Endocrinology Flashcards
What is Addison’s disease?
Definition ¬– failure of the adrenal glands to function, more specifically Addison’s refers to autoimmune destruction of the adrenal glands and is the most common cause of primary hypoadrenalism in the UK
What are the main causes of primary hypoadrenalism?
Primary
Autoimmune destruction of the adrenal glands (80% in the UK)
TB (most common cause worldwide)
Adrenal metastases (generally from lung, breast or renal cancer) and Lymphoma
Opportunistic infections in HIV
Congenital adrenal hyperplasia – no production of cortisol or aldosterone just testosterone
Antiphospholipid syndrome and SLE
Adrenal haemorrhage - Waterhouse-Frederiksen syndrome (bilateral adrenal haemorrhage secondary to meningococcal sepsis)
What are the secondary causes of primary hypoadrenalism?
Pituitary disorders such as tumours, irradiation and infiltration
Iatrogenic due to long standing steroid use (negatively inhibiting the pituitary axis) which becomes apparent on withdrawal of steroids.
What are the clinical features of primary hypoadrenalism?
Fatigue Weakness Anorexia and weight loss Nausea and vomiting Salt craving Hyperpigmentation (due to excess ACTH) especially in palmer creases (only primary causes) Vitiligo Loss of pubic hair in women Postural hypotension Mood changes such as depression, psychosis
Low Sodium, high potassium, and high urea and ametabolic acidosis Low glucose Anaemia High ACTH (unless secondary cause) Adrenal Autoantibodies
How should suspected primary hypoadrenalism be investigated?
TFTs
FBC and U&Es
9am Cortisol - >500nmol/l Addison’s very unlikely, <100nmol/l is highly abnormal and anywhere inbetween should prompt an ACTH test
Synacthen Test – 250ug ACTH analogue given IM and cortisol measured 30min before and after
Adrenal autoantibodies e.g. anti-21-hydroxylase
How is primary hypoadrenalism managed?
Replacement of steroids
Glucocorticoids activity such as Prednisolone, dexamethasone, and betamethasone
Steroids with very high mineralocorticoid activity such as Fludrocortisone
Steroids with glucocorticoid activity and high mineralocorticoid activity – hydrocortisone
Patient education regarding not missing doses, MedicAlert bracelets and steroid cards and extra steroids if strenuous activity and double steroids if febrile, injured or stressed
How does an Addisonian crisis present?
Presentation
Shock (high HR, hypotensive, oliguria, weak, confused, comatosed)
Hypoglycaemia
Can be precipitated by: infection, trauma, surgery and missed medication
How is an Addisonian crisis managed?
Management Bloods for cortisol and ACTH Check Us and Es Hydrocortisone STAT then 100mg every 8 hours (note no fludrocortisone is required) IV fluid bolus Monitor BMs Fludrocortisone may be needed Look for underlying cause
What is diabetes insipidus?
Definition – Passage of large volumes of dilute water due to: reduced ADH secretion by the posterior pituitary (Cranial DI) or impaired response to ADH by the kidneys (Nephrogenic DI)
What are the cranial or central causes of DI?
Cranial DI
• Idiopathic in 50% of cases
• Tumour of the pituitary or near it
• Trauma – head injury or cranial infection
• Histiocytosis X and Craniopharyngiomas
• Wolfram’s Syndrome – association of cranial diabetes insipidus, diabetes mellitus, optic atrophy and deafness
What are the nephrogenic causes of diabetes insipidus?
Nephrogenic DI
• Congenital defect in ADH receptor
• Metabolic – low potassium or high calcium
• Drug – lithium or demeclocycline
• Tubule interstitial disease – obstruction, sickle cell and pyelonephritis
What are the clinical features of diabetes insipidus?
Polyuria
Polydipsia (which can become all consuming)
Dehydration and Hypernatremia
How should suspected diabetes insipidus be investigated?
