Week 9 - Endocrine

Question 1

Define Diabetes Mellitus?

Answer 1

Metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbances of carbohydrate, protein & fat metabolism resulting from defects in insulin secretion, insulin action, or both

Question 2

List 3 characteristics of diabetes mellitus?

Answer 2

1. Glycosuria - Depletion of Energy Stores
2. Glycosuria - Osmotic Diuresis
3. Glucose Shifts - Swollen Ocular Lenses

Question 3

List the 5 symptoms associated with glycosuria in diabetes mellitus?

Answer 3

1. Tired
2. Weak
3. Weight loss
4. Difficulty concentrating
5. Irritability

Question 4

List 6 symptoms of glycosuria osmotic diuresis in diabetes mellitus?

Answer 4

1. Polyuria
2. Polydipsia (excessive drinking)
3. Thirst
4. Dry mucous membranes
5. Reduced skin turgor
6. Postural hypotension

Question 5

What is the symptom for glucose shifts in diabetes mellitus?

Answer 5

Blurred vision

Question 6

List the 3 types of presentations of diabetes mellitus?

Answer 6

1. Ketone production
2. Depletion of energy stores (ie. muscle)
3. Complications (T2DM)

Question 7

List the 7 symptoms of ketone production is diabetes mellitus?

Answer 7

1. Nausea
2. Vomiting
3. Abdominal pain
4. Heavy/rapid breathing
5. Acetone breath
6. Drowsiness
7. Coma

Question 8

List the 4 symptoms of depletion of energy stores (ie. muscle) in diabetes mellitus?

Answer 8

1. Weakness
2. Polyphagia (excessive eating)
3. Weight loss
4. Growth retardation in young

Question 9

List the 4 complications of T2DM?

Answer 9

1. Macrovascular
2. Microvascular
3. Neuropathy
4. Infection

Question 10

What is the normal fasting & 2hr plasma glucose?

Answer 10

• Fasting: <7

- 2hr: <7.8

Question 11

What is the IGT (Impaired glucose tolerance) fasting & 2hr plasma glucose?

Answer 11

• Fasting: <7

- 2hr: 7.8-11.0

Question 12

What is the WHO criteria for a diagnosis of diabetes mellitus?

Answer 12

• Fasting plasma glucose >7.0 mmol/L
• Random plasma glucose >11.1 mmol/L
• 1 abnormal values diagnostic if symptomatic
• 2 abnormal values if diagnostic if asymptomatic

Question 13

What should the HbA1c be for a diagnosis of diabetes?

Answer 13

6.5% or 48 mmol/mol

Question 14

What should diabetes NOT be diagnosed based on?

Answer 14

NOT be diagnosed on the basis of glycosuria or a BM stick

Question 15

When is OGTT only required for?

Answer 15

Diagnosis of Impaired fasting glycaemia (IFG) or Gestational diabetes mellitus (GDM)

Question 16

List the 5 classifications of diabetes?

Answer 16

1. Maturity Onset Diabetes of the Young (MODY)
2. T2DM
3. Secondary DM
4. Latent Autoimmune Diabetes of Adulthood (LADA)
5. T1DM

Question 17

What does SAID stand for?

Answer 17

Severe autoimmune diabetes

Question 18

What does SIDD stand for?

Answer 18

Severe insulin-deficient diabetes

Question 19

What does SIRD stand for?

Answer 19

Severe insulin-resistant diabetes

Question 20

What does MOD stand for?

Answer 20

Mild obesity-related diabetes

Question 21

What does MARD stand for?

Answer 21

Mild age-related diabetes

Question 22

What are the 2 types of primary diabetes?

Answer 22

1. Type 1 DM

2. Type 2 DM

Question 23

What is Type 2 diabetes mellitus a combination of?

Answer 23

Insulin resistance & insulin deficiency

Question 24

Describe the presentation of type 1 diabetes mellitus?

Answer 24

• <30 usually
• Lean patient
• Weeks of symptoms
• Northern European higher risk

Question 25

Describe the pathogenesis of type 1 diabetes mellitus?

Answer 25

- HLA DR3 or DR4 in 90% | - Autoimmune

Question 26

Describe the clinical presentation of type 1 diabetes mellitus?

Answer 26

- Insulin Deficiency +/- Ketoacidosis | - Dependent on Insulin for survival

Question 27

Describe type 1 diabetes mellitus biochemically?

Answer 27

C Peptide Innappropriate/negative

Question 28

Describe the presentation of type 2 diabetes mellitus?

Answer 28

- >30 usually - Overweight patient - Months/Years of symptoms - Asian, African, Polynesian & American Indian higher risk

Question 29

Describe the pathogenesis of type 2 diabetes mellitus?

Answer 29

- No HLA links | - No immune disturbance

Question 30

Describe the clinical presentation of type 2 diabetes mellitus?

Answer 30

- Partial Insulin Deficiency at presentation +/- Hyperosmolar state - May need Insulin

Question 31

Describe type 2 diabetes mellitus biochemically?

Answer 31

C peptide positive

Question 32

What does a plasma ketone reading of below 0.6mmol/L indicate?

Answer 32

Normal range & no action is needed

Question 33

What does a plasma ketone reading of 0.6-1.5mmol/L indicate?

Answer 33

- Development of a problem that may require medical assistance - Call your healthcare team

Question 34

What does a plasma ketone reading of above 1.5mmol/L indicate?

Answer 34

- In the presence of hyperglycaemia indicates high risk of DKA - Contact healthcare team immediately for advice

Question 35

What are the islet autoantibodies?

Answer 35

Markers of autoimmune process associated with T1DM

Question 36

What are islet autoantibodies present in?

Answer 36

- 80% of T1DM if combination of glutamic acid decarboyxylase (GAD) & insulinoma-associated antigen -2 (IA2) measured (<1% of MODY) - Some patients with T2DM have positive antibodies (progress more quickly to insulin)

Question 37

When are islet autoantibodies most useful in T2DM?

Answer 37

3-5 years from diagnosis (overlap with T2DM/MODY before, especially in obese)

Question 38

Describe C-peptide?

Answer 38

- Secreted in equimolar concentrations to insulin | - Useful marker of endogenous insulin secretion

Question 39

When is a C-peptide measurement most useful?

Answer 39

3-5 years from diagnosis (overlap with T2DM/MODY before especially in obese)

Question 40

Where can you measure C-peptide?

Answer 40

Blood or urine (urine C peptide/creatinine ratio)

Question 41

What % of diabetes mellitus is type 1?

Answer 41

10%

Question 42

What is the definition of type 1 diabetes?

Answer 42

Chronic, progressive metabolic disorder characterised by hyperglycaemia & the absence of insulin secretion

Question 43

Describe the pathogenesis of type 1 diabetes mellitus?

Answer 43

- Results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans - Occurs in genetically susceptible subjects & is probably triggered by 1+ environmental agents

Question 44

List the 7 steps of type 1 diabetes mellitus disease progression?

Answer 44

1. Genetic risk 2. Immune activation- beta cells are attacked 3. Immune response- development of single autoantibody 4. Stage 1- normal blood sugar, => autoantibodies 5. Stage 2- abnormal blood sugar, >2 autoantibodies 6. Stage 3- clinical diagnosis => 2 autoantibodies 7. Stage 4- Long standing T1D

Question 45

If you have a relative with diabetes mellitus, you are at a ____ greater risk of developing T1D?

Answer 45

15x

Question 46

List the 7 possible factors which reports have found to increase the risk of T1DM (no associations have been verified and many have been contradicted)?

Answer 46

1. Viral infections (enterovirus) 2. Immunisations 3. Diet (cow's milk) 4. Higher socioeconomic status 5. Obesity 6. Vitamin D deficiency 7. Perinatal factors ie. maternal age, history of preeclampsia, neonatal jaundice & low birth weight (reduced risk)

Question 47

What is the lifetime risk of developing T1DM with an affected monozygotic twin?

Answer 47

- 30% within 10yrs of diagnosis of the twin | - 65% concordance by age 60yrs 5% of DM

Question 48

What % of diabetes mellitus is type 2?

Answer 48

90%

Question 49

What is the definition of type 2 diabetes mellitus?

Answer 49

Chronic, progressive metabolic disorder characterised by hyperglycaemia, insulin resistance & relative impairment of insulin deficiency

Question 50

Describe the pathogenesis of type 2 diabetes mellitus?

Answer 50

- Common with a prevalence that rises markedly with increasing levels of obesity - Most likely arises through a complex interaction among many genes & environmental factors

Question 51

Describe the epidemiology of type 2 diabetes mellitus?

Answer 51

- 39% have at least 1 parent with the disease | - Prevalence varies remarkably among ethnic groups living in the same

Question 52

What % of diabetes mellitus is MODY?

Answer 52

1-2% (often unrecognised)

Question 53

What is MODY caused by?

Answer 53

- Caused by change in a single gene (monogenic) | - Autosomal dominant (50% chance of inheriting)

Question 54

What does MODY stand for?

Answer 54

Maturity onset diabetes of the young

Question 55

What are the 3 main features of MODY?

Answer 55

1. Often <25yrs onset 2. Runs in families from 1 generation to next 3. Managed by diet, oral antihyperglycemic agents (OHAs), insulin (not always)

Question 56

What does IDDM stand for?

Answer 56

Insulin dependent diabetes mellitus

Question 57

List the 5 clinical features of Latent Autoimmune Diabetes of Adulthood (LADA)?

Answer 57

- Onset usually >25 - 0 parents affected - Rarely obese - Variable insulin treatment, usually within months or years of diagnosis - Polygenic inheritance - GAD autoantibodies

Question 58

List the 5 clinical features of Early Onset Type 2 Diabetes?

Answer 58

- Onset 25-40 - 2 parents affected - Obesity is common - No insulin treatment initially - Polygenic double gene dose inheritance - No GAD autoantibodies

Question 59

List the 5 clinical features of Maturity Onset Diabetes of the Young (MODY)?

Answer 59

- Onset <25 - 1 parent affected - Rarely obese - No insulin treatment initially - Monogenic autosomal dominant inheritance - No GAD autoantibodies

Question 60

What is gestational diabetes mellitus (GDM)?

Answer 60

Carbohydrate intolerance with onset, or diagnosis, during pregnancy

Question 61

List 3 risk factors for gestational diabetes mellitus (GDM)?

Answer 61

1. High BMI 2. Previous macrosomic baby/ gestational diabetes 3. Family history/ethnic prevalence of diabetes

Question 62

What should all pregnant women with risk factors of gestational diabetes mellitus have?

Answer 62

OGTT (oral glucose tolerance test) at 24 to 28 weeks

Question 63

What is the internationally agreed criteria for gestational diabetes using 75g OGTT?

Answer 63

- Fasting venous plasma glucose ≥ 5.1 mmol/l, OR - 1hr value ≥ 10 mmol/l, OR - 2hrs after OGTT ≥ 8.5 mmol/l

Question 64

List the 7 causes of secondary diabetes?

Answer 64

1. Genetic Defects of beta-cell function 2. Genetic defects in insulin action 3. Disease of exocrine pancreas 4. Endocrinopathies 5. Immunosuppressive agents 6. Anti Psychotics 7. Genetic syndromes associated with DM

Question 65

Give 4 examples of Diseases of the exocrine pancreas which can cause secondary diabetes?

Answer 65

1. Pancreatitis 2. Carcinoma 3. Cystic fibrosis 4. Haemochromatosis

Question 66

Give 3 examples of endocrinopathies which can cause secondary diabetes?

Answer 66

1. Acromegaly 2. Cushings 3. Phaeochromocytoma

Question 67

Give 3 examples of immunosuppressive agents which cause secondary diabetes?

Answer 67

1. Glucocorticoids 2. Tacrolimus 3. Ciclosporin

Question 68

Give 5 examples of genetic syndromes associated with secondary diabetes?

Answer 68

1. Down’s Syndrome 2. Friedreich’s Ataxia 3. Turner’s 4. Myotonic Dystrophy 5. Kleinfelter’s Syndrome

Question 69

Describe the production & release of insulin?

Answer 69

- Produced in beta cells (75% of the islets of Langerhans of the pancreas) - Released by exocytosis into the portal venous system which leads it directly to the liver (50%)

Question 70

What is the principle stimulant of insulin secretion?

Answer 70

Glucose

Question 71

What is the basal secretion of insulin?

Answer 71

~40 microgram/h under fasting conditions, there are increases of secretion linked to meals

Question 72

What mediates the entry of glucose into beta cells?

Answer 72

GLUT2 (type 2 glucose transporters)

Question 73

How does the beta cell depolarise?

Answer 73

- Glucose trapped within cell & is metabolised to create ATP - Increased ATP:ADP ratio causes ATP-gated K+ channels in the cellular membrane to close up, preventing K+ from being shunted across the cell membrane - Rise in + charge inside cell leads to depolarisation

Question 74

What is the net effect of beta cell depolarisation?

Answer 74

Activation of voltage-gated calcium channels, which transport calcium ions into the cell

Question 75

What does the brisk increase in beta cell intracellular calcium conc trigger?

Answer 75

- Export of the insulin-storing granules by exocytosis | - Ultimate result is the export of insulin from beta cells & its diffusion into nearby blood vessels

Question 76

Insulin release is a ______ process?

Answer 76

Biphasic

Question 77

What 2 things occur in the beta cells after the 1st fast response phase of insulin secretion?

