Medicine/Surgery - Endocrine Flashcards
What is DKA and its main causes?
Diabetic ketoacidosis
Mainly complication of T1
causes: illness, infection, UTI, pregnancy, surgery, MI, insulin dosing issues (forgetting/purposefully not taking), eating disorders
Describe the pathophysiology of DKA
No insulin in the body to utilise the glucose
Glucose broken down by beta-oxidation instead producing acidic ketone bodies
These ketone bodies lower pH of blood causing metabolic acidosis
Kidneys are overwhelmed by XS ketones and glucose = osmotic diuresis
What are the following biochemical features in DKA?
1) Na
2) K
3) urinary ketones
4) plasma ketones
5) BM
6) ABG
1) Na low (as the hyperglycaemia leads to the osmotic shift of water from the intracellular -> extracellullar space and Na goes too?)
2) K low (as the hyperglycaemia leads to the osmotic shift of water from the intracellular -> extracellullar space and K goes too?)
3) Urinary ketones (high)
4) Plasma ketones (>3)
5) BM (>11)
6) ABG (metabolic acidosis)
How might a patient in DKA present
dehydrated, hypotensive tachycardic cold compensatory Kussmaul breathing pear-drop breath delirium/coma polyuria, polydipsia weak cramps abdominal pain blurred vision
How would you investigate DKA?
Bloods: FBC, CRP, U&E, BM, ABG Blood cultures Urine culture/dipstick ECG CXR
What is the diagnosis of DKA based on the triad of?
Acidaemia (low pH)
High glucose >11
High plasma ketones >3 (or 2+ on dipstick!)
How is DKA treated?
IV access 0.9% saline + 50U insulin (IV) Once BM <15, start 5% dextrose IV May need potassium chloride replacement depending on hypokalaemia severity Consider thromboprophylaxis
Define HHS and its causes
hyperglycaemic hyperosmolar state
Features of: hyperglycaemia, hypovolaemia, hyperosmolality WITOHUT acidosis/ketones
also called HONK (hyperosmolar non-ketotic state)
Usually T2DM complication
Infection, drugs (steroids), CV events, sepsis, MI
What is the pathophysiology of HHS and its signs/symptoms
Some residual insulin production in T2DM therefore no B-oxidation of ketoacidosis
Develops more insidiously meaning the hyperglycaemia and dehydration are more profound
Hx will be ~1 week
Fts: confusion, dehydration
What are the following biochemical features in HHS?
1) plasma ketones
2) BM
3) ABG
1) plasma ketones - <3
2) BM much higher e.g. >30
3) ABG = usually pH >7.3
What investigations are carried out for HHS?
Bloods: FBC, CRP, U&E, BM, ABG Blood cultures Urine culture/dipstick ECG CXR
How is HHS treated?
IV 0/9% saline
May add insulin once BM has plateaued
Thromboprophylaxis/urinary catheter
Define hypoglycaemia and its causes
BM of <2.8 in non-insulin treated individual or <4 in an insulin treated pt
Mainly as a complication of insulin therapy
Causes in diabetics:
- increased physical activity
- missed meals
- accidental insulin overdose
Causes in non-diabetics:
EX - exogenous drugs
P - pituitary insufficiency (e.g. lack of cortisol, cannot oppose the effects of insulin!)
L - liver failure
A - Addison’s (causing lack of cortisol)
I - Islet cell tumour (making XS insulin)
N - non-pancreatic neoplasm (making insulin-like hormone)
What are the S/Sx of hypoglycaemia?
Related to glucose deprivation: delirium, drowsy, speech difficulties, nausea, headache
Related to ANS activation: sweating, anxiety, hunger, tremor, palpitations
How is hypoglycaemia investigated?
FBC BM Insulin levels C-peptide Ketones
How is hypoglycaemia treated?
if BM <4 10g oral glucose (wait 10 mins, if BM still <4 then repeat) (give oral glucose up to 3 cycles) ?IM glucagon
What are the rules with hypoglycaemia and the DVLA?
