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Phase 2a > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

What is endocrinology?

A

The study of hormones, their receptors, the intracellular signalling pathways and their associated diseases.

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2
Q

Define endocrine secretions.

A

Secretions directed into the surrounding fluid so it can enter the bloodstream/lymph and act at distant sites.

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3
Q

Define exocrine secretions.

A

Glandular secretions poured into a duct to site of action - act locally (eg. pancreas - amylase, lipase)

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4
Q

Define paracrine secretions.

A

Cellular secretions/signals that act on adjacent cells.

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5
Q

Define autocrine secretions.

A

Cellular signals/secretions that feedback on the same cell that secreted the hormone.

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6
Q

Define negative feedback.

A
  • Initial stimulus causes response
  • Response feedback for stimulus to reduce
  • Response loop shuts off
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7
Q

Define positive feedback.

A
  • Initial stimulus causes response
  • Response causes stimulus to increase
  • Response continues to increase
  • Outside factor required to shut of feedback cycle
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8
Q

What are the features of peptide hormones?

A
  • Variable size (3 to 180 amino acids)
  • Form linear or ring structures
  • May bind to carbohydrates (eg. LH, FSH)
  • Hydrophilic and water soluble
  • Stored in secretory granules
  • Released in bursts or rhythmic cycle
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9
Q

Give an example of a peptide hormone.

A

Insulin.

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10
Q

How does insulin exert its effect?

A
  1. Binding to its receptor causes phosphorylation of the intracellular tyrosine residues
  2. Offsets the tyrosine kinase signal transduction pathway
  3. Decreases plasma glucose level.
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11
Q

By which mechanisms does the action of insulin decrease blood glucose?

A
  • Translocation of Glut-4 transporter
  • Glycogen synthesis
  • Glycolysis
  • Fatty acid synthesis
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12
Q

What are the two types of amine hormones?

A
  • Tryptophan-derived amines (melatonin)
  • Tyrosine-derived amines (catecholamines and thyroid hormones)
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13
Q

Where are catecholamines secreted from?

A
  • Adrenaline and noradrenaline → Adrenal Medulla
  • Dopamine → Hypothalamus
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14
Q

How does the effect of adrenaline and noradrenaline differ?

A

Both in the sympathetic nervous system:
- Adrenaline has larger effect on the heart
- Noradrenaline has larger effect on blood vessels

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15
Q

What receptors do adrenaline and noradrenaline act upon?

A

Adrenoreceptors.

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16
Q

What effect does α-adrenoreceptor activation have on the body?

A

Vasoconstriction.

(α1 receptors mainly involve smooth muscle contraction)

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17
Q

What effect does β-adrenoreceptor activation have on the body?

A
  1. β1 increases cardiac output
    - Increases HR, conduction velocity and stroke volume
  2. β2 causes smooth muscle relaxation
    - In the bronchi, GI tract and veins (vasodilation)
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18
Q

Are iodothyronines hydrophillic or hydrophobic?

A

Hydrophobic.

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19
Q

Name the 2 iodothyronines.

A
  • Thyroxine (T4)
  • Triiodothyronine (T3)
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20
Q

Where is T4 produced?

A

T4 is produced by the thyroid gland (more abundant).

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21
Q

Where is T3 produced?

A

T4 is converted to T3 in the periphery.

(only 20% of T3 in circulation is secreted by the thyroid)

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22
Q

What enzyme converts T4 to T3 in peripheral circulation?

A

Iodothyronine deiodinase.

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23
Q

What are the two classes of steroid hormone?

A

Corticosteroids and sex steroids.

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24
Q

What are the 5 steroid hormone sub-classes?

A

Categorised in terms of the receptor they bind to:
- Glucocorticoids (corticosteroid)
- Mineralocorticoids (corticosteroid)
- Androgens (sex steroid)
- Estrogens (sex steroid)
- Progestogens (sex steroid)

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25
Q

What are steroid hormones derived from?

A

Cholesterol.

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26
Q

Are steroid hormones fat-soluble?

A

Yes.

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27
Q

How are steroid hormones transported around the body?

A

Vitamin D binding protein.

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28
Q

Describe the process of steroid hormones exerting their effect in cells.

A
  1. Diffuses through plasma membrane and binds to receptor in cytoplasm
  2. Receptor-hormone complex moves into nucleus
  3. Binding initiates transcription of gene to mRNA
  4. mRNA directs protein synthesis
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29
Q

How is steroid hormone secretion controlled?

A
  • Basal secretion can be continuous or pulsatile
  • Release inhibiting factors (dopamine inhibiting prolactin etc)
  • Releasing factors
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30
Q

Give examples of releasing factors (control of hormone secretion).

A
  • Humoral stimulus (eg. low calcium causes release of PTH)
  • Neural stimulus (SNS stimulates adrenal glands to release adrenaline)
  • Hormone stimulus (hypothalamus releases hormone to stimulate pituitary gland)
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31
Q

Define appetite and hunger.

A

Appetite = The desire to eat food.

Hunger = The need to eat food

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32
Q

Define satiety.

A

The feeling of fullness.

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33
Q

What is the equation of BMI?

A

BMI = weight (kg) / height (metres squared)

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34
Q

What are the BMI categories?

A

<18.5 = underweight
18.5 - 24.9 = normal weight
25 - 29.9 = overweight
30 - 39.9 = obese
>40 = morbidly obese

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35
Q

What does the satiety cascade tell us?

A

We have an internal physiological drive to eat - prompting thoughts of food and motivating consumption.

We also have an external physiological drive - sometimes we eat in the absence of hunger.

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36
Q

What area of the brain is important in appetite regulation?

A

The hypothalamus:
- Lateral hypothalamus = hunger centre
- Ventromedial hypothalamic nucleus = satiety centre

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37
Q

What factors are released by the gut?

A
  • Ghrelin
  • Peptide YY
  • GLP-1
  • CCK
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38
Q

Describe the features of ghrelin.

A
  • 28 AA chain with acyl side chain
  • Stimulates GH release
  • Stimulates appetite
  • Secreted from the stomach
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39
Q

Describe the features of Peptide YY.

A
  • 36 AA chain, binds to NPY receptors
  • Inhibits gastric motility
  • Reduces appetite
  • Secreted from neuroendocrine cells in the ileum, pancreas and colon
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40
Q

Describe the role of CCK.

A
  • Delays gastric emptying time
  • Gallbladder contraction
  • Insulin release
  • Acting via the vagus nerve (satiety)
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41
Q

What factors are released by adipose tissue and the pancreas?

