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MBChB Year 3 > Week 9 - Endocrine > Flashcards

Week 9 - Endocrine Flashcards

1
Q

Define Diabetes Mellitus?

A

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

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2
Q

List 3 characteristics of diabetes mellitus?

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

List the 5 symptoms associated with glycosuria in diabetes mellitus?

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

List 6 symptoms of glycosuria osmotic diuresis in diabetes mellitus?

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

What is the symptom for glucose shifts in diabetes mellitus?

A

Blurred vision

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6
Q

List the 3 types of presentations of diabetes mellitus?

A
  1. Ketone production
  2. Depletion of energy stores (ie. muscle)
  3. Complications (T2DM)
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7
Q

List the 7 symptoms of ketone production is diabetes mellitus?

A
  1. Nausea
  2. Vomiting
  3. Abdominal pain
  4. Heavy/rapid breathing
  5. Acetone breath
  6. Drowsiness
  7. Coma
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8
Q

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

A
  1. Weakness
  2. Polyphagia (excessive eating)
  3. Weight loss
  4. Growth retardation in young
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9
Q

List the 4 complications of T2DM?

A
  1. Macrovascular
  2. Microvascular
  3. Neuropathy
  4. Infection
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10
Q

What is the normal fasting & 2hr plasma glucose?

A
  • Fasting: <7

- 2hr: <7.8

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11
Q

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

A
  • Fasting: <7

- 2hr: 7.8-11.0

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12
Q

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

A
  • 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
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13
Q

What should the HbA1c be for a diagnosis of diabetes?

A

6.5% or 48 mmol/mol

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14
Q

What should diabetes NOT be diagnosed based on?

A

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

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15
Q

When is OGTT only required for?

A

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

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16
Q

List the 5 classifications of diabetes?

A
  1. Maturity Onset Diabetes of the Young (MODY)
  2. T2DM
  3. Secondary DM
  4. Latent Autoimmune Diabetes of Adulthood (LADA)
  5. T1DM
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17
Q

What does SAID stand for?

A

Severe autoimmune diabetes

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18
Q

What does SIDD stand for?

A

Severe insulin-deficient diabetes

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19
Q

What does SIRD stand for?

A

Severe insulin-resistant diabetes

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20
Q

What does MOD stand for?

A

Mild obesity-related diabetes

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21
Q

What does MARD stand for?

A

Mild age-related diabetes

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22
Q

What are the 2 types of primary diabetes?

A
  1. Type 1 DM

2. Type 2 DM

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23
Q

What is Type 2 diabetes mellitus a combination of?

A

Insulin resistance & insulin deficiency

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24
Q

Describe the presentation of type 1 diabetes mellitus?

A
  • <30 usually
  • Lean patient
  • Weeks of symptoms
  • Northern European higher risk
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25
Q

Describe the pathogenesis of type 1 diabetes mellitus?

A
  • HLA DR3 or DR4 in 90%

- Autoimmune

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26
Q

Describe the clinical presentation of type 1 diabetes mellitus?

A
  • Insulin Deficiency +/- Ketoacidosis

- Dependent on Insulin for survival

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27
Q

Describe type 1 diabetes mellitus biochemically?

A

C Peptide Innappropriate/negative

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28
Q

Describe the presentation of type 2 diabetes mellitus?

A
  • > 30 usually
  • Overweight patient
  • Months/Years of symptoms
  • Asian, African, Polynesian & American Indian higher risk
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29
Q

Describe the pathogenesis of type 2 diabetes mellitus?

A
  • No HLA links

- No immune disturbance

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30
Q

Describe the clinical presentation of type 2 diabetes mellitus?

A
  • Partial Insulin Deficiency at presentation +/- Hyperosmolar state
  • May need Insulin
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31
Q

Describe type 2 diabetes mellitus biochemically?

A

C peptide positive

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32
Q

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

A

Normal range & no action is needed

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33
Q

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

A
  • Development of a problem that may require medical assistance
  • Call your healthcare team
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34
Q

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

A
  • In the presence of hyperglycaemia indicates high risk of DKA
  • Contact healthcare team immediately for advice
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35
Q

What are the islet autoantibodies?

A

Markers of autoimmune process associated with T1DM

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36
Q

What are islet autoantibodies present in?

A
  • 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)
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37
Q

When are islet autoantibodies most useful in T2DM?

A

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

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38
Q

Describe C-peptide?

A
  • Secreted in equimolar concentrations to insulin

- Useful marker of endogenous insulin secretion

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39
Q

When is a C-peptide measurement most useful?

A

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

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40
Q

Where can you measure C-peptide?

A

Blood or urine (urine C peptide/creatinine ratio)

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41
Q

What % of diabetes mellitus is type 1?

A

10%

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42
Q

What is the definition of type 1 diabetes?

A

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

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43
Q

Describe the pathogenesis of type 1 diabetes mellitus?

A
  • 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
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44
Q

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

A
  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
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45
Q

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

A

15x

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46
Q

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)?

A
  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)
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47
Q

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

A
  • 30% within 10yrs of diagnosis of the twin

- 65% concordance by age 60yrs 5% of DM

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48
Q

What % of diabetes mellitus is type 2?

A

90%

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49
Q

What is the definition of type 2 diabetes mellitus?

A

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

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50
Q

Describe the pathogenesis of type 2 diabetes mellitus?

A
  • Common with a prevalence that rises markedly with increasing levels of obesity
  • Most likely arises through a complex interaction among many genes & environmental factors
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51
Q

Describe the epidemiology of type 2 diabetes mellitus?

A
  • 39% have at least 1 parent with the disease

- Prevalence varies remarkably among ethnic groups living in the same

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52
Q

What % of diabetes mellitus is MODY?

A

1-2% (often unrecognised)

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53
Q

What is MODY caused by?

A
  • Caused by change in a single gene (monogenic)

- Autosomal dominant (50% chance of inheriting)

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54
Q

What does MODY stand for?

A

Maturity onset diabetes of the young

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55
Q

What are the 3 main features of MODY?

A
  1. Often <25yrs onset
  2. Runs in families from 1 generation to next
  3. Managed by diet, oral antihyperglycemic agents (OHAs), insulin (not always)
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56
Q

What does IDDM stand for?

A

Insulin dependent diabetes mellitus

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57
Q

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

A
  • Onset usually >25
  • 0 parents affected
  • Rarely obese
  • Variable insulin treatment, usually within months or years of diagnosis
  • Polygenic inheritance
  • GAD autoantibodies
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58
Q

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

A
  • Onset 25-40
  • 2 parents affected
  • Obesity is common
  • No insulin treatment initially
  • Polygenic double gene dose inheritance
  • No GAD autoantibodies
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59
Q

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

A
  • Onset <25
  • 1 parent affected
  • Rarely obese
  • No insulin treatment initially
  • Monogenic autosomal dominant inheritance
  • No GAD autoantibodies
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60
Q

What is gestational diabetes mellitus (GDM)?

A

Carbohydrate intolerance with onset, or diagnosis, during pregnancy

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61
Q

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

A
  1. High BMI
  2. Previous macrosomic baby/ gestational diabetes
  3. Family history/ethnic prevalence of diabetes
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62
Q

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

A

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

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63
Q

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

A
  • Fasting venous plasma glucose ≥ 5.1 mmol/l, OR
  • 1hr value ≥ 10 mmol/l, OR
  • 2hrs after OGTT ≥ 8.5 mmol/l
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64
Q

List the 7 causes of secondary diabetes?

A
  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
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65
Q

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

A
  1. Pancreatitis
  2. Carcinoma
  3. Cystic fibrosis
  4. Haemochromatosis
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66
Q

Give 3 examples of endocrinopathies which can cause secondary diabetes?

A
  1. Acromegaly
  2. Cushings
  3. Phaeochromocytoma
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67
Q

Give 3 examples of immunosuppressive agents which cause secondary diabetes?

A
  1. Glucocorticoids
  2. Tacrolimus
  3. Ciclosporin
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68
Q

Give 5 examples of genetic syndromes associated with secondary diabetes?

A
  1. Down’s Syndrome
  2. Friedreich’s Ataxia
  3. Turner’s
  4. Myotonic Dystrophy
  5. Kleinfelter’s Syndrome
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69
Q

Describe the production & release of insulin?

A
  • 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%)
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70
Q

What is the principle stimulant of insulin secretion?

A

Glucose

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71
Q

What is the basal secretion of insulin?

A

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

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72
Q

What mediates the entry of glucose into beta cells?

A

GLUT2 (type 2 glucose transporters)

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73
Q

How does the beta cell depolarise?

A
  • 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
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74
Q

What is the net effect of beta cell depolarisation?

A

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

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75
Q

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

A
  • Export of the insulin-storing granules by exocytosis

- Ultimate result is the export of insulin from beta cells & its diffusion into nearby blood vessels

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76
Q

Insulin release is a ______ process?