Blood Glucose
Serum and plasma osmolality (urine osmolality >700mOsm/kg excludes diabetes insipidus)
Urine to Plasma Osmolality ratio (can be up to 2:1, if greater then DI is excluded)
Check Pituitary function
8 Hour Water Deprivation test
Deprive from fluid for 8 hours checking urine osmolality every 2 hours and venous every 4. If urine osmolality ever exceeds 600mmol/L then stop test – this is normal. If it remains under 600mmol/L then after 8 hours trial desmopressin. If remains dilute then Nephrogenic, if concentrated after desmopressin then Cranial.
How is diabetes insipidus managed?
Cranial/Central
MRI
Desmopressin – synthetic analogue of ADH
Nephrogenic Treat cause Bendroflumethiazide NSAIDs can lower urine output Low salt/protein diet
What is the emergency management of diabetes insipidus?
Urgent plasma U&Es, serum, and urine osmolality
Monitor Urine output
IV fluids to keep up with water loss. However, if severely hypernatraemic lower this slowly by a maximum of 12mmol/L per day.
Do NOT use 0.45% saline.
Desmopressin 2mcg IM can be used
What is type 1 diabetes mellitus?
Definition – Insulin deficiency from autoimmune destruction of insulin secreting beta cells in the pancreas, usually first manifests when young although LADA (late autoimmune diabetes adults) is documented, and these patients are often misdiagnosed as T2DM.
What causes type 1 diabetes mellitus?
Autoantibodies to pancreatic beta cells in the islets of Langerhans in the pancreas
Steroids Antipsychotics Pancreatic surgery Cushing’s disease Acromegaly Pheochromocytoma Hyperthyroidism Pregnancy
What are the clinical features of type 1 diabetes mellitus?
Weight loss Polyuria Polydipsia Visual blurring Genital thrush Lethargy Persistent hyperglycaemia despite diet and weight loss DKA – abdominal pain, vomiting, reduced GCS
How is diabetes investigated and diagnosed?
Oral Glucose Tolerance test (fasting CBG then 75g glucose then BM after 2hrs)
Fasting Blood Glucose
HbA1c measures glycosylated haemoglobin
If symptomatic
Fasting CBG > 7mmol/L
Random CBG or glucose tolerance test > 11.1mmol/L
HbA1c > 6.5% or 48mmol/l (but a value less than this does not exclude diabetes)
If Asymptomatic the above criteria but must be demonstrated on two separate occasions
Pre diabetes = HbA1c between 42-47mmol/l (6-6.4%) or a fasting glucose 6.1-6.9 or Oral glucose tolerance test between 7.8 and 11.0 at the 2 hour mark.
How is type 1 diabetes mellitus managed?
What regimen? BP? Target BM? Monitoring?
Insulin
Multiple daily injection termed ‘basal-bolus’ insulin regimens are preferred (rapid/short-acting bolus before meals and intermediate/long-long insulin twice daily) over twice daily mixed insulin regimens.
BD detemir is the regimen of choice plus rapid acting insulin before meals
If BMI > 25 then consider adding metformin.
Blood pressure should be managed at 135/85 unless then have albuminemia or 2 or more features of metabolic syndrome in which case it should be 130/80. Note, unless afro-Caribbean ACEi are always first line in diabetics due to the renoprotective effect.
Control blood glucose levels between 4-7mmol/L before meals and fasting blood glucose/waking at 5-7 mmol/L
Monitor HbA1c every 3-6months with a target levels of 48mmol/l (6.5%) in adults.
How should someone with type 1 diabetes mellitus monitor their glucose levels and what levels should they aim for?
Patients are recommended to self-monitor at least 4 times a day, usually then is done before each meal and before bed. Monitoring should increase with frequency hypoglycaemic episodes, during illness, before during and after sport, when planning pregnancy, during pregnancy and while breast feeding.
Control blood glucose levels between 4-7mmol/L before meals and fasting blood glucose/waking at 5-7 mmol/L
What is type 2 diabetes mellitus?
