Endocrinology Flashcards
Liraglutide for weight loss
Must meet three criteria:
- BMI >= 35
- or >= 32.5 if BAME
- Non-diabetic hyperglycaemia
- HbA1c 42-47 or fasting glucose 5.5-6.9
- High risk of cardiovascular disease
Dose:
- Liraglutide 3mg OD
- Must be used in conjunction with weight loss services and low-calorie diet.
Papillary thyroid cancer
The most common type of thyroid cancer (70%)
- F > M
- Ages 30-40
Features:
- Often encapsulated
- Multifocal
- Can spread via lymphatics
- Compressive symptoms
- Highly differentiated and derived from thyroid epithelium
Management:
- Thyroid resection + radioactive iodide + thyroid replacement
MODY
A familial form of non-insulin-dependent diabetes featuring beta-cell dysfunction without autoantibodies or ketosis
Aetiology:
- HNF1A mutations (50%)
- Glucokinase mutations (30%)
- HNF4A mutations
Management:
- HNF1A/4A subtypes:
- 1st line - sulfonyureas
- 2nd line - insulin
- GCK subtype
- Primarily lifestyle measures
Medullary thyroid cancer
Malignancy of the parafollicular thyroid cells
- 5% of thyroid cancers
- Associated with MEN2A and MEN2B (20%),
rest are sporadic cases
Investigations:
- Bloods
- Hypercalcaemia
- Raised calcitonin and CEA
- US thyroid
- FNA/biopsy
Management:
- Thyroidectomy
- Consider in childhood if FHx of MEN2
- Screen for concurrent phaeochromocytoma
- Monitor response via calcitonin and CEA levels
Diabetic bone disease
Typically forms of renal osteodystrophy
Adynamic bone disease
- Seen in diabetes, dialysis (esp peritoneal), excessive vitamin D supplements
- Low bone turnover, decreased osteoclasts, minimal osteoid seams, poor mineralisation
- High Ca, low PTH
Secondary/tertiary hyperparathyroidism
Management:
- Low phosphate diet or binders
- Calcium + vitamin D supplements
- Cinacelet for patients who are dialysis-dependent
Insulin
Production:
- Beta-cells
- A + B peptides joined with a disulphide bridge, C-peptide cleaved
Secretion:
- Secreted in response to - oral intake, high BMs (via GLUT4), exercise
- Release potentiated by incretins (GLP-1, GIP)
Actions:
- Acts on RTKs
- Stimulates skeletal muscle GLUT4 and
therefore uptake
- Promotes glycogen synthesis
- Suppresses liver gluconeogenesis
- Suppresses fat/amino acid metabolism
Diabetes - diagnosis
Asymptomatic + 2 biochemical criteria or symptomatic + 1 biochemical criterion
Random glucose > 11.1
Fasting glucose > 7
Glucose tolerance test > 11.1 after 2hr
(NB fasting glucose 6.0-6.9 is impaired fasting glycaemia)
T1DM - targets
5-7 mmol on waking
4-7 mmol any other time
Hyperglycaemia - aetiology
Endocrine
- Thyrotoxicosis
- Cushing’s disease
- Phaeochromocytoma
- Acromegaly
Pancreatic:
- Autoimmune (T1)
- Insufficiency (T3)
Drugs:
- Steroids
- Thiazide diuretics
Inherited:
- Friederich’s ataxia
Other:
- Infection
- Intracranial pathology e.g. seizures, tumour
Insulin regimes
Basal-bolus
- Give 50% basal, split remaining 50% for prandial dosing
- Starting daily dose - 0.1 units/kg
- Increment by 10-20% to achieve finer control
VRII
- IV short-acting insulin (50u of actrapid in 50ml of NaCl 0.9%) + 5% glucose +/- 0.3% KCL (40mmol)
- Rate adjusted according to BMs
- Continue any basal insulin
CRII
- 0.1 units/kg/hr
- Continue any basal insulin
Acute correction of hyperglycaemia
- 1 unit drops BMs by roughly 2mmol
- More specifically:
- Insulin sensitivity factor (drop in BMs per 1
unit) = daily insulin / 100
- Current BMs - target BMs / ISF
- Maximum effect 2-4hr after administration
- If > 50% of BMs are out of range, adjust basal dosing
VRII