A

Biphasic

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77
Q

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

A
  1. 2nd phase of insulin release (slower)

2. Beta cells regenerate the stores of insulin initially depleted in the 1st fast response phase

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78
Q

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

A
  • 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
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79
Q

What is the treatment for type 1 diabetes mellitus?

A

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

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80
Q

Give 5 examples of insulin?

A
  1. Rapid acting- Aspart, Lispro, Glulisine
  2. NPH
  3. Detemir
  4. Glargine (Lantus/Toujeo)
  5. Tresiba (Degludec)
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81
Q

What are the 3 doses of insulin?

A
  1. Once-daily basal insulin
  2. Twice-Daily mix-insulin
  3. Basal-bolus therapy
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82
Q

Describe Levemir insulin?

A
  • Shortest (~16hrs)

- BD>OD in T1DM

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83
Q

What is the duration of Lantus insulin?

A

~20hrs OD

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84
Q

What is the duration of Toujeo insulin?

A

~24hrs OD

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85
Q

What is the duration of Degludec insulin?

A

=> 24hrs OD

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86
Q

Describe Insulin glargine (Lantus®)?

A
  • 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
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87
Q

Describe OptiPen® Pro & OptiSet® pen delivery devices?

A
  • OptiPen® Pro is a reusable insulin cartridge pen

- OptiSet® is a prefilled pen with a facility to preset the dosage

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88
Q

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

A

Novorapid/Fiasp Humalog, Apidra

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89
Q

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

A
  1. Levemir (Detemir)

2. Lantus/Toujeo (Glargine) 3. Tresiba (Degludec)

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90
Q

What are the 2 analogues for mixed human Humulin M3?

A
  1. Novomix 30

2. Humalog Mix 25/50

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91
Q

What are the 5 PROS of insulin pens?

A
  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
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92
Q

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

A
  • 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
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93
Q

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

A
  1. Reactions
  2. Infections at the cannula site
  3. Tube blockage
  4. Pump malfunction
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94
Q

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

A

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

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95
Q

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

A
  1. Islet cell transplant

2. Pancreatic transplant

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96
Q

What type of molecule is insulin?

A

Peptide

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97
Q

What is Whipples Triad in Hypoglycaemia?

A
  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
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98
Q

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

A
  • Inhibition of insulin release

- Signs: general malaise, headache, nausea

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99
Q

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

A
  • Release of counter regulatory hormones glucagon & adrenaline
  • Signs: autonomic symptoms, sweating, palpitations, shaking, nausea, anxiety, hunger
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100
Q

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

A

No symptoms

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101
Q

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

A
  • Impairment of cognitive function & concentration, inability to perform complex tasks
  • Signs: confusion, drowsiness, odd behaviour, speech difficulty, incoordination, weakness, visual change, dizziness, tiredness
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102
Q

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

A
  • EEG changes

- Sign: seizures

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103
Q

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

A
  1. Coma

2. Convulsions

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104
Q

Describe the severity scale of hypoglycaemia?

A
  • MILD: autonomic
  • MODERATE: autonomic & neuroglycopaenic
  • SEVERE: autonomic & neuroglycopaenic
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105
Q

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

A
  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
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106
Q

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

A
  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
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107
Q

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?

A

Home capillary blood glucose (CBG) diary

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108
Q

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

A
  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
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109
Q

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

A
  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
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110
Q

What type of diabetes is more prone to diabetic ketoacidosis?

A

Mainly T1DM but now recognise ketosis prone T2DM

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111
Q

Describe the mortality of diabetic ketoacidosis?

A
  • Mortality in young: cerebral oedema 70-80% deaths

- Mortality in adults: severe hypokalaemia, ARDS, illness causing decompensation

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112
Q

What are the 3 factors to diabetic ketoacidosis?

A
  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
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113
Q

Describe the pathophysiology of diabetic ketoacidosis?

A

Absolute or relative insulin deficiency + Increase in stress hormones –>

  1. Lipolysis: FFAs: ketogenesis
  2. Gluconeogenesis: severe hyperglycaemia
  3. Osmotic diuresis + acidosis: dehydration
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114
Q

List the 7 clinical features of diabetic ketoacidosis?

A
  1. Osmotic Symptoms
  2. Weight Loss
  3. Breathlessness- Kussmaul respiration
  4. Abdominal pains, especially in children
  5. Leg cramps
  6. Nausea & vomiting
  7. Confusion
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115
Q

List the 4 main precipitating factors of diabetic ketoacidosis?

A
  1. Insulin omission- 33%
  2. Infections- 20-38%
  3. New-onset DM- 5-39%
  4. Acute Illness (MI, trauma, pancreatitis)- 10-20%
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116
Q

List the 5 other precipitants of ketoacidosis?

A
  1. Steroids
  2. CSII Pump failure
  3. Substance abuse
  4. Deliberate omission of Insulin dose
  5. Eating disorder
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117
Q

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

A
  1. Weight management
  2. Avoidance of hypoglycaemia
  3. Escaping domestic situation
  4. Depression
  5. Attention seeking
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118
Q

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

A
  1. 6-8 litres of water (100ml/kg)
  2. Sodium 500-1000mmol
  3. Chloride 350mmol
  4. Potassium 300-1000 (3-5 mmol/Kg)
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119
Q

What are the 3 treatments for DKA?

A
  1. Fluid- restoration of circulatory volume ie. crystalloid. Clearance of ketones ie. 10% dextrose
  2. Potassium
  3. Insulin
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120
Q

How long is the DKA care pathway?

A

0-4hrs (4hrs until discharge)

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121
Q

Describe a Hyperglycaemic Hyperosmolar State (HHS)?

A
  • Hypovolaemia
  • Very high blood glucose > 30mmol/L
  • Serum osmolality >320mOsmol/l
  • Bicarbonate usually > 15mmol/l
  • Absence of significant ketones
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122
Q

What is osmolality equal to?

A

2 x (Na + K) + Urea + Glu

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123
Q

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

A

Ketoacidosis

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124
Q

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

A

Coma (watch GCS)

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125
Q

Describe the prevalence of Hyperglycaemic Hyperosmolar State (HHS)?

A
  • Less than 1% diabetes related admissions annually

- Elderly (55-70yrs), first presentation T2DM in 30%

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126
Q

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

A
  1. Infection- 60%
  2. Poor compliance- 30%
  3. Drugs
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127
Q

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

A
  1. Fluid- 0.9% sodium chloride
  2. Insulin- low dose 0.05units/kg/hr
  3. Other- LMWH, Foot protection
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128
Q

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

A
  • 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
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129
Q

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

A
  • Rate of fall no more than 5mmol/L/hr

- Only start when glucose not falling with fluid alone

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130
Q

What are the 2 microvascular complications of diabetes?

A
  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
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131
Q

Describe the foot complications of diabetes?

A

Neuropathy/foot disease-

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

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132
Q

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

A
  1. Previous history of stroke- 7%
  2. Abnormal ECG- 18%
  3. Hypertension- 35%
  4. Intermittent claudication- 4.5%
  5. Absent foot pulses- 13%
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133
Q

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

A

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

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134
Q

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

A

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

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135
Q

What is the management for retinopathy in diabetes?

A

Annual photographic retinal screening with triggers for ophthalmology referral

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136
Q

What is the management for nephropathy in diabetes?

A

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

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137
Q

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

A

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

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138
Q

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

A
  • 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
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139
Q

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

A
  1. Symptoms
  2. When was diabetes diagnosed?
  3. Co-morbidities
  4. Drug history
  5. Family history
  6. Smoking
  7. Alcohol
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140
Q

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

A
  1. BMI

2. BP

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141
Q

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

A
  1. HbA1c
  2. Lipids
  3. Renal function
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142
Q

List 8 pathophysiological failures which contribute to hyperglycaemia?

A
  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
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143
Q

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

A
  1. Insulin resistance
  2. Decrease insulin production
  3. Increase blood glucose
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144
Q

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

A
  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
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145
Q

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

A
  1. DPP4 Inhibitors
  2. GLP-1 agonists
  3. Metformin
  4. Sulphonylureas
  5. Thiazolidinediones (TZDs)
  6. Insulin
  7. SGLT-2 inhibitors
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146
Q

How does metformin work?

A

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

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147
Q

What 3 effects does Metformin have on the liver?

A
  1. Reduced fatty acid & cholesterol synthesis
  2. Increased lipid oxidation
  3. Reduced gluconeogenesis
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148
Q

What effect does Metformin have on the skeletal muscle?

A

Increased lipolysis & lipogenesis

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149
Q

What effect does Metformin have on adipose?

A

Reduced lipolysis & lipogenesis

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150
Q

What effect does Metformin have on vascular endothelium?

A

Increased nitric oxide (NO) bio-availability

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151
Q

What 2 effects does Metformin have on the heart?

A
  1. Increased fatty acid uptake & oxidation

2. Increased glucose uptake & glycolysis

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152
Q

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

A
  1. Weight loss
  2. Increased insulin sensitivity
  3. Improved glycaemia
  4. Improved lipid profile
  5. Improved vascular function
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153
Q

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

A
  • 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
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154
Q

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

A

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

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155
Q

List the 6 limitations of older type 2 diabetes therapies?

