Endocrinology Flashcards
Which MODY uses sulfonylurea for treatment?
MODY3
Diagnostic criteria for diabetes
Hba1c > 6.5%
Fasting glucose > 7
Random glucose > 1.1
OGTT - meeting above criteria
GDM diagnosis
OGTT 24-28 weeks
Fasting > 5
1 hour > 10
2 hour > 8.5
MoA of metformin
Suppresses hepatic gluconeogenesis
SLGT2 benefit in diabetic nephropathy - mechanism
Reduce intraglomerular pressure due to increased afferent arteriole resistance
Reduced hyperfiltration
Which SGLT2 has higher risk of amputations?
Canglifozin
Benefit of degludec vs lantus/levemir
Reduces overnight hypoglycaemia
Types of Type 1 Diabetes
Type 1A - immune.
- Usually polygenetic
- Monogenic - AIRE (Polyendocrinopathy), FOXP3 (IPEX)
Polyendocrinopathy
X linked
Enteropathy
IPEX
FOXP3 gene
HLA associated with diabetes
HLA DR3 and HLA DR4 (have both = 50%)
Pathophys of T1DM
T cell mediate process
T1DM Ab’s
GAD
Insulin
IA-2
ZnT8
Anti-CD3 reducing time of onset T1DM
Tepiluzimab
Name of principal where long term complications of diabetes occur if there is poor control early
Metabolic memory
Glargin vs detemir
Gargine - hexamers under skin, delay absoprtion
Detemir - binds albumin, prolongs half life
Meal ratio calculation
500/TDD
1 unit of insulin for how many g for of CHO
Insulin sensitivity factor
100/TDD
1 unit of insulin drops BGL by how manny mmol/L
Evidence for CGM (continuous gucose monitor)
REduction in Hba1c
Reduces hypos
Improves time in range (closed loop therapy)
Whipple’s triad
Symptoms of low BGL
Low BGL
Symptoms imrpove after correcting BGL
Lymphocytic hypophysitis
- Features
- Differentiate from Sheehan syndrome
Hypopituitarism and headaache postpartum, no PPH
Sheehan - PPH, ischaemic infarction of pituitary causing hypopituitarism
Apoplexy
Haemorrahge into pituitary adenoma
Acute headache, diplopia, hypopituitarism
GH physiology
- Period when it is highest
- Stimulator and Inhibitor
- MoA
Puberty
GHRH stimulates, somostatin inhibits
Binds to receptors on liver, causing dimerisation + phosphorylation and IGF-1 release.
Effects - CHO and fat breakdown, protein buildup
Diagnosis of Acromegaly
Elevated IGF1? - diagnoses
Equivocal
- OGTT - GH not adequately suppressed
Proceed to pituitary MRI
Treatment of acromegaly
Somostatin analogues
- Octreotide
- Pasireotide - causes new onset diabetes in 60%
Pegvisomant
- Recombinant GH molecule, prevents receptor dimerisation. Enhances insulin sensitivity
Test for GH deficiency
Serum IGF1
Equivocal, do provocation tests:
- Macromelin test (grehlin, stimulates GH release)
- GHRH test
Treatment prolactinoma
Cabergoline - ergot Da receptor agonist
A/E of cabergoline
Valvular heart disease
False positive elevated PRL, without any symptoms (galactorrhoea, amenorrhoea)
Macroprolactin - PRL bound to Ig’s
Ostoporosis agents
- Prevent breakdown
Bisphopsphonate - prevent osteoclast binding and induce apoptosis
Denosumab - RANK-L
SERM’s - inhibit osteoclasts through upregulating OPG
Bone anabolic agents
Teriparitide - increase osteoblast activity
Romosozumab -inhibits sclerostin, which inhibits osteoblast formation. Increases osteoblast activity
Physiology of FGF23
- When released
- Effects
- Klotho
Hyperphosphataemia
Decreases phosphate reabsorption
Decreases calcitriol synthesis (reducing intestinal absorption)
Suppresses PTH (suppress vit D)
Klotho is a co-receptor that enhanced FGF23. Depleted in CKD, so reduced efefct of FGF23 in CKD (on kidneys, parathyroid) –> lead to CKD MBD
Calcium sensing receptor
- Function
- Defects
Senses iCa, increases PTH release in response to low levels
Inactivation - causes familial hypocalcuric hypercalcaemia (excess PTH release as iCa not sensed)
Cincalcet - CasR sensitiser, sensitising to Ca and suppressing PTH release (in CKD-MBD)
Bone resorption markers
Urine NTX
Serum CTX
Bone formation markers
BSAP
PINP
Ca replacement when on PPI
Ca citrate
Denosumab
- Risk of not taking within 4 weeks
Spontaneous vertebral fractures
- Need to take bisphosphonate cover
Denosumab - cf with bisphosphonates
Increased eczema and infection risk
Less renal dose adjustment
Atypical femur fracture
- Presentation
- Management
Indolent groin pain whilst on bisphosphonate
Stop bisphopshonate/denosumab immediately and refer to orthopaedic centre
Bisphosphonates duration
5 years for oral, 3 years for IV
Continue in high risk (Age > 70, low T score, high risk fragility fracture)
Drug holiday for 2-3 years, recheck T score
Phentermine
- MoA
- Use
- A/E
Adrenergic agent suppresses appetite
Obesity
Adrenergic A?E
Orlistat
- MoA
- A/E
Lipase inhibitor, reduces fat absorption
Steatorrhoea, flatulence, oxalate stones
Criteria for bariatric surgery
BMI > 40
BMI >35 and failed medical therapy
Pathogenesis of thyroid eye and skin disease
TSH receptors and IGF-1 receptors on orbital fibroblasts and skin
Excess TSH stimulates receptors in eye muscles and skin
–> excess GAG secretion, fluid accumulation.
–> Extraocular muscle swelling, proptosis, pretibial myxoedema
Specific and non-specific features of Grave’s disease
Specific - periorbital oedema, proptosis, conjunctival inflammation
Non-specific - lid lag, stare
Treatment of Grave’s eye disease
- Everyone
- Mod/severe
Treat hyperthyroid, stop smoking, conservative with drops
Severe
- steroids
- Teprotumumab - IGF-R inhibitor