Answer 77

1. 2nd phase of insulin release (slower) | 2. Beta cells regenerate the stores of insulin initially depleted in the 1st fast response phase

Question 78

Describe the incremental (above basal) plasma insulin concentration profiles in response to a physiological entry of glucose via a meal?

Answer 78

- NOT a biphasic pattern - Insulin response observed after food cannot be accounted for solely by associated changes in blood glucose level, it depends on other factors ie. free fatty acids & other secretagogues in the meal, the neurally activated cephalic phase, & GI hormones

Question 79

What is the treatment for type 1 diabetes mellitus?

Answer 79

Insulin via subcutaneous injections (its a peptide so cannot be given orally)

Question 80

Give 5 examples of insulin?

Answer 80

1. Rapid acting- Aspart, Lispro, Glulisine 2. NPH 3. Detemir 4. Glargine (Lantus/Toujeo) 5. Tresiba (Degludec)

Question 81

What are the 3 doses of insulin?

Answer 81

1. Once-daily basal insulin 2. Twice-Daily mix-insulin 3. Basal-bolus therapy

Question 82

Describe Levemir insulin?

Answer 82

- Shortest (~16hrs) | - BD>OD in T1DM

Question 83

What is the duration of Lantus insulin?

Answer 83

~20hrs OD

Question 84

What is the duration of Toujeo insulin?

Answer 84

~24hrs OD

Question 85

What is the duration of Degludec insulin?

Answer 85

=> 24hrs OD

Question 86

Describe Insulin glargine (Lantus®)?

Answer 86

- Clear, colourless solution for administration in a single daily dose - Delivered using the OptiPen® Pro or OptiSet® pen delivery devices - Can be used as a basal insulin in combination with oral antidiabetic agents or prandial insulin - Not suitable for mixing with other insulins prior to injection

Question 87

Describe OptiPen® Pro & OptiSet® pen delivery devices?

Answer 87

- OptiPen® Pro is a reusable insulin cartridge pen | - OptiSet® is a prefilled pen with a facility to preset the dosage

Question 88

What are the 2 analogues for short/rapid (bolus) human Actrapid & Humulin S?

Answer 88

Novorapid/Fiasp Humalog, Apidra

Question 89

What are the 3 analogues for intermediate/long (basal) human Insulatard & Humulin I?

Answer 89

1. Levemir (Detemir) | 2. Lantus/Toujeo (Glargine) 3. Tresiba (Degludec)

Question 90

What are the 2 analogues for mixed human Humulin M3?

Answer 90

1. Novomix 30 | 2. Humalog Mix 25/50

Question 91

What are the 5 PROS of insulin pens?

Answer 91

1. Convenient & easier transport than vial & syringe 2. More accurate dosages 3. Easier to use for impairments in visual & fine motor skills 4. Less pain (as polished & coated needles are not dulled by insertion into a vial of insulin before a second insertion into the skin) 5. Can be used without being noticed

Question 92

Describe the purpose of Continuous Subcutaneous Insulin infusion (CSII)/ "pump therapy"?

Answer 92

- Have the potential to make it easier to achieve glucose control with less danger of severe & incapacitating hypoglycaemia - However, the efficacy of this compared to SMBG is still debatable

Question 93

List the 4 infrequent complications of Continuous Subcutaneous Insulin infusion (CSII)/ "pump therapy"?

Answer 93

1. Reactions 2. Infections at the cannula site 3. Tube blockage 4. Pump malfunction

Question 94

What is the main CON of Continuous Subcutaneous Insulin infusion (CSII)/ "pump therapy"?

Answer 94

Expensive- costs for batteries, reservoirs, infusion sets, insulin, lancets, test strips & glucometers

Question 95

What are the 2 curative treatments for type 1 diabetes mellitus?

Answer 95

1. Islet cell transplant | 2. Pancreatic transplant

Question 96

What type of molecule is insulin?

Answer 96

Peptide

Question 97

What is Whipples Triad in Hypoglycaemia?

Answer 97

1. Symptom of low blood glucose: autonomic or neuroglycopaenic 2. Measured plasma glucose: < 2.8mmol= normal. <4.0mmol= insulin-treated DM 3. Better after glucose

Question 98

Describe the physiology & signs of 4.6mmol/L blood glucose?

Answer 98

- Inhibition of insulin release | - Signs: general malaise, headache, nausea

Question 99

Describe the physiology & signs of 3.8mmol/L blood glucose?

Answer 99

- Release of counter regulatory hormones glucagon & adrenaline - Signs: autonomic symptoms, sweating, palpitations, shaking, nausea, anxiety, hunger

Question 100

What do 70-80% of people with a blood glucose level of 3.8mmol/L have?

Answer 100

No symptoms

Question 101

Describe the physiology & signs of 2.5-2.8mmol/L blood glucose?

Answer 101

- Impairment of cognitive function & concentration, inability to perform complex tasks - Signs: confusion, drowsiness, odd behaviour, speech difficulty, incoordination, weakness, visual change, dizziness, tiredness

Question 102

Describe the physiology & sign of <2mmol/L blood glucose?

Answer 102

- EEG changes | - Sign: seizures

Question 103

What are the 2 signs of <1.5mmol/L blood glucose?

Answer 103

1. Coma | 2. Convulsions

Question 104

Describe the severity scale of hypoglycaemia?

Answer 104

- MILD: autonomic - MODERATE: autonomic & neuroglycopaenic - SEVERE: autonomic & neuroglycopaenic

Question 105

List 4 things hypoglycaemic patients need to do when/before driving?

Answer 105

1. CBG> 5mmol/l before driving, carry CHO, identifiers 2. If between 4-5 mmol/l then eat before driving 2 hours at a time 3. Do not drive if feeling hypo or CBG <4 mmol/l 4. If hypo: 1 hour before driving (from onset) & CBG>5

Question 106

What are the DVLA hypo guidances for driving with group 1 entitlement hypoglycaemic patients on insulin?

Answer 106

1. Adequate hypo awareness 2. Notify if >1 severe hypo whilst awake in 12 months or most recent <3months when filling form 3. Home capillary blood glucose (CBG) monitoring evidence 4. Not a danger to the public 5. Acuity & visual fields OK

Question 107

What do Group 1 entitlement patients on tablets with a risk of hypos e.g. sulphonylureas have to bring when driving, according to the DVLA?

Answer 107

Home capillary blood glucose (CBG) diary

Question 108

What are the DVLA hypo guidances for driving with group 2 entitlement with insulin resistant diabetes mellitus (IRDM)?

Answer 108

1. Full hypo awareness & understanding of risks 2. No severe hypos in 12 months 3. Home capillary blood glucose (CBG) monitoring evidence: 3 months of recordings 4. Not a danger to the public 5. Acuity & visual fields OK

Question 109

What are the DVLA hypo guidances for driving with group 2 entitlement with tablets risk of hypoglycaemia?

Answer 109

1. No severe hypos in 12 months 2. Full hypo awareness & understanding of risks 3. CBG checks at least twice daily & more often for driving

Question 110

What type of diabetes is more prone to diabetic ketoacidosis?

Answer 110

Mainly T1DM but now recognise ketosis prone T2DM

Question 111

Describe the mortality of diabetic ketoacidosis?

Answer 111

- Mortality in young: cerebral oedema 70-80% deaths | - Mortality in adults: severe hypokalaemia, ARDS, illness causing decompensation

Question 112

What are the 3 factors to diabetic ketoacidosis?

Answer 112

1. Metabolic acidosis: venous bicarbonate < 18mmol. H+ > 45 mEq/L. pH < 7.3 2. Plasma glucose: >13.9mmol/l 3. Urinary / plasma ketones: ≥2+ urinary/ >3mmol/L

Question 113

Describe the pathophysiology of diabetic ketoacidosis?

Answer 113

Absolute or relative insulin deficiency + Increase in stress hormones --> 1. Lipolysis: FFAs: ketogenesis 2. Gluconeogenesis: severe hyperglycaemia 3. Osmotic diuresis + acidosis: dehydration

Question 114

List the 7 clinical features of diabetic ketoacidosis?

Answer 114

1. Osmotic Symptoms 2. Weight Loss 3. Breathlessness- Kussmaul respiration 4. Abdominal pains, especially in children 5. Leg cramps 6. Nausea & vomiting 7. Confusion

Question 115

List the 4 main precipitating factors of diabetic ketoacidosis?

Answer 115

1. Insulin omission- 33% 2. Infections- 20-38% 3. New-onset DM- 5-39% 4. Acute Illness (MI, trauma, pancreatitis)- 10-20%

Question 116

List the 5 other precipitants of ketoacidosis?

Answer 116

1. Steroids 2. CSII Pump failure 3. Substance abuse 4. Deliberate omission of Insulin dose 5. Eating disorder

Question 117

What are 5 reasons why someone might deliberately stop taking their insulin?

Answer 117

1. Weight management 2. Avoidance of hypoglycaemia 3. Escaping domestic situation 4. Depression 5. Attention seeking

Question 118

List the 4 typical key losses in DKA & how much is lost?

Answer 118

1. 6-8 litres of water (100ml/kg) 2. Sodium 500-1000mmol 3. Chloride 350mmol 4. Potassium 300-1000 (3-5 mmol/Kg)

Question 119

What are the 3 treatments for DKA?

Answer 119

1. Fluid- restoration of circulatory volume ie. crystalloid. Clearance of ketones ie. 10% dextrose 2. Potassium 3. Insulin

Question 120

How long is the DKA care pathway?

Answer 120

0-4hrs (4hrs until discharge)

Question 121

Describe a Hyperglycaemic Hyperosmolar State (HHS)?

Answer 121

- Hypovolaemia - Very high blood glucose > 30mmol/L - Serum osmolality >320mOsmol/l - Bicarbonate usually > 15mmol/l - Absence of significant ketones

Question 122

What is osmolality equal to?

Answer 122

2 x (Na + K) + Urea + Glu

Question 123

What is not present in Hyperglycaemic Hyperosmolar State (HHS)?

Answer 123

Ketoacidosis

Question 124

What may proceed Hyperglycaemic Hyperosmolar State (HHS) proceed to?

Answer 124

Coma (watch GCS)

Question 125

Describe the prevalence of Hyperglycaemic Hyperosmolar State (HHS)?

Answer 125

- Less than 1% diabetes related admissions annually | - Elderly (55-70yrs), first presentation T2DM in 30%

Question 126

What are the 3 precipitating factors for Hyperglycaemic Hyperosmolar State (HHS)?

Answer 126

1. Infection- 60% 2. Poor compliance- 30% 3. Drugs

Question 127

What are the 3 treatment for Hyperglycaemic Hyperosmolar State (HHS)?

Answer 127

1. Fluid- 0.9% sodium chloride 2. Insulin- low dose 0.05units/kg/hr 3. Other- LMWH, Foot protection

Question 128

Describe the fluid treatment for Hyperglycaemic Hyperosmolar State (HHS)?

Answer 128

- Aim for a positive fluid balance of 3-6L by 12 hours - Only switch to 0.45% sodium chloride if osmolality not falling despite positive fluid balance - Rate of fall in sodium should not exceed 10mmol in 24 hours

Question 129

Describe the insulin treatment for Hyperglycaemic Hyperosmolar State (HHS)?

Answer 129

- Rate of fall no more than 5mmol/L/hr | - Only start when glucose not falling with fluid alone

Question 130

What are the 2 microvascular complications of diabetes?

Answer 130

1. Retinopathy- leading cause of blindness in the working population in developed world. 1st microvascular complication for patients with diabetes 2. Nephropathy- 30-40% of patients with diabetes, 23% of patients starting dialysis have diabetes as the primary case, but poorer survival on it

Question 131

Describe the foot complications of diabetes?

Answer 131

Neuropathy/foot disease- | Life-time risk for a foot ulcer is 25%. 80% of non-traumatic amputations occur in patients with diabetes

Question 132

What are the 5 signs & symptoms of cardiovascular complications in type 2 diabetes?

Answer 132

1. Previous history of stroke- 7% 2. Abnormal ECG- 18% 3. Hypertension- 35% 4. Intermittent claudication- 4.5% 5. Absent foot pulses- 13%

Question 133

What is the most costly complication of diabetes in relation to in-patient care?

Answer 133

Peripheral vascular disease (diabetic are 15x more likely to undergo amputation)

Question 134

What is the 2nd major cause of death in type 2 diabetes?

Answer 134

Stroke (accounting for 15% of all deaths in T2DM)

Question 135

What is the management for retinopathy in diabetes?

Answer 135

Annual photographic retinal screening with triggers for ophthalmology referral

Question 136

What is the management for nephropathy in diabetes?

Answer 136

Annual monitoring of renal function & urinary albumin excretion, referral to renal team if nephropathy progesses e.g. CKD4; macroalbuminuria

Question 137

What is the management for neuropathy/foot disease in diabetes?

Answer 137

Annual foot-screening (minimum) with risk stratification & referral to podiatry/vascular as appropriate e.g. progressive neuropathy, structural change, ischaemia

Question 138

What is the management for cardiovascular disease (CVD) in diabetes?

Answer 138

- Keep BP <130/80, lower if nephropathy - Statin therapy if T2DM and age >40 regardless of DM duration & baseline cholesterol - Consider in T1DM especially if complications

Question 139

What are 7 factors of the history which will help you decide what to do for T2DM?

Answer 139

1. Symptoms 2. When was diabetes diagnosed? 3. Co-morbidities 4. Drug history 5. Family history 6. Smoking 7. Alcohol

Question 140

What are 2 factors in examination which will help you decide what to do for T2DM?