A
  • Leptin (adipose tissue)
  • Insulin (pancreas)
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42
Q

How does Leptin decrease appetite?

A

Leptin is sensed by the arcuate nucleus of the hypothalamus, where it stimulates the release of anti-appetite factors and inhibits the release of pro-appetite factors.

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43
Q

How does decreased levels of leptin lead to obesity?

A

Through leptin gene deficiency or leptin receptor mutation.

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44
Q

What is the diagnostic criteria for Diabetes Mellitus if symptomatic?

A
  • Fasting glucose greater than or equal to 7mmol/L
  • Random glucose greater than or equal to 11mmol/L
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45
Q

What is the diagnostic criteria for Diabetes Mellitus if asymptomatic?

A

The same as if symptomatic, but must be demonstrated on two separate occasions.

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46
Q

How is HbA1c used in the diagnosis of Diabetes Mellitus?

A
  • A HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus
  • A HbA1c of less than 6.5% does not exclude diabetes (not as sensitive as fasting samples)
  • In asymptomatic patients, test must be repeated for confirmation
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47
Q

When is Type 1 Diabetes Mellitus usually diagnosed?

A

Commonly between 5-15 years of age, but can occur at any age.

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48
Q

What is the prevalence of Type 1 Diabetes Mellitus?

A

Relatively rare: 3/1000 among children and adolescents, ~300,00 patients in the UK.

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49
Q

What are the presenting features of Type 1 Diabetes Mellitus?

A
  1. Thirst - osmotic activation of hypothalamus
  2. Polyuria - osmotic diuresis
  3. Weight loss - lipid and muscle loss due to unrestrained gluconeogenesis
  4. Hunger - lack of energy resources
  5. Blurred vision - altered acuity due to uptake of glucose/water
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50
Q

Which three main features indicate Type 1 Diabetes Mellitus?

A
  • Weight loss
  • Short history of severe symptoms
  • Moderate or large urinary ketones
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51
Q

Give 5 complications associated with Diabetes Mellitus.

A
  1. Diabetic Retinopathy
  2. Diabetic Nephropathy
  3. Stroke
  4. Cardiovascular disease
  5. Diabetic Neuropathy
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52
Q

What are the other types of Diabetes (other than Type 1 and 2)?

A
  • Maturity Onset Diabetes of Youth (MODY)
  • Pancreatic Diabetes
  • “Endocrine Diabetes” (acromegaly/Cushings)
  • Malnutrition related Diabetes
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53
Q

Describe the pathogenesis of Type 1 Diabetes Mellitus.

A

An insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction.

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54
Q

Why is it becoming more difficult to differentiate between Type 1 and 2 Diabetes?

A
  • Increased levels of obesity (T2DM is being diagnosed in younger patients)
  • T1DM patients are more likely to be obese
  • Uncontrolled T2DM can present with weight loss and ketonuria
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55
Q

How can we distinguish between Type 1 and 2 Diabetes Mellitus?

A
  • Early onset in childhood
  • BMI normal or below the normal range
  • Acute onset of osmotic symptoms
  • Prone to ketoacidosis
  • High levels of islet autoantibodies
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56
Q

What are the aims of treatment for Type 1 Diabetes Mellitus?

A
  • Relieve symptoms
  • Prevent DKA
  • Prevent microvascular disease and macrovascular complications
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57
Q

What are the microvascular complications of Type 1 Diabetes Mellitus?

A
  • Around 30% in the UK will develop diabetic nephropathy
  • Those with nephropathy tend to develop proliferative retinopathy and severe neuropathy
  • Can have a major effect on quality of life
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58
Q

What is the role of basal insulin in Type 1 Diabetes Mellitus therapy?

A
  • Control glucose between meals and at night
  • Adjusted to maintain fasting blood glucose between 5-7mmol/L
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59
Q

What is the best treatment for Type 1 Diabetes Mellitus?

A

Intensive basal-bolus insulin therapy.

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60
Q

What is the role of bolus insulin?

A

To manage glucose according to carbohydrate intake and pre-meal glucose.

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61
Q

Why should we introduce insulin to those with Type 2 Diabetes Mellitus?

A

Progressive damage to pancreatic beta-cells resulting in poor glucose control requires insulin therapy.

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62
Q

Which type of insulin is initiated first in Type 2 Diabetes Mellitus?

A

Usually basal insulin.

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63
Q

What is useful about prandial insulins?

A

Faster action means they can be adapted to the meal that is eaten.

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64
Q

What are the 3 approaches to insulin therapy in Type 2 Diabetes?

A
  • Once daily basal insulin
  • Twice daily mix-insulin
  • Basal-bolus therapy
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65
Q

What is hypoglycaemia?

A

Low plasma glucose causing impaired brain function.

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66
Q

What are the clinical definitions of hypoglycaemia?

A
  • Mild: self-treated (many episodes are asymptomatic)
  • Severe: required help for recovery
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67
Q

What are the glucose values for neutropenia and hypoglycaemia?

A

Neutropenia - 3mmol/L

Hypoglycaemia - 3.9mmol/L

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68
Q

What are the classifications of hypoglycaemia?

A
  • Level 1 (plasma glucose under 3.9mmol/L, no symptoms)
  • Level 2 (plasma glucose under 3.0mmol/L)
  • Non-severe symptomatic (mild hypoglycaemia)
  • Severe symptomatic (severe hypoglycaemia)
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69
Q

What are the common autonomic symptoms of hypoglycaemia?

A
  • Trembling
  • Palpitations
  • Sweating
  • Anxiety
  • Hunger
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70
Q

What are the common neuroglycopenic symptoms of hypoglycaemia?

A
  • Difficulty concentrating
  • Confusion
  • Weakness
  • Drowsiness/dizziness
  • Vision changes
  • Difficulty speaking
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71
Q

What are the other non-specific symptoms of hypoglycaemia?

A

Nausea and headache.

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72
Q

What is significant about the relationship between HbA1c levels and hypoglycaemic episodes?

A

The higher the HbA1c levels, the higher the glucose levels can be when the patient experiences a hypoglycaemic episode.

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73
Q

What are the risk factors for severe hypoglycaemia in Type 1 Diabetes?

A
  • History of severe episodes
  • HbA1c > 48mmol/L
  • Long duration of diabetes
  • Renal impairment
  • Impaired awareness of hypoglycaemia
  • Extremes of age
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74
Q

What are the risk factors for hypoglycaemia in Type 2 diabetes?

A
  • Advancing age
  • Cognitive impairment
  • Depression
  • Aggressive treatment of glycaemia
  • Impaired awareness of hypoglycaemia
  • Duration of multidose insulin therapy
  • Renal impairment and other comorbidities
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75
Q

What normally prevents hypoglycaemia?