IV short-acting insulin (50u of actrapid in 50ml of NaCl 0.9%) + 5% glucose +/- 0.3% KCL (40mmol)
Indications:
- Missing > 1 meal
- Always in T1DM, T2DM depends on control
- Pre-elective surgery
- Always in T1DM, T2DM depends on control
- Step-down post-CRII
- Poorly controlled diabetes requiring urgent surgery
- Extreme vomiting
Cessation:
- Aim to stop as soon as patient is tolerating oral intake
- Re-establish on regular insulin, then take down VRII after 60 min
DKA
Diagnosis:
- Hyperglycaemia - > 11.0
- Ketosis - +++ ketonuria, > 3 mmol
- Acidosis - pH < 7.3, HCO3 < 15
Management:
- Fluid rehydration
- 1L/1hr 0.9% NaCl
- Following bags over 2, 2, 4, 4, 6 hr
- Add KCl when K+ < 5.5
- Add 10% glucose when BMs < 14
- CRII
- 0.1 units/kg/hr
- Continue basal insulin
- Increase by 1 unit/hr until achieving fall in
ketones > 0.5 mmol/hr
- Identify any underlying cause and treat alongside
- Urgent CT head if any drop in GCS to assess for cerebral oedema
Continue until pH > 7.3 and ketones < 0.6
Transition to subcutaneous insulin
Cerebral oedema in DKA
A possible complication of rapid fluid resuscitation in DKA, most commonly seen in paediatric patients
Features:
- Headache
- Agitation
- Bradycardia + hypertension (Cushing’s)
- Coma
Urgent neuroimaging if any drop in GCS during treatment for DKA
Management:
- Restrict fluids to 50% of regime
- Hypertonic saline (2.7% or 3% 2.5-5 ml/kg over 10-15 minutes) or mannitol
HHS
Diagnosis:
- BMs > 33
- Serum osmolarity > 320
- Absence of significant ketosis or acidosis
Management:
- Aggressive fluid resuscitation
- Initial fluid bolus 20ml/kg then 250ml/hr 0.9%
NaCl + KCl
- Add 5% glucose if falling > 5mmol/hr
- Should achieve improvement in BMs and osmolarity with fluids alone
Somogyi and dawn phenomena
Somogyi phenomenon
- Rebound high BMs in response to low BMs
e.g. morning hyperglycaemia due to insulin-
induced hypoglycaemia overnight
Dawn phenomenon
- Rise in BMs in the morning due to fall in endogenous insulin + rise in endogenous GH
Mauriac syndrome
The result of poor glycaemic control in childhood
Features:
- Massive hepatomegaly - excessive glycogen production
- Short stature - growth failure
- Obesity
- Delayed sexual maturation
Hypoglycaemia - management
Symptomatic but BMs > 4
- Small carbohydrate snack or meal
BMs < 4, asymptomatic or well
- Fast-acting carbohydrate e.g. glucogel, juice
- If not responding after 3 treatments or 45 min, give IM glucagon or IV glucose
- Once stabilised, provide long-acting carbohydrate
Comatose:
- IM glucagon 1mg
- If fails or agitated, 200 ml glucose 10% IV
Diabetic eye disease - classification
Retinopathy:
- Mild NPDR
- 1 or more microaneurysms
- Moderate NPDR
- Microaneurysms
- Blot haemorrhages
- Hard exudates
- Cotton wool spots - retinal infarctions -
venous beading, IRMAs in early stages
- Severe NPDR/pre-proliferative
- Blot haemorrhages and microaneurysms in
4 quadrants
- Venous beading in at least 2 quadrants
- IRMA in at least 1 quadrant
- PDR
- Retinal neovascularisation with risk of
vitreous haemorrhage
- Fibrous tissue anterior to retinal disc
Maculopathy:
- Hard exudates and oedema of the disc
- Not scored, presence of any maculopathy is worrying
Diabetic eye disease - management
Pathophysiology:
- Chronic hyperglycaemia leads to weakening and rupture of retinal blood vessels with subsequent leakage of blood and exudate
- As blood flow worsens, hypoxia leads to production of VEGF and neovascularisation
- New blood vessels are fragile and prone to rupture
Screening:
- Every 1-2 years once > 12 y.o.