Answer 140

1. BMI | 2. BP

Question 141

What are 3 investigations which will help you decide what to do for T2DM?

Answer 141

1. HbA1c 2. Lipids 3. Renal function

Question 142

List 8 pathophysiological failures which contribute to hyperglycaemia?

Answer 142

1. Increased glucose reabsorption 2. Impaired insulin secretion 3. Increased hepatic glucose production 4. Increased lipolysis 5. Decreased glucose uptake 6. Neurotransmitter dysfunction 7. Decreased incretin effect 8. Increased glucagon secretion

Question 143

What are 3 targets for the treatment of type 2 diabetes?

Answer 143

1. Insulin resistance 2. Decrease insulin production 3. Increase blood glucose

Question 144

Describe the 6 pathophysiological factors which lead to type 2 diabetes?

Answer 144

1. Reduction in insulin release in response to glucose: reduced 1st phase response 2. Failure of pulsatility of insulin secretion 3. Abnormality of insulin formation 4. Progressive beta cell failure 5. Loss of beta cell sensitivity to glucose 6. Delayed insulin secretion in response to oral glucose

Question 145

List 7 drugs which are used to treat type 2 diabetes?

Answer 145

1. DPP4 Inhibitors 2. GLP-1 agonists 3. Metformin 4. Sulphonylureas 5. Thiazolidinediones (TZDs) 6. Insulin 7. SGLT-2 inhibitors

Question 146

How does metformin work?

Answer 146

Activation of adenosine monophosphate activated protein kinase (AMPK) to inhibit gluconeogenesis

Question 147

What 3 effects does Metformin have on the liver?

Answer 147

1. Reduced fatty acid & cholesterol synthesis 2. Increased lipid oxidation 3. Reduced gluconeogenesis

Question 148

What effect does Metformin have on the skeletal muscle?

Answer 148

Increased lipolysis & lipogenesis

Question 149

What effect does Metformin have on adipose?

Answer 149

Reduced lipolysis & lipogenesis

Question 150

What effect does Metformin have on vascular endothelium?

Answer 150

Increased nitric oxide (NO) bio-availability

Question 151

What 2 effects does Metformin have on the heart?

Answer 151

1. Increased fatty acid uptake & oxidation | 2. Increased glucose uptake & glycolysis

Question 152

What are the 5 overall effects of Metformin on the body?

Answer 152

1. Weight loss 2. Increased insulin sensitivity 3. Improved glycaemia 4. Improved lipid profile 5. Improved vascular function

Question 153

Describe the mechanism of action of sulphonylureas on pancreatic beta cells?

Answer 153

- Bind & close ATP-sensitive K+ (KATP) channels on cell membrane, which depolarises the cell by preventing K+ exiting - Opens voltage-gated Ca2+ channels - Rise in intracellular Ca2+ -->increased secretion of mature insulin & therefore decrease plasma glucose

Question 154

What is the evidence for type 2 diabetes benefits from Pioglitazone?

Answer 154

Secondary prevention of macrovascular events in the PROactive study (randomised controlled trial)

Question 155

List the 6 limitations of older type 2 diabetes therapies?

Answer 155

1. Weight gain (SU, TZD, insulin) 2. Hypogylcaemia (SU, insulin) 3. Concerns over CV safety (TZD) 4. Concerns over cancer risks (TZD, some insulins) 5. Limited options in patients with renal disease 6. Natural history of disease not altered

Question 156

What is the incretin effect?

Answer 156

The difference in insulin response between orally delivered & IV delivered glucose

Question 157

What happens to DPP-4 when they are inhibited?

Answer 157

Rapidly inactivated to GLP-1 & GIP

Question 158

What is the effect of increased GLP-1 & GIP on the pancreas beta cells?

Answer 158

Increased insulin --> Increased glucose uptake in fat & muscle

Question 159

What is the effect of increased GLP-1 & GIP on the pancreas alpha cells?

Answer 159

Decreased glucagon --> Decreased glucose production in the liver

Question 160

What effect does Increased GLP-1 have on the hypothalamus?

Answer 160

Decreased appetite

Question 161

What effect does Increased GLP-1 have on the stomach?

Answer 161

Decreased gastric emptying

Question 162

What are incretins?

Answer 162

- Group of metabolic hormones (GLP-1 & GIP) that stimulate a decrease in blood glucose levels - They are released after eating & augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans

Question 163

List the 4 PROS/CONS of incretin based therapy?

Answer 163

1. Weight loss 2. Risk of hypoglycaemia 3. Likely benefit? 4. Special groups- elderly & renal impairment as it is renally excreted

Question 164

Give an example of a SGLT-2 inhibitor drug?

Answer 164

Empagliflozin

Question 165

What are the advantages of SGLT-2 inhibitor drugs for treating type 2 diabetes?

Answer 165

Reduces hyperglycaemia, BP & CV risk

Question 166

Describe SGLT-2 inhibitor drugs for treating type 2 diabetes?

Answer 166

- Inhibit SGLT2 in the PCT & so increase glucose excretion in the urine  - Used when HbA1c>53mmol/mol

Question 167

Describe the treatment pathway for type 2 diabetes?

Answer 167

Lifestyle changes (diet & exercise) --> Oral diabetes therapy --> GLP-1s --> Insulin

Question 168

What should all development programmes for T2D rule out?

Answer 168

Unacceptable increase in CV risk

Question 169

Give 4 examples of DPP4 inhibitor drugs used to treat type 2 diabetes?

Answer 169

1. Sitagliptin 2. Alogliptin 3. Vildagliptin 4. Omarigliptin

Question 170

Give 6 examples of GLP1 agonist drugs used to treat type 2 diabetes?

Answer 170

1. Semaglutide 2. Lixisenatide 3. Liraglutide 4. Exenatide 5. Dulaglutide 6. Albiglutide

Question 171

Give 4 examples of SGLT2 inhibitor drugs used to treat type 2 diabetes?

Answer 171

1. Empagliflozin 2. Canagliflozin 3. Ertugliflozin 4. Dapagliflozin

Question 172

Describe the mechanism of action of DPP4 inhibitors?

Answer 172

- Inhibit DPP4 which normally breaks down incretins | - Results in increased insulin

Question 173

When would you use DPP4 inhibitors?

Answer 173

Should be considered, usually as dual or triple therapy, for lowering HbA1c

Question 174

Describe the 3 cases in which GLP-1 agonists would be used?

Answer 174

1. Considered when BMI => 30kg/m2 in combo with oral glucose-lowering drugs or basal insulin as 3rd/4th line treatment, when adequate control has not been achieved 2. Considered as an alternative to insulin in people who combo of oral agents have been inadequate & insulin would otherwise be the next option 3. Type 2 diabetes & established CV disease, Liraglutide should be considered

Question 175

Describe the mechanism of action of SGLT2 inhibitors?

Answer 175

- Work at proximal tubule in kidneys | - Act to reduce glucose reabsorption & increase glucose excretion

Question 176

When would you use SGLT2 inhibitors?

Answer 176

- Considered as add-on therapy to Metformin in people with T2DM - T2DM & established CV disease, Empagliflozin & Canagliflozin should be considered

Question 177

What is the 1st line (in addition to lifestyle measurements) drugs for T2DM?

Answer 177

1. Metformin OR | 2. Sulphonylurea if osmotic symptoms or intolerant to metformin

Question 178

What is the 2nd line (in addition to lifestyle measurements) drugs for T2DM?

Answer 178

1. Sulphonylurea OR 2. SGLT2 inhibitor OR 3. DPP-4 inhibitor OR 4. Pioglitazone (thiazolidinedione)

Question 179

What is the set glycaemic target for T2DM?

Answer 179

HbA1c <7% (53mmol/mol)

Question 180

What is the 3rd line (in addition to lifestyle measurements) drugs for T2DM?

Answer 180

1. Sulphonylurea OR 2. SGLT2 inhibitor OR 3. DPP-4 inhibitor OR 4. Pioglitazone (thiazolidinedione) OR 5. Injectable GLP-1 agonist OR 6. Injectable basal insulin

Question 181

When would you need to get a specialist to treat T2DM (4th line)?

Answer 181

If not reaching target after 3-6months, review adherence

Question 182

What would you do to the other drugs when prescribing a 3rd line injectable GLP-1 agonist for T2DM?

Answer 182

- Stop DPP-4 inhibitor - Consider reducing sulphonylurea - Continue metformin - Can continue Pioglitazone - Can continue SGLT2 inhibitor

Question 183

What would you do to the other drugs when prescribing 3rd line injectable basal insulin for T2DM?

Answer 183

- Can continue metformin, Pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor - Can reduce/stop sulphonylurea

Question 184

Describe the type of basal insulin given as a 3rd line treatment for T2DM?

Answer 184

- Inject before bed | - Use NPH (isophane) insulin or longer-acting analogues according to risk of hypoglycaemia

Question 185

What 4 T2DM drugs have a CV benefit?

Answer 185

1. Metformin 2. SGLT-2 inhibitors 3. Pioglitazone 4. GLP-1 agonist

Question 186

What 2 T2DM drugs have a high hypoglycaemic risk?

Answer 186

1. Sulphonylurea | 2. Basal insulin

Question 187

What 3 T2DM drugs can cause weight gain?

Answer 187

1. Sulphonylurea 2. Basal insulin 3. Pioglitazone

Question 188

What T2DM drugs have the lowest chance of side effects?

Answer 188

DPP-4 inhibitors

Question 189

What 2 T2DM drugs have GI side effects?

Answer 189

1. Metformin | 2. GLP-1 agonists

Question 190

What main adverse effect does SGLT2- inhibitors have?

Answer 190

Genital mycotic

Question 191

What main adverse effect does Pioglitazone have?

Answer 191

Oedema/fractures

Question 192

What should you do if a T2DM patient need insulin intensification?

Answer 192

Add prandial insulin or switch to twice daily mixed biphasic insulin

Question 193

Describe the 2 concluding factors of past evidence/cases to efficient & sensible diabetic control?

Answer 193

1. All patients should have an individualised approach including defining treatment specific targets & whether these are aimed at symptomatic or prognostic benefit 2. All treatment choices should be reviewed regularly balancing benefit & risks of therapeutic intervention

Question 194

What 5 hormones does the anterior pituitary release?

Answer 194

1. ACTH 2. GH 3. TSH 4. Gonadotropins (FSH, LH) 5. Prolactin

Question 195

What 2 hormones does the posterior pituitary release?

Answer 195

1. ADH | 2. Oxytocin

Question 196

What 5 hormones does the hypothalamus release?

Answer 196

1. Growth hormone releasing hormone (GHRH) 2. Gonadotrophin releasing hormone (GnRH) 3. Corticotrophic releasing hormone (CRH) 4. Thyroid releasing hormone (TRH) 5. Dopamine

Question 197

List the 5 cell types in the anterior pituitary?

Answer 197

1. Somatotrophs (50%) 2. Gonadotrophs (10%) 3. Corticotrophs (10-15%) 4. Thyrotrophs (5%) 5. Lactotrophes (20%)

Question 198

Describe the ADH regulation of water balance?

Answer 198

Osmoreceptors in the hypothalamus --> Increase ADH release from the posterior pituitary --> Decrease free water excretion in the kidneys

Question 199

What are 4 other names for ADH?

Answer 199

1. AVP 2. Vasopressin 3. Arginine vasopressin 4. Argipressin

Question 200

What are the 6 rules of endocrinology?

Answer 200

1. Most hormones levels fluctuate- random level ie. cortisol 2. Too much of a hormone?- suppress it 3. Not enough of a hormone?- stimulate it 4. Do biochemical tests first & imaging later 5. Primary= problem with gland itself 6. Secondary= problem elsewhere

Question 201

What is fT4?

Answer 201

Thyroxine

Question 202

What would you give 1st before starting a patient on thyroxine & testosterone?

Answer 202

Hydrocortisone

Question 203

What type of surgery do we do for a pituitary adenoma?

Answer 203

Transphenoidal surgery

Question 204

Describe hypopituitarism?

Answer 204

- Failure of (anterior) pituitary function | - Can affect single hormonal axis or all hormones (panhypopituitarism)

Question 205

What does hypopituitarism lead to?

Answer 205

Secondary gonadal/thyroid/adrenal failure

Question 206

What is the treatment for hypopituitarism?

Answer 206

Need multiple hormone replacement

Question 207

List the 6 causes of hypopituitarism?

Answer 207

1. Tumours 2. Radiotherapy 3. Infarction / haemorrhage (apoplexy) 4. Infiltration (eg sarcoid) 5. Trauma 6. Lymphocytic hypophysitis (autoimmune)

Question 208

What 2 things are associated with Infarction / haemorrhage (apoplexy) causing hypopituitarism?

Answer 208

1. Associated headache / visual disturbance | 2. Associated postpartum pituitary gland necrosis (Sheehan’s syndrome)

Question 209

What would you give as replacement for ACTH deficiency?

Answer 209

Hydrocortisone

Question 210

What would you give as replacement for TSH deficiency?

Answer 210

Thyroxine

Question 211

What would you give as replacement for FSH/LH deficiency?

Answer 211

- Testosterone (males) | - Oestrogen (females)

Question 212

What would you give as replacement for GH deficiency?

Answer 212

Growth hormone (children)

Question 213

What would you give as replacement for PRL (prolactin) deficiency?