A

Counter-regulatory hormones
- Glucagon
- Adrenaline

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76
Q

How might counter-regulatory hormones fail to prevent hypoglycaemia?

A

The threshold for secretion of counter-regulatory hormones can be altered, allowing for a lower value of glucose to be maintained and risking hypoglycaemia.

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77
Q

What is the impact of non-severe hypoglycaemia?

A
  • Reduced quality of life
  • Fear of hypoglycaemia
  • Mental illness comorbidity
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78
Q

What are the consequences of hypoglycaemia?

A
  • Accidents
  • Fear
  • Quality of life
  • Prevents desirable HbA1c targets
  • Cognitive dysfunction
  • Seizures/coma
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79
Q

What forms part of the screening for risk of severe hypoglycaemia?

A
  • Low HbA1c
  • Long duration of diabetes
  • History of previous hypoglycaemia
  • Impaired awareness of hypoglycaemia
  • Daily insulin dose
  • Physically active
  • Impaired renal function
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80
Q

What is a red flag for impaired awareness of hypoglycaemia?

A

Onset of symptoms below 0.3mmol/L in blood glucose monitoring.

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81
Q

When and what should patients be educated on hypoglycaemia?

A
  • If they are on insulin or sulphonylureas
  • How to identify and treat symptoms
  • Reporting episodes to doctor or educator
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82
Q

What is the treatment for hypoglycaemia?

A
  1. Recognise symptoms
  2. Confirm need for treatment with plasma glucose test
  3. Treat with 15g fast-acting carbohydrate to relieve symptoms
  4. Retest in 15 minutes to ensure blood glucose > 4mmol/L and retreat if needed
  5. Eat a long-acting carb to prevent the recurrence of symptoms
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83
Q

What hormone regulates the increase in serum calcium?

A

Parathyroid hormone (PTH)

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84
Q

Where does PTH secretion occur?

A

Chief cells in parathyroid glands
- Possess calcium-sensing receptors on the cell surface

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85
Q

How does PTH act on bone to increase serum calcium?

A

Stimulates osteoclasts to release ionic Ca2+ for reabsorption

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86
Q

How does PTH act on the kidneys to increase serum calcium?

A
  • ↑ passive calcium reabsorption by the PCT - only 1% excreted
  • ↓ phosphate reabsorption - 20% excreted
  • ↑ 1-alpha-hydroxylation of vitamin D to form 1,25-dihydroxyvitamin D (facilitates calcium absorption in the intestines)
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87
Q

How does PTH act on the intestines to increase serum calcium?

A

↑ calcium absorption via 1,25-dihydroxyvitamin D

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88
Q

Which hormone regulates the decrease in serum calcium?

A

Calcitonin.

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89
Q

Where does Calcitonin secretion occur?

A

C-cells in the thyroid - stimulated by increased serum calcium.

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90
Q

How does Calcitonin decrease serum calcium?

A
  • Reduces bone resorption by inhibiting osteoclast activity
  • Reduce renal reabsorption
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91
Q

How else is serum calcium regulated?

A

Negative feedback - increased serum PTH leads to reduced secretion.

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92
Q

What is the normal level of serum calcium?

A

2.2 to 2.6 mmol/L

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93
Q

What level of serum calcium is regarded as mild-moderate hypocalcemia?

A

1.9 to 2.2 mmol/L

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94
Q

What level of serum calcium is regarded as severe hypocalcaemia?

A

< 1.9 mmol/L

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95
Q

What are the clinical features of hypocalcaemia?

A
  • Paraesthesia - abnormal skin sensation
  • Tetany - spasms of the hands, feet, larynx (premature labour)
  • Seizures
  • Basal ganglia calcification
  • Cataracts
  • Chvostek and Trousseau signs
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96
Q

What is Chvostek sign?

A

Tap over the facial nerve, looking for spasm of the facial muscles.

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97
Q

What is the Trousseau sign?

A

Inflate blood pressure cuff to 20mmHg above systolic for 3-5 minutes - look for carpopedal spasm.

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98
Q

What ECG abnormality suggests possible hypocalcaemia?

A

Long QT interval:
- Primarily the prolonging of the ST segment.
- Slow ventricular repolarisation due to reduced calcium entering the cell through L-type channels.

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99
Q

Why does Vitamin D deficiency cause hypocalcaemia?

A

Inactive Vitamin D is converted to 1,25-dihydroxyvitamin D, which facilitates absorption by the gut.

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100
Q

Give 2 examples of conditions associated with hypoparathyroidism.

A
  • Acute pancreatitis (increased calcitonin release)
  • Di George Syndrome
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101
Q

What is DiGeorge Syndrome?

A

A developmental abnormality of the third and fourth branchial pouches of the pharyngeal arches:
- Hypoparathyroidism
- Immunodeficiency
- Cardiac defects
- Cleft palate

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102
Q

What is pseudohypoparathyroidism?

A

A condition associated with the resistance of the body to PTH.

Causes Type 1 Albright hereditary osteodystrophy, which presents with the following signs:
- Short stature
- Obesity
- Round facies
- Mild learning difficulties
- Subcutaneous ossification
- Short fouth metacarpals

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103
Q

What level of serum calcium is regarded as mild hypercalcaemia?

A

2.7 to 2.9 mmol/L

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104
Q

What level of serum calcium is regarded as moderate hypercalcaemia?

A

3.0 to 3.4 mmol/L

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105
Q

What level of serum calcium is regarded as severe hypercalcaemia?

A

> 3.4 mmol/L

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106
Q

What are the clinical features of hypercalcaemia?

A
  • Bones - osteoporosis, osteoitis fibrosa cystica
  • Stones - renal stones
  • Groans - neurological symptoms
  • Moans - constipation, nausea
  • Polyuria (thirst)
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107
Q

What ECG abnormality suggests possible hypercalcaemia?

A

Short QT interval
- Primarily the shortening of the ST segment
- Faster ventricular repolarisation due to increased calcium entering the cell through L-type channels

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108
Q

What are the causes of hypercalcaemia?

A

90% of the time caused by malignancies or hyperparathyroidism.

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109
Q

What is primary hyperparathyroidism?

A

Hyperparathyroidism casued by:
- Sporadic single benign adenoma (97%)
- Parathyroid hyperplasia (2.5%)
- Parathyroid carcinoma (0.5%)

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110
Q

What is secondary hyperparathyroidism?

A

The result of another condition that lowers blood calcium levels, affecting parathyroid function.

