Endocrinology

Question 1

Type 1a vs. Type 1b diabetes

Answer 1

Type 1a - immune mediated (95%)
Type 1b - idiopathic (<5%)

Question 2

Autoantibodies in T1DM

Answer 2

• Glutamic acid decarboxylase (GAD65)
• Insulin (IAA)
• Tyrosine phosphatases (IA-2, IA-2B)
• ZnT8

Not routinely used in diagnosis
Presence of autoantibodies predicts risk of developing clinical diabetes

Question 3

Diagnosis of T1DM

Answer 3

Random BSL >11.1 with keoacidosis

Question 4

Clinical clues towards T1DM in diagnosis

Answer 4

○ Rate of development of hyperglycaemia symptoms
○ Presence of ketosis
○ Personal/family history of AI disorders
○ Absence of family history of T2DM
○ Absence of other features of metabolic syndrome
○ Failure to respond to non-insulin treatments
Low/undetectable C-peptide

Question 5

HLA associations in T1DM?

Answer 5

Accounts for 50% of genetic risk

HLA-DR2 confers protection
HLA-DR3 and HLA-DR4 confer risk

Strong linkage with HLA-DQA and HLA-DQB

Question 6

Risk of T1DM with family history

Answer 6

Question 7

Latent autoimmune diabetes of adulthood (LADA) - features

Answer 7

• Subtype of Type 1 diabetes
• Slow progressive destruction of beta cells
• May respond to oral agents initially
• More likely to have autoimmune history
• Less likely to have features of metabolic syndrome
• Age of onset usually ≥30
• Positive titre of at least 1 auto antibody
• Starting insulin early may preserve beta cell function

Question 8

Idiopathic T1DM (Type 1b) - features

Answer 8

○ Permanent insulinopenia (low/undetectable plasma C-peptide)
○ Ketoacidosis prone
○ No evidence of B cell autoimmunity
○ Strongly inherited - not HLA associated
○ Most are Africa/Asian ancestry

Question 9

Autoimmune conditions associated with T1DM

Answer 9

• AI thyroid disease*
• Addison’s disease
• Coeliac disease*
• Vitiligo
• AI hepatitis
• Myasthenia gravis
• AI gastritis* (increased risk of pernicious anaemia/B12 def)
• Regular screening encouraged

Question 10

Autoimmune Polyendocrine Sndromes - type 2 - features

Answer 10

• Characterised by presence of Addison’s disease with AI thyroid disease and/or T1DM
• Female predominance
• Most common of the Autoimmune Polyendocrine Syndromes

Question 11

Typical starting dose of insulin

Answer 11

0.5 units/kg/day
50% as basal insulin

Question 12

Human insulin vs. insulin analogues

Answer 12

Analogues associated with:
- Less hypoglycaemia
- Less weight gain
- Lower HbA1C

Question 13

CSII vs. MDI (multiple daily injections)

Answer 13

Modest advantages for HbA1C lowering
Lower severe hypoglycaemia risk

Question 14

Insulin Carbohydrate Ratio (ICR)

Answer 14

How many grams of carbohydrate are covered/disposed of by 1 unit of insulin

Question 15

Insulin Sensitivity Factor (ISF)

Answer 15

How much 1 unit of rapid acting insulin will generally lower BSL over 2-4 hours
- Expressed as mmol/L

Question 16

SGLT2i in T1DM - outcomes of EASE trials?

Answer 16

• HbA1C reduction
• Body weight reduction
• Lower total daily insulin requirement (up to 13%)
• Lower SBP
• Increased risk of ketoacidosis with 10mg & 25mg
• No significant different in severe hypoglycaemic episodes

Question 17

Surgical options for T1DM?

Answer 17

• Whole pancreas transplantation
  > Performed with curative intent
  > Usually performed with renal transplant
• Islet cell transplantation
  > Indications: severe recurrent hypos/hypo unawareness

Both require lifelong immunosuppression to prevent graft rejection

Question 18

Risk factors for hypoglycaemic unawareness

Answer 18

• Increasing age
• Duration of disease
• Aggressive glycaemic control
• Frequent hypoglycaemic events
• Autonomic neuropathy
• Medications including beta blockers

Clarke Survey - assessment tool
- Score ≥4 = significantly impaired awareness of hypoglycaemia

Question 19

Level 1 vs. 2 vs. 3 hypoglycaemia

Answer 19

Level 1: typical symptoms associated with measured BSL of <4

Level 2: BSL <3, level at which neuroglycopenic symptoms expected to begin

Level 3: severe, requiring another person’s assistance

Question 20

What medications cause false positive aldosterone-renin ratios?

Answer 20

Beta blockers
Methyldopa, clonidine
NSAIDs

Question 21

What medications cause false negative aldosterone-renin ratios?

Answer 21

ACEi/ARBs
All diuretics
Dihydropyridine CCBs

Question 22

Results suggestive of Paget disease?

Answer 22

Isolated elevation of ALP
Normal calcium/phosphate/PTH
Xray - bone deformation/sclerotic/osteolytic lesions

Question 23

1st line management of Paget disease?

Answer 23

Bisphosphonates

Question 24

How to differentiate primary hyperparathyroidism vs. familial hypocalciuric hypercalcaemia?

Answer 24

Urinary calcium
Urinary Ca/Cr ratio

Both of these will be LOW in FHH
(<100mg/day and ratio <0.01)
In FHH: also have high serum Mg due to low urinary Mg

Question 25

What causes familial hypocalciuric hypercalcaemia?

Answer 25

Inactivating mutation in calcium sensing receptor in PTH and kidneys

Question 26

Polyglandular autoimmune syndrome type 2?

Answer 26

Primary adrenal insufficiency (Addison’s Disease)
T1DM
Autoimmune thyroid disease