Answer 213

No replacement

Question 214

What are 4 causes of high prolactin?

Answer 214

1. Prolactinomas (tumours of pituitary gland) 2. Physiological- lactation/pregnancy 3. Drugs (that block dopamine)- Tricyclics/ antiemetics/antipsychotics 4. “Stalk” effect- due to loss of inhibitory dopamine from hypothalamus

Question 215

What are the 4 key questions to ask for pituitary tumours?

Answer 215

1. How big is it? < 1cm micro (adenoma) > 1cm macro (adenoma) 2. Is it releasing any hormones? 3. Is it stopping the rest of the pituitary from working normally? 4. Is it compressing surrounding tissues? eg optic chiasm

Question 216

What are the 3 types of pituitary tumours?

Answer 216

1. Non-functioning (majority) so they just grow 2. Functioning 3. Others- Craniopharyngioma, pituitary cancer, Rathke’s cyst

Question 217

List 4 functioning pituitary tumours?

Answer 217

1. Prolactin (prolactinoma) 2. GH (acromegaly) 3. ACTH (Cushing’s disease) 4. TSH (TSHoma)

Question 218

Describe non-functioning pituitary tumours?

Answer 218

- Commonest (25 % of all pituitary tumours) | - No hormonal release

Question 219

List 4 problems that non-functioning pituitary tumours cause?

Answer 219

1. Visual field defects 2. Headache 3. Stops other pituitary hormones working 4. Eye movement problems (cranial nerve disturbance)

Question 220

What 4 investigations would you do for non-functioning pituitary tumours?

Answer 220

1. Imaging (MRI) 2. Visual field assessment 3. Prolactin 4. Other pituitary hormones

Question 221

What are the 3 treatments for non-functioning pituitary tumours?

Answer 221

1. Surgery (help protect vision) 2. RT if its aggressive 3. Medical management unhelpful

Question 222

What is a prolactinoma?

Answer 222

Pituitary tumours releasing prolactin (2nd most common type of pituitary tumour)

Question 223

Describe the 2 sizes of prolactinomas?

Answer 223

1. Micro < 1 cm | 2. Macro > 1 cm

Question 224

List the 5 clinical features of prolactinomas?

Answer 224

1. Galactorrhoea 2. Headaches 3. Mass effect 4. Visual field defect 5. Amenorrhoea / erectile dysfunction

Question 225

Describe the 3 ways to diagnose a prolactinoma?

Answer 225

1. Serum prolactin usually > 6000 2. MRI pituitary 3. Test remaining pituitary function- gonadal function & thyroid hormones most affected

Question 226

Describe the medical treatment of prolactinomas?

Answer 226

Dopamine agonists help to bring down prolactin & shrink the tumour

Question 227

Give 3 examples of Dopamine agonists used in the treatment of prolactinomas?

Answer 227

1. Cabergoline 2. Bromocriptine 3. Quinagolide (these drugs are also used in Parkinson’s disease)

Question 228

What are 2 scenarios for surgical treatment of prolactinomas?

Answer 228

1. Visual field compromise | 2. Failure of medical therapy

Question 229

Describe prolactinomas in pregnancy?

Answer 229

- Pituitary gland gets bigger in pregnancy - Dopamine agonists contraindicated - Prolactin unhelpful - Can’t do serial MRI in pregnancy - Monitor visual fields if macroprolactinoma

Question 230

What is Acromegaly caused by?

Answer 230

Pituitary tumour secreting Growth Hormone - Post puberty ie after growth plates fused - Gigantism

Question 231

List the 6 clinical features of acromegaly?

Answer 231

1. Sweats & headaches 2. Alteration of facial features 3. Increased hand & feet size 4. Visual impairment 5. Cardiomyopathy 6. Inter-dental space

Question 232

Describe the prevalence of acromegaly?

Answer 232

Rare- 20 new cases per year in Scotland

Question 233

What is acromegaly usually?

Answer 233

Macroadenoma

Question 234

What are the 4 ways to diagnose Acromegaly?

Answer 234

1. Glucose tolerance test 2. Glucose should suppress GH 3. Measure IGF-1- long half-life, more useful than random GH 4. Then MRI

Question 235

What is the 1st line treatment for acromegaly?

Answer 235

Surgery (often tumour can't be filly removed)

Question 236

List the 3 drugs used to treat acromegaly?

Answer 236

1. Somatostatin analogue- Octreotide, before & after surgery 2. Dopamine agonist 3. GH receptor agonist- Pegvisomant

Question 237

When would you use radiotherapy to treat acromegaly?

Answer 237

Residual tumour/ ongoing symptoms

Question 238

Describe the inheritance of acromegaly?

Answer 238

- Familial isolated pituitary adenoma | - Same mutation of AIP

Question 239

What one cause of Cushing's disease?

Answer 239

Pituitary tumour releasing ACTH

Question 240

What are the 8 clinical features of Cushing's disease?

Answer 240

1. Weight gain 2. Thin skin 3. Easy bruising 4. Increased BP 5. Osteoporosis 6. Buffalo hump 7. Increased abdominal fat 8. Moon face with red cheeks

Question 241

How do you try suppress Cushing's disease?

Answer 241

Dexamethasone suppression testing

Question 242

What is the 1st line treatment for Pituitary tumour causing Cushing's disease?

Answer 242

Surgery

Question 243

What are 3 treatments for Pituitary tumour causing Cushing's disease if surgery fails?

Answer 243

1. Bilateral adrenalectomy 2. Medical therapy- Ketoconazole / metyrapone 3. Radiotherapy

Question 244

What is a TSHoma?

Answer 244

- Pituitary tumour releasing TSH - Rare - Causes high TSH & high fT4

Question 245

What is Diabetes insipidus?

Answer 245

ADH deficiency- central or cranial

Question 246

List the 2 clinical features of Diabetes insipidus?

Answer 246

1. Polydipsia- chronic excessive thirst accompanied by excessive fluid intake 2. Polyuria- urine output > 3 L/day

Question 247

What are the 2 differential diagnosis for Diabetes insipidus?

Answer 247

1. Nephrogenic diabetes insipidus | 2. Psychogenic polydipsia

Question 248

List 9 causes of central diabetes insipidus (Deficiency of ADH)?

Answer 248

1. Idiopathic 2. Trauma 3. Pituitary tumour 4. Pituitary surgery 5. Pregnancy 6. Familial 7. Wegeners 8. Sarcoidosis 9. Lymphocytic panhypophysitis

Question 249

How would you diagnose diabetes insipidus?

Answer 249

- Try to stimulate its release - Water deprivation test to see if they are able to stop urinating - Assess ability to concentrate urine with ADH

Question 250

What are the 2 ways to treat diabetes insipidus?

Answer 250

1. Treat underlying cause | 2. Desmopressin (DDAVP)- Spray, tablets or injection

Question 251

What are the 3 parts of the adrenal cortex & what hormones do they produce?

Answer 251

1. Glomerulosa- Aldosterone (salt) 2. Fasciculata- Cortisol (sugar) 3. Reticularis- Androgens (sex)

Question 252

What cells does the adrenal medulla contain & what do they produce?

Answer 252

Chromograffin cells- catecholamines (adrenaline & noradrenaline)

Question 253

Describe the regulation of the renin-angiotensin system?

Answer 253

- Renin is activated in response to decrease BP - Leads to production of Angiotensin II which causes direct (vasoconstriction) & indirect (aldosterone) methods of BP elevation

Question 254

What are the steps of the renin-angiotensin system?

Answer 254

Angiotensinogen --> (via renin) Angiotensin I --> (via angiotensin-converting enzyme) Angiotensin II --> Aldosterone --> Salt retention & BP rises

Question 255

What are the steps in the HPA axis to produce cortisol/androgen?

Answer 255

Corticotropin releasing hormone (hypothalamus) --> Adrenocorticotropic hormone (anterior pituitary) --> Cortisol (adrenal cortex) --> Negative feedback

Question 256

What 3 factors make the hypothalamus produce and release CRH?

Answer 256

1. Illness 2. Stress 3. Time of day

Question 257

What % of hypertension cases have no known cause (essential/primary)?

Answer 257

>90%

Question 258

What are 10% of hypertension cases?

Answer 258

Secondary to another disorder eg. renal disease, hormone excess

Question 259

What 3 factors make secondary hypertension more likely?

Answer 259

1. Young 2. Resistant/severe hypertension 3. Clinical suspicion

Question 260

What is Hypertension + Hypokalaemia?

Answer 260

Primary Aldosteronism

Question 261

What 3 things would you test for in the blood of someone with suspected aldosterone adrenal dysfunction?

Answer 261

1. Aldosterone (100-400pmol/l) 2. Renin (5-44.9 μIU/ml) 3. Aldosterone:renin ratio (ARR) (>35 suspicious)

Question 262

What is the commonest secondary cause of hypertension?

Answer 262

Primary aldosteronism (prevalence approx 11%)

Question 263

What are the 2 causes of primary aldosteronism?

Answer 263

1. Adenoma- 40% | 2. Bilateral hyperplasia- 60%

Question 264

What is present in 50% of primary aldosteronism cases?

Answer 264

Hypokalaemia

Question 265

What is the best screening tool for primary aldosteronism?

Answer 265

Aldosterone-renin-ratio (ARR) | - If increased, then consider further testing

Question 266

What should you do if there is confirmed aldosterone excess?

Answer 266

Stop medications if possible!: - Definitely stop β blockers and MR antagonists - Alternative drugs include α-blockers/verapamil/ hydralazine

Question 267

Describe the saline suppression test?

Answer 267

- 2L saline over 4 hours | - 4h aldosterone >270 pmol/l highly suspicious

Question 268

Describe the surgical management of primary aldosteronism?

Answer 268

- Unilateral laparoscopic adrenalectomy - Only if adrenal adenoma - Cure of hypokalaemia - Cures hypertension in 30-70% cases

Question 269

Describe the medical management of primary aldosteronism?

Answer 269

Use MR antagonists (spironolactone or eplerenone)

Question 270

What 4 tests could you do to check if someones cortisol was elevated?

Answer 270

1. 24 hr Urinary free cortisol 2. Urine cortisol: creat ratio x 3 3. Dexamethasone suppression test either overnight or low dose test over 48 hours 4. Late night salivary cortisol

Question 271

List the 3 ACTH dependent causes of Cushing's syndrome?

Answer 271

1. Pituitary adenoma (68%) Cushing’s Disease 2. Ectopic ACTH 12% 3. Ectopic CRH <1%

Question 272

List the 3 ACTH independent causes of Cushing's syndrome?

Answer 272

1. Adrenal adenoma 10% 2. Adrenal carcinoma 8% 3. Nodular hyperplasia 1%

Question 273

What is the best imaging technique for Cushing's disease?

Answer 273

CT adrenals

Question 274

What are the 2 treatments for an adrenal adenoma causing Cushing's disease?

Answer 274

1. Laparoscopic right adrenalectomy | 2. Short term requirement for hydrocortisone replacement therapy

Question 275

Describe congenital adrenal hyperplasia?

Answer 275

- Autosomal recessive disorder of the cortex - Range of genetic disorders relating to defects in steroidogenic genes - Most common CYP21 (21α hydroxylase)

Question 276

Describe female congenital adrenal hyperplasia?

Answer 276

Ambiguous genitalia

Question 277

Describe male congenital adrenal hyperplasia?

Answer 277

- Adrenal crisis (Hypotension, hyponatraemia) | - Early virilisation

Question 278

What is the treatment for congenital adrenal hyperplasia?

Answer 278

Mineralocorticoid & glucocorticoid replacement

Question 279

List 5 urinary catecholamines that are raised in a Phaeochromocytoma?

Answer 279

1. Noradrenaline 2. Adrenaline 3. Dopamine 4. Free Metadrenaline 5. Free normetadrenaline

Question 280

What is affected in Phaeochromocytoma?

Answer 280

Adrenal medulla (overproduction of catecholamines)

Question 281

What is affected in a Paraganglioma?

Answer 281

Extra-adrenal neural crest cells eg sympathetic ganglia

Question 282

Describe the prevalence of phaeochromocytoma?

Answer 282

Rare, 2-8/million cases per year

Question 283

Describe the signs/symptoms of phaeochromocytoma?

Answer 283

- Hypertension (intermittent in 50%) - Episodes of headache, palpitations, pallor and sweating - Also tremor, anxiety, nausea, vomiting, chest or abdo pain - Crises last 15 mins - Often well in between crises

Question 284

Upto 25% of phaeochromocytoma cases are associated with what 4 genetic conditions?

Answer 284

1. MEN 2. VHL 3. SDHB & SDHD mutations 4. Neurofibromatosis

Question 285

What % of phaeochromocytoma are malignant?

Answer 285

15-20% (5 year survival <50%)

Question 286

What % of phaeochromocytoma are benign?

Answer 286

80-85% ( recurrence rate <10% & 5 year survival 96%)

Question 287

Describe the 3 pre-operative treatments for phaeochromocytoma?

Answer 287

1. Alpha-blockade initially- phenoxybenzamine or doxazosin 2. Then beta blocker if tachycardic- Labetolol or bisoprolol 3. Encourage salt intake

Question 288

What are 2 primary adrenal insufficiencies?

Answer 288

1. Addison’s disease | 2. Autoimmune destruction

Question 289

List the 5 clinical features of adrenal insufficiency?

