muscle tone increased - colic, wheeze, dysphagia
- Orientation impaired (confusion)
- Dermatitis
- Impetigo herpetiformis (decreased Ca + pustules in pregnancy)
- Chovsteks, cardiomyopathy (increased QTc –> Torsades de Pointes)
Causes of hypoparathyroidism?
Autoimmune - Isolated autoimmune hypoparathyroidism Congenital: DiGeorge - Cardiac abnormality - Abnormal facies - Thymic aplasia - Cleft palate - Hypocalcaemia - Chr 22
Iatrogenic
- Surgery
- Radiation
Hypomagneasemia - Required for both PTH section + action on target tissues.
May cause hypocalcaemia + render patient unresponsive to treatment with calcium + Vit D.
Investigations for hypoparathyroidism?
decreased Ca, increased PO4, decreased PTH, normal ALP.
Management of hypoparathyroidism?
Ca supplements
Calcitriol
In emergency - Infuse Calcium at a Ca <1.88 alongside magnesium.
Thiazide diuretics can reduce the rate of urinary calcium excretion.
What is pseudohypoparathyroidism?
- Failure of target organ response to PTH
- Symptoms of hypocalcaemia
- Short 4th and 5th metacarpals, short stature
- Investigtions = decreased Ca, increased PTH
Management = Ca + calcitriol
What is pseudopseudohypoparathyroidism?
Normal maternal receptors in kidney –> Normal biochem.
Abnormal paternal receptors in body –> psuedohypoparathyroidism phenotype.
What is Cushing’s Syndrome?
Clinical state produced by chronic glucocorticoid excess
Consider pseudo-Cushings in alcoholics or in severe depression. False positive dexamethasone suppression test. Thought to be excess alcohol decreased liver’s ability to clear cortisol.
Differentiate with insulin stress test to differentiate true and pseudo-Cushing’s.
Features of Cushing’s Syndrome? - Catabolic Effects
- Proximal myopathy
- Striae
- Bruising
- Osteoporosis
Features of Cushing’s Syndrome? - Glucocorticoid Effects
DM
Obesity
Features of Cushing’s Syndrome? - Mineralocorticoid Effects
HTN
Hypokalaemia
Appearance of a person with Cushing’s Syndrome?
- Moon face
- Acne and hirsuitism
- Interscapular and supraclavicular fat pads
- Centripetal obesity
- Striae
- Thin limbs
- Bruising
- Thin skin
What is ACTH-independent CUshing’s?
- Decreased ACTH due to -ve feedback.
- No suppression with any dose of dexamethasone.
Causes of ACTH independent Cushing’s Syndrome?
- Iatrogenic steroids: commonest cause
- Adrenal adenoma/Ca: carcinoma often –> virilisation
- Adrenal nodular hyperplasia
- Carney complex: LAME syndrome:
- myxomatous neoplasms, cardiac, endocrine, cutaneous and neural
- pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue nevus.
- McCune-Albright
What is ACTH- Dependent Cushing’s?
ACTH is raised
Causes of ACTH-Dependent Cushing’s
Cushing’s Disease
- Bilateral adrenal hyperplasia from ACTH-secreting pituitary tumour. MRI pituitary does not rule out Cushing’s Disease. Often too small.
- Cortisol suppression with high-dose dex
Ectopic-ACTH
- SCLC
- Carcinoid tumour
- Skin pigmentation, metabolic alkalosis, weight loss, hyperglycaemia
- No suppression with any dose of dex.
- Characteristically presents with very low potassium level.
Investigations for Cushing’s Syndrome?
Cushings can present with a hypokalaemic metabolic alkalosis - aldosterone acts on sodium hydrogen channels in kidney.
1st: 24hr urinary free cortisol
- Late night serum or salivary cortisol (>50micrograms/24hr)
Highest @ 9AM, lowest @ midnight (elevated)
then check ACTH levels (if low = adrenal source = cushings syndrome. If high pituitary/ectopic).
Then: - Dexamethasone suppression test
Low dose is to differentiate patients with CS from those who do not have CS.
High dose - distinguish patients with Cushing’s disease (Suppressed) from those with ectopic ACTH (not suppressed).