A
  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
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156
Q

What is the incretin effect?

A

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

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157
Q

What happens to DPP-4 when they are inhibited?

A

Rapidly inactivated to GLP-1 & GIP

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158
Q

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

A

Increased insulin –> Increased glucose uptake in fat & muscle

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159
Q

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

A

Decreased glucagon –> Decreased glucose production in the liver

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160
Q

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

A

Decreased appetite

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161
Q

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

A

Decreased gastric emptying

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162
Q

What are incretins?

A
  • 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
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163
Q

List the 4 PROS/CONS of incretin based therapy?

A
  1. Weight loss
  2. Risk of hypoglycaemia
  3. Likely benefit?
  4. Special groups- elderly & renal impairment as it is renally excreted
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164
Q

Give an example of a SGLT-2 inhibitor drug?

A

Empagliflozin

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165
Q

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

A

Reduces hyperglycaemia, BP & CV risk

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166
Q

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

A
  • Inhibit SGLT2 in thePCT& so increase glucose excretion in the urine
  • Used when HbA1c>53mmol/mol
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167
Q

Describe the treatment pathway for type 2 diabetes?

A

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

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168
Q

What should all development programmes for T2D rule out?

A

Unacceptable increase in CV risk

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169
Q

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

A
  1. Sitagliptin
  2. Alogliptin
  3. Vildagliptin
  4. Omarigliptin
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170
Q

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

A
  1. Semaglutide
  2. Lixisenatide
  3. Liraglutide
  4. Exenatide
  5. Dulaglutide
  6. Albiglutide
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171
Q

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

A
  1. Empagliflozin
  2. Canagliflozin
  3. Ertugliflozin
  4. Dapagliflozin
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172
Q

Describe the mechanism of action of DPP4 inhibitors?

A
  • Inhibit DPP4 which normally breaks down incretins

- Results in increased insulin

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173
Q

When would you use DPP4 inhibitors?

A

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

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174
Q

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

A
  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
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175
Q

Describe the mechanism of action of SGLT2 inhibitors?

A
  • Work at proximal tubule in kidneys

- Act to reduce glucose reabsorption & increase glucose excretion

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176
Q

When would you use SGLT2 inhibitors?

A
  • Considered as add-on therapy to Metformin in people with T2DM
  • T2DM & established CV disease, Empagliflozin & Canagliflozin should be considered
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177
Q

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

A
  1. Metformin OR

2. Sulphonylurea if osmotic symptoms or intolerant to metformin

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178
Q

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

A
  1. Sulphonylurea OR
  2. SGLT2 inhibitor OR
  3. DPP-4 inhibitor OR
  4. Pioglitazone (thiazolidinedione)
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179
Q

What is the set glycaemic target for T2DM?

A

HbA1c <7% (53mmol/mol)

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180
Q

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

A
  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
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181
Q

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

A

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

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182
Q

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

A
  • Stop DPP-4 inhibitor
  • Consider reducing sulphonylurea
  • Continue metformin
  • Can continue Pioglitazone
  • Can continue SGLT2 inhibitor
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183
Q

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

A
  • Can continue metformin, Pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor
  • Can reduce/stop sulphonylurea
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184
Q

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

A
  • Inject before bed

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

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185
Q

What 4 T2DM drugs have a CV benefit?

A
  1. Metformin
  2. SGLT-2 inhibitors
  3. Pioglitazone
  4. GLP-1 agonist
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186
Q

What 2 T2DM drugs have a high hypoglycaemic risk?

A
  1. Sulphonylurea

2. Basal insulin

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187
Q

What 3 T2DM drugs can cause weight gain?

A
  1. Sulphonylurea
  2. Basal insulin
  3. Pioglitazone
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188
Q

What T2DM drugs have the lowest chance of side effects?

A

DPP-4 inhibitors

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189
Q

What 2 T2DM drugs have GI side effects?

A
  1. Metformin

2. GLP-1 agonists

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190
Q

What main adverse effect does SGLT2- inhibitors have?

A

Genital mycotic

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191
Q

What main adverse effect does Pioglitazone have?

A

Oedema/fractures

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192
Q

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

A

Add prandial insulin or switch to twice daily mixed biphasic insulin

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193
Q

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

A
  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
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194
Q

What 5 hormones does the anterior pituitary release?

A
  1. ACTH
  2. GH
  3. TSH
  4. Gonadotropins (FSH, LH)
  5. Prolactin
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195
Q

What 2 hormones does the posterior pituitary release?

A
  1. ADH

2. Oxytocin

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196
Q

What 5 hormones does the hypothalamus release?

A
  1. Growth hormone releasing hormone (GHRH)
  2. Gonadotrophin releasing hormone (GnRH)
  3. Corticotrophic releasing hormone (CRH)
  4. Thyroid releasing hormone (TRH)
  5. Dopamine
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197
Q

List the 5 cell types in the anterior pituitary?

A
  1. Somatotrophs (50%)
  2. Gonadotrophs (10%)
  3. Corticotrophs (10-15%)
  4. Thyrotrophs (5%)
  5. Lactotrophes (20%)
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198
Q

Describe the ADH regulation of water balance?

A

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

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199
Q

What are 4 other names for ADH?

A
  1. AVP
  2. Vasopressin
  3. Arginine vasopressin
  4. Argipressin
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200
Q

What are the 6 rules of endocrinology?

A
  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
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201
Q

What is fT4?

A

Thyroxine

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202
Q

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

A

Hydrocortisone

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203
Q

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

A

Transphenoidal surgery

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204
Q

Describe hypopituitarism?

A
  • Failure of (anterior) pituitary function

- Can affect single hormonal axis or all hormones (panhypopituitarism)

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205
Q

What does hypopituitarism lead to?

A

Secondary gonadal/thyroid/adrenal failure

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206
Q

What is the treatment for hypopituitarism?

A

Need multiple hormone replacement

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207
Q

List the 6 causes of hypopituitarism?

A
  1. Tumours
  2. Radiotherapy
  3. Infarction / haemorrhage (apoplexy)
  4. Infiltration (eg sarcoid)
  5. Trauma
  6. Lymphocytic hypophysitis (autoimmune)
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208
Q

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

A
  1. Associated headache / visual disturbance

2. Associated postpartum pituitary gland necrosis (Sheehan’s syndrome)

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209
Q

What would you give as replacement for ACTH deficiency?

A

Hydrocortisone

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210
Q

What would you give as replacement for TSH deficiency?

A

Thyroxine

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211
Q

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

A
  • Testosterone (males)

- Oestrogen (females)

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212
Q

What would you give as replacement for GH deficiency?

A

Growth hormone (children)

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213
Q

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

A

No replacement

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214
Q

What are 4 causes of high prolactin?

A
  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
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215
Q

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

A
  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
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216
Q

What are the 3 types of pituitary tumours?

A
  1. Non-functioning (majority) so they just grow
  2. Functioning
  3. Others- Craniopharyngioma, pituitary cancer, Rathke’s cyst
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217
Q

List 4 functioning pituitary tumours?

A
  1. Prolactin (prolactinoma)
  2. GH (acromegaly)
  3. ACTH (Cushing’s disease)
  4. TSH (TSHoma)
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218
Q

Describe non-functioning pituitary tumours?

A
  • Commonest (25 % of all pituitary tumours)

- No hormonal release

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219
Q

List 4 problems that non-functioning pituitary tumours cause?

A
  1. Visual field defects
  2. Headache
  3. Stops other pituitary hormones working
  4. Eye movement problems (cranial nerve disturbance)
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220
Q

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

A
  1. Imaging (MRI)
  2. Visual field assessment
  3. Prolactin
  4. Other pituitary hormones
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221
Q

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

A
  1. Surgery (help protect vision)
  2. RT if its aggressive
  3. Medical management unhelpful
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222
Q

What is a prolactinoma?

A

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

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223
Q

Describe the 2 sizes of prolactinomas?

A
  1. Micro < 1 cm

2. Macro > 1 cm

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224
Q

List the 5 clinical features of prolactinomas?

A
  1. Galactorrhoea
  2. Headaches
  3. Mass effect
  4. Visual field defect
  5. Amenorrhoea / erectile dysfunction
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225
Q

Describe the 3 ways to diagnose a prolactinoma?

A
  1. Serum prolactin usually > 6000
  2. MRI pituitary
  3. Test remaining pituitary function- gonadal function & thyroid hormones most affected
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226
Q

Describe the medical treatment of prolactinomas?

A

Dopamine agonists help to bring down prolactin & shrink the tumour

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227
Q

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

A
  1. Cabergoline
  2. Bromocriptine
  3. Quinagolide (these drugs are also used in Parkinson’s disease)
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228
Q

What are 2 scenarios for surgical treatment of prolactinomas?

A
  1. Visual field compromise

2. Failure of medical therapy

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229
Q

Describe prolactinomas in pregnancy?