Answer 289

1. Anorexia, weight loss 2. Fatigue/lethargy 3. Dizziness and low BP 4. Abdominal pain, vomiting, diarrhoea 5. Skin pigmentation

Question 290

Describe the "suspicious biochemistry" associated with adrenal insufficiency?

Answer 290

- Decrease Na - Increase K - Hypoglycaemia

Question 291

What are 4 ways to diagnose adrenal insufficiency?

Answer 291

1. Short synACTHen test 2. ACTH levels 3. Renin/aldosterone levels 4. Adrenal autoantibodies

Question 292

Describe the short synACTHen test for diagnosing adrenal insufficiency?

Answer 292

- Measure plasma cortisol before & 30 min after IV ACTH injection - Normal: baseline >250nmol/L, post ACTH >480

Question 293

Describe the ACTH levels in adrenal insufficiency?

Answer 293

Increased & causes skin pigmentation

Question 294

Describe the renin/aldosterone levels in adrenal insufficiency?

Answer 294

- Increase Renin | - Decreased aldosterone

Question 295

If plasma ACTH is low then where is the source of cortisol?

Answer 295

Adrenal source

Question 296

Describe High dose dexamethasone suppression test in localising cortisol source?

Answer 296

- If pituitary, cortisol will suppress to <50% | - No response in ectopic ACTH

Question 297

Describe the CRH test in localising cortisol source?

Answer 297

- Exaggerated response in pituitary disease | - No response in ectopic ACTH

Question 298

Describe the imaging in localising cortisol source?

Answer 298

- Adrenal CT or MRI - Pituitary MRI only detects 50% of ACTH producing pituitary tumours - Optimal imaging for ectopic tumours unclear (CT/PET/MRI)

Question 299

Describe the epidemiology of Hypoglycaemia?

Answer 299

Uncommon cause of symptoms in adults, except in those with DM treated with glucose-lowering meds

Question 300

What is the definition of hypoglycaemia in patients with diabetes mellitus?

Answer 300

Biochemical threshold of plasma glucose less than 4 mmol/L1

Question 301

What is the definition of hypoglycaemia in patients with NO diabetes mellitus?

Answer 301

Glucose <3.0 mmol/L (some protocols 2.2 mmol/L)

Question 302

Describe the 2 types of hypoglycaemic symptoms?

Answer 302

1. Autonomic- sweating, palpitations, pallor, tremors, nausea, irritability, hunger 2. Neuroglycopenic- inability to concentrate, confusion, drowsiness, personality change, slurred speech, incoordination, weakness, dizziness, vision impairment, headache, seizures, coma

Question 303

Describe the hypoglycaemia symptoms in patients with diabetes?

Answer 303

Autonomic symptoms occur before neuroglycopenic symptoms

Question 304

What are the 4 key factors to ascertain in hypoglycaemia?

Answer 304

1. Whipple’s triad exists? 2. Ensure that there is definite (not home blood glucose monitoring (HBGM)) evidence of a low glucose level 3. Do symptoms occur in the fasting or the postprandial state? 4. Take a full past medical history, family history & drug history

Question 305

What is the diagnostic strategy for hypoglycaemia?

Answer 305

Replicate conditions in which hypoglycaemia would be expected

Question 306

What are the 2 ways to investigate hypoglycaemia?

Answer 306

1. Post Prandial- ideally mixed meal test up to 5 hours. OGTT can be misleading 2. 72 hour fast

Question 307

Describe the glyceamic response to glucagon?

Answer 307

Insulin's antiglycogenolytic & hyperinsulineamia permits retention of glycogen in the liver hence they have an exaggerated response to IV glucagon 1mg

Question 308

What does the ketogenic effects of insulinomas cause?

Answer 308

Plasma beta-Hydroxybutyric acid (BHOB) concentrations are lower than normal subjects

Question 309

List 7 investigations for hypoglycaemia?

Answer 309

1. Glucose 2. Insulin 3. C peptide 4. SU screen 5. Beta hydroxybutyrate- low in Insulinoma 6. Pro Insulin- low with exogenous Insulin 7. Insulin Antibodies- can be taken at any time

Question 310

Describe the 72hr fast investigation for hypoglycaemia?

Answer 310

Provoke the homeostatic response that keeps blood glucose conc from falling to concs that cause symptoms in the absence of food

Question 311

What are the most important components of a 72hr fast investigation for hypoglycaemia?

Answer 311

Glucagon, Adrenaline> GH/Cortisol

Question 312

When is a 72hr fast investigation complete?

Answer 312

At plasma glucose at 2.5 mmol/L, 72 hours have elapsed or when plasma glucose is < 3 if Whipple’s triad previously documented

Question 313

What are the plasma glucose ranges in young, lean, healthy, women?

Answer 313

2.2 – 3.0 or even lower after prolonged periods of fasting, without symptoms

Question 314

What are 2 localising studies for hypoglycaemia?

Answer 314

1. Radiology- CT, MRI, EUS | 2. Arterial Calcium Stimulation- Endogenous hyperinsulinaemic hypoglycaemia & negative imaging

Question 315

What is Arterial Calcium Stimulation good for distinguishing?

Answer 315

Focal (Insulinoma) from diffuse disease (nesidioblastosis/islet cell hypertrophy)

Question 316

Describe how to perform Arterial Calcium Stimulation?

Answer 316

Injection of calcium gluconate into gastroduodenal, splenic & sup mesenteric artery with sampling of hepatic venous Insulin levels (double or tripling of basal insulin concentrations)

Question 317

What are the 2 pancreatic causes of spontaneous hypoglycaemia?

Answer 317

1. Insulinoma | 2. Non Insulinoma Pancreatogenic hypoglycaemia (NIPH) - Nesidioblastosis, MEN1

Question 318

What are the 5 non islet cell tumour causes of spontaneous hypoglycaemia?

Answer 318

1. IGF II secreting tumours (Mesenchymal tumours, Carcinomas of the liver, stomach & adrenals) 2. Lymphoma 3. Myeloma 4. Leukaemias 5. Metastatic Cancer

Question 319

What are the 2 autoimmune causes of hypoglycaemia?

Answer 319

1. Autoimmune Insulin 2. Syndrome | Anti Insulin Receptor

Question 320

What are the 2 reactive causes of hypoglycaemia?

Answer 320

1. Post Gastric Surgery | 2. Alcohol Provoked Reactive Hypoglycaemia

Question 321

List 14 drugs which can induce hypoglycaemia?

Answer 321

1. Insulin 2. Indomethacin 3. Sulfonylurea 4. Lithium 5. Repaglinide 6. Levofloxacin 7. Salicylates 8. Heparin 9. Quinine 10. Trimethoprim 11. Haloperidol 12. Pentamidine 13. Beta Blockers 14. Disopyramide

Question 322

What are 2 dietary toxins which can cause hypoglycaemia?

Answer 322

1. Alcohol | 2. Mushrooms causing acute liver failure

Question 323

What are 3 organ failures which can cause hypoglycaemia?

Answer 323

1. Severe Liver Disease 2. End Stage Renal Disease & Renal Dialysis 3. Congestive Cardiac Failure

Question 324

What are 3 endocrine disease which can cause hypoglycaemia?

Answer 324

1. Hypopituitarism 2. Adrenal Failure 3. Hypothyroidism

Question 325

What are 6 miscellaneous causes of hypoglycaemia?

Answer 325

1. Inborn errors of metabolism 2. Sepsis 3. Starvation 4. Anorexia Nervosa 5. Total parenteral nutrition 6. Severe excessive exercise

Question 326

What are the 2 endocrine society diagnostic approaches for hypoglycaemia?

Answer 326

1. Ill or Medicated Individual | 2. Seemingly Well Individual

Question 327

Describe the 4 parts to the "Ill or Medicated Individual" diagnostic approach to hypoglycaemia?

Answer 327

1. Drugs 2. Critical Illness- Hepatic, Renal or Cardiac Failure Sepsis, including malaria, Inanition (prolonged undernutrition) 3. Hormone Deficiency- Cortisol 4. Non Islet Cell Tumour

Question 328

Describe the 2 parts to the "Seemingly Well Individual" diagnostic approach to hypoglycaemia?

Answer 328

1. Endogenous Hyperinsulinism | 2. Accidental, Surreptitious, Malicious hypoglycaemia

Question 329

Describe 3 Endogenous Hyperinsulinism's?

Answer 329

1. Insulinoma 2. Functional islet-cell disorders (Nesidioblastosis)- Noninsulinoma pancreatogenous hypoglycaemia, post gastric bypass hypoglycaemia 3. Insulin Autoimmune hypoglycaemia- antibody to Insulin & antibody to Insulin Receptor

Question 330

What are the 6 functions of calcium?

Answer 330

1. Muscle contraction 2. Bone growth & remodelling 3. Second messenger signalling 4. Stabilisation of membranes 5. Enzyme co-factor e.g. in blood coagulation 6. Secretion of hormones e.g. insulin

Question 331

Describe the distribution of calcium?

Answer 331

- Skeleton- 99% - Intracellular- 0.01% - Extracellular- 0.99%

Question 332

What is Intracellular calcium stored?

Answer 332

1. Endoplasmic reticulum | 2. Mitochondria

Question 333

Describe extracellular calcium?

Answer 333

- 45% ionised (free) | - 55% bound (albumin, lactate, phosphate)

Question 334

What is the total amount of extracellular calcium (ionised & bound)?

Answer 334

2.2-2.6 mmol/L

Question 335

What is extracellular ionised calcium regulated by?

Answer 335

Parathyroid hormone (PTH) & Vitamin D

Question 336

Describe the parathyroid glands?

Answer 336

- Usually 4 glands (2-6) - Posterior aspect of thyroid gland - 10% are ectopic - Weigh 30-50mg

Question 337

What are the parathyroid glands supplied by?

Answer 337

Inferior thyroid artery (caution during thyroid surgery)

Question 338

Describe the parathyroid hormones effect on the kidneys?

Answer 338

- Reabsorption of calcium at distal tubule - Internalises sodium-phosphate co-transporters at proximal tubule - Inhibits Na+/H+ leading to bicarbonate wasting

Question 339

Describe the parathyroid hormones effects on bones?

Answer 339

- Increased number & activity of osteoclasts in continuous PTH exposure – increased bone reabsorption - Intermittent exposure increases anabolic activity of osteoblasts – if you give recombinant PTH for osteoporosis --> bone development

Question 340

Describe the parathyroid hormones effects on the gut?

Answer 340

- Stimulates synthesis of active form of Vit D in kidney (1,25 dihydroxy cholecalciferol) - Thereby increases calcium absorption from the gut

Question 341

Where is the parathyroid hormone stored?

Answer 341

Chief cells of parathyroid gland

Question 342

What is parathyroid hormone secretion controlled by?

Answer 342

Calcium sensing receptor (CaSR)

Question 343

What is familial hypocalciuric hypercalcaemia associated with?

Answer 343

Loss of function mutations

Question 344

What do calcimetic drugs target?

Answer 344

CaSR & inhibit PTH secretion

Question 345

What 2 things are activated when calcium rises?

Answer 345

1. CaSR | 2. Calcium sensing proteases

Question 346

What does CaSR activation cause?

Answer 346

- Inhibits transcription of PTH gene | - PTH secretion inhibited

Question 347

What does calcium sensing proteases activation cause?

Answer 347

PTH broken down/inactivated

Question 348

What effect does calcium sensing receptors have on the kidneys?

Answer 348

- Increases urinary calcium & magnesium excretion | - Increases sodium, potassium & chloride excretion

Question 349

What effect does calcium sensing receptors have on the thyroid?

Answer 349

Stimulates calcitonin secretion

Question 350

Where are the thyroid calcium sensing receptors located?

Answer 350

Expressed in C-cells

Question 351

Where else are calcium sensing receptors expressed?

Answer 351

Brain, intestine & bone where role less well understood

Question 352

Describe vitamin D?

Answer 352

- Steroid hormone i.e. needs to bind to a nuclear receptor (vitamin D receptor) - Acts to increase serum calcium levels

Question 353

What does UV light transfer 7-dehydrocholesterol | into?

Answer 353

Cholecalciferol (D3)

Question 354

What are the 2 sources of Vitamin D?

Answer 354

1. Cholecalciferol (D3) from the skin | 2. Ergosterol from the diet

Question 355

What is Ergosterol transformed into?

Answer 355

Ergocalciferol (D2)

Question 356

What are Ergocalciferol (D2) & Cholecalciferol (D3) transferred into in the liver?

Answer 356

Calcidol (25- hydroxycholecalciferol) which is the storage form of Vit D

Question 357

What is Calcidol (25- hydroxycholecalciferol) transferred into in the kidneys?

Answer 357

Calcitriol (1-25 dihydroxycholecalciferol) which is the active form of Vit D

Question 358

What is another name for Vitamin D?

Answer 358

1-25 dihydroxycholecalciferol

Question 359

What are the 6 actions of Vitamin D/1-25 dihydroxycholecalciferol?

Answer 359

1. Increases calcium & phosphate absorption from gut 2. Bone mineralisation & mobilises calcium stores 3. Immunomodulation (B and T-lymphocytes) 4. Increases muscle strength 5. Reduces insulin resistance 6. Interacts with RAAS, role in prevention of CVD

Question 360

What are the 3 different metabolites of Vitamin D?

Answer 360

1. Vitamin D 2. 25-hydroxycholecalciferol (25-OHD3) 3. 1,25 dihydroxycholecalciferol (1,25-OHD3)

Question 361

Describe the measurement of 25-hydroxycholecalciferol | (25-OHD3)?