- ACTH (but ACTH degrees v quick after venepuncture to determine whether this is ACTH dependent or independent
- localisation: CT, MRI
- DEXA scan
Bilateral inferior petrosal sinus vein sampling - best test to confirm pituitary vs ectopic) .
CRH stimulation - if pituitary source then cortisol rises
If ectopic/adrenal then no change in cortisol.
Management of Cushing’s?
- Disease?: Trans-sphenoidal excision
- Adrenal adenoma/Ca: Adrenelectomy
- Ectopic ACTH: tumour excision, metyrapone (inhibits cortisol synthesis).
What is Nelson’s Syndrome?
Rapid enlargement of a pituitary adenoma following bilateral adrenelectomy for Cushing's syndrome . - Not typically performed nowadays. - Presentations Mass effect: bitemporal hemianopia Hyperpigmentation
Removal of both adrenal glands eliminates the production of cortisol, and the lack of cortisol’s negative feedback can allow any pre-existing pituitary adenoma to grow unchecked.
Production of the ACTH leading to increased MSH and hyperpigmentation.
What is primary hyperaldosteronism?
Excess aldosterone independent of the RAS
Features of primary hyperaldosteronism?
- Hypokalaemia: weakness, hypotonia, hyporeflexia, cramps
- Paraesthesia
- HTN
Causes of primary hyperaldosteronism?
- Bilateral adrenal hyperplasia (70%)
- Adrenocortical adenoma (30%): Conn’s Syndrome.
- Adrenocortical carcinoma?
Investigations for primary hyperaldosteronisM?
- U+E: increased Na, Decreased K, Alkalosis
- Take care with diuretics, hypotensives, laxatives, steroids
- Aldosterone: renin ratio: increased with primary. High aldosterone, low renin.
- ECG: flat/inverted T waves, U waves, depressed ST segment, prolonged PR and QT intervals (hypokalaemia)
- Adrenal CT/MRI -
Management of primary hyperaldosteronism?
Conn’s: Laparoscopic adrenalectomy
Hyperplasia: spironolactone, eplerenone (aldosterone antagonists)
2nd line is laparoscopic adrenalectomy
Secondary hyperaldosteronism?
Due to increased renin from decreased renal perfusion?
Causes of secondary hyperaldosteronism?
- RAS (renal artery stenosis)
- Diuretics
- CCF
- Hepatic failure
- Nephrotic syndrome
Investigations
- Aldosterone: renin ratio normal.
Management of RAS
- anti HTN with captopril, enalapril but not if bilateral?
- + aspirin
2nd line is renal artery stenting
What is Bartter’s Syndrome?
- AR
- Blockage of NaCl reabsorption in loop of Henle (as if taking frusemide)
- Congenital salt wasting –> RAS activation –> hypokalaemia and metabolic alkalosis
- Normal BP
What is primary adrenal insufficiency?
Addison’s - Destruction of adrenal cortex –> glucocorticoid and mineralocorticoid deficiency
Causes of Addison’s
Primary = TB, addison’s
Secondary - Low ACTH - Pituitary failure. Doesn’t present with the hyperpigmentation.
- Autoimmune destruction: 80%
- TB: worldwide most common
- Metastasis: lung, breast, kidney
- Haemorrhage: Waterhouse-Friedrichson - Adrenal haemorrhage following massive meningitis.
- Congenital: CAH
Symptoms of Adrenal insufficiency
- Weight loss + anorexia
- Nausea, abdo pain, diarrhoea, constipation
- Lethargy, depression
- Hyperpigmentation: buccal mucosa, palmar creases
- Postural hypotension –> Dizziness, faints
- Hypoglycaemia
- Vitiligo
- Addisonian crisis
Investigations for Adrenal Insufficiency?
Bloods
- Decreased Na, increased K
- Decreased glucose
- Decreased Ca
- Anaemia
- Morning serum cortisol
Short SYnACTHen test
- Cortisol before and after tetracosactide
- Exclude Addison’s if increased cortisol (measure the amount of cortisol produced).