Definition – high blood glucose levels due to reduced insulin production and increased insulin resistance. Much more common in obese, middle aged people but increasingly seen in the younger generations.
What causes type 2 diabetes mellitus?
Causes
Obesity
Lack of exercise
Calorie and alcohol excess
Steroids Antipsychotics Pancreatic surgery Cushing’s disease Acromegaly Pheochromocytoma Hyperthyroidism Pregnancy
What are the clinical features of type 2 diabetes mellitus?
Asymptomatic
Development of complications such as diabetic foot ulcers, retinopathy, nephropathy etc.
How often should someone with type 2 diabetes mellitus have their HbA1c checked and what targets should they aim for?
Monitor HBA1C every 3-6 months until stable and then every 6 months. If managing with just lifestyle or lifestyle and metformin then HbA1c target is 48mmol/l or 6.5%, if managing with any drugs that can cause hypoglycaemia then the target is 53mmol/l or 7%. IN the elderly consider relaxing these targets.
If a patient can tolerate metformin what is the stepwise treatment procedure of type 2 diabetes mellitus> ?
Treatment of T2DM
• Lifestyle modification (diet, weight control and exercise)
• Metformin and titrate up or down as required
• If hbA1c rises above 58mmol/mol, dual therapy with metformin and:
1. DPP4 inhibitor (gliptin)
2. Thiazolidinedione (glitazone)
3. Sulphonylurea
4. SGLT-2i (gliflozin)
• If hbA1c rises again to above 58mmol/mol, triple therapy with metformin and:
1. DPP4 inhibitor (gliptin) and a sulphonylurea
2. Thiazolidinedione (glitazone) and a sulphonylurea
3. Sulphonylurea and SGLT-2i (gliflozin)
4. Thiazolidinedione and a SGLT-2i (gliflozin)
5. Insulin therapy
• If triple therapy not effective, not tolerated or contraindicated and BMI > 35 then metformin, +sulphonylurea + GLP-1 mimic
If metformin is not tolerated or contraindicated what is the step wise treatment procedure for type 2 diabetes mellitus?
When metformin not tolerated or contraindicated
• If the HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions, consider one of the following:
1. sulfonylurea
2. gliptin
3. pioglitazone
• If the HbA1c has risen to 58 mmol/mol (7.5%) then one of the following combinations should be used:
1. gliptin + pioglitazone
2. gliptin + sulfonylurea
3. pioglitazone + sulfonylurea
• If despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy
How should blood pressure be controlled in type 2 diabetes mellitus?
Blood pressure is now controlled at the same levels as other patients - < 140/90. Note, unless afro-Caribbean ACEi are always first line in diabetics due to the renoprotective effect.
What drugs should continue when starting insulin therapy for type 2 diabetes mellitus?
Insulin therapy
When starting insulin in T2DM metformin should be continued whilst other drugs should be reviewed. Recommendations are to start with human NPH insulin taken at bedtime or twice daily when needed.
What is metformin, how does it work, what are the side effects and give some examples.
Is usually stopped on admission to hospital and be wary of lactic acidosis and GI symptoms (consider modified release). Taken orally as a tablet that increases insulin sensitivity and decreases hepatic gluconeogenesis. Cannot causes hypoglycaemia.
What is a sulphonylurea, how does it work, what are the side effects and give some examples.
Stimulate pancreatic beta cells to secrete insulin, given as an oral tablet. SE include hypoglycaemia, increased appetite, and weight gain SIADH, and liver dysfunction (cholestatic). Examples include gliclazide and glimepiride.
What is a glitazone, how does it work, what are the side effects and give some examples.
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake. Taken orally as a tablet. SE include weight gain, fluid retention, liver dysfunction, bladder cancer risk and fractures. Only currently available drug is pioglitazone.
What is a gliptin, how does it work, what are the side effects and give some examples.