Answer 361

Generally accepted for functional measurement of Vit D status as it is the most abundant & stable metabolite

Question 362

What should you be wary of in 25-OHD3 measurement?

Answer 362

Renal disease

Question 363

What is the concentration of 1,25 dihydroxycholecalciferol | (1,25-OHD3)?

Answer 363

50-125 pmol/L

Question 364

What is the concentration of severe 25-OHD3 deficiency?

Answer 364

<15 nmol/L

Question 365

What is the concentration of 25-OHD3 adequacy?

Answer 365

>50nmol/L

Question 366

When do you get symptoms in hypercalcaemia?

Answer 366

Once calcium >3mmol/L

Question 367

List the 5 symptoms of hypercalcaemia?

Answer 367

1. Muscle weakness, bone pain, osteoporosis 2. Anorexia, nausea, constipation, pancreatitis 3. Polyuria, nephrogenic DI, stones, nephrocalcinosis 4. Shortening of QTc, bradycardia, hypertension 5. Confusion, depression, fatigue, coma

Question 368

What are the 3 aetiologies for PTH-mediated (elevated/normal PTH) Hypercalcaemia?

Answer 368

1. Primary hyperparathyroidism 2. Familial syndromes e.g. MEN-1 and MEN-2 3. Familial hypocalciuric hypercalcaemia

Question 369

What are the 7 aetiologies for PTH-independent (undetectable PTH) hypercalcaemia?

Answer 369

1. Malignancy 2. Granulomatous disorders 3. Vitamin D toxicity 4. Drugs: Thiazides, Lithium, Calcium supplements 5. Adrenal insufficiency 6. Milk-alkali syndrome 7. Immobilisation

Question 370

What are the 3 hypercalcaemia differentials for increased calcium & PTH (or normal PTH)?

Answer 370

1. Parathyroid overactivity 2. Familial hypocalciuric hypercalcaemia 3. Lithium

Question 371

What is the hypercalcaemia differentials for increased calcium & decreased PTH?

Answer 371

Parathyroid-independent: - Malignancy - Drugs - Granulomatous disease etc

Question 372

What are 7 investigations to seek the underlying cause of hypercalcaemia?

Answer 372

1. History & examination 2. Chest x-ray 3. FBC/ESR 4. TFTs 5. Myeloma screen 6. Synacthen test 7. Vit D

Question 373

What is the commonest cause of hypercalcaemia in hospitalised patients?

Answer 373

Malignancy ie. solid organ tumours & haematological malignancies

Question 374

Malignancy causes hypercalcaemia through increased bone resorption & calcium release through what 3 possible mechanisms?

Answer 374

1. Osteolytic metastases & myeloma 2. Tumour secretion of PTHrP 3. Tumour production of 1,25 dihydroxycholecalciferol by activated macrophages. Occurs in lymphoma

Question 375

Describe Tumour secretion of PTHrP?

Answer 375

- Binds to PTH receptor & stimulates bone resorption & renal calcium reabsorption - Can be measured directly - Squamous cell lung cancer, oesophageal cancer, renal cell carcinoma, breast cancer

Question 376

Describe Vitamin D Toxicity causing PTH independent hypercalcaemia?

Answer 376

- Increased bone resorption & gut absorption - Ingestion of high doses of calcitriol (e.g. hypoparathyroid or renal disease) - Resolves within 48 hrs of stopping offending agent

Question 377

Describe endogenous production of 1,25 dihydroxycholecalciferol causing PTH independent hypercalcaemia?

Answer 377

- Lymphoma, sarcoid, Wegeners granulomatosis - Extra-renal activation of cholecalciferol - Usually responsive to steroid treatment

Question 378

Describe Adrenal insufficiency causing PTH independent hypercalcaemia?

Answer 378

Increased proximal tubule calcium reabsorption & increased bone resorption

Question 379

Describe Milk-Alkali syndrome causing PTH independent hypercalcaemia?

Answer 379

- Hypercalcaemia, metabolic alkalosis, renal insufficiency | - Due to ingestion of calcium & antacids

Question 380

What are the 5 general principles for managing hypercalcaemia?

Answer 380

1. Stop offending / contributing medications 2. Rehydration- Normal saline 3-4 litres in first 24 hours unless contraindicated 3. + / - loop diuretic to promote calciuria 4. Bisphosphonates 5. Steroids

Question 381

Describe Bisphosphonates for managing hypercalcaemia?

Answer 381

- Inhibit bone resorption - Zoledronic acid 4mg IV - Takes effect within 24-48 hrs - Last several weeks

Question 382

When are steroids effective for managing hypercalcaemia?

Answer 382

Effective in haematological malignancy, vitamin D intoxication, granulomatous disease

Question 383

What are the 3 causes of primary hyperparathyroidism?

Answer 383

1. 85% isolated parathyroid adenoma 2. 14% parathyroid hyperplasia-often associated with familial conditions e.g. MEN etc 3. <1% parathyroid carcinoma

Question 384

Describe the 3 types of end-organ damage associated with primary hyperparathyroidism?

Answer 384

1. Bone- Osteoporosis (peripheral cortical bone), Other radiological changes e.g. bone cysts; subperiosteal resorption 2. Kidneys- Renal calculi, Nephrocalcinosis, Renal impairment 3. Other, e.g. pancreatitis

Question 385

What are 5 investigations to confirm the diagnosis of primary hyperparathyroidism?

Answer 385

1. Drugs 2. U&Es 3. PTH 4. Urine calcium: creatinine ratio (differentiate from FHH where usually <0.01) 5. Vit D (deficiency can cause elevated PTH)

Question 386

What are the 2 investigations to confirm the diagnosis of primary hyperparathyroidism?

Answer 386

1. DEXA | 2. KUB/renal USS

Question 387

What are other conditions you should think about regarding primary hyperparathyroidism?

Answer 387

Consider MEN-1 or MEN-2 if <40 years old or history of hyperparathyroidism in 1st degree relative

Question 388

What should you do if surgery is indicated in primary hyperparathyroidism?

Answer 388

Localise abnormal gland via 2 separate techniques: 1. Sestamibi & 2. Ultrasound neck (Minimally invasive neck exploration)

Question 389

What are brown tumours a result of?

Answer 389

Excess osteoclast activity

Question 390

What are brown tumours made of?

Answer 390

Collection of osteoclasts, poorly mineralised bone & fibrous tissue

Question 391

How are brown tumours "brown"?

Answer 391

Haemosiderin deposition

Question 392

What are the 3 management options for primary hyperparathyroidism?

Answer 392

1. Parathyroidectomy 2. Observation if no end-organ damage or unfit for surgery 3. Medical treatment only indicated if not fit for surgery (lung disease, frailty)

Question 393

What are the 5 reasons to do/explore a Parathyroidectomy for primary hyperparathyroidism?

Answer 393

1. Calcium > 3.0 mmol/L 2. Hypercalciuria 3. Osteoporosis 4. Age under 50 years 5. Intractable symptoms ie. renal stones

Question 394

Describe the observational management of primary hyperparathyroidism?

Answer 394

- Annual bone profile, renal function, urinary calcium (nurse led clinic) - DEXA & renal US every 3 years

Question 395

Describe the medical treatment for primary hyperparathyroidism?

Answer 395

- Bisphosphonates preserve bone mass but little effect on calcium - Calcium sensing receptor agonists (Cinacalcet) 30mg BD: Reduces serum (not urine!) calcium but doesn’t prevent end-organ damage

Question 396

What are the 2 mechanical complications of parathyroidectomy?

Answer 396

1. Vocal cord paresis | 2. Haematoma causing tracheal compression

Question 397

What are the 3 metabolic complications of parathyroidectomy?

Answer 397

1. Transient hypocalcaemia (suppression of remaining glands) 2. May require oral calcium / vit D supplementation 3. “Hungry bones”

Question 398

Describe the "Hungry bones" complication of parathyroidectomy?

Answer 398

- Uncommon - Occurs in patients who have significant bone disease pre-op or very elevated PTH - Sudden withdrawal of PTH leads to imbalance between bone formation & resorption – marked net increase in uptake of calcium, phosphate & magnesium by bone

Question 399

What does the "Hungry bones" complication of parathyroidectomy require as treatment?

Answer 399

Calcium & vitamin D supplementation

Question 400

What are 5 causes of Vitamin D deficiency?

Answer 400

1. Poor sunlight exposure (i.e. elderly or housebound) 2. Malabsorption 3. Gastrectomy 4. Enzyme inducing drugs e.g. anticonvulsants 5. Renal disease (impaired hydroxylation of 250H Calcitriol)

Question 401

What is osteomalacia?

Answer 401

- Failure to ossify bones in adulthood as a result of Vit D deficiency - Hypo-mineralisation of trabecular & cortical bone

Question 402

How does osteomalacia present?

Answer 402

Insidiously with bone pain, proximal myopathy & hypocalcaemia

Question 403

Describe the blood results of osteomalacia?

Answer 403

- Low calcium - Low phosphate - High alk phos - Low Vit D - Elevated PTH

Question 404

What are the 2 drug treatments for Vitamin D deficiency?

Answer 404

1. Cholecalciferol (D3)- Vit D3 | 2. Alfacalcidol (i.e. active Vit D)

Question 405

Describe the effect of Cholecalciferol (D3)- Vit D3 in Vitamin D deficiency?

Answer 405

- Restore body stores - Correct metabolic disturbance - Heal bony abnormalities - Biochemistry may not settle for several months: calcium can return back to normal quite quickly but PTH can take a while

Question 406

What dose of Cholecalciferol (D3)- Vit D3 would you give for a Vitamin D deficiency?

Answer 406

- 800-1600 units per day | - Or, single large dose of Ergocalciferol / D2 (150,000-300,000 units)

Question 407

What 2 pathologies is Alfacalcidol (i.e. active Vit D) effective in?

Answer 407

1. Renal impairment | 2. Hypoparathyroidism (cannot activate Vit D in gut)

Question 408

Describe Alfacalcidol (i.e. active Vit D) for Vitamin D deficiency?

Answer 408

- Not measured by traditional lab Vit D assay (25-OHD3) | - Higher risk of hypercalcaemia

Question 409

Where is testosterone produced?

Answer 409

Leydig cells

Question 410

Describe testosterone production?

Answer 410

- Steroid hormone - Circulates bound to SHBG & albumin - Free testosterone is active - Activated to more potent form in target tissues

Question 411

What 5 things does testosterone help grow?

Answer 411

1. Sex organs 2. Skeletal muscle (enlargement) 3. Epiphyseal plates 4. Larynx growth (change shape & deepen voice) 5. 2° characteristics

Question 412

What are the 3 other effects of testosterone?

Answer 412

1. Erythropoesis (women have a lower haemoglobin than men) | 2. Behaviour

Question 413

What are the 5 adult effects of testosterone?

Answer 413

1. Muscle mass 2. Mood 3. Bone mass 4. Libido 5. Body shape

Question 414

What are the 3 fertility effects of testosterone?

Answer 414

1. Libido 2. Erectile Function 3. Spermatogenesis

Question 415

Where are spermatocytes produced?

Answer 415

Leydig & Sertoli Cells

Question 416

What do Spermatocytes mature into?

Answer 416

Spermatozoa

Question 417

Describe the purpose of Sertoli cells?

Answer 417

- Blood-testis barrier - Remove damaged spermatocytes - Secrete androgen binding protein

Question 418

What does aromatase convert?

Answer 418

Testosterone --> Oestrogen

Question 419

Describe the control steps of gonadal function?

Answer 419

GnRH (hypothalamus) --> LH & FSH (anterior pituitary) --> Leydig & Sertoli cells (testis) --> Androgen & anabolic effects (negative feedback)

Question 420

List the 4 clinical features of hypogonadism in a child/young adult?

Answer 420

1. Slow growth in teens 2. No pubertal growth spurt 3. Small testes & phallus 4. Lack of 2° sexual development

Question 421

List the 5 main clinical features of hypogonadism in an adult?

Answer 421

1. Depression/low mood 2. Poor libido 3. Erectile problems 4. Poor muscle bulk/power 5. Poor energy

Question 422

List the 6 other clinical features of hypogonadism in an adult?

Answer 422

1. Sparse body/facial hair 2. Gynaecomastia 3. Gynoid weight gain 4. Great head hair 5. Short phallus 6. Small testes- abnormal consistency

Question 423

Describe the ICP concept of growth?

Answer 423

- Infantile via IU growth +/- GH - Childhood via GH & T4 - Pubertal via GH & Sex steroids

Question 424

What is used in specialised endocrine clinics as a tool to see male pubertal testis development?

Answer 424

Orchidometer

Question 425

What are 4 important factors in a specialist endocrine clinic consultation?

Answer 425

1. Height 2. Weight 3. History- growth, family, sexual, drug, social 4. Examination

Question 426

What are 2 ways to test for sex steroid deficiency?

Answer 426

1. Testosterone- Early morning. Free testosterone > 200. Total testosterone > 16. Sex hormone-binding globulin (SHBG) 2. LH & FSH- Help determine possible pituitary cause

Question 427

How do you check for male fertility?

Answer 427

Semen analysis

Question 428

What is primary gonadal failure?

Answer 428

Testicular problem

Question 429

Describe the blood results of Hypogonadotrophic Hypogonadism?

Answer 429

Low testosterone, LH +/- FSH +/- increased prolactin, decreased cortisol, decreased IGF-1/GH, decreased TSH & increased sodium

Question 430

What are the 6 causes of Hypopituitarism?