A
  • Pituitary gland gets bigger in pregnancy
  • Dopamine agonists contraindicated
  • Prolactin unhelpful
  • Can’t do serial MRI in pregnancy
  • Monitor visual fields if macroprolactinoma
230
Q

What is Acromegaly caused by?

A

Pituitary tumour secreting Growth Hormone

  • Post puberty ie after growth plates fused
  • Gigantism
231
Q

List the 6 clinical features of acromegaly?

A
  1. Sweats & headaches
  2. Alteration of facial features
  3. Increased hand & feet size
  4. Visual impairment
  5. Cardiomyopathy
  6. Inter-dental space
232
Q

Describe the prevalence of acromegaly?

A

Rare- 20 new cases per year in Scotland

233
Q

What is acromegaly usually?

A

Macroadenoma

234
Q

What are the 4 ways to diagnose Acromegaly?

A
  1. Glucose tolerance test
  2. Glucose should suppress GH
  3. Measure IGF-1- long half-life, more useful than random GH
  4. Then MRI
235
Q

What is the 1st line treatment for acromegaly?

A

Surgery (often tumour can’t be filly removed)

236
Q

List the 3 drugs used to treat acromegaly?

A
  1. Somatostatin analogue- Octreotide, before & after surgery
  2. Dopamine agonist
  3. GH receptor agonist- Pegvisomant
237
Q

When would you use radiotherapy to treat acromegaly?

A

Residual tumour/ ongoing symptoms

238
Q

Describe the inheritance of acromegaly?

A
  • Familial isolated pituitary adenoma

- Same mutation of AIP

239
Q

What one cause of Cushing’s disease?

A

Pituitary tumour releasing ACTH

240
Q

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

A
  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
241
Q

How do you try suppress Cushing’s disease?

A

Dexamethasone suppression testing

242
Q

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

A

Surgery

243
Q

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

A
  1. Bilateral adrenalectomy
  2. Medical therapy- Ketoconazole / metyrapone
  3. Radiotherapy
244
Q

What is a TSHoma?

A
  • Pituitary tumour releasing TSH
  • Rare
  • Causes high TSH & high fT4
245
Q

What is Diabetes insipidus?

A

ADH deficiency- central or cranial

246
Q

List the 2 clinical features of Diabetes insipidus?

A
  1. Polydipsia- chronic excessive thirst accompanied by excessive fluid intake
  2. Polyuria- urine output > 3 L/day
247
Q

What are the 2 differential diagnosis for Diabetes insipidus?

A
  1. Nephrogenic diabetes insipidus

2. Psychogenic polydipsia

248
Q

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

A
  1. Idiopathic
  2. Trauma
  3. Pituitary tumour
  4. Pituitary surgery
  5. Pregnancy
  6. Familial
  7. Wegeners
  8. Sarcoidosis
  9. Lymphocytic panhypophysitis
249
Q

How would you diagnose diabetes insipidus?

A
  • Try to stimulate its release
  • Water deprivation test to see if they are able to stop urinating
  • Assess ability to concentrate urine with ADH
250
Q

What are the 2 ways to treat diabetes insipidus?

A
  1. Treat underlying cause

2. Desmopressin (DDAVP)- Spray, tablets or injection

251
Q

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

A
  1. Glomerulosa- Aldosterone (salt)
  2. Fasciculata- Cortisol (sugar)
  3. Reticularis- Androgens (sex)
252
Q

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

A

Chromograffin cells- catecholamines (adrenaline & noradrenaline)

253
Q

Describe the regulation of the renin-angiotensin system?

A
  • Renin is activated in response to decrease BP
  • Leads to production of Angiotensin II which causes direct (vasoconstriction) & indirect (aldosterone) methods of BP elevation
254
Q

What are the steps of the renin-angiotensin system?

A

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

255
Q

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

A

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

256
Q

What 3 factors make the hypothalamus produce and release CRH?

A
  1. Illness
  2. Stress
  3. Time of day
257
Q

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

A

> 90%

258
Q

What are 10% of hypertension cases?

A

Secondary to another disorder eg. renal disease, hormone excess

259
Q

What 3 factors make secondary hypertension more likely?

A
  1. Young
  2. Resistant/severe hypertension
  3. Clinical suspicion
260
Q

What is Hypertension + Hypokalaemia?

A

Primary Aldosteronism

261
Q

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

A
  1. Aldosterone (100-400pmol/l)
  2. Renin (5-44.9 μIU/ml)
  3. Aldosterone:renin ratio (ARR) (>35 suspicious)
262
Q

What is the commonest secondary cause of hypertension?

A

Primary aldosteronism (prevalence approx 11%)

263
Q

What are the 2 causes of primary aldosteronism?

A
  1. Adenoma- 40%

2. Bilateral hyperplasia- 60%

264
Q

What is present in 50% of primary aldosteronism cases?

A

Hypokalaemia

265
Q

What is the best screening tool for primary aldosteronism?

A

Aldosterone-renin-ratio (ARR)

- If increased, then consider further testing

266
Q

What should you do if there is confirmed aldosterone excess?

A

Stop medications if possible!:

  • Definitely stop β blockers and MR antagonists
  • Alternative drugs include α-blockers/verapamil/ hydralazine
267
Q

Describe the saline suppression test?

A
  • 2L saline over 4 hours

- 4h aldosterone >270 pmol/l highly suspicious

268
Q

Describe the surgical management of primary aldosteronism?

A
  • Unilateral laparoscopic adrenalectomy
  • Only if adrenal adenoma
  • Cure of hypokalaemia
  • Cures hypertension in 30-70% cases
269
Q

Describe the medical management of primary aldosteronism?

A

Use MR antagonists (spironolactone or eplerenone)

270
Q

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

A
  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
271
Q

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

A
  1. Pituitary adenoma (68%) Cushing’s Disease
  2. Ectopic ACTH 12%
  3. Ectopic CRH <1%
272
Q

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

A
  1. Adrenal adenoma 10%
  2. Adrenal carcinoma 8%
  3. Nodular hyperplasia 1%
273
Q

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

A

CT adrenals

274
Q

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

A
  1. Laparoscopic right adrenalectomy

2. Short term requirement for hydrocortisone replacement therapy

275
Q

Describe congenital adrenal hyperplasia?

A
  • Autosomal recessive disorder of the cortex
  • Range of genetic disorders relating to defects in steroidogenic genes
  • Most common CYP21 (21α hydroxylase)
276
Q

Describe female congenital adrenal hyperplasia?

A

Ambiguous genitalia

277
Q

Describe male congenital adrenal hyperplasia?

A
  • Adrenal crisis (Hypotension, hyponatraemia)

- Early virilisation

278
Q

What is the treatment for congenital adrenal hyperplasia?

A

Mineralocorticoid & glucocorticoid replacement

279
Q

List 5 urinary catecholamines that are raised in a Phaeochromocytoma?

A
  1. Noradrenaline
  2. Adrenaline
  3. Dopamine
  4. Free Metadrenaline
  5. Free normetadrenaline
280
Q

What is affected in Phaeochromocytoma?

A

Adrenal medulla (overproduction of catecholamines)

281
Q

What is affected in a Paraganglioma?

A

Extra-adrenal neural crest cells eg sympathetic ganglia

282
Q

Describe the prevalence of phaeochromocytoma?

A

Rare, 2-8/million cases per year

283
Q

Describe the signs/symptoms of phaeochromocytoma?

A
  • 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
284
Q

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

A
  1. MEN
  2. VHL
  3. SDHB & SDHD mutations
  4. Neurofibromatosis
285
Q

What % of phaeochromocytoma are malignant?

A

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

286
Q

What % of phaeochromocytoma are benign?

A

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

287
Q

Describe the 3 pre-operative treatments for phaeochromocytoma?

A
  1. Alpha-blockade initially- phenoxybenzamine or doxazosin
  2. Then beta blocker if tachycardic- Labetolol or bisoprolol
  3. Encourage salt intake
288
Q

What are 2 primary adrenal insufficiencies?

A
  1. Addison’s disease

2. Autoimmune destruction

289
Q

List the 5 clinical features of adrenal insufficiency?

A
  1. Anorexia, weight loss
  2. Fatigue/lethargy
  3. Dizziness and low BP
  4. Abdominal pain, vomiting, diarrhoea
  5. Skin pigmentation
290
Q

Describe the “suspicious biochemistry” associated with adrenal insufficiency?

A
  • Decrease Na
  • Increase K
  • Hypoglycaemia
291
Q

What are 4 ways to diagnose adrenal insufficiency?

A
  1. Short synACTHen test
  2. ACTH levels
  3. Renin/aldosterone levels
  4. Adrenal autoantibodies
292
Q

Describe the short synACTHen test for diagnosing adrenal insufficiency?

A
  • Measure plasma cortisol before & 30 min after IV ACTH injection
  • Normal: baseline >250nmol/L, post ACTH >480
293
Q

Describe the ACTH levels in adrenal insufficiency?

A

Increased & causes skin pigmentation

294
Q

Describe the renin/aldosterone levels in adrenal insufficiency?