- increased 9am ACTH (usually Low)
Other tests: 21-hydroxylase Abs: +Ve in 80% of AI disease
Plasma renin and aldosterone
CXR: evidence of TB
AXR: adrenal calcification
8am cortisol: no morning elevation suggests Addison’s
Short Synacthen test
- Exclude addison’s disease if cortisol rises to adequate level
Long Synacthen test
- Diagnose Addison’s disease if cortisol does not rise to adequate levels
Management of Adrenal insufficiency?
Replace
- Hydrocortisone
- Fludrocortisone
Advice
- Don’t suddenly stop steroids
- Increased steroids during intercurrent illness, injury. Double hydrocortisone dose, same fludrocortisone dose.
Hydrocortisone - 2/3 dose. Patients typically require 20-30mg per day. Majority given in the morning dose.
- Wear a medic-alert bracelet
F/up
- Watch for autoimmune disease
What is secondary adrenal insufficiency?
ie. Hypothalamus or pituitary failure
Causes
- Chronic steroid use –> suppression of HPA axis
- Pituitary apoplexy/Sheehan
- Pituitary microadenoma
Features
- Normal mineralocorticoid
- No pigmentation
What is an Addisonian Crisis?
Presentation
- Shocked: Increased HR, postural drop, oliguria, confused.
- Hypoglycaemia
- Hyponatraemia
- Hyperkalaemia
- Usually known Addisonian or chronic steroid user.
Precipitants to an addisonian crisis?
- Infection
- Trauma
- Surgery
- Stopping long-term steroids
- Pregnancy due to immune-regulatory changes following pregnancy.
Management of an Addisonian Crisis?
- Bloods: Cortisol, ACTH, U+E, - Cultures
- Check CBG: glucose may be needed
- Hydrocortisone 100mg IV 6hrly
- IV crystalloid - normal saline over 30-60 mins or with dextrose if hypoglycaemic.
- Repeat hydrocortisone 6hrly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action.
- Septic Screen
- Treat underlying cause
What is a Phaeochromocytoma?
- Catecholamine-producing tumours arising from sympathetic paraganglia
- Usually found in adrenal medulla
- Extra-adrenal phaeo’s found by aortic bifurcation.
What is the rule of 10s in Phaeochromocytoma?
10% malignant
10% extra-adrenal
10% bilateral
10% part of hereditary syndrome
Phaeo’s are associated with which hereditary syndromes?
MEN2a and 2b
- Neurofibrimatosis
- Von HIppel-Lindau: RCC + cerebellar signs
Presentation of phaeochromocytoma?
- Triad: episodic headache, sweating and tachycardia
- Other adrenergic features Increased BP, palpitations
Anxiety
Headache, tremor, dizziness
Anxiety
D/v, abdo pain
Heat intolerance, flushes
May have precipitant
- Straining, abdo palpation
- Exercise, stress
- B-b, IV contrast, TCAs, GA.
Investigations for phaeo?
- 24hr urine catecholamines, metanephrines, normetanephrines, creatinine.
- plasma catecholamines, metanephrines, normetanephrines,
- Also Vanillylmandelic acid
- Abdo CT/MRI
- MIBG Scan
Management of Phaeo?
Non-hypertensive crisis? Non malignant
Do alpha-blockage first, then B-blockade pre-op.
Give alpha first. After 24hrs then give B-Blocker.
- Phenoxybenzamine (alpha 2 blockade). Phaeochromocytoma = give PHenoxybenzamine before beta-blockers.
- Then monitor BP post-op for decreased BP.
Then offer atenolol 25-100mg.
Then surgical excision of the tumour (adrenelectomy)
If malignant - Surgical debulking and then use MIBG.
If monotherapy - consider labetalol as this is both alpha and beta blockade.
How to manage a HTN crisis in a phaeo?
Features of HTN crisis
- pallor
- Pulsating headache
- Feeling of impending doom
- very high BP (>180)
- increased ST and cardiogenic shock
Management
- Phentolamine 2-5mg IV (a-block) or labetalol 50mg IV
- repeat to safe BP
Phenoxybenzamine 10mg/PO when BP controlled.
- elective surgery after 4-6 weeks to allow full alpha-blockage and volume expansion
Define MEN?