Answer 430

1. Pituitary tumour 2. Pituitary surgery/radiotherapy 3. Head injury 4. Kallmann's syndrome 5. Cerebellar ataxia 6. Genetic syndrome

Question 431

What is the commonest form of isolated gonadotrophin deficiency?

Answer 431

Kallmann’s Syndrome

Question 432

Describe Kallmann’s Syndrome?

Answer 432

Failure of cell migration of GnRH cells to hypothalamus from Olfactory placode

Question 433

What can Kallmann’s syndrome be associated with?

Answer 433

- Aplasia/hypoplasia of olfactory lobes – giving anosmia or hyposmia - Deafness, renal agenesis, cleft lip/palate - Micropenis ± cryptorchidism

Question 434

Describe the 4 types of inheritance patterns for Kallmann’s syndrome?

Answer 434

1. Familial with variable penetration 2. X-linked – Absence of KAL gene (KAL1) 3. Autosomal Dominant (KAL2) 4. Autosomal Recessive (KAL3)- other genetic causes of IHH exist (e.g Kisspeptin/GPR54 mutations)

Question 435

What are the 2 effects of Kallmann’s syndrome in childhood?

Answer 435

1. Poor growth | 2. Undescended testes

Question 436

What are the 4 effects of Kallmann’s syndrome in adolescence?

Answer 436

1. Poor growth 2. Small testes 3. Micropenis 4. Delayed/absent puberty features

Question 437

What are the 4 effects of Kallmann’s syndrome in adults?

Answer 437

1. Slow, but adequate growth 2. Small testes 3. Small phallus 4. Hypogonadal features

Question 438

Describe the blood results of primary gonadal disease?

Answer 438

- Low Testosterone - Normal/High LH/FSH - Normal prolactin

Question 439

What are 5 effects of Primary Gonadal Failure?

Answer 439

1. Adult Leydig cell failure 2. Cryptorchidism 3. Complex genetic syndromes 4. Klinefelter's syndrome (chromosome defects) 5. Seminiferous tubule failure

Question 440

What are 4 causes of Adult Leydig cell & Seminiferous tubule failure?

Answer 440

1. Trauma 2. Chemotherapy 3. Radiotherapy 4. Multisystem disorders

Question 441

What is the commonest genetic cause of male hypogonadism?

Answer 441

Klinefelter’s Syndrome

Question 442

Describe Klinefelter’s Syndrome?

Answer 442

- XXY (but other sex chromosome variations exist) - Clinically manifests at puberty - Increased LH & FSH but seminiferous tubules regress & Leydig cells do not function normally

Question 443

Describe testis androgen production in Klinefelter’s Syndrome?

Answer 443

- Decreased testosterone | - Increased oestrogen

Question 444

Describe the wide clinical variation (due to LH surges) of Klinefelter’s Syndrome?

Answer 444

- Delayed puberty - Suboptimal genital development - Reduced 2° male sexual characteristics - Persistent gynaecomastia - Azospermia - Behavioural issues/learning difficulties

Question 445

What is the treatment for Klinefelter’s Syndrome?

Answer 445

Androgen replacement ± psychological support ± fertility counselling

Question 446

Describe the 2 parts to HypoG treatment?

Answer 446

1. Androgen Replacement Therapy- oral, IM, Topical | 2. Fertility Treatment- hCG, Recombinant LH & FSH, GnRH pumps

Question 447

What are the 6 side effects of androgen replacement therapy?

Answer 447

1. Mood issues (aggression/behaviour change) 2. Libido issues 3. Increased haematocrit 4. Possible prostate effects 5. Acne, sweating 6. Gynaecomastia

Question 448

Describe the drug abuse regarding testosterone therapy?

Answer 448

- Cycling, athletics, baseball, Powerlifting - Complex doping regimes: Masking agents, LH/GnRH, Tamoxifen - ‘Natural’ supplements: ‘testosterone boosters’

Question 449

What is Bimanual synkinesia?

Answer 449

- Left & right upper limbs, esp hands & fingers execute exactly the same movement even though only one hand is intentionally moved - It is also called "mirror hand movements" & persists throughout life

Question 450

What is a special clinical feature of Kallmann's syndrome?

Answer 450

You cannot smell

Question 451

What mutation is present in Hypogonadotrophic hypogonadism (pituitary origin)?

Answer 451

KAL1

Question 452

What is primary amenorrhoea?

Answer 452

Never had a period

Question 453

What are the 3 causes of amenorrhoea?

Answer 453

1. Genitourinary abnormalities 2. Chromosomal abnormalities ie. Turners syndrome 3. Secondary hypogonadism (pituitary/ hypothalamic causes)

Question 454

Describe Genitourinary abnormalities causing primary amenorrhoea?

Answer 454

Congenital absence of uterus, cervix or vagina: - Rokitansky syndrome - Androgen insensitivity syndrome

Question 455

List 3 Secondary hypogonadism associated with primary amenorrhoea?

Answer 455

1. Kallmans syndrome 2. Pituitary disease 3. Hypothalamic amenorrhoea ie. low BMI, stress, illness

Question 456

What is secondary amenorrhoea?

Answer 456

No periods for 6 months

Question 457

List 4 causes of secondary amenorrhoea?

Answer 457

1. Uterine- Ashermans syndrome 2. Ovarian- PCOS, Premature ovarian failure 3. Pituitary- Prolactinoma, Pituitary tumour 4. Hypothalamic- Weight loss, stress, drugs e.g. opiates

Question 458

What are the 4 other causes of amenorrhoea?

Answer 458

1. Physiological- Pregnancy, Lactation 2. Iatrogenic- contraception 3. Thyroid dysfunction 4. Hyperandrogenism- Cushing's syndrome related to adrenal tumour, CAH, Adrenal or ovarian tumour

Question 459

What is the definition of Hirsutism?

Answer 459

Excess hair growth in a male pattern due to increased androgens & increased skin sensitivity to androgens

Question 460

What are the 2 ovarian causes of hirsutism?

Answer 460

1. PCOS- 95% | 2. Androgen secreting tumour- <1%

Question 461

What are the 2 adrenal causes of hirsutism?

Answer 461

1. Congenital adrenal hypertrophy- <1% | 2. Androgen secreting tumour- <1%

Question 462

Classic presentation of PCOS is with symptoms of what?

Answer 462

Anovulation (amenorrhoea, oligomenorrhoea, irregular cycles) & associated symptoms of Hyperandrogenism (hirsutism, acne, alopecia)

Question 463

Describe the prevalence of PCOS?

Answer 463

- Affects >5% women of reproductive age | - Commonest cause of anovulatory infertility (80%)

Question 464

What are the typical endocrine features of PCOS?

Answer 464

Raised testosterone & LH

Question 465

What 2 things is PCOS also associated with?

Answer 465

1. Metabolic abnormalities | 2. Increased risk of type 2 diabetes

Question 466

Describe there cause of PCOS?

Answer 466

- Heterogeneous disorder of unclear aetiology | - Complex interaction of metabolic, hypothalamic, pituitary, ovarian & adrenal mechanisms

Question 467

What are the 3 elements of the pathophysiology of PCOS?

Answer 467

1. Gonadotrophins (LH & FSH) 2. Androgens 3. Insulin resistance

Question 468

Describe the 2 gonadotrophin levels in PCOS?

Answer 468

1. Increased LH concentration | 2. Decreased FSH

Question 469

How/why is LH increased in PCOS?

Answer 469

- Increased LH receptors in PCOS ovaries | - Support ovarian theca cells: Increased ovarian androgen production

Question 470

How/why is FSH decreased in PCOS?

Answer 470

- Low constant levels result in continuous stimulation of follicles without ovulation - Decreased conversion of androgens to oestrogens in granulosa cells

Question 471

What does testosterone (androgen) come from?

Answer 471

Cholesterol

Question 472

What does testosterone turn into during androgen biosynthesis?

Answer 472

Dihydrotestosterone

Question 473

What turns into testosterone during androgen biosynthesis?

Answer 473

- Androstenediol (from DHEA) | - Androstenedione

Question 474

What are the 3 increased androgens in PCOS?

Answer 474

1. Testosterone 2. Androstenedione 3. DHEA-S

Question 475

What androgen is increased the most in PCOS?

Answer 475

Androstenedione

Question 476

Describe the locations of circulating DHEA-S androgen in women?

Answer 476

- Ovary: <5 - Adrenal: >95 - Peripheral conversion: 0

Question 477

Describe the locations of circulating Androstenedione (A) androgen in women?

Answer 477

- Ovary: 60 - Adrenal: 35 - Peripheral conversion: 5 (from DHEA-S)

Question 478

Describe the locations of circulating Testosterone (T) | androgen in women?

Answer 478

- Ovary: 60 - Adrenal: 5 - Peripheral conversion: 35 (from Androstenedione)

Question 479

Describe the locations of circulating Dihydrotestosterone (DHT) androgen in women?

Answer 479

- Ovary: 0 - Adrenal: 0 - Peripheral conversion: 100 (from Androstenedione & Testosterone)

Question 480

What increases androgen production?

Answer 480

Theca cells under influence of LH

Question 481

What 2 disordered enzyme actions affect androgen biosynthesis?

Answer 481

1. Ovarian enzyme expression | 2. Peripheral conversion

Question 482

Describe Sex hormone-binding globulin (SHBG) associated with androgen biosynthesis?

Answer 482

- Produced in liver, binds testosterone | - Only free testosterone is biologically active: Hyperandrogenism, Hyperinsulinaemia

Question 483

What is reduced in women with PCOS/increased BMI?

Answer 483

Insulin sensitivity

Question 484

What type of women with PCOS are more symptomatic?

Answer 484

Overweight/obese

Question 485

Describe the cause vs association of insulin sensitivity in PCOS?

Answer 485

- Insulin stimulates theca cells of ovaries - Insulin reduces hepatic production of sex hormone-binding globulin (SHBG) - Increased circulating androgens

Question 486

What are the 3 clinical factors of Polycystic Ovary Syndrome?

Answer 486

1. Hirsutism 2. Oligomenorrhea 3. Polycystic ovaries

Question 487

Describe the pathological cycle of Polycystic Ovary Syndrome (PCOS)?

Answer 487

Androgens --> Gonadotrophin (increased LH) --> Insulin Resistance (hyperinsuminaemia) --> Adiposity

Question 488

What 5 investigations would confirm the profile of PCOS?

Answer 488

1. Testosterone 2. Andrestenedione 3. DHEAS 4. SHBG 5. FSH/LH

Question 489

What are 2 other features in PCOS that need assessed?

Answer 489

1. Type 2 diabetes | 2. Abnormal lipids

Question 490

What leads to oligo-ovulation hirsutism?

Answer 490

Insulin resistance --> Increased insulin --> Decreased SHBG + Increased androgen --> Increased free testosterone --> Oligo-ovulation hirsutism

Question 491

What are 2 treatments to decrease insulin in PCOS (which would lead to increased ovulation & decreased hirsutism)?

Answer 491

1. Weight loss interventions | 2. Insulin sensitisers

Question 492

What are the 4 theories of metformin in treatment of PCOS?

Answer 492

1. For obese & non obese 2. Improves Insulin sensitivity 3. Leads to decreased LH levels & increased SHBG & hence decreased FAI 4. “May regulate ovulatory function & hence menstruation”

Question 493

What can metformin be added with in the treatment of PCOS?

Answer 493

Clomiphene

Question 494

What are the 3 factors regarding Metformin in treatment of PCOS?

Answer 494

1. Not useful for treatment of infertility 2. Not very effective for treatment of hirsutism 3. May have a place in management of women at high risk of developing diabetes

Question 495

List the 6 pharmacological treatments for Hirsutism & get 1 example of each?

Answer 495

1. Ovarian Androgen Suppression- COCP (Dianette ideal) 2. Adrenal Androgen Suppression- Corticosteroids 3. Androgen Receptor Antagonist- Spironolactone 4. 5 alpha reductase inhibition- Finasteride 5. Insulin Sensitisers- Metformin 6. Topical Inhibitors- Eflornithine

Question 496

Describe the effect of calorie restriction on insulin & fertility in obese women with PCOS?

Answer 496

- Modest (5-10%) weight reduction associated with vast improvement in metabolic indices - Diet & lifestyle changes improve ovulation rate & fertility

Question 497

What causes the juxtaglomerular apparatus in the kidneys to produce renin?

Answer 497

Decrease in renal perfusion

Question 498

What are the 5 effects of angiotensin II?

Answer 498

1. Increase sympathetic activity 2. Tubule Na+, Cl- reabsorption & K+ excretion. H2O retention 3. Aldosterone secretion 4. Arteriolar vasoconstriction & increase in BP 5. ADH secretion --> collecting duct H2O absorption

Question 499

What produces & secretes aldosterone?

Answer 499

Adrenal glands

Question 500

What are the 3 biochemistry results which suggest aldosterone excess?

Answer 500

1. Serum potassium <3mmol/L 2. Urine potassium >30mmol/d 3. Mild alkalosis

Question 501

What are the 4 exceptions to typical biochemistry results in aldosterone excess?

Answer 501

1. 30% have normal K 2. Many on drugs that lower BP (circulatory volume) 3. Some anti-hypertensives lower serum K 4. Best to be on alpha blocker for test

Question 502

Describe the 3 parts to a screening test for Conn's syndrome?