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111
Q

What is tertiary hyperparathyroidism?

A

A result of chronic secondary hyperparathyroidism (eg. kidney failure)

High levels of PTH production over a long period of time result in parathyroid hyperplasia, causing PTH overproduction, increasing serum calcium above physiological range.

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112
Q

What is puberty?

A

Puberty describes the physiological, morphological and behavioural changes as the gonads switch from infantile to adult forms.

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113
Q

What are the definitive signs of puberty?

A

Girls - menarche (first menstrual bleed)

Boys - first ejaculation

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114
Q

What controls the development of secondary sexual characteristics?

A

Girls:
- Ovarian oestrogens (growth of breasts and genitalia)
- Ovarian and adrenal androgens (pubic and axillary hair)

Boys:
- Testicular androgens (external genitalia, pubic hair growth, enlargement of larynx and laryngeal muscles)

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115
Q

What are the tanner stages?

A

A scale of physical development through puberty.

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116
Q

What is the volume of testes that signifies> the commencement of puberty?

A

> 3ml (>2.5cm in longest diameter)

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117
Q

What is used to measure testicular volume in ml?

A

Orchidometer.

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118
Q

What is Thelarche and what initiates it?

A

Breast development, initiated by oestrogen.

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119
Q

How long does Thelarche take to complete?

A

3 years.

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120
Q

What are the effects of oestrogen on breast tissue?

A
  • Ductal proliferation
  • Site specific adipose deposition
  • Enlargement of the areola and nipple
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121
Q

What other hormones are involved in breast development?

A
  • Prolactin
  • Glucocorticoids
  • Insulin
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122
Q

Describe the maturation of the uterus.

A
  • Corpus:cervix ratio flips from 1:2 to 2:1
  • Changes from tubular shape to pear shape
  • Increases in length and volume
  • Endometrium thickens
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123
Q

Describe the maturation of the ovaries.

A
  • Volume increases
  • Change from non-functional to multicystic
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124
Q

What are the Mullerian structures?

A
  • Fallopian tubes
  • Uterus
  • Uterine cervix
  • Superior aspects of the vagina
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125
Q

Describe the maturation of the vagina.

A
  • Becomes a duller red
  • Epithelium thickens
  • Cornification of the superficial layer of stratified squamous epithelium
  • pH changes from neutral to acidic
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126
Q

Describe the maturation of the external genitalia caused by oestrogen.

A
  • Labia majora and minora increase in size and thickness
  • Rugation and change in colour of labia majora
  • Hymen thickens
  • Clitoris enlarges
  • Vestibular glands begin secretion
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127
Q

Describe the maturation of the external genitalia caused by adrenal and ovarian androgens.

A

Growth of pubic hair.

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128
Q

What is adrenarche?

A
  • Maturation process of the adrenal gland
  • Specialised subset of cells arises forming the androgen producing zona reticularis
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129
Q

When does adrenarche occur?

A
  • Peri-puberty
  • Premature or exaggerated adrenarche can occur up to 2 years prior to puberty
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130
Q

What hormone is associated with adrenarche?

A
  • DHEA
  • DHEA-S
  • Both precursors of androgens
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131
Q

What happens physiologically during adrenarche?

A
  • Mild advance in bone age
  • Axillary hair growth
  • Mild acne
  • Body odor
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132
Q

What is precocious puberty?

A

Early puberty.

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133
Q

Which population of patients is more likely to have ‘true’ precocious puberty?

A

Up to 80% of patients are female.

If male patients present with precocious puberty, differential diagnoses (brain tumour) should be ruled out before a diagnosis of idiopathic puberty is given.

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134
Q

What is precocious pseudopuberty?

A

Resembles puberty, but not from normal hypothalamus activation.

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135
Q

What can cause precocious pseudopuberty?

A
  • Adrenal sex hormones excess
  • hCG Secreting Tumours
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136
Q

What is the main cause of delayed puberty?

A

Idiopathic - delayed activation of the hypothalamic pulse generator (more common in men).

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137
Q

How is idiopathic delayed puberty diagnosed?

A

Diagnosis of exclusion.

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138
Q

What is relevant in the family history for idiopathic delay in growth and puberty?

A
  • Late menarche in mother or sister
  • Delayed growth spurt in father
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139
Q

What is hypogonadotropic hypogonadism?

A

Kallman Syndrome - sexual infantilism related to gonadotropin deficiency.

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140
Q

What is hypergonadotrophic hypogonadism?

A

Primary gonadal failure.

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141
Q

What do delays in puberty lead to?

A
  • Delay in acquisition of secondary sex characteristics
  • Psychological problems
  • Defects in reproduction
  • Reduced peak bone mass
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142
Q

What are indications for investigation for delayed puberty in girls?

A
  • Lack of breast development by age 13
  • More than five years between breast development and menarche
  • Lack of pubic hair by 14
  • Absent menarche by age 15-16
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143
Q

What are indications for investigation for delayed puberty in boys?

A
  • Lack of testicular enlargement by age 14
  • Lack of pubic hair by age 15
  • More than 5 years to complete genital enlargement
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144
Q

What does onset of puberty correlate to?

A

Bone age.

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145
Q

What should be considered when taking a history? (Delayed puberty)

A
  • Totally absent, or started then stopped
  • Family history
  • Review of symptoms
  • Perinatal history
  • Prior medical illnesses
  • Medication
  • Psychosocial deprivation
  • Neurological symptoms
  • Cancer history
  • Testicular injury
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146
Q

What can X-rays help identify? (Puberty)

A
  • Bone age
  • Delayed bone age in growth hormone
  • Advanced bone age in precocious puberty
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147
Q

What is primary gonadism?

A
  • AKA hypergonadotrophic hypogonadism
  • Gonads not responding to stimulus so hypothalamus and pituitary are more stimulated
  • FSH/LH will both be high
  • Sex hormones will be low
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148
Q

What is secondary hypogonadism?

A

An issue with the pituitary.

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149
Q

What is tertiary hypogonadism?

A

An issue with the hypothalamus

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150
Q

What are the causes of hypogonadotropic hypogonadism?

A
  • CNS disorders (eg. tumours)
  • Isolated Gonadotropin Deficiency (eg. Kallmann’s Syndrom)
  • Miscellaneous disorders (eg. Prader-Willi syndrome)
  • Idiopathic and genetic hormone deficiencies
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151
Q

Which sex is more affected by Kallmann syndrome?

A
  • Mainly male patients
  • 4:1 ratio M:F
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152
Q

What symptoms are associated with Kallmann syndrome?

A

Anosmia.