Multiple Endocrine Neoplasia
- Functioning hormone tumours in multiple organs
- all autosomal dominant
What does MEN1 Consist of?
3 Ps
- Pituitary adenoma: prolactin or GH
- Parathyroid adenoma/hyperplasia: ABNORMAL CALCIUM GIVE AWAY.
- Pancreatic tumours: gastrinoma or insulinoma
May also present with Zollinger-Ellison syndrome = multiple gastroduodenal ulcers. High dose PPI
Most commonly present with Hypercalcaemia
What does MEN2A consist of?
2 Ps PPT
Thyroid Medullary Carcinoma
Parathyroid
Phaeochromocytoma - PHAEO is the give away
What does MEN2B consist of?
MMP
Thyroid Medullary carcinoma
Phaeochromocytoma
Marfanoid habitus
What is the Carney Complex/LAME syndrome?
- Lentigenes: spotty skin pigmentation \: Differential: peutz-jehgers - Atrial Myxoma - Endocrine tumours: pituitary, adrenal hyperplasia - Schwannomas
What is Peutz-Jegher’s
Mucocutaneous freckles on lips, oral mucosa and palms
GI hamartomas: obstruction
Pancreatic endocrine tumours
Increased risk of cancer: CRC, pancreas, liver, lungs, breast
Von Hippel-Lindau?
- renal cysts
- Bilateral renal cell carcinoma
Haemangioblastomas - often in the cerebellum –> cerebellar signs - Phaeochromocytoma
- pancreatic endocrine tumours
Neurofibromatosis NF1?
Dermal neurofibromas Cafe-au-lait spots Lisch nodules Axillary freckling Phaeochromocytomas
What is Schmidt’s syndrome?
- Polygenic
- Addisons
- Thyroid disease: hypothyroidism or Graves
- T1DM
Polyendocrine Syndromes
Causes of hypopituitarism?
Hypothalamic
- Kallmann’s (anosmia + GnRH Deficiency)
- Tumour
- Inflammation, infection, ischaemia
Pituitary stalk?
- Trauma
- Surgery
- Tumour (craniopharyngioma)
Pituitary
- Irradiation
- Tumour
- Ischaemia: apoplexy, Sheehan’s
- Infiltration: HH, amyloid
What are the most common causes of panhypopituitarism?
Surgery
Tumour
Irradiation
What are the features of panhypopituitarism?
Hormone deficiency
- GH: central obesity, atherosclerosis, decreased CO, decreased strength
- LH/FSH
M: decreased libido, ED, decreased hair growth
F: decreased libido, amenorrhoea, breast atrophy
- TSH: hypothyroidism (prolactin excess can cause TRH reduction and therefore TSH reduction).
- ACTH: secondary adrenal failure
Investigations for hypopituitarism?
Basal hormone tests?
Dynamic pituitary function tests?
- Insulin test –> increased cortisol and increased Growth hormone in response to hypoglycaemia
- GnRH –> Increased LH/FSH
- TRH –> Increased T4 and increased PRL.
MRI brain
Management is by treating underlying cause and hormone replacement.
What % of intracranial tumours are pituitary tumours?
10%
Classification of pituitary tumours?
Microadenoma <1cm
Macroadenoma >1cm
Secretory function - secretory/functioning vs non-secretory/functioning adenoma.
What is the pathology of pituitary tumours?
- Most are non-secretory
- 50% produce PRL
- Others produce GH or ACTH?
Features of pituitary tumours? Mass effect features?
Mass effects
- Headache
- Visual field defect: bitemporal hemianopia
- CN palsies: 3,4,5,6 (pressure on cavernous sinus)
- Diabetes insipidus
- CSF rhinorrhoea
Hormone effects of pituitary tumours?
PRL –> galactorrhoea, decreased libido, amenorrhoea, erectile dysfunction (this is because increased PRL goes to decreased GnRH –> decreased LH and FSH)
GH –> Acromegaly
ACTH –> Cushing’s Disease
Investigations for pituitary tumours?
MRI
Visual field tests
Hormones: PRL, IGF, ACTH, Cortisol, TFTs, LH/FSH
Suppression test
Management of pituitary tumours?