Answer 502

1. Measure renin & aldosterone 2. Plasma renin / aldosterone ratio >35 and aldosterone >300 3. Send quickly BUT don’t send on ice

Question 503

Describe ambulant renin & aldosterone levels in Conn's syndrome?

Answer 503

- Renin: <50mIU/L (ambulant) | - Aldosterone: 100-800 pmol/L (ambulant)

Question 504

What is the condition called when there is excess aldosterone production?

Answer 504

Conn's syndrome

Question 505

What are 2 other tests for Conn's syndrome?

Answer 505

1. Salt loading test | 2. Adrenal vein sampling

Question 506

What is the biochemistry in secondary hyperaldosteronism?

Answer 506

- Renin & Aldosterone Increased | - Effective Circulatory Volume Decreased

Question 507

What are the 3 possible causes of secondary hyperaldosteronism?

Answer 507

1. Heart Failure 2. Cirrhosis of the Liver 3. Nephrotic Syndrome

Question 508

Describe the anatomy of the adrenal glands?

Answer 508

- Small retroperitoneal structures - Medial & lateral limbs - Cannot usually differentiate cortex from medulla on imaging - Upside down “Y”

Question 509

Describe adrenal adenomas on a CT scan?

Answer 509

Fatty & therefore low density

Question 510

Describe the prevalence of adrenal adenomas?

Answer 510

- Common incidental findings | - 1-4% incidence

Question 511

Describe how you would diagnose adrenal adenomas?

Answer 511

- Contrast CT: <30 HU diagnostic, >50% washout | - Dynamic CT: Measure density at 80 secs & 10 mins

Question 512

Describe an MRI for looking at the adrenals?

Answer 512

- Chemical Shift imaging - Variations of nuclear magnetic resonance frequencies of the same kind of nucleus, due to variations in the electron distribution

Question 513

What is the pathological specimen appearance of Conn's adenoma?

Answer 513

Bright yellow due to the high amount of lipids

Question 514

What is the special histological stain used for looking at adrenal adenomas/tumours?

Answer 514

Melan A (brown stain)

Question 515

Describe the micro appearance of a cortical adenoma?

Answer 515

Consist of varying proportions of lipid rich clear cells & compact cells forming cords & nests with abundant vasculature

Question 516

What are present in Conn's syndrome?

Answer 516

Spironolactone bodies (given pre-op to stabilise hypertension & reverse hypokalaemia)

Question 517

Describe the micro appearance of benign adrenal tumours?

Answer 517

Bland, uniform cells and no evidence of an infiltrating pattern of growth

Question 518

Describe the micro appearance of a cortical carcinoma?

Answer 518

- Large, irregular tumour cell nuclei | - Coagulative necrosis

Question 519

What is autonomous aldosterone production associated with biochemically?

Answer 519

Increased BP & decreased K+

Question 520

List 4 primary causes of mineralocorticoid excess (aldosterone)?

Answer 520

1. Suppressed renin levels 2. Conn’s syndrome (adenoma) 3. Bilateral adrenal hyperplasia 4. Adrenal carcinoma

Question 521

List 5 secondary causes of mineralocorticoid excess (aldosterone)?

Answer 521

1. 2° to elevated renin levels 2. Renal hypoperfusion 3. Heart failure 4. Cirrhosis 5. Nephrotic syndrome

Question 522

What is 1 other weird cause of mineralocorticoid excess (aldosterone)?

Answer 522

Liquorice ingestion

Question 523

Describe Conn's syndrome?

Answer 523

An aldosterone producing adrenal adenoma causing renal sodium retention, potassium loss, suppressed renin & resistant hypertension

Question 524

What are the 3 investigations & results for Conn's syndrome?

Answer 524

1. Biochemistry- decreased K & renin, increased aldosterone:renin ratio 2. Imaging- CT/MRI to localise adenoma 3. Adrenal vein sampling- gradient of aldosterone measurements from both adrenal veins

Question 525

List 9 medications which can induce false positives/negatives on renin & aldosterone measurements?

Answer 525

1. Methyldopa 2. Clonidine 3. Beta Blockers 4. Alpha Blockers 5. ACE inhibitors 6. AT2RB 7. Ca Channel antagonists 8. Diuretics 9. NSAIDS

Question 526

Describe the 2 forms of management for Conn's syndrome?

Answer 526

1. Medical- Aldosterone antagonist spironolactone, multiple antihypertensive agents 2. Surgical- Unilateral adrenalectomy

Question 527

Describe the U&E's in Addison's disease?

Answer 527

- Na+ decreased | - Urea increased

Question 528

Describe the 3 steps in the Synacthen test?

Answer 528

1. Basal bloods ACTH & cortisol are taken 2. Synacthen 250 microgram IV given 3. After 30mins cortisol is checked

Question 529

What is a satisfactory response in the Synacthen test?

Answer 529

30min Cortisol >480 nmol/L

Question 530

Describe the adrenal glands in Addison's disease?

Answer 530

Atrophic, small & thin

Question 531

Describe Addison's disease?

Answer 531

- Also known as primary adrenal insufficiency & hypocortisolism - Long-term endocrine disorder in which the adrenal glands do not produce enough steroid hormones - Usually due to autoimmune destruction

Question 532

List 6 primary causes of Addison's disease?

Answer 532

1. Autoimmune- isolated or with APS 2. Metastatic cancer (colonic carcinoma) 3. Infectious- Tuberculosis, Fungal, HIV, Syphilis 4. Adrenal haemorrhage or infarction 5. Drugs 6. Adrenoleukodystrophy

Question 533

How would you manage Addison's disease initially?

Answer 533

1. Hydrocortisone | 2. Insulin dose titration

Question 534

List the 6 symptoms of adrenal insufficiency (Addison's disease)?

Answer 534

1. Weakness, tiredness, fatigue 2. Anorexia 3. GI Symptoms- nausea, vomiting, constipation, abdo pain, diarrhoea 4. Salt craving 5. Postural dizziness 6. Muscle/Joint Pain

Question 535

List the 10 clinical signs of adrenal insufficiency (Addison's disease)?

Answer 535

1. Weight loss 2. Hyperpigmentation 3. SBP<110mmHg 4. Vitiligo 5. Hyponatraemia 6. Hyperkalaemia 7. Hypercalcaemia 8. Renal Impairment 9. Anaemia 10. Eosinophilia

Question 536

List 6 drugs which could be the primary cause of adrenal insufficiency (Addison's disease)?

Answer 536

1. Ketoconazole 2. Phyenytoin 3. Barbituates 4. Rifampicin 5. Mitotane 6. Metyrapone

Question 537

Describe autoimmune Addison's disease?

Answer 537

- Antibodies against steroidogenic enzymes (most common 21 hydroxylase) - Antibodies against all 3 zones of the adrenal cortex - Present in 86% patients

Question 538

What are 3 secondary causes of adrenal insufficiency (Addison's disease)?

Answer 538

1. Panhypopituitarism 2. Isolated ACTH deficiency 3. Familial cortisol-binding globulin (CBG, transcortin) deficiency

Question 539

List the 4 causes of Panhypopituitarism leading to adrenal insufficiency (Addison's disease)?

Answer 539

1. Tumours- pituitary, met, craniophayngioma 2. Infection- TB 3. Inflammation- sarcoidosis, lymphocytic hypophysitis, haemochromatosis, histiocytosis X 4. Iatrogenic- surgery, radiotherapy

Question 540

List 2 causes of Tertiary suppression of the hypothalamo-pituitary-adrenal axis?

Answer 540

1. Chronic high-dose glucocorticoid therapy | 2. After the cure of Cushing's syndrome

Question 541

What is Autoimmune Polyendocrine Syndrome Type 2 a combination of?

Answer 541

Triad of addison’s, AI thyroiditis & T1Dm

Question 542

Describe Autoimmune Polyendocrine Syndrome Type 2?

Answer 542

- More common in females - Presents in adulthood - Polygenic - 1/6 relatives have an unsuspected illness!

Question 543

List 6 conditions that are associated with Autoimmune Polyendocrine Syndrome Type 2?

Answer 543

1. PA 2. Coeliac Disease 3. Primary hypogonadism 4. Alopecia 5. MG 6. Stiff Man Syndrome

Question 544

What are the 3 direct effects of growth hormone?

Answer 544

1. Increased protein synthesis 2. Reduced glucose transport & metabolism 3. Increased lipolysis

Question 545

What is the indirect effect of growth hormone?

Answer 545

Via Insulin-like Growth Factors I & II IGF 1 --> growth of soft tissues, bone & viscera

Question 546

What 3 things cause the hypothalamus to excrete GHRH & Somatostatin?

Answer 546

1. Sleep 2. Exercise 3. Stress

Question 547

What inhibits growth hormone release from the pituitary?

Answer 547

Somatostatin (IGF 1)

Question 548

What are the 2 screening tests for acromegaly?

Answer 548

1. IGF-1 usually elevated but not diagnostic | 2. OGTT for growth hormone suppression

Question 549

Describe the OGTT screening test for acromegaly?

Answer 549

- 75g glucose - 2hr test - Normal: GH suppression to undetectable - Acromegaly: stays >2ug/L

Question 550

What 5 parts of the pituitary would you assess in imaging?

Answer 550

1. Central structure 2. Infundibulum 3. Anterior / Posterior Pituitary 4. Sella 5. Parasellar Structures

Question 551

What type of imaging is best to see the pituitary?

Answer 551

- CT useful for assessing calcification e.g craniopharyngioma - MRI investigation of choice

Question 552

What is the special histological stain use to assess growth hormone release?

Answer 552

Monoclonal antibody immune stain (brown)

Question 553

List the 7 risks of long term exposure to elevated GH levels (acromegaly)?

Answer 553

1. Arthropathy 2. Neuropathy 3. Cardiovascular disease 4. Hypertension 5. Respiratory disease 6. Malignancy 7. Carbohydrate intolerance

Question 554

Describe the Arthropathy risk in long term exposure to elevated GH levels (acromegaly)?

Answer 554

- Unrelated to age of Onset - Usually occurs with long duration - Reversibility: rapid symptomatic improvement, irreversibility of bone & cartilage lesions

Question 555

Describe the neuropathy risk in long term exposure to elevated GH levels (acromegaly)?

Answer 555

- Peripheral Nerves: Intermittent anesthesias, Sensorimotor polyneuropathy - Reversibility: Onion bulbs (whorls) do not regress

Question 556

List 4 cardiovascular risks in long term exposure to elevated GH levels (acromegaly)?

Answer 556

1. LV Diastolic Dysfunction decreased 2. LV Mass Increased 3. Arrythmias 4. Fibrous connective tissue hyperplasia

Question 557

Describe the hypertension risk in long term exposure to elevated GH levels (acromegaly)?

Answer 557

- Exacerbates Cardiomyopathy | - Reversibility: May progress even if GH secretion reduced

Question 558

Describe the respiratory disease risk in long term exposure to elevated GH levels (acromegaly)?

Answer 558

- Upper airways obstruction - Soft tissue overgrowth - Reversibility: Improves with reduction on GH secretion

Question 559

Describe the malignancy risk in long term exposure to elevated GH levels (acromegaly)?

Answer 559

- Colonic Polpys | - Effect of therapy on risk unknown

Question 560

Describe the Carbohydrate Intolerance risk in long term exposure to elevated GH levels (acromegaly)?

Answer 560

- Diabetes Mellitus | - Reversibility: Improves with reduced GH secretion

Question 561

What are the 2 types of causes for acromegaly?

Answer 561

1. Excess GH secretion | 2. Excess GH releasing hormone secretion

Question 562

List 5 causes of GH secretion leading to acromegaly?

Answer 562

1. Pituitary: 98% 2. GH cell adenoma (60%) 3. Mixed GH/Prolactin cell adenoma (25%) 4. GH cell carcinoma 5. MEN 1 (GH cell adenoma)

Question 563

List 2 causes of excess GH Releasing Hormone Secretion leading to acromegaly?

Answer 563

1. Central e.g. ganglioneuroma | 2. Peripheral e.g. Bronchial Carcinoid, adrenal adenoma, Medullary Thyroid Carcinoma, Phaeochromocytoma

Question 564

What is the management for acromegaly?

Answer 564

- Surgery: 50-60% normal IGF1 levels | - Radiotherapy: works over a longer time duration & may render patient pan hypo pit

Question 565

What are the 2 medical therapies for acromegaly?

Answer 565

1. Dopamine agonists 2. Octreotide 3. Pegvisomant (typically given post-surgery)

Question 566

Describe Dopamine agonists in the treatment of acromegaly?

Answer 566

- Lower serum GH & IGF1 in 10-40% | - Pituitary tumour shrinkage in 5%

Question 567

What type of drug is Pegvisomant?

Answer 567

Competitive antagonist of native GH at the cell membrane GH receptor

Question 568

What are the 9 investigations for acromegaly?

Answer 568

1. OGF1 2. OGTT 3. Cortisol 4. LH 5. FSH 6. Testosterone 7. Prolactin 8. TSH 9. fT4

Question 569

What are the 3 options for GH excess?

Answer 569

1. Neurosurgery- transphenoidal removal of microadenoma 2. Medical therapy - octreotide, lanreotide (somatostatin analogues) 3. Radiotherapy

Question 570

List the 5 complications of transphenoidal removal of microadenoma surgery?

Answer 570

1. Residual tumour 2. Post Op Pan Hypopituiraism 3. Injury to carotid arteries 4. CSF Leak 5. Injury to Optic Chiasm