Increases incretin levels which inhibit glucagon secretion. Taken orally as a tablet. SE are rare but there is an increased risk of pancreatitis. Does not cause weight gain. Examples include Vildagliptin and sitagliptin.
What is a gliflozin, how does it work, what are the side effects and give some examples.
SGLT-2 inhibitors - inhibit reabsorption of glucose in the kidneys, take orally as a tablet. SE include UTI, normoglycemic ketosis and increased risk of amputation – monitor feet closely. Preferred by patients as they often result in weight loss. Examples include canagliflozin, dapagliflozin and empagliflozin.
What is a GLP1 agonist, how does it work, what are the side effects and give some examples.
Incretin mimic which inhibits glucagon secretion, given SC. SE include nausea, vomiting and pancreatitis. Also liked by patients as they result in weight loss. Examples include Exenatide. Given within 60 minutes before the morning and evening meals, do not given after a meal.
What advice should be given to patients with diabetes for days when they are ill?
- Increase frequency of CBG to four hourly or more often
- Drink plenty of fluid
- If unable to eat maintain carbohydrates with sugary drinks
- Always have access to a mobile phone
- Do not stop oral hypoglycaemics even if intake is low (stress response increases glucose levels). Only exception is metformin if dehydrated due to renal impact.
- If on insulin never stop due to risks of DKA
What are the 2 ways of classifying insulin?
Manufacturing process
Porcine – extracted and purified from pig pancreas
Human sequence insulin – either produced by enzyme modification of porcine insulin (emp) or biosynthetically by recombinant DNA using bacteria (crb, prb) or yeast (pyr)
Analogues
Duration of action
Rapid-acting insulin – onset in 5 mins, peak in 1 hour and duration of 3-5 hours
Short-acting insulin – onset in 30mis, peak at 3 hours and duration 6-8 hours
Intermediate-acting insulin – onset in 2 hours, peak at 5-8 hours and duration 12-18 hours
Long-acting insulin analogues – onset in 1-2 hours, flat profile and duration up to 24 hours
Give some examples of premixed insulin preperations
Novomix 30 – 30% aspart (rapid) and 70 aspart protamine (intermediate)
Humalog Mix25 – 25% lispro (rapid) and 75% lispro protamine (intermiedate)
Humulin M3 – 30% soluble isophane (short) and 70% isophane (intermediate)
How is insulin usually given and what advice is important to give to patients?
Vast majority of insulin is given SC and it is important to rotate injection sites to prevent lipodystrophy. Insulin pumps are available which delivers continuous basal infusion and patient activated bolus doses at meal times.
How is prediabetes managed?
Lifestyle modifications
At least yearly follow-up with blood tests
Metformin if adult at high risk if despite lifestyle modifications their results are not improving or getting worse.
What are the DVLA rules for patients with diabetes?
To hold a HGV license the following standard must be met
- No severe hypoglycaemic events in the last 12 months
- Driver is fully hypoglycaemic aware
- Adequate control of condition by regular monitoring at least twice daily and times relevant to driving – done using a device with a memory function
- Shows understanding of the risks of hypoglycaemia
For driving regular vehicles whilst taking insulin
- Hypoglycaemic aware
- No more than one episode of hypoglycaemia requiring assistance in the past 12 months
- No relevant visual impairment
If on any tablets that can induce hypoglycaemia then there must have been no more than one episode of hypoglycaemia requiring assistance in the past 12 months.
For any other tablets there is no need to make the DVLA aware
Why does diabetic foot disease occur?
This occurs due to peripheral neuropathy and peripheral arterial disease which can both occur in diabetes.
What are the clinical features of diabetic foot disease?
Loss of sensation
Absent pulses
Reduced ABPI
Intermittent claudication
How are patients with diabetes screened for diabetic foot disease?
All patients with diabetes should be screened annually by checking for ischaemia – palpating both pulses in the foot and screening for loss of sensation.