Notify DVLA if taking insulin
BMs should be >5 to drive
Only drive 2hrs at a time
If >1 hypoglycaemic attack has occurred whilst awake in the last year, then you are not allowed to drive at all
Describe the basal bolus insulin regimen
- long acting insulin given at night
- rapid infusion given 3x a day (once before each meal)
Describe the bi-basal (twice daily) insulin regimen
- at breakfast a mix of intermediate+short/rapid insulin is given, and then the same before dinner
What is the pathophysiology of T2DM?
Acquired resistance to the effects of insulin initially (?chemicals released from adipose tissue?? or high dietary carbohydrate?)
Pancreas tries to compensate by going into overdrive
Eventually insulin deficiency occurs
What are the S/Sx of T2DM
TTTT UTI/candida Poor concentration/mood changes Dry mucous membranes Postural hypotension Visual changes Headaches... Acanthosis nigricans
What are the WHO criteria for diagnosing DM?
1) venous glucose readings of
- BM >7 (fasting)
- BM >11.1 (random)
- HbA1C >48
2) symptomatic
3) HbA1C >48
Describe the management of T2DM
Lifestyle: diet, weight, smoking cessation, less alcohol, exercise (can increase insulin sensitivity)
Pharmacological:
Monotherapy -> metformin
Dual therapy -> add sulphonylurea/thiozoladinedone/SGLT2i/GLP1
Triple therapy -> add DPP-4/insulin
Name two reasons as to why a patient may have a falsely high HbA1c reading:
Post splenectomy (reduced RBC turnover and cells are exposed to glucose for a longer time)
Medications e.g. opioids
Define metabolic syndrome
Central obesity (BMI > 30) plus 2 of:
- DM
- HTN (>130/85)
- Hyperlipidaemia
- Fasting glucose >5.6
Describe IGT
Impaired glucose tolerance
Fasting BM normal but 2-hrs post glucose measurement is high
Usually impaired GLUT4 expression on muscle leading to impaired 1st and 2nd phase insulin secretion
5% can progress to T2DM
Describe IFG
Fasting glucose high but 2hr post-glucose measurement normal
Normally hepatic issue with impaired 1st phase insulin secretion
5% can progress to T2DM
Describe the pathophysiology of T1DM
Autoimmune destruction of pancreatic islets and B cells
Leads to severe insulin deficiency
Due to genetics (HLA-DR3/4) + environmental factors (cows milk, lack of vit D…)
Common autoantibodies: IAA, IA2, GAD (glutamic acid decarboxylate)
Describe the S/Sx of T2DM
TTTT UTI/candida Poor concentration/mood changes Dry mucous membranes Postural hypotension Visual changes Headaches... Acanthosis nigricans
Define the cut off values for ‘pre-diabetes’
Combination of IGT + IFG
Random BM 7.8-11.1
Fasting BM 6.1-7
Describe autoimmune polyendocrine syndrome
Triad of:
- T1DM
- Addison’s
- Autoimmune thyroiditis
What will the C-peptide measurement be like in T1DM?
Very low!
What is the treatment regimen for T1DM?
SC insulin (basal bolus or biphasic)
Target HBA1C <53!!!!!!
Address all RFx
Only curative option = islet cell/pancreatic transplantation
Describe the pathophysiology underlying diabetic micro/macrovascular complications
Poorly controlled DM
High blood glucose -> leads to vessel inflammation and atherosclerosis
Thickening of capillary basement membranes
Microvascular damage = localised response to generalised vascular injury
Describe the main macrovascular complications and their treatment
Coronary -> MI/infarction (4x greater risk)
Cerebral -> TIA/stroke (2x greater risk)
Peripheral -> claudication/ischaemia
Management: BP control, reduce RFx (diet, smoking, exercise), statins, aspirin
Describe the main microvascular complications and their treatment
Treatment = good glycaemic control!!!