A
  • Increase Renin

- Decreased aldosterone

295
Q

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

A

Adrenal source

296
Q

Describe High dose dexamethasone suppression test in localising cortisol source?

A
  • If pituitary, cortisol will suppress to <50%

- No response in ectopic ACTH

297
Q

Describe the CRH test in localising cortisol source?

A
  • Exaggerated response in pituitary disease

- No response in ectopic ACTH

298
Q

Describe the imaging in localising cortisol source?

A
  • Adrenal CT or MRI
  • Pituitary MRI only detects 50% of ACTH producing pituitary tumours
  • Optimal imaging for ectopic tumours unclear (CT/PET/MRI)
299
Q

Describe the epidemiology of Hypoglycaemia?

A

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

300
Q

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

A

Biochemical threshold of plasma glucose less than 4 mmol/L1

301
Q

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

A

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

302
Q

Describe the 2 types of hypoglycaemic symptoms?

A
  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
303
Q

Describe the hypoglycaemia symptoms in patients with diabetes?

A

Autonomic symptoms occur before neuroglycopenic symptoms

304
Q

What are the 4 key factors to ascertain in hypoglycaemia?

A
  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
305
Q

What is the diagnostic strategy for hypoglycaemia?

A

Replicate conditions in which hypoglycaemia would be expected

306
Q

What are the 2 ways to investigate hypoglycaemia?

A
  1. Post Prandial- ideally mixed meal test up to 5 hours. OGTT can be misleading
  2. 72 hour fast
307
Q

Describe the glyceamic response to glucagon?

A

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

308
Q

What does the ketogenic effects of insulinomas cause?

A

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

309
Q

List 7 investigations for hypoglycaemia?

A
  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
310
Q

Describe the 72hr fast investigation for hypoglycaemia?

A

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

311
Q

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

A

Glucagon, Adrenaline> GH/Cortisol

312
Q

When is a 72hr fast investigation complete?

A

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

313
Q

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

A

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

314
Q

What are 2 localising studies for hypoglycaemia?

A
  1. Radiology- CT, MRI, EUS

2. Arterial Calcium Stimulation- Endogenous hyperinsulinaemic hypoglycaemia & negative imaging

315
Q

What is Arterial Calcium Stimulation good for distinguishing?

A

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

316
Q

Describe how to perform Arterial Calcium Stimulation?

A

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

317
Q

What are the 2 pancreatic causes of spontaneous hypoglycaemia?

A
  1. Insulinoma

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

318
Q

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

A
  1. IGF II secreting tumours (Mesenchymal tumours, Carcinomas of the liver, stomach & adrenals)
  2. Lymphoma
  3. Myeloma
  4. Leukaemias
  5. Metastatic Cancer
319
Q

What are the 2 autoimmune causes of hypoglycaemia?

A
  1. Autoimmune Insulin 2. Syndrome

Anti Insulin Receptor

320
Q

What are the 2 reactive causes of hypoglycaemia?

A
  1. Post Gastric Surgery

2. Alcohol Provoked Reactive Hypoglycaemia

321
Q

List 14 drugs which can induce hypoglycaemia?

A
  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
322
Q

What are 2 dietary toxins which can cause hypoglycaemia?

A
  1. Alcohol

2. Mushrooms causing acute liver failure

323
Q

What are 3 organ failures which can cause hypoglycaemia?

A
  1. Severe Liver Disease
  2. End Stage Renal Disease & Renal Dialysis
  3. Congestive Cardiac Failure
324
Q

What are 3 endocrine disease which can cause hypoglycaemia?

A
  1. Hypopituitarism
  2. Adrenal Failure
  3. Hypothyroidism
325
Q

What are 6 miscellaneous causes of hypoglycaemia?

A
  1. Inborn errors of metabolism
  2. Sepsis
  3. Starvation
  4. Anorexia Nervosa
  5. Total parenteral nutrition
  6. Severe excessive exercise
326
Q

What are the 2 endocrine society diagnostic approaches for hypoglycaemia?

A
  1. Ill or Medicated Individual

2. Seemingly Well Individual

327
Q

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

A
  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
328
Q

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

A
  1. Endogenous Hyperinsulinism

2. Accidental, Surreptitious, Malicious hypoglycaemia

329
Q

Describe 3 Endogenous Hyperinsulinism’s?

A
  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
330
Q

What are the 6 functions of calcium?

A
  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
331
Q

Describe the distribution of calcium?

A
  • Skeleton- 99%
  • Intracellular- 0.01%
  • Extracellular- 0.99%
332
Q

What is Intracellular calcium stored?

A
  1. Endoplasmic reticulum

2. Mitochondria

333
Q

Describe extracellular calcium?

A
  • 45% ionised (free)

- 55% bound (albumin, lactate, phosphate)

334
Q

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

A

2.2-2.6 mmol/L

335
Q

What is extracellular ionised calcium regulated by?

A

Parathyroid hormone (PTH) & Vitamin D

336
Q

Describe the parathyroid glands?

A
  • Usually 4 glands (2-6)
  • Posterior aspect of thyroid gland
  • 10% are ectopic
  • Weigh 30-50mg
337
Q

What are the parathyroid glands supplied by?

A

Inferior thyroid artery (caution during thyroid surgery)

338
Q

Describe the parathyroid hormones effect on the kidneys?

A
  • Reabsorption of calcium at distal tubule
  • Internalises sodium-phosphate co-transporters at proximal tubule
  • Inhibits Na+/H+ leading to bicarbonate wasting
339
Q

Describe the parathyroid hormones effects on bones?

A
  • 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
340
Q

Describe the parathyroid hormones effects on the gut?

A
  • Stimulates synthesis of active form of Vit D in kidney (1,25 dihydroxy cholecalciferol)
  • Thereby increases calcium absorption from the gut
341
Q

Where is the parathyroid hormone stored?

A

Chief cells of parathyroid gland

342
Q

What is parathyroid hormone secretion controlled by?

A

Calcium sensing receptor (CaSR)

343
Q

What is familial hypocalciuric hypercalcaemia associated with?

A

Loss of function mutations

344
Q

What do calcimetic drugs target?

A

CaSR & inhibit PTH secretion

345
Q

What 2 things are activated when calcium rises?

A
  1. CaSR

2. Calcium sensing proteases

346
Q

What does CaSR activation cause?

A
  • Inhibits transcription of PTH gene

- PTH secretion inhibited

347
Q

What does calcium sensing proteases activation cause?

A

PTH broken down/inactivated

348
Q

What effect does calcium sensing receptors have on the kidneys?

A
  • Increases urinary calcium & magnesium excretion

- Increases sodium, potassium & chloride excretion

349
Q

What effect does calcium sensing receptors have on the thyroid?

A

Stimulates calcitonin secretion

350
Q

Where are the thyroid calcium sensing receptors located?

A

Expressed in C-cells

351
Q

Where else are calcium sensing receptors expressed?

A

Brain, intestine & bone where role less well understood

352
Q

Describe vitamin D?

A
  • Steroid hormone i.e. needs to bind to a nuclear receptor (vitamin D receptor)
  • Acts to increase serum calcium levels
353
Q

What does UV light transfer 7-dehydrocholesterol

into?

A

Cholecalciferol (D3)

354
Q

What are the 2 sources of Vitamin D?

A
  1. Cholecalciferol (D3) from the skin

2. Ergosterol from the diet

355
Q

What is Ergosterol transformed into?

A

Ergocalciferol (D2)

356
Q

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

A

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

357
Q

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

A

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

358
Q

What is another name for Vitamin D?

A

1-25 dihydroxycholecalciferol

359
Q

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

A
  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
360
Q

What are the 3 different metabolites of Vitamin D?

A
  1. Vitamin D
  2. 25-hydroxycholecalciferol
    (25-OHD3)
  3. 1,25 dihydroxycholecalciferol
    (1,25-OHD3)
361
Q

Describe the measurement of 25-hydroxycholecalciferol

(25-OHD3)?

A

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

362
Q

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

A

Renal disease

363
Q

What is the concentration of 1,25 dihydroxycholecalciferol

(1,25-OHD3)?

A

50-125 pmol/L

364
Q

What is the concentration of severe 25-OHD3 deficiency?

A

<15 nmol/L

365
Q

What is the concentration of 25-OHD3 adequacy?

A

> 50nmol/L

366
Q

When do you get symptoms in hypercalcaemia?

A

Once calcium >3mmol/L

367
Q

List the 5 symptoms of hypercalcaemia?

A
  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
368
Q

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

A
  1. Primary hyperparathyroidism
  2. Familial syndromes e.g. MEN-1 and MEN-2
  3. Familial hypocalciuric hypercalcaemia
369
Q

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

A
  1. Malignancy
  2. Granulomatous disorders
  3. Vitamin D toxicity
  4. Drugs: Thiazides, Lithium, Calcium supplements
  5. Adrenal insufficiency
  6. Milk-alkali syndrome
  7. Immobilisation
370
Q

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

A
  1. Parathyroid overactivity
  2. Familial hypocalciuric hypercalcaemia
  3. Lithium
371
Q

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

A

Parathyroid-independent:

  • Malignancy
  • Drugs
  • Granulomatous disease etc
372
Q

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

A
  1. History & examination
  2. Chest x-ray
  3. FBC/ESR
  4. TFTs
  5. Myeloma screen
  6. Synacthen test
  7. Vit D
373
Q

What is the commonest cause of hypercalcaemia in hospitalised patients?