What are the risk classifications for diabetic foot disease?
Low risk – no risk factors except callus alone
Moderate risk – deformity or neuropathy or non-critical limb ischaemia
High risk – previous ulceration or amputation, on dialysis, neuropathy, and non-critical limb ischaemia together or either combined with a callus/deformity
Anyone who is moderate or high risk should be followed up by local diabetic foot centre
What is diabetic ketoacidosis?
Starvation state in which the body converts fats into ketones for use by the brain. Primarily this occurs in type 1 DM and is often how it first presents. Occasionally it can occur in type 2 under conditions of extreme stress.
What causes ketoacidosis?
Lack of available glucose to cells due to insulin deficiency or resistance.
Risk of euglycemic DKA with SGLT-2 inhibitors (gliflozins).
This can be triggered by: infection, surgery, MI, pancreatitis, chemotherapy, antipsychotics, wrong insulin dose, missed doses and non-compliance.
What are the signs and symptoms of ketoacidosis?
Gradual drowsiness Vomiting Dehydration Abdominal pain Polyuria and polydipsia Ketoic breath Kussmaul respiration (deep hyperventilation) Coma and deep sleeps Acidaemia Hyperglycaemia Ketonaemia and/or Ketonuria
How should suspected ketoacidosis be investigated?
ABG Blood glucose Serum ketones or urine dipstick ECG and chest x-ray Serum and urine osmolality if indicated
What are the diagnostic criteria for diabetic ketoacidosis?
Glucose > 11.1mmol/l or known DM
pH < 7.3
Bicarbonate < 15mmol/l
Ketones > 3 mmol/l or urine ketones ++ on dipstick
What are the criteria for severe DKA and what should happen as a result?
If severe DKA then immediate review by a senior and consider HDU/ITU admission.
Severe DKA indicated by blood ketones > 6mmol/L, Venous bicarbonate <5mmol/L, pH < 7, Potassium < 3.5mmol/L on admission, GCS < 12/abnormal AVPU/EWS > 6, O2 sats on air < 92%, Systolic BP < 90, Pulse > 100 or < 60, or anion gap above 16.
How is DKA managed?
- Fluid replacement with isotonic saline initially (be wary of cerebral oedema in the young), give first litre over 1 hour then follow the proforma
- IV Insulin 50U in 50ml saline at 0.1U/kg/h fixed rate. If likely to be delay >15mins in administration of fixed rate insulin then give STAT 10 units SC or IM.
- Switch to variable rate insulin once ketones are < 0.6mmol/l
- Once blood glucose is <14mmol/l start 10% dextrose at 125ml/hour and review rate of saline to avoid overload
- Continue patients regular long-acting insulin but stop their short acting
- Correct hypokalaemia and monitor potassium levels closely – < 5.5 give replacement in the saline, <3.5 senior review and if >5.5 no potassium should be given.
- Prescribe thromboprophylaxis
What complications should you be aware of in DKA?
Complications Gastric stasis Thromboembolism Arrhythmias secondary to potassium derangement ARDS AKI
What is hyperosmolar hyperglycaemic state?
This is a medical emergency and usually tricky to manage with a significant mortality. Out of control hyperglycaemia results in an osmotic diuresis leading to severe dehydration and electrolyte deficiencies.
Typically, this presents in the elderly with and usually with T2DM but is increasingly common in the young and like DKA can be the original presentation of T2DM.
What is the pathophysiology of HHS?
- Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
- Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
- Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
What are the clinical features of HHS and what are the diagostic criteria?
This presents over a number of days and so the dehydration and metabolic disturbance are often worse than in DKA.
Fatigue and lethargy
Nausea and vomiting
Diagnosis
Blood glucose levels > 30mmol/l without significant ketonaemia (<3mmol/l or urine ketones < 2+) or acidosis (pH >7.3)
Raised osmolality >320mosmol/kg (2Na + glucose + urea)
Hypovolaemia
How should suspected HHS be investigated?