- Retinopathy (annual screening)
- Peripheral neuropathy (analgesia, gabapentin, vibration/sensory testing)
- Nephropathy (optimise BP and BM control)
- Autonomic neuropathy (e.g. may need catheter)
- Diabetic feet (foot screening, appropriate footwear)
- Mononeuropathy (altered motor/sensory function)
Define gestational DM and its pathophysiology
Any degree of insulin insensitivity which occurs with onset or pregnancy
Carbohydrate intolerance occurs as placenta produces hormones making you resistant to insulin
The insulin needs during pregnancy are increased and the pancreas cannot keep up with demands -> hyperglycaemia
Describe causes of secondary DM
Genetics (Down syndrome, Turners, Kleinfelters)
Pancreatic disease (cancer, pancreatitis)
Endocrinopathies (Cushing’s, phaeochromocytoma)
Immunosuppressants (steroids)
Drugs (antipsychotics)
Define monogenic diabetes and its three main features
Also called MODY Non-insulin requiring DM that develops <25yrs Caused by single gene mutation Inheritance pattern is normally AD 3 main features: - run in families - <25yrs onset - managed with diet, exercise, oral hypoglycaemics (+/- insulin)
Describe diabetes insipidus
XS quantities of dilute urine (>3L) and thirst every day
Low serum gravity and osmolality
Hypernatraemia
Either cranial (not enough ADH made) or nephrogenic (kidneys not responsive to ADH)
How is diabetes insipidus diagnosed?
8hr water deprivation test (to try and stimulate natural ADH release)
Collect urine every 2hrs and measure urine volume and osmolality, and plasma osmolality and body weight
If plasma osmolality is high and urine osmolality is low, then work out if cranial/nephrogenic:
Give desmopressin and measure urine osmolality over the next 4 hrs:
- if urine becomes more concentrated (higher osmolality) -> cranial issue
- if not = nephrogenic issue
How is diabetes insipidus treated?
Give desmopressin if cranial
Treat polyuria with thiazide diuretics
Remove the underlying cause e.g. tumour
Which is the active thyroid hormone (T3/4?)
T3!!
T4 can be converted into T3 in the periphery
Describe causes of hypothyroidism
Hashimotos most common (anti-thyroid peroxidase enzyme which converts I2 -> Io in colloid filled lumen before T3/4 are made (autoimmune!)
Iatrogenic (lithium, PTH, carbimazole)
De-quervians (subacute thyroiditis -> where a hypothyroid phase can follow the hyper phase)
Primary atrophic hypothyroidism (diffuse lymphocytic infiltration of thyroid gland leading to atrophy)
Congenital
Secondary = hypopituitarism
What are the signs/symptoms of hypothyroidism?
BRADYCARDIA! Bradycardia Reflexes relax slowly Ataxia Dry hair/skin Yawning (tired) Cold intolerance Ascites/oedema Round puffy face Defeated demeanour (low mood) Immobile Anaemia Loss lateral 1/3 eyebrow Constipation Infertility Goitre Pretibial myxoedema
How is hypothyroidism investigated
Bloods: TFTs. autoantibodies (anti-TPO)
low cholesterol and high Na (due to ADH release)
Radioactive iodine uptake tests
How is hypothyroidism treated?
Levothyroxine (synthetic T4) (MAY CAUSE ANGINA so taper dose in CAD)
Amiodarone -> has an iodine rich structure
Describe the causes of hyperthyroidism
Graves (autoimmune, most common) - autoantibodies made against TSH receptor Thyroid adenoma Drug induced Multinodular goitre Ectopic thyroid tissue De Quervians (viral infection causing high T3/4) Amiodarone Iatrogenic
Secondary - pituitary adenoma
What are the S/Sx of hyperthyroidism?
Tachycardia Warm moist skin Tremor Palmar erythema Thin hair Lid retraction/lag Goitre Thyroid bruit Weight loss Diarrhoea Heat intolerance Hungry... Pretibial myxoedema Thyroid acropatchy (HYPER ONLY!) Thyroid eye disease in Grave's only -> exophthalmos, ophthalmoplegia
How is hyperthyroidism investigated?
TFTs Autoantibodies Bloods (?infection/de Quervians) Radioactive iodine uptake test Check eyes FNA neck lump Imaging
How is hyperthyroidism treated?
Carbimazole
PTU (propylthiouracil)
Block and replace regimen -> carbimazole + levothyroxine
Surgery Radioactive iodine (BUT may worsen eye disease)
Why should aspirin be avoided in hyperthyroidism
Displaces T3/4 from protein carriers, increasing levels of circulating T3/4
Name a side effect of PTU/carbimazole
Agranulocytosis and neutropenic sepsis!