A

Malignancy ie. solid organ tumours & haematological malignancies

374
Q

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

A
  1. Osteolytic metastases & myeloma
  2. Tumour secretion of PTHrP
  3. Tumour production of 1,25 dihydroxycholecalciferol by activated macrophages. Occurs in lymphoma
375
Q

Describe Tumour secretion of PTHrP?

A
  • 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
376
Q

Describe Vitamin D Toxicity causing PTH independent hypercalcaemia?

A
  • 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
377
Q

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

A
  • Lymphoma, sarcoid, Wegeners granulomatosis
  • Extra-renal activation of cholecalciferol
  • Usually responsive to steroid treatment
378
Q

Describe Adrenal insufficiency causing PTH independent hypercalcaemia?

A

Increased proximal tubule calcium reabsorption & increased bone resorption

379
Q

Describe Milk-Alkali syndrome causing PTH independent hypercalcaemia?

A
  • Hypercalcaemia, metabolic alkalosis, renal insufficiency

- Due to ingestion of calcium & antacids

380
Q

What are the 5 general principles for managing hypercalcaemia?

A
  1. Stop offending / contributing medications
  2. Rehydration- Normal saline 3-4 litres in first 24 hours unless contraindicated
    • / - loop diuretic to promote calciuria
  4. Bisphosphonates
  5. Steroids
381
Q

Describe Bisphosphonates for managing hypercalcaemia?

A
  • Inhibit bone resorption
  • Zoledronic acid 4mg IV
  • Takes effect within 24-48 hrs
  • Last several weeks
382
Q

When are steroids effective for managing hypercalcaemia?

A

Effective in haematological malignancy, vitamin D intoxication, granulomatous disease

383
Q

What are the 3 causes of primary hyperparathyroidism?

A
  1. 85% isolated parathyroid adenoma
  2. 14% parathyroid hyperplasia-often associated with familial conditions e.g. MEN etc
  3. <1% parathyroid carcinoma
384
Q

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

A
  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
385
Q

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

A
  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)
386
Q

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

A
  1. DEXA

2. KUB/renal USS

387
Q

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

A

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

388
Q

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

A

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

389
Q

What are brown tumours a result of?

A

Excess osteoclast activity

390
Q

What are brown tumours made of?

A

Collection of osteoclasts, poorly mineralised bone & fibrous tissue

391
Q

How are brown tumours “brown”?

A

Haemosiderin deposition

392
Q

What are the 3 management options for primary hyperparathyroidism?

A
  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)
393
Q

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

A
  1. Calcium > 3.0 mmol/L
  2. Hypercalciuria
  3. Osteoporosis
  4. Age under 50 years
  5. Intractable symptoms ie. renal stones
394
Q

Describe the observational management of primary hyperparathyroidism?

A
  • Annual bone profile, renal function, urinary calcium (nurse led clinic)
  • DEXA & renal US every 3 years
395
Q

Describe the medical treatment for primary hyperparathyroidism?

A
  • 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
396
Q

What are the 2 mechanical complications of parathyroidectomy?

A
  1. Vocal cord paresis

2. Haematoma causing tracheal compression

397
Q

What are the 3 metabolic complications of parathyroidectomy?

A
  1. Transient hypocalcaemia (suppression of remaining glands)
  2. May require oral calcium / vit D supplementation
  3. “Hungry bones”
398
Q

Describe the “Hungry bones” complication of parathyroidectomy?

A
  • 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
399
Q

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

A

Calcium & vitamin D supplementation

400
Q

What are 5 causes of Vitamin D deficiency?

A
  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)
401
Q

What is osteomalacia?

A
  • Failure to ossify bones in adulthood as a result of Vit D deficiency
  • Hypo-mineralisation of trabecular & cortical bone
402
Q

How does osteomalacia present?

A

Insidiously with bone pain, proximal myopathy & hypocalcaemia

403
Q

Describe the blood results of osteomalacia?

A
  • Low calcium
  • Low phosphate
  • High alk phos
  • Low Vit D
  • Elevated PTH
404
Q

What are the 2 drug treatments for Vitamin D deficiency?

A
  1. Cholecalciferol (D3)- Vit D3

2. Alfacalcidol (i.e. active Vit D)

405
Q

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

A
  • 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
406
Q

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

A
  • 800-1600 units per day

- Or, single large dose of Ergocalciferol / D2 (150,000-300,000 units)

407
Q

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

A
  1. Renal impairment

2. Hypoparathyroidism (cannot activate Vit D in gut)

408
Q

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

A
  • Not measured by traditional lab Vit D assay (25-OHD3)

- Higher risk of hypercalcaemia

409
Q

Where is testosterone produced?

A

Leydig cells

410
Q

Describe testosterone production?

A
  • Steroid hormone
  • Circulates bound to SHBG & albumin
  • Free testosterone is active
  • Activated to more potent form in target tissues
411
Q

What 5 things does testosterone help grow?

A
  1. Sex organs
  2. Skeletal muscle (enlargement)
  3. Epiphyseal plates
  4. Larynx growth (change shape & deepen voice)
  5. 2° characteristics
412
Q

What are the 3 other effects of testosterone?

A
  1. Erythropoesis (women have a lower haemoglobin than men)

2. Behaviour

413
Q

What are the 5 adult effects of testosterone?

A
  1. Muscle mass
  2. Mood
  3. Bone mass
  4. Libido
  5. Body shape
414
Q

What are the 3 fertility effects of testosterone?

A
  1. Libido
  2. Erectile Function
  3. Spermatogenesis
415
Q

Where are spermatocytes produced?

A

Leydig & Sertoli Cells

416
Q

What do Spermatocytes mature into?

A

Spermatozoa

417
Q

Describe the purpose of Sertoli cells?

A
  • Blood-testis barrier
  • Remove damaged spermatocytes
  • Secrete androgen binding protein
418
Q

What does aromatase convert?

A

Testosterone –> Oestrogen

419
Q

Describe the control steps of gonadal function?

A

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

420
Q

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

A
  1. Slow growth in teens
  2. No pubertal growth spurt
  3. Small testes & phallus
  4. Lack of 2° sexual development
421
Q

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

A
  1. Depression/low mood
  2. Poor libido
  3. Erectile problems
  4. Poor muscle bulk/power
  5. Poor energy
422
Q

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

A
  1. Sparse body/facial hair
  2. Gynaecomastia
  3. Gynoid weight gain
  4. Great head hair
  5. Short phallus
  6. Small testes- abnormal consistency
423
Q

Describe the ICP concept of growth?

A
  • Infantile via IU growth +/- GH
  • Childhood via GH & T4
  • Pubertal via GH & Sex steroids
424
Q

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

A

Orchidometer

425
Q

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

A
  1. Height
  2. Weight
  3. History- growth, family, sexual, drug, social
  4. Examination
426
Q

What are 2 ways to test for sex steroid deficiency?

A
  1. Testosterone- Early morning. Free testosterone > 200. Total testosterone > 16. Sex hormone-binding globulin (SHBG)
  2. LH & FSH- Help determine possible pituitary cause
427
Q

How do you check for male fertility?

A

Semen analysis

428
Q

What is primary gonadal failure?

A

Testicular problem

429
Q

Describe the blood results of Hypogonadotrophic Hypogonadism?

A

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

430
Q

What are the 6 causes of Hypopituitarism?

A
  1. Pituitary tumour
  2. Pituitary surgery/radiotherapy
  3. Head injury
  4. Kallmann’s syndrome
  5. Cerebellar ataxia
  6. Genetic syndrome
431
Q

What is the commonest form of isolated gonadotrophin deficiency?

A

Kallmann’s Syndrome

432
Q

Describe Kallmann’s Syndrome?

A

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

433
Q

What can Kallmann’s syndrome be associated with?

A
  • Aplasia/hypoplasia of olfactory lobes – giving anosmia or hyposmia
  • Deafness, renal agenesis, cleft lip/palate
  • Micropenis ± cryptorchidism
434
Q

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

A
  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)
435
Q

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

A
  1. Poor growth

2. Undescended testes

436
Q

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

A
  1. Poor growth
  2. Small testes
  3. Micropenis
  4. Delayed/absent puberty features
437
Q

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

A
  1. Slow, but adequate growth
  2. Small testes
  3. Small phallus
  4. Hypogonadal features
438
Q

Describe the blood results of primary gonadal disease?

A
  • Low Testosterone
  • Normal/High LH/FSH
  • Normal prolactin
439
Q

What are 5 effects of Primary Gonadal Failure?