- Increased frequency as disease worsens
Management:
- Lifestyle factors + BM control
- Focal photocogulation
- Panretinal photocoagulation (PRC)
- Targets peripheries to kill tissue, reducing
overall oxygen demand
- Loss of peripheral vision, worsening night
vision, may worsen macula oedema
- Anti-VEGF injections
- Contraindicated if stroke or MI within the last
3 months
Calcium homeostasis
Absorption
- GIT
- Renal reabsorption
Storage:
- 99% calcium hydroxyapatite in the bones
- Remainin 1% in cells + serum
- Protein-bound
- Chelated - for transport
- Ionised - used in cellular signalling
PTH:
- Secreted in response to hypocalcaemia, from parathyroid glands (x 4)
- Stimulates bone resorption
- Increases renal calcium reasbsorption
- Increases renal vitamin D activation
Vitamin D
- Increases in response to hypocalcaemia
- Metabolised in two steps into 1,25-dihydroxyvitamin D (calcitriol)
- Increased expression of GIT calcium-binding
proteins -> increased absorption
- Stimulates bone resorption
Calcitonin
- Secreted from parafollicular C cells (thyroid) in response to hypercalcaemia
- Inhibits bone resorption
- Inhibits renal reabsorption of calcium
Hypocalcaemia
Aetiology
- CKD with secondary hyperparathyroidism
- PTH deficiency (e.g. post-surgery)
- Vitamin D insufficiency
Signs:
- Trousseau’s
- Sustained wrist spasm after inflating
sphygmomanometer on arm
- Chvostek’s
- Facial muscle spasm after tapping just below
zygomatic bone
- Prolonged QTc
- Muscle tetany
Hyperparathyroidism
Primary
- Oversecretion - adenoma, cancer (incl MEN), hyperplasia
- High PTH and Ca2+, low PO4
Secondary
- Increased secretion due to low Ca2+ or low vitamin D (esp. CKD)
- Ca2+ and PO4 may be normal as PTH secretion is compensatory
- High PTH, low/normal Ca2+, high/normal PO4
Tertiary
- Gland hypertrophy secondary to prolonged secondary hyperparathyroidism after cause is treated
- Very high PTH, high Ca2+, high PO4
Hypercalcaemia
Aetiology
- Hyperparathyroidsm
- primary, tertiary
- Malignancy
- PTHrP secretion
- Milk alkali syndrome
- Excessive intake of Ca2+-containing alkali
- Thiazide diuretics
- due to hypocalciuria
- Vitamin D toxicity
- Paget’s disease
Features:
- Bony pain
- Constipation
- Chondrocalcinosis + nephrocalcinosis
- Psychiatric - depression, psychosis
- Polyuria + polydipsia
Milk alkali syndrome
Aetiology:
- Excessive intake of Ca2+-containing alkalis e.g. antacids, calcium carbonate (osteoporosis)
Features:
- Hypercalcaemia
- Metabolic alkalosis
- Hypocholraemic + hypokalaemic
- Nausea, vomiting, polyuria, polydipsia
- Renal impairment
Pseudohypoparathyroidism
Hereditary end-organ resistance to PTH
Can have low Ca2+ and high PO4 or be biochemically normal - kidneys favour maternal gene with imprinting so retain PTH sensitivity
Features:
- Short stature + rounded face + short 4th/5th metacarpals
- High PTH
- Mental retardation
- Calcified choroid plexus
Cortisol homeostasis
The main human glucocorticoid
Follows a circadian pattern - highest in morning and declines over the day
Additionally secreted as an acute stress response to consolidate SNS responses
- Amygdala triggers SNS signalling into HPA
Antagonises insulin effects and secretion of TSH, GHRH, ADH. Stimulates glucagon secretion
Effects:
- Catabolic state
- mobilises glucose, suppresses glucose uptake
into the tissue
- later causes protein degradation and wasting
- Fat redistribution
- Immunomodulatory
- promotes a TH2 response to prevent
excessive and harmful inflammation
- Bone resorption
- Water and fluid retention
- via mineralocorticoid secretion
- helps to increase BP
- Gastric acid secretion