Extremely important to differentiate between HHS and DKA ABG Blood glucose Blood ketones Urine dipstick Serum osmolality
How is HHS managed?
To manage HHS we must normalise osmolality gradually, replace fluid and electrolytes and normalise blood glucose gradually. Fluid loss is usually 100-220ml/kg.
- IV fluids – normal saline of 1l in the first hour then follow the proforma. Only switch to 0.45% under direction of a senior if 0.9% has not had the desired response i.e. osmolality increasing (or decreasing by <3mosmol/kg/h) and Na is increasing. Aim for a positive fluid balance of 2-3l by 6 hours, 3-6l by 12 hours and replacement of the rest over the remaining 12 hours.
- Catheterise within first hour to monitor output
- Fixed rate insulin 50U in 50ml saline given at 0.05U/kg/h ONLY if significant ketonaemia is present (>1mmol/l) or ketonuria > ++ or glucose levels dropping by <5mmol/l/h despite adequate fluid replacement. Withhold all normal anti-diabetic and insulin regimes if starting IV insulin
- Correct hypokalaemia and monitor potassium levels closely – < 5.5 give replacement in the saline (20mmol in 500ml), <3.5 senior review and if >5.5 no potassium should be given.
- Once blood glucose is <14mmol/l start 10% dextrose at 62.5ml/hour and review rate of saline to avoid overload
- Glucose levels should not fall faster than 4-6mmol/h and sodium rising is only a concern if osmolality is not declining at the same time
- Aim for target blood glucose of 10-15mmol/l
- Complete normalisation of electrolytes and osmolality may take 72 hours
What complications should you be aware of in HHS?
MI, stroke, and peripheral arterial thrombosis
Seizures
Cerebral oedema
Central pontine myelinolysis if serum osmolality declines too quickly
What is the most common cause of hypoglycaemia?
Usually as a result of insulin overdose. Some tablet medications can cause hypos such as sulphonylureas.
What are the clinical features of hypoglycaemia?
Sweating and trembling Hungry Anxiety Poor concentration Palpitations Tingling of lips and pale Vague/confused Convulsions Coma
Describe the presentation and management of mild hypoglycaemia?
Mild – adults who are conscious, orientated, and able to swallow
- Glucojuice
- Cold high sugar drink – 150-200ml
- Dextrose tablets
- Test CBG 10-15mins later, if still <4mmol/l then repeat up to maximum of 3 times
- If till hypoglycaemic, consider glucagon 1mg IM or 150-200ml of 10% IV glucose over 15 minutes
- Once CBG > 4mmol/l give long-acting carbohydrate but do not omit insulin dose, if due give after meal
- Recheck CBG in 30-60mins and regularly for the next 48hours
Describe the presentation and management of moderate hypoglycaemia?
Moderate – patients conscious and able to swallow but confused, agitated or aggressive
- If capable treat as mild
- If not capable and cooperative give 1.5-2tubes of glucose gel
- Test CBG 10-15mins later, if still <4mmol/l then repeat up to maximum of 3 times
- If still hypoglycaemic, consider glucagon 1mg IM or 150-200ml of 10% IV glucose over 15 minutes
- Once CBG > 4mmol/l give long-acting carbohydrate but do not omit insulin dose, if due give after meal
- Recheck CBG in 30-60mins and regularly for the next 48hours
Describe the presentation and management of severe hypoglycaemia?
Severe – patient unconscious/aggressive/NBM or CBG < 2.6mmol/l
- Check ABCDE
- Stop IV insulin
- Secure IV access and give 75ml or or 150-200ml of 10% IV glucose over 15 minutes
- Consider IM glucagon in the absence of IV access
- Re-check CBG after 10mins and if remains <4mmol/l repeat IV glucose or consider glucose infusion 50ml/hr
- Recheck CB and medical review
- Restart IV insulin infusion once CBG >4mmol/l