Replace hormones
- Prolactinoma - Give Dopamine Agonist = Cabergoline/bromocriptine
Treat hormone excess
Surgical - transsphenoidal pituitary adenomectomy.
- pre-op hydrocortisone
- Post-op dynamic pituitary test
What is pituitary apoplexy?
Rapid pituitary enlargement due to bleed into a tumour
- Mass effect
Headache, meningism, decreased GCS
Bitemporal hemianopia
- CVS collapse due to acute hypopituitarism
- Rx: Urgent hydrocortisone 100mg IV.
What is a craniopharyngeoma?
- Originates from Rathke’s pouch
- Commonest childhood intracranial tumour
- growth failure
- Calcification seen on CT/MRI
Causes of hyperprolactinoma?
Excess pituitary production
- Pregnancy, breastfeeding
- Prolactinoma (PRL >5000)
- Hypothyroidism (increased TRH)
Disinhibition by compression of pituitary stalk (stalk effect compression of dopamine)
- Pituitary adenoma
Most common type and produce an excess of prolactin. Non-secreting adenomas are next most common, the GH secreting and then ACTH secreting adenomas.
-Craniopharyngioma
Dopamine antagonists (commonest cause)
- Antiemetics: metoclopramide
- Antipsychotics: risperidone, haldol
Symptoms of hyperprolactinaemia?
- Amenorrhoea
- Infertility
- Galactorrhoea
- Decreased Libido
- ED
- Mass effect from prolactinoma
Investigations for hyperprolactinaemia?
- Basal PRL: >5000 = prolactinoma
- Pregnancy test, TFTs
MRI
Management of hyperprolactinaemia?
1st line: cabergoline or bromocriptine
Da agonist, decreased PRL secretion and decreased tumour size
SE: nausea, postural hypotension lung fibrosis
2nd line: trans-sphenoidal excision
- If visual or pressure symptoms don’t respond to medical management.
Acromegaly causes?
- Pituitary acidophil adenoma in 99%
- Hyperplasia from GHRN secreting carcinoid tumour
GH stimulates bone and soft tissue growth through increased IGF1
Symptoms of acromegaly?
- Acroparaesthesia
- Amenorrhoea, decreased libido
- Headache
- Snoring
- Sweating
- Arthralgia, back ache
- Carpal tunnel (50%)
Signs of acromegaly? Hands
- Spade-like
- Thenar wasting
- Boggy sweaty palms (if active)
- Increased skin fold thickness
- Carpal tunnel: decreased sensation + thenar wasting.
Check for raised ICP (look for bitemporal hemianopia)
- 3 Gs
Gynaecomastia, goitre, glycosuria
Signs of acromegaly? Face
- Prominent supraorbital ridges
- Scalp fold: cutis verticis gyrata
- Coarse face, wide nose, big ears
- Prognathism: look from side
- Macroglossia
- Widely-spaced teeth
- Goitre
Other features of acromegaly
- Puffy, oily, darkened skin
- Proximal weakness + arthropathy
- Pituitary mass effect: bitemporal hemianopia
Complications of acromegaly?
Endocrine
- Impaired glucose tolerance (40%)
- Diabetes (15%)
Cardiovascular
- increased BP
- LVH
- Cardiomyopathy
- Increased IHD and increased stroke
Neoplasia
- Increased risk of CRC
Could be part of MEN1
Investigations of acromegaly?
- Increased IGF1 is now first line.
Increased glucose, increased Ca,
- increased PO4
- Glucose tolerance test
GH fails to suppress with glucose in acromegaly (not first line anymore) - Visual fields and acuity
- MRI
Management for acromegaly?
1st line: trans-sphenoidal excision
2nd line: somatostatin analogues - octreotide (increased risk of gallstones) - if tumours or surgery fail to achieve remission of acromegaly.
3rd line: GH antagonist - pegvisomant
4th line: radiotherapy
Diabetes insipidus symptoms?
Polyuria
Polydipsia
Dehydration
Hypernatraemia: lethargy, thirst, confusion, coma.
Nephrogenic vs central
Causes of cranial diabetes insipidus?