A
  1. Adult Leydig cell failure
  2. Cryptorchidism
  3. Complex genetic syndromes
  4. Klinefelter’s syndrome (chromosome defects)
  5. Seminiferous tubule failure
440
Q

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

A
  1. Trauma
  2. Chemotherapy
  3. Radiotherapy
  4. Multisystem disorders
441
Q

What is the commonest genetic cause of male hypogonadism?

A

Klinefelter’s Syndrome

442
Q

Describe Klinefelter’s Syndrome?

A
  • XXY (but other sex chromosome variations exist)
  • Clinically manifests at puberty
  • Increased LH & FSH but seminiferous tubules regress & Leydig cells do not function normally
443
Q

Describe testis androgen production in Klinefelter’s Syndrome?

A
  • Decreased testosterone

- Increased oestrogen

444
Q

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

A
  • Delayed puberty
  • Suboptimal genital development
  • Reduced 2° male sexual characteristics
  • Persistent gynaecomastia
  • Azospermia
  • Behavioural issues/learning difficulties
445
Q

What is the treatment for Klinefelter’s Syndrome?

A

Androgen replacement ± psychological support ± fertility counselling

446
Q

Describe the 2 parts to HypoG treatment?

A
  1. Androgen Replacement Therapy- oral, IM, Topical

2. Fertility Treatment- hCG, Recombinant LH & FSH, GnRH pumps

447
Q

What are the 6 side effects of androgen replacement therapy?

A
  1. Mood issues (aggression/behaviour change)
  2. Libido issues
  3. Increased haematocrit
  4. Possible prostate effects
  5. Acne, sweating
  6. Gynaecomastia
448
Q

Describe the drug abuse regarding testosterone therapy?

A
  • Cycling, athletics, baseball, Powerlifting
  • Complex doping regimes: Masking agents, LH/GnRH, Tamoxifen
  • ‘Natural’ supplements: ‘testosterone boosters’
449
Q

What is Bimanual synkinesia?

A
  • 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
450
Q

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

A

You cannot smell

451
Q

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

A

KAL1

452
Q

What is primary amenorrhoea?

A

Never had a period

453
Q

What are the 3 causes of amenorrhoea?

A
  1. Genitourinary abnormalities
  2. Chromosomal abnormalities ie. Turners syndrome
  3. Secondary hypogonadism (pituitary/ hypothalamic causes)
454
Q

Describe Genitourinary abnormalities causing primary amenorrhoea?

A

Congenital absence of uterus, cervix or vagina:

  • Rokitansky syndrome
  • Androgen insensitivity syndrome
455
Q

List 3 Secondary hypogonadism associated with primary amenorrhoea?

A
  1. Kallmans syndrome
  2. Pituitary disease
  3. Hypothalamic amenorrhoea ie. low BMI, stress, illness
456
Q

What is secondary amenorrhoea?

A

No periods for 6 months

457
Q

List 4 causes of secondary amenorrhoea?

A
  1. Uterine- Ashermans syndrome
  2. Ovarian- PCOS, Premature ovarian failure
  3. Pituitary- Prolactinoma, Pituitary tumour
  4. Hypothalamic- Weight loss, stress, drugs e.g. opiates
458
Q

What are the 4 other causes of amenorrhoea?

A
  1. Physiological- Pregnancy, Lactation
  2. Iatrogenic- contraception
  3. Thyroid dysfunction
  4. Hyperandrogenism- Cushing’s syndrome related to adrenal tumour, CAH, Adrenal or ovarian tumour
459
Q

What is the definition of Hirsutism?

A

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

460
Q

What are the 2 ovarian causes of hirsutism?

A
  1. PCOS- 95%

2. Androgen secreting tumour- <1%

461
Q

What are the 2 adrenal causes of hirsutism?

A
  1. Congenital adrenal hypertrophy- <1%

2. Androgen secreting tumour- <1%

462
Q

Classic presentation of PCOS is with symptoms of what?

A

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

463
Q

Describe the prevalence of PCOS?

A
  • Affects >5% women of reproductive age

- Commonest cause of anovulatory infertility (80%)

464
Q

What are the typical endocrine features of PCOS?

A

Raised testosterone & LH

465
Q

What 2 things is PCOS also associated with?

A
  1. Metabolic abnormalities

2. Increased risk of type 2 diabetes

466
Q

Describe there cause of PCOS?

A
  • Heterogeneous disorder of unclear aetiology

- Complex interaction of metabolic, hypothalamic, pituitary, ovarian & adrenal mechanisms

467
Q

What are the 3 elements of the pathophysiology of PCOS?

A
  1. Gonadotrophins (LH & FSH)
  2. Androgens
  3. Insulin resistance
468
Q

Describe the 2 gonadotrophin levels in PCOS?

A
  1. Increased LH concentration

2. Decreased FSH

469
Q

How/why is LH increased in PCOS?

A
  • Increased LH receptors in PCOS ovaries

- Support ovarian theca cells: Increased ovarian androgen production

470
Q

How/why is FSH decreased in PCOS?

A
  • Low constant levels result in continuous stimulation of follicles without ovulation
  • Decreased conversion of androgens to oestrogens in granulosa cells
471
Q

What does testosterone (androgen) come from?

A

Cholesterol

472
Q

What does testosterone turn into during androgen biosynthesis?

A

Dihydrotestosterone

473
Q

What turns into testosterone during androgen biosynthesis?

A
  • Androstenediol (from DHEA)

- Androstenedione

474
Q

What are the 3 increased androgens in PCOS?

A
  1. Testosterone
  2. Androstenedione
  3. DHEA-S
475
Q

What androgen is increased the most in PCOS?

A

Androstenedione

476
Q

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

A
  • Ovary: <5
  • Adrenal: >95
  • Peripheral conversion: 0
477
Q

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

A
  • Ovary: 60
  • Adrenal: 35
  • Peripheral conversion: 5 (from DHEA-S)
478
Q

Describe the locations of circulating Testosterone (T)

androgen in women?

A
  • Ovary: 60
  • Adrenal: 5
  • Peripheral conversion: 35 (from Androstenedione)
479
Q

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

A
  • Ovary: 0
  • Adrenal: 0
  • Peripheral conversion: 100 (from Androstenedione & Testosterone)
480
Q

What increases androgen production?

A

Theca cells under influence of LH

481
Q

What 2 disordered enzyme actions affect androgen biosynthesis?

A
  1. Ovarian enzyme expression

2. Peripheral conversion

482
Q

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

A
  • Produced in liver, binds testosterone

- Only free testosterone is biologically active: Hyperandrogenism, Hyperinsulinaemia

483
Q

What is reduced in women with PCOS/increased BMI?

A

Insulin sensitivity

484
Q

What type of women with PCOS are more symptomatic?

A

Overweight/obese

485
Q

Describe the cause vs association of insulin sensitivity in PCOS?

A
  • Insulin stimulates theca cells of ovaries
  • Insulin reduces hepatic production of sex hormone-binding globulin (SHBG)
  • Increased circulating androgens
486
Q

What are the 3 clinical factors of Polycystic Ovary Syndrome?

A
  1. Hirsutism
  2. Oligomenorrhea
  3. Polycystic ovaries
487
Q

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

A

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

488
Q

What 5 investigations would confirm the profile of PCOS?

A
  1. Testosterone
  2. Andrestenedione
  3. DHEAS
  4. SHBG
  5. FSH/LH
489
Q

What are 2 other features in PCOS that need assessed?

A
  1. Type 2 diabetes

2. Abnormal lipids

490
Q

What leads to oligo-ovulation hirsutism?

A

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

491
Q

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

A
  1. Weight loss interventions

2. Insulin sensitisers

492
Q

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

A
  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”
493
Q

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

A

Clomiphene

494
Q

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

A
  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
495
Q

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

A
  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
496
Q

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

A
  • Modest (5-10%) weight reduction associated with vast improvement in metabolic indices
  • Diet & lifestyle changes improve ovulation rate & fertility
497
Q

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

A

Decrease in renal perfusion

498
Q

What are the 5 effects of angiotensin II?

A
  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
499
Q

What produces & secretes aldosterone?

A

Adrenal glands

500
Q

What are the 3 biochemistry results which suggest aldosterone excess?

A
  1. Serum potassium <3mmol/L
  2. Urine potassium >30mmol/d
  3. Mild alkalosis
501
Q

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

A
  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
502
Q

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

A
  1. Measure renin & aldosterone
  2. Plasma renin / aldosterone ratio >35 and aldosterone >300
  3. Send quickly BUT don’t send on ice
503
Q

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

A
  • Renin: <50mIU/L (ambulant)

- Aldosterone: 100-800 pmol/L (ambulant)

504
Q

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

A

Conn’s syndrome

505
Q

What are 2 other tests for Conn’s syndrome?

A
  1. Salt loading test

2. Adrenal vein sampling

506
Q

What is the biochemistry in secondary hyperaldosteronism?

A
  • Renin & Aldosterone Increased

- Effective Circulatory Volume Decreased

507
Q

What are the 3 possible causes of secondary hyperaldosteronism?