ADH defective release
Idiopathic Congenital: wolfram syndrome Tumours Trauma Vascular: haemorrhage (Sheehan's) Infection: meningoencephalitis Infiltration: sarcoidosis
Causes of nephrogenic diabetes insipidus?
Kidney is resistant or insensitive.
Congenital
metabolic: decreased K, Increased Ca.
Drugs: Lithium, demecleocycline, vaptans
Post-obstructive uropathy
Investigations of Diabetes Insipidus
Diagnosis - Water deprivation test
- Deprived of fluids for 8hrs, serum osmolality, urine volume and urine osmolality measured. +Ve if there is a suboptimal response in urinary concentration.
- Desmopressin stimulation test (to distinguish nephrogenic from central.
BLoods: U+E, Ca, glucose
Urine and plasma osmolality
- A low urine osmolality in conjunction with high serum osmolality strongly suggests DI.
- Exclude DI if U:P osmolality >2 (concentration)
Differential for Diabetes Insipidus?
DM
Diuretics or Lithium
Primary Polydipsia
Management of Diabetes Insipidus?
Cranial:
Find cause: MRI brain
Desmopression PO
Nephrogenic: treat cause
Sexual characterisitcs - Hirsuitism causes?
Familial Idiopathic Increased androgens - Ovary: PCOS - Adrenal: CUshings, adrenal Ca - Drugs: steroids
Features of PCOS?
Features
- 2nd oligo/amenorrhoea –> Infertility
Obesity
Acne, hirsuitism
US: bilateral polycystic ovaries
Hormones: increased testosterone, decreased SHBG, increased LH:FSH ratio
Management
- Metformin
- COCP
- Clomifene for infertility
Gynacomastia causes?
- Cirrhosis
- Hypogonadism
- Hyperthyroidism (increased ratio of oestrogen to androgen - increased in SHBG)
- Oestrogen - or HCG producing tumours: e.g testicular
- Drug: spiro, digoxin, oestrogen
Erectile dysfunction causes?
Organic causes
- Smoking
- ETOH
- DM
- Endo: hypogonadism, hyperthyroidism, increased Prolactin
- Neuro: MS, autonomic neuropathy, cord lesion
- Pelvic surgery: bladder, prostate
- Penile abnormalities: Peyronie’s disease.
Patient with T2DM has STEMi and is on simvastatin, gliclazide and metformin. How should he be managed in CCU?
Stop metformin and gliclazide. Start IV insulin infusion.
Benefits of tight glycaemic control following MI. Manage hyperglycaemia in patients admitted to hospital for an ACS by keeping blood glucose below 11. Consider dose-adjusted insulin infusion with monitoring of blood glucose.
Thyroid gland
Inspect Palpate LAN Percuss behind sternum Auscultate (thyroid bruit)
Causes of thyrotoxicosis
Graves TMnG Adenoma Viral/postpartum thyroiditis Amiodarone
Endocrine causes of HTN?
Hyperaldosteronism: conn’s CAH
- Low potassium
Phaeochromocytoma - phenoxybenzamine followed by propanolol
Nelson’s syndrome
Pituitary enlargement following bilateral adrenalectomy - high ACTH and pigmentation.
Vit D deficiency
Fatigue
Proximal myopathy
Muscle aches and pain
Non-PTH causes of hypercalcaemia
Hyperthyroidism
Malignancy:
PTHrP - SCC of breast, lung
- Multiple myeloma - old man with back pain (could be Paget’s - check the Alk Phos) - look at total protein
- Mets - bone pain, Ca sign
- Prostate Ca - PSA.
- Sarcoidosis - increased 1,25 dihydrox Vit D - in granulomata of the lungs - action of interferon. Polyuria/Polydipsia.
Bradycardia - Artificially elevated by calcium, high BP. Reflex sinus brady.
Osteoporosis
At risk groups (PM, Steroids, Immobilie, chronic inflammatory conditions)
Check BMD, Vit D
- Exclude osteomalaica
High risk/post fracture -
- bisphosphonates (Stand 30 mins after). No Need for DEXA.
- Very poor oral absorption - stand up, big glass of water
- Ulcer
- CI in osteomalacia
Types of corticosteroids
- Minimal glucocorticoid activity, high MC activity = Fludrocortisone
- Glucocorticoid activity, high mineralocorticoid activity, = Hydrocortisone
- Predominant glucocorticoid activity, low mineralocorticoid activity = Prednisolone
- Dexamethasone = least amount of mineralocorticoid.
Hyrocortisone:
G 1, M 1.
Prednisolone:
G 4, M 0.8.
Fludricortisone:
G 15, M 150
Aldosterone:
G 0, M 500
Dexamethasone:
G 40, M 0’
Glucocorticoid side-effects
- endocrine: impaired glucose regulation, increased
- appetite/weight gain, hirsutism, hyperlipidaemia
- Cushing’s syndrome: moon face, buffalo hump, striae
- musculoskeletal: osteoporosis, proximal myopathy, avascular necrosis of the femoral head
- immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis
- psychiatric: insomnia, mania, depression, psychosis. Rare cause of prednisolone is to cause steroid psychosis.
- gastrointestinal: peptic ulceration, acute pancreatitis
ophthalmic: glaucoma, cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
Mineralocorticoid side-effects
fluid retention
hypertension
Subclinical hypothyroidism
Watch and wait
TSH is between 4 - 10mU/L and the free thyroxine level is within the normal range
if < 65 years with symptoms suggestive of hypothyroidism, give a trial of levothyroxine. If there is no improvement in symptoms, stop levothyroxine
‘in older people (especially those aged over 80 years) follow a ‘watch and wait’ strategy, generally avoiding hormonal treatment’
if asymptomatic people, observe and repeat thyroid function in 6 months
TSH is > 10mU/L and the free thyroxine level is within the normal range start treatment (even if asymptomatic) with levothyroxine if <= 70 years 'in older people (especially those aged over 80 years) follow a 'watch and wait' strategy, generally avoiding hormonal treatment'
Pituitary incidentaloma
If found within the sellar, lab investigations must be done to determine if it is functional or non-functional.
Gynaecomastia drugs?
DISCO
Digoxin Isoniazid Spironolactone Cimetidine Other (e.g. oestrogens, cannabis, finasteride)
CODES
C: cirrhosis O: obesity D: digoxin E: oestrogen S: spironolactone
Sick euthyroid?
Common in unwell, elderly patients and often need no treatment.
Abnormal TFTs are very common in elderly patients when they are unwell.
IN the majority of cases TSH is within the normal range (inappropriately normal given the low thyroxine and T3).
MODY
Maturity onset diabetes of the young. Type Hepatic Nuclear Factor 1 Alpha.
HNF1a accounts for 70% of MODY cases.
Sulphonylureas (gliclazide) are the optimal treatment in HNF1a-MODY
MODY = T2DM in patients < 25 yrs old. Typically inherited as an autosomal dominant condition.
MODY 3 = HNF1 alpha associated witH HCC.
MODY 2 = Defect in glucokinase gene.
MODY 5 = Liver and renal cyst.
Typically in patients <25.
A family history of early onset diabetes is often present.
Ketosis is not a feature at presentation.
Patients with the most common form are very sensitive to suphonylureas, insulin is not usually necessary.
Gastroparesis
Erractic blood glucose control, bloating and vomtiing .
Can occur in diabetics due to neuropathy of the vagus nerve, causing abnormal gut movement.
Metoclopramide is a pro-kinetic drug that can improve gastric emptying.
Causes of raised prolactin?
Prolactin is secreted by the anterior pituitary gland. Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonist such as bromocriptine may be used to control galactorrhoea.
Pregnancy Prolactinoma Physiological PCOS Primary hypothyroidism Phenothiazines, metocloPramide, domPeridone.
Thiazolidinediones?
Pioglitazone - insulin into the zone.
Reduces peripheral insulin resistance.
PPAR gamma receptor.
SE: Increased risk of bladder cancer. Weight gain, liver impairment: LFTs, fliud retention. Risk of fractures, bladder cancer.
Absolute contraindiation to heart failure due to fluid retention
SGLT-2 inhibitor?
Canagliflozin · Empagliflozin · Dapagliflozin
Prevents the reabsorption of glucose from the proximal renal tubule, resulting in more glucose being secreted in the urine.