A
  1. Heart Failure
  2. Cirrhosis of the Liver
  3. Nephrotic Syndrome
508
Q

Describe the anatomy of the adrenal glands?

A
  • Small retroperitoneal structures
  • Medial & lateral limbs
  • Cannot usually differentiate cortex from medulla on imaging
  • Upside down “Y”
509
Q

Describe adrenal adenomas on a CT scan?

A

Fatty & therefore low density

510
Q

Describe the prevalence of adrenal adenomas?

A
  • Common incidental findings

- 1-4% incidence

511
Q

Describe how you would diagnose adrenal adenomas?

A
  • Contrast CT: <30 HU diagnostic, >50% washout

- Dynamic CT: Measure density at 80 secs & 10 mins

512
Q

Describe an MRI for looking at the adrenals?

A
  • Chemical Shift imaging
  • Variations of nuclear magnetic resonance frequencies of the same kind of nucleus, due to variations in the electron distribution
513
Q

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

A

Bright yellow due to the high amount of lipids

514
Q

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

A

Melan A (brown stain)

515
Q

Describe the micro appearance of a cortical adenoma?

A

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

516
Q

What are present in Conn’s syndrome?

A

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

517
Q

Describe the micro appearance of benign adrenal tumours?

A

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

518
Q

Describe the micro appearance of a cortical carcinoma?

A
  • Large, irregular tumour cell nuclei

- Coagulative necrosis

519
Q

What is autonomous aldosterone production associated with biochemically?

A

Increased BP & decreased K+

520
Q

List 4 primary causes of mineralocorticoid excess (aldosterone)?

A
  1. Suppressed renin levels
  2. Conn’s syndrome (adenoma)
  3. Bilateral adrenal hyperplasia
  4. Adrenal carcinoma
521
Q

List 5 secondary causes of mineralocorticoid excess (aldosterone)?

A
  1. 2° to elevated renin levels
  2. Renal hypoperfusion
  3. Heart failure
  4. Cirrhosis
  5. Nephrotic syndrome
522
Q

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

A

Liquorice ingestion

523
Q

Describe Conn’s syndrome?

A

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

524
Q

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

A
  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
525
Q

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

A
  1. Methyldopa
  2. Clonidine
  3. Beta Blockers
  4. Alpha Blockers
  5. ACE inhibitors
  6. AT2RB
  7. Ca Channel antagonists
  8. Diuretics
  9. NSAIDS
526
Q

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

A
  1. Medical- Aldosterone antagonist spironolactone, multiple antihypertensive agents
  2. Surgical- Unilateral adrenalectomy
527
Q

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

A
  • Na+ decreased

- Urea increased

528
Q

Describe the 3 steps in the Synacthen test?

A
  1. Basal bloods ACTH & cortisol are taken
  2. Synacthen 250 microgram IV given
  3. After 30mins cortisol is checked
529
Q

What is a satisfactory response in the Synacthen test?

A

30min Cortisol >480 nmol/L

530
Q

Describe the adrenal glands in Addison’s disease?

A

Atrophic, small & thin

531
Q

Describe Addison’s disease?

A
  • 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
532
Q

List 6 primary causes of Addison’s disease?

A
  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
533
Q

How would you manage Addison’s disease initially?

A
  1. Hydrocortisone

2. Insulin dose titration

534
Q

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

A
  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
535
Q

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

A
  1. Weight loss
  2. Hyperpigmentation
  3. SBP<110mmHg
  4. Vitiligo 5. Hyponatraemia
  5. Hyperkalaemia
  6. Hypercalcaemia
  7. Renal Impairment
  8. Anaemia
  9. Eosinophilia
536
Q

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

A
  1. Ketoconazole
  2. Phyenytoin
  3. Barbituates
  4. Rifampicin
  5. Mitotane
  6. Metyrapone
537
Q

Describe autoimmune Addison’s disease?

A
  • Antibodies against steroidogenic enzymes (most common 21 hydroxylase)
  • Antibodies against all 3 zones of the adrenal cortex
  • Present in 86% patients
538
Q

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

A
  1. Panhypopituitarism
  2. Isolated ACTH deficiency
  3. Familial cortisol-binding globulin (CBG, transcortin) deficiency
539
Q

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

A
  1. Tumours- pituitary, met, craniophayngioma
  2. Infection- TB
  3. Inflammation- sarcoidosis, lymphocytic hypophysitis, haemochromatosis, histiocytosis X
  4. Iatrogenic- surgery, radiotherapy
540
Q

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

A
  1. Chronic high-dose glucocorticoid therapy

2. After the cure of Cushing’s syndrome

541
Q

What is Autoimmune Polyendocrine Syndrome Type 2 a combination of?

A

Triad of addison’s, AI thyroiditis & T1Dm

542
Q

Describe Autoimmune Polyendocrine Syndrome Type 2?

A
  • More common in females
  • Presents in adulthood
  • Polygenic
  • 1/6 relatives have an unsuspected illness!
543
Q

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

A
  1. PA
  2. Coeliac Disease
  3. Primary hypogonadism
  4. Alopecia
  5. MG
  6. Stiff Man Syndrome
544
Q

What are the 3 direct effects of growth hormone?

A
  1. Increased protein synthesis
  2. Reduced glucose transport & metabolism
  3. Increased lipolysis
545
Q

What is the indirect effect of growth hormone?

A

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

546
Q

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

A
  1. Sleep
  2. Exercise
  3. Stress
547
Q

What inhibits growth hormone release from the pituitary?

A

Somatostatin (IGF 1)

548
Q

What are the 2 screening tests for acromegaly?

A
  1. IGF-1 usually elevated but not diagnostic

2. OGTT for growth hormone suppression

549
Q

Describe the OGTT screening test for acromegaly?

A
  • 75g glucose
  • 2hr test
  • Normal: GH suppression to undetectable
  • Acromegaly: stays >2ug/L
550
Q

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

A
  1. Central structure
  2. Infundibulum
  3. Anterior / Posterior Pituitary
  4. Sella
  5. Parasellar Structures
551
Q

What type of imaging is best to see the pituitary?

A
  • CT useful for assessing calcification e.g craniopharyngioma
  • MRI investigation of choice
552
Q

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

A

Monoclonal antibody immune stain (brown)

553
Q

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

A
  1. Arthropathy
  2. Neuropathy
  3. Cardiovascular disease
  4. Hypertension
  5. Respiratory disease
  6. Malignancy
  7. Carbohydrate intolerance
554
Q

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

A
  • Unrelated to age of Onset
  • Usually occurs with long duration
  • Reversibility: rapid symptomatic improvement, irreversibility of bone & cartilage lesions
555
Q

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

A
  • Peripheral Nerves: Intermittent anesthesias, Sensorimotor polyneuropathy
  • Reversibility: Onion bulbs (whorls) do not regress
556
Q

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

A
  1. LV Diastolic Dysfunction decreased
  2. LV Mass Increased
  3. Arrythmias
  4. Fibrous connective tissue hyperplasia
557
Q

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

A
  • Exacerbates Cardiomyopathy

- Reversibility: May progress even if GH secretion reduced

558
Q

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

A
  • Upper airways obstruction
  • Soft tissue overgrowth
  • Reversibility: Improves with reduction on GH secretion
559
Q

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

A
  • Colonic Polpys

- Effect of therapy on risk unknown

560
Q

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

A
  • Diabetes Mellitus

- Reversibility: Improves with reduced GH secretion

561
Q

What are the 2 types of causes for acromegaly?

A
  1. Excess GH secretion

2. Excess GH releasing hormone secretion

562
Q

List 5 causes of GH secretion leading to acromegaly?

A
  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)
563
Q

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

A
  1. Central e.g. ganglioneuroma

2. Peripheral e.g. Bronchial Carcinoid, adrenal adenoma, Medullary Thyroid Carcinoma, Phaeochromocytoma

564
Q

What is the management for acromegaly?

A
  • Surgery: 50-60% normal IGF1 levels

- Radiotherapy: works over a longer time duration & may render patient pan hypo pit

565
Q

What are the 2 medical therapies for acromegaly?

A
  1. Dopamine agonists
  2. Octreotide
  3. Pegvisomant (typically given post-surgery)
566
Q

Describe Dopamine agonists in the treatment of acromegaly?

A
  • Lower serum GH & IGF1 in 10-40%

- Pituitary tumour shrinkage in 5%

567
Q

What type of drug is Pegvisomant?

A

Competitive antagonist of native GH at the cell membrane GH receptor

568
Q

What are the 9 investigations for acromegaly?

A
  1. OGF1
  2. OGTT
  3. Cortisol
  4. LH
  5. FSH
  6. Testosterone
  7. Prolactin
  8. TSH
  9. fT4
569
Q

What are the 3 options for GH excess?

A
  1. Neurosurgery- transphenoidal removal of microadenoma
  2. Medical therapy - octreotide, lanreotide (somatostatin analogues)
  3. Radiotherapy
570
Q

List the 5 complications of transphenoidal removal of microadenoma surgery?

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

MBChB Year 3 (15 decks)

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