SE: Genital infections, DKA. such as thrush.
Biguanides?
Metformin - GI upset, lactic acidosis
GLP-1 mimetics?
Exenatide
SE: Nausea, vomiting, pancreatitis.
Congenital adrenal hyperplasia?
AR disorders
Affecting steroid biosynthesis
Response to resultant low cortisol levels the anterior pituitary secretes high levels of ACTH
ACTH stimulates production of adrenal androgens that may virilize a female infant.
21-hydroxylase deficiency
11-beta hydroxylase deficiency
17-hydroxylase deficiency
Sulphonylureas + side effects
Gliclazide
Increase insulin secretion.
SE: hypoglycaemic episodes and weight gain
Can also lead to hyponatraemia 2ndry to SIADH, bone marrow suppression, hepatotoxicity, peripheral neuropathy.
Avoid in breastfeeding and pregnancy.
Orlistat + MOA
Pancreatic lipase inhibitor
Inhibits pancreatic lipases.
Orlistat is a pancreatic lipase inhibitor used in the management of obesity. Adverse effects include faecal urgency/incontinence and flatulence. A lower dose version is now available without prescription (‘Alli’). NICE have defined criteria for the use of orlistat. It should only be prescribed as part of an overall plan for managing obesity in adults who have:
BMI of 28 kg/m^2 or more with associated risk factors, or
BMI of 30 kg/m^2 or more
continued weight loss e.g. 5% at 3 months
orlistat is normally used for < 1 year
Sitagliptin class + MOA
Dpp-4 inhibitors. Give to patients who are obese.
Reduce the breakdown of incretins, which thereby decreass glucagon secretion.
Klinefelter’s syndrome?
XXY
features
- Often taller than average
- Lack of secondary sexual characteristics
- small, firm testes
- infertile
- Gynaecomastia
- Elevated gonadotrophin
LADA?
Latent autoimmune diabetes of adulthood.
despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune -cell failure is slow.
In contrast to type 2 diabetes, patients are typically younger and without an increased body habitus. In contrast to type 1 diabetes, insulin is not usually required in the early stages of the disease.
Diagnosis may be aided through a Glutamic Acid Decarboxylase (GAD) Autoantibodies test and evidence of other autoimmune diseases.
Stress response to surgery: Hormones that increased
GH Cortisol Renin ACTH Aldosterone Prolactin ADH Glucagon
ACTH and growth hormone (GH) is stimulated by hypothalamic releasing factors, corticotrophin releasing factor (CRF) and somatotrophin (or growth hormone releasing factor)
Perioperative increased prolactin secretion occurs by release of inhibitory control
Secretion of thyroid stimulating hormone (TSH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) does not change significantly
ACTH stimulates cortisol production within a few minutes of the start of surgery. More ACTH is produced than needed to produce a maximum adrenocortical response.
Significant increases within 4-6 hours of surgery (>1000 nmol litre-1).
The usual negative feedback mechanism fails and concentrations of ACTH and cortisol remain persistently increased.
The magnitude and duration of the increase correlate with the severity of stress and the response is not abolished by the administration of corticosteroids.
The metabolic effects of cortisol are enhanced:
An important vasopressor and enhances haemostasis
Renin is released causing the conversion of angiotensinogen to angiotensin I
Angiotensin II formed by ACE on angiotensin 1, which causes the secretion of aldosterone from the adrenal cortex. This increases sodium reabsorption at the distal convoluted tubule
Stress response to surgery; hormones that decreased?
Insulin - Steroids oppose the action of insulin and stimulate hepatic gluconeogenesis.
Testosterone
Oestrogen
Neuroblastoma?
Raised urinary vanillylmandelic acid and homovanillic acid levels
Acarbose
Decreased glucose absorption in the gut.
Galactorrhea?
Caused by Chlorpromazine - antipsychotic
DM Sick day rules
ncrease frequency of blood glucose monitoring to four hourly or more frequently
Encourage fluid intake aiming for at least 3 litres in 24hrs
If unable to take struggling to eat may need sugary drinks to maintain carbohydrate intake
It is useful to educate patients so that they have a box of ‘sick day supplies’ that they can access if they become unwell
Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis