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153
Q

What causes Kallmann syndrome?

A
  • Failure of migration of GnRH neurones from the hypothalamus to the pituitary
  • X-linked, autosomal recessive or dominant
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154
Q

What are the main conditions that fall under hypergonadotrophic hypogonadism?

A
  • In men: Klinefelter’s syndrome (47XXY)
  • In women: Turner’s syndrome and its variants
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155
Q

What is Turner’s syndrome?

A
  • 45X0
  • Loss of an X chromosome
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156
Q

What risks are associated with Kleinfelter syndrome?

A

20-fold increased risk of breast cancer.

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157
Q

What replacement therapy options exist for women?

A
  • Ethinyloestradiol (tablet)
  • Oestrogen (tablet/transdermal)
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158
Q

What replacement therapy options exist for men?

A
  • Testosterone enanthate (IM) - most common
  • Testosterone transdermal becoming more common
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159
Q

What are the general symptoms of hypothyroidism?

A
  • Weight gain
  • Tiredness
  • Constipation
  • Cold intolerance
  • Poor concentration
  • Poor sleep pattern
  • Dry skin
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160
Q

Give examples of primary causes of hypothyroidism.

A
  • Autoimmune conditions
  • Hashimotos
  • Atrophic thyroiditis
  • Prior surgery
  • Drugs (eg. amiodarone)
  • Iodine deficiency
  • Congenital
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161
Q

Give examples of transient causes of hypothyroidism.

A
  • Post partum thyroiditis
  • Subacute thyroiditis
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162
Q

Give a secondary cause of hypothyroidism.

A

Hypopituitarism.

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163
Q

What drugs can commonly cause hypothyroidism?

A
  • Iodine, inorganic or organic iodide
  • Iodinated contrast agents
  • Amiodarone
  • Lithium
  • Thionamides
  • Interferon alpha
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164
Q

Give some consequences of hypothyroidism during pregnancy.

A
  • Gestational hypertension and pre-eclampsia
  • Placental abruption
  • Post partum haemorrhage
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165
Q

Give some consequences to the baby if hypothyroidism during pregnancy is untreated.

A
  • Low birth weight
  • Preterm delivery
  • Neonatal goitre (swelling of thyroid)
  • Neonatal respiratory distress
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166
Q

Which drug is used to treat hypothyroidism?

A

Synthetic L-thyroxine (T4) - 1.6mg/kg

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167
Q

How does the monitoring of TSH and T4 differ in primary and secondary/tertiary hypothyroidism?

A

Primary - monitor TSH
- L-thyroxine (T4) is titrated until TSH is within normal range

Secondary/tertiary - monitor serum T4
- TSH will always be low

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168
Q

How is pre-existing hypothyroidism treated during pregnancy?

A
  • Preconception counselling (ideal preconception TSH <2.5 mlU/L)
  • Increase thyroxine dose by 30%
  • Arrange thyroid function tests in early pregnancy
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169
Q

How are new presentations of overt hypothyroidism treated during pregnancy?

A

Aim to normalise ASAP
- Start thyroxine 50-100mcg and measure thyroid function every 4-6 weeks

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170
Q

What is Subclinical Hypothyroidism?

A

Early mild form of hypothyroidism characterised by high TSH levels but free T4 and T3 are normal.

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171
Q

What groups of people undergo targeted screening for hypothyroidism during pregnancy?

A
  • Age > 30
  • BMI > 40
  • Miscarriage preterm labour
  • Personal or family history
  • Goitre
  • Type 1 diabetes
  • Head and neck irradiation
  • Amiodarone, lithium or contrast use
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172
Q

What is hyperthyroidism?

A

High serum thyroid hormones caused by;
- Overproduction of thyroid hormone
- Leakage of preformed hormone from thyroid
- Ingestion of excess thyroid hormone

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173
Q

What are common symptoms of hyperthyroidism?

A
  • Weight loss
  • Heat intolerance
  • Sweating
  • Diarrhoea
  • Tachycardia
  • Anxiety
  • Tremor
  • Menstrual disturbance
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174
Q

How do the clinical signs of primary and secondary hyperthyroidism differ?

A

Primary:
- Increased (free) T4
- Increased (free) T3
- Reduced TSH

Secondary:
- Increased (free) T4
- Increased (free) T3
- Excessively high TSH

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175
Q

Give some examples of causes of hyperthyroidism.

A

85-90% due to Graves disease.

Less commonly caused by:
- Toxic adenoma or multi nodular goitre
- Gestational thyrotoxicosis
- Trophoblastic neoplasia
- TSHoma

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176
Q

What is Graves’ disease?

A

An autoimmune disease characterised by the development of TSH-receptor activating antibodies - leading to hyperthyroidism.

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177
Q

Give some clinical manifestations of Graves’ disease.

A
  • Diffuse goitre (enlargement of entire thyroid)
  • Thyroid eye disease
  • Pretibial myxoedema
  • Acropachy - soft tissue swelling of hands and clubbing of fingers
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178
Q

What is pretibial myxoedema?

A

An excess of glycosaminoglycans in the dermis and subcutis of the skin resulting in waxy, orange appearance of the skin.

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179
Q

What drugs most commonly cause hyperthyroidism?

A
  • Iodine, inorganic or organic iodide
  • Radiocontrast agents
  • Amiodarone
  • Lithium
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180
Q

Give some consequences of hyperthyroidism during pregnancy if inadequately treated.

A
  • Intrauterine growth resistance (IUGR)
  • Low birth weight
  • Pre-eclampsia
  • Preterm delivery
  • Risk of stillbirth and miscarriage
181
Q

What drugs are used to treat hyperthyroidism?

A
  • Beta-blockers (eg. propranolol) - symptomatic treatment
  • Anti-thyroid medication (Thionamides)
182
Q

How do thionamides work?

A

They prevent thyroid peroxidase enzyme coupling and iodinating tyrosine residues on thyroglobulin, reducing T3 and T4.

183
Q

Name common side effects of thionamides in the treatment of hyperthyroidism.

A
  • Rash
  • Arthralgia
  • Neuritis
  • Thrombocytopenia
  • Hepatitis
  • Vasculitis
  • Agranulocytosis
184
Q

What is Foetal Thyrotoxicosis?

A

Transplacental transfer of thyroid-stimulating autoantibodies from mother to fetus. Autoantibodies bind to the fetal TSH receptors and increase secretion of thyroid hormones.

Begins around the 20th week and is managed with anti-thyroid medication.

185
Q

What complications is Foetal Thyrotoxicosis associated with?

A
  • IUGR
  • Foetal goitre
  • Foetal tachycardia
  • Preterm delivery
  • Foetal demise
186
Q

What is Gestational Thyrotoxicosis?

A

A transient form of thyrotoxicosis caused by excessive stimulation of thyroid gland by hCG. Leads to raised free T4 but low TSH.

Limited to the first 12-16 weeks of pregnancy.

187
Q

What complications is Gestational Thyrotoxicocis associated with?

A
  • Multiple gestation
  • Hydatidiform mole
  • Hyperplacentosis
  • Choriocarcinoma
188
Q

What changes in metabolism occur during pregnancy?

A
  • ↑ erythropoetin, cortisol, and noradrenaline
  • ↑ cardiac output
  • ↑ plasma volume
  • High cholesterol triglycerides
  • Pro-thrombotic and inflammatory state
  • Insulin resistance
189
Q

What medical conditions are associated with pregnancy?

A
  • Pre-eclampsia (hypertension associated with seizures)
  • Obstetric cholestasis
  • Gestational hyperthyroidism
  • Postpartum thyroiditis
  • Gestational diabetes
  • Transient diabetes insipidus
  • Post-natal depression
  • Post-natal autoimmune disease
190
Q

Describe thyroid gland development.

A
  • Foetal thyroid follicles and thyroxine synthesis occurs at 10 weeks
  • Foetal thyroid axis matures at 15-20 weeks
  • Foetus is reliant on maternal T4 for the first trimester
191
Q

What changes to mother’s thyroid function occur during the first trimester?

A
  • ↑ Thyroid Binding Globulin (TBG)
  • ↑ HCG - stimulates TSH receptor
  • ↑ Free T4 and total T4
  • ↑ Iodine clearance
  • ↓ TSH
192
Q

What changes to foetal thyroid function occur throughout pregnancy?

A

First trimester:
- Initial ↑ in TBG, total and free T4 and TSH

Second trimester:
- ↑ in total T3

Third trimester:
- ↑ in free T3

193
Q

What type of hormones are TSH, LH, FSH and hCG?

A

Glycoprotein hormones. They have the same α-subunit but a different β-subunit.

194
Q

What is the normal range for TSH during each trimester?

A

First trimester - 0.1-2.5 mIU/L
Second trimester - 0.2-3.0 mIU/L
Third trimester - 0.3-3.0 mIU/L

195
Q

What is Amiodarone?

A

A potent anti-arrhythmic used in individuals with AF.

196
Q

Why does amiodarone commonly cause thyroid dysfunction?

A
  • High in iodine (37% by weight)
  • Lipid soluble
  • Long elimination half life
197
Q

What two thyroid complications are commonly induced by amiodarone?

A
  • Amiodarone Induced Hypothyroidism (AIH)
  • Amiodarone Induced Thyrotoxicosis (AIT)
198
Q

What is Amiodarone-Induced Hypothyroidism?

A

Amiodarone has an inhibitory effect on thyroid hormone synthesis, leading to the downregulation of peripheral receptors and hypothyroidism.

199
Q

What is Type 1 Amiodarone-Induced Thyrotoxicosis?

A

Increased synthesis and release of thyroid hormone-induced by drug-related iodine excess.

Usually associated with pre-existing thyroid disease.

200
Q

What is Type 2 Amiodarone-Induced Thyrotoxicosis?

A

Destruction of the thyroid caused by direct toxicity of amiodarone.

Characterised by excessive release of thyroid hormones without excessive production.

201
Q

What does vasopressin bind to?

A
  • GPCR
  • V1a in vasculature
  • V2 in renal collecting tubules
  • V1b in brain
202
Q

What controls the release of vasopressin?

A
  • Osmoreceptors in the hypothalamus (routine)
  • Baroreceptors in the brain stem and great vessels (emergency)
203
Q

Define osmolality.

A

Concentration per kilo.

204
Q

What drives osmolality?

A
  • The number of molecules
  • Size irrelevant (a molecule of sodium has the same effect as a molecule of albumin)
205
Q

What molecules are present at a high enough concentration to affect osmolality?

A
  • Sodium
  • Potassium
  • Chloride
  • Bicarbonate
  • Urea
  • Glucose
206
Q

What exogenous molecules can affect osmolality?

A
  • Alcohol
  • Methanol
  • Polyethylene glycol
  • Manitol
207
Q

What is the normal osmolality range?

A

282-295 mOsmol/kg

208
Q

How is osmolality calculated?

A
  • 2x [Na] mmol/L
  • [Glucose] mmol/L
  • [Urea] mmol/L
  • All added together - sodium doubled to take into account anions associated with it
209
Q

What drives the gap between calculated and actual osmolality?

A
  • Usually due to alcohol
  • 1-10 mOsmol/kg gap
210
Q

What is the mechanism of action of vasopressin in the kidney?

A
  • Acts on the V2 receptors
  • Stimulates an intracellular cascade
  • Aquaporin-2 proteins are synthesised and inserted into the apical membrane
  • Permeability to water is increased
  • Increased reabsorption of water
211
Q

What are the signs of Diabetes Insipidus?

A
  • Polyuria
  • Polydypsia
  • No glycosuria
212
Q

What are the diagnostic parameters for diabetes insipidus?

A
  • > 3L urine per day
  • Check renal function
  • Check serum calcium
213
Q

What are the biochemical signs of Diabetes Insipidus?

A
  • Inappropriately dilute urine for plasma osmolality
  • Serum osmolality >300 and urine osmolality >200
  • Normonatraemia or hypernatremia
  • Water deprivation test
214
Q

What is Cranial Diabetes Insipidus?

A

Lack of vasopressin.

215
Q

What are the acquired causes of Cranial Diabetes Insipidus?

A
  • Idiopathic
  • Tumours (eg. Craniopharyngioma)
  • Trauma
  • Infections (TB, Encephalitis, Meningitis)
  • Vascular (aneurysm, infarction)
  • Inflammatory (neurosarcoidosis etc)
216
Q

What are the primary causes of Cranial Diabetes Insipidus?

A
  • Genetic (DIDMOAD)
  • Developmental (septic-optic dysplasia)
217
Q

What is Nephrogenic Diabetes Insipidus?

A

Resistance to vasopressin action.

218
Q

What are the acquired causes of Nephrogenic Diabetes Insipidus?

A
  • Osmotic diuresis (Diabetes Mellitus)
  • Drugs (Lithium, Demeclocycline, Tetracycline)
  • Chronic renal failure
  • Post-operative uropathy
  • Metabolic (hypercalcaemia, hypokalaemia)
  • Infiltrative (amyloid)
219
Q

What are the familial causes of Nephrogenic Diabetes Insipidus?

A
  • X-links (V2 receptor defect)
  • Autosomal (aquaporin 2 defect)
220
Q

How is Cranial Diabetes Insipidus managed?

A
  • Treatment of underlying condition
  • Desmopressin (tablets, nasal spray or injection)
221
Q

How is Nephrogenic Diabetes Insipidus managed?

A
  • Try to avoid precipitating drugs
  • Congenital diabetes insipidus is very difficult to manage
222
Q

What is the definition of hyponatraemia and when is it considered severe?

A
  • Serum sodium <135mmol/L
  • Severe is serum sodium <125mmol/L
223
Q

What is the normal range for sodium?

A

137-144mmol/L

224
Q

What is the difference between acute and chronic hyponatraemia and how does this affect its management?

A

Acute (48 hours):
- Rapid correction is safer and may be necessary

Chronic (CNS adapts):
- Correction must be slow
- <8mmol/24hr

225
Q

What are the features of Sydrome of Innapropriate Antidiuretic Hormone Secretion?

A
  • Too much vasopressin
  • Low osmolality
  • Plasma sodium low
  • Urine inappropriately concentrated
  • Water retention - ECF volume increased mildly
  • Increased GFR
  • Normal thyroid and adrenal function
  • Less sodium reabsorbed in PCT
226
Q

What are the clinical features of SIADH?

A
  • Normal circulating volume
  • No oedema
227
Q

What are the main causes of SIADH?

A
  • CNS disorders
  • Tumours
  • Respiratory causes
  • Drugs
228
Q

What are the treatment goals for SIADH?

A
  • Allow/facilitate increase in serum sodium
  • Treat the underlying condition
  • Identify and stop any causative drug
  • If acute - daily U&Es
  • If chronic - weekly to monthly U&Es
  • Sodium >130mmol/L
229
Q

What is the management of SIADH?

A
  • Diagnose and treat underlying condition
  • Fluid restriction <1L/24hr
  • If sodium <125mmol/L - hypertonic N/Saline
  • < 8-10mmol/L - increase in sodium per 24 hours
230
Q

When would you consider administering hypertonic saline?

A

Symptomatic hyponatraemia.

231
Q

What precautions should be taken when giving hypertonic saline?

A

Not to increase sodium by more than 10mmol/L in the first 24 hours and 18mmol/L in the first 48 hours.

232
Q

Give 3 details of the Anterior Pituitary.

A
  • Glandular tissue
  • Accounts for 75% of total weight
  • Develops from the roof of the mouth (Rathke’s pouch)
233
Q

Give 3 details of the Posterior Pituitary.

A
  • Nerve tissue
  • Contains axons that originate in the hypothalamus
  • Nerves from the floor of the 3rd ventricle
234
Q

What anatomical structures make up the Parasellar Area?

A
  • Pituitary gland
  • Hypothalamus
  • Optic chiasm
  • Pituitary stalk
235
Q

Name some common pituitary mass lesions.

A
  • Non-functioning pituitary adenoma
  • Endocrine active pituitary adenomas
  • Functional and non-functional pituitary carcinoma
  • Metastases in pituitary (breast, lung, stomach, kidney)
  • Pituitary cysts
236
Q

What is a Non-Functioning Pituitary Adenoma? (NFPA)

A

A benign growth in the pituitary gland that does not produce excessive hormones.

237
Q

What is the incidence of NFPAs?

A
  • Account for 10-15% of primary intracranial tumours
  • Account for 14-28% of clinically relevant pituitary adenomas
  • Usually diagnosed between 20-60 years
238
Q

When is surgery considered for removal of an NFPA?

A

If the tumour is progressively invasive:
- Large size
- Invasion of the cavernous sinus
- Lobulated suprasellar margins

Also if the tumour is near the optic chiasma, or pituitary apoplexy (may bleed into optic chiasm)

239
Q

What is a Craniopharyngioma?

A

A rare type of brain tumour derived from pituitary gland embryonic tissue.

240
Q

Where does a Craniopharyngioma arise from?

A

Squamous epithelial remnants of Rathke’s pouch.

241
Q

What are the clinical subtypes of Craniopharyngiomas?

A
  • Adamantinous (classical)
  • Papillary
242
Q

What is an Adamantious Craniopharyngioma?

A
  • Cystic lobulated tumour filled with thick, oily protein rich blood products and/or cholesterol
  • Presents with calcification
  • Consists of reticular epithelial cells with an appearance similar to enamel pulp of developing teeth
243
Q

Which group is Adamantious Craniopharyngioma more common in?

A

Children.

244
Q

What is a Squamous Papillary Craniopharyngioma?

A
  • Well circumscribed, formed of masses of metaplastic squamous cells
  • Tumour is more solid (wet keratin is absent and calcification is rare)
245
Q

Are Squamous Papillary Craniopharyngioma more common in children or adults?

A

Almost exclusively found in adults.

246
Q

What are the symptoms associated with Craniopharyngioma?

A
  • Headaches and raised ICP
  • Visual defects
  • Hormonal imbalances
  • Behavioural change (due to frontal or temporal extension)
247
Q

Give examples of hormonal imbalances caused by Craniopharyngioma.

A
  • Short stature and delayed puberty in children
  • Decreased libido
  • Amenorrhea
  • Diabetes Insipidus
248
Q

What is a Rathke’s Cyst?

A
  • Non-neoplastic tumour comprised of a single layer of epithelial cells
  • Mucoid, cellular or serous components in cyst fluid
  • Occur as sella or suprasella tumours
249
Q

Where do Rathke’s Cysts arise from?

A

Cuboidal epithelium remnants of the Rathke’s pouch.

250
Q

What are the symptoms of Rathke’s Cysts?

A
  • Most are small and asymptomatic
  • Headache
  • Amenorrhea
  • Hypopituitarism
  • Hydrocephalus
251
Q

What is a meningioma?

A

A tumour forming from the three membranous layers of the meninges.

252
Q

Describe the features of Meningiomas?

A
  • The commonest tumour of the region after pituitary adenoma
  • Slow growing
  • 90% benign
  • Often a complication of radiotherapy
253
Q

What are the symptoms of a Meningioma?

A
  • Loss of visual activity
  • Visual field defects (eg. diplopia)
  • Endocrine dysfunction
  • Focal seizures
254
Q

What is Lymphocytic Hypophysitis?

A

The pituitary gland becomes infiltrated by lymphocytes, resulting in pituitary enlargement and impaired function.

255
Q

What are the clinical subtypes of Lymphocytic Hypophysitis?

A
  • Adenohypophysitis (LAH) - autoimmune inflammation of the anterior pituitary
  • Infundibuloneurohypophysitis (LINH) - autoimmune inflammation of the posterior pituitary lobe
  • Panhypophysitis - inflammation of the entire pituitary gland
256
Q

Is LAH more common in men or women?

A

Women - 6:1 ratio

257
Q

What is the average age of presentation for LAH?

A
  • Women → 35 years (often associated with pregnancy or postpartum
  • Men → 45 years
258
Q

Name some of the local consequences of pituitary tumours.

A
  • Visual field defects
  • Headaches
  • Cranial nerve palsy
  • Temporal lobe epilepsy
  • CSF Rhinorrhoea
259
Q

How would you investigate pituitary tumour-related visual field defects?

A

Red pin test.

260
Q

Why is testing for normal pituitary function difficult?

A
  • Secretes many hormones (GH, LH, FSH, ACTH, TSH, ADH)
  • May have deficiency of one or all
  • Circadian rhythms and pulsatile nature of secretions
261
Q

What is the common guiding principle for pituitary function?

A

If the peripheral target organ is working normally, the pituitary is functioning normally.

262
Q

Name some associated conditions of Growth Hormone deficiency.

A
  • Short stature
  • Abnormal body composition
  • Reduced muscle mass
  • Poor quality of life
263
Q

Name some associated conditions of LH/FSH deficiency.

A
  • Hypogonadism
  • Reduced sperm count
  • Infertility
  • Menstruation problems
264
Q

Name an associated condition of TSH deficiency.

A

Hypothyroidism.

265
Q

Name some associated conditions of ACTH deficiency.

A
  • Adrenal failure
  • Decreased pigment
266
Q

Name some associated conditions of ADH deficiency.

A
  • Diabetes insipidus
  • Decreased water absorption in kidney
  • Polyuria and polydipsia
267
Q

When would you use an MRI for radiological evaluation of pituitary tumours?

A

Visualisation of soft tissues and vascular structures
- T1-weighted images of fatty structures
- T2-weighted images for high water content structures

(No exposure to ionising radiation)

268
Q

When would you use a CT scans for radiological evaluation of pituitary tumours?

A
  • Visualisation of bony structures and calcifications within soft tissue
  • Better at determining diagnosis of tumours with calcification (eg. germinomas, craniopharyngiomas and meningiomas)
269
Q

What are the disadvantages of CT scanning compared with MRI?

A
  • Less optimal for soft tissue
  • Exposure to radiation
  • Requires use of an intravenous contrast medium
270
Q

What are the clinical signs of Primary Hypothyroidism?

A

Raised TSH with low free T4.

271
Q

What are the clinical signs of Hypopituitarism? (Differences between men and women)

A
  • Low free T4 with normal/low TSH.
  • Low testosterone with low/normal LH and FSH.
  • Low oestradiol with normal/low LH and FSH.
  • Low cortisol with low/normal ACTH.
272
Q

What are the clinical signs of Graves’ disease?

A

Suppressed TSH and high free T4.

273
Q

What are the clinical signs of Thyrotropinoma (TSHoma)?

A

High free T4 with normal/high TSH.

274
Q

What are the clinical signs of hormone resistance?

A

High free T4 with normal/high TSH.

275
Q

What are the clinical signs of primary hypogonadism in men?

A

Low testosterone with raised LH/FSH.

276
Q

What are the clinical signs of anabolic steroid use?

A

Suppressed LH with testosterone.

277
Q

What are the expected oestradiol and LH/FSH levels in plasma before puberty?

A
  • Oestradiol very low/undetectable
  • Low LH and FSH (FSH slightly higher than LH)
278
Q

What are the expected oestradiol and LH/FSH levels in plasma after puberty?

A
  • Pulsatile LH increases
  • Oestradiol increases
279
Q

What are the expected oestradiol and LH/FSH levels in plasma during the monthly menstrual cycle?

A
  • Mid-cycle surge in LH and FSH
  • Oestradiol increases throughout the cycle
280
Q

What are the clinical signs of Primary Ovarian Failure?

A
  • High LH and FSH (FSH higher than LH)
  • Low oestradiol
281
Q

What are the clinical signs of Primary Adrenal Sufficiency?

A
  • Low cortisol with high ACTH
  • Poor response to synacthen
282
Q

How is a Water Deprivation Test conducted?

A
  1. Deprive the patient of water and measure serum and urine osmolality:
    - If the patient has Diabetes Insipidus serum osmolality will increase but urine osmolality will remain normal
  2. The patient is given Desmopressin:
    - If the patient has Cranial DI - plasma osmolality decreases and urine osmolality increases
    - If the patient has Nephrogenic DI - plasma osmolality increases and urine osmolality remains low
283
Q

How is Growth Hormone deficiency treated?

A

Growth Hormone Replacement Therapy
- Injection everyday
- Aiming for mid-range IGF-1 levels

284
Q

How is LH/FSH deficiency treated in women?

A

Oestrogen Replacement Therapy
- Oral oestrogen or combined with progesterone
- Alleviate symptoms including flushes, night sweats and vaginal atrophy
- Reduces risk of CVD, osteoporosis and mortality

285
Q

How is LH/FSH deficiency treated in men?

A

Testosterone Replacement Therapy
- Different types of formulations eg. gels, injections, oral
- Must carefully monitor testosterone levels, FBC and Prostate Specific Antigen
- Improves bone mineral density, libido, function and energy levels

286
Q

How is TSH deficiency treated?

A

Levothyroxine tablets (1.6micrograms/kg/day)
- Aim to establish mid to upper half of reference range
- Higher doses usually required in patients on oestrogen or in pregnancy

287
Q

How is ACTH deficiency treated?

A

Hydrocortisone Replacement Therapy
- Current therapy is inadequate in establishing circadian release of hydrocortisone
- Adequacy varies with gut length and transit time

288
Q

How is ADH deficiency treated?

A

DDAVP (Desmopressin therapy)
- Different formulations eg. subcutaneous, oral, intranasal, sublingual
- Adjusted according to symptoms
- Must monitor sodium levels

289
Q

What is Acromegaly?

A

A condition caused by an excess of growth hormone which occurs in adulthood, following epiphyseal fusion.

290
Q

What is gigantism?

A

A condition caused by an excess of growth hormone which occurs in childhood, prior to epiphyseal fusion.

Defined by height >2SD for the patients age and sex

291
Q

What is the mean age of diagnosis of Acromegaly?

A

44 years - mean duration of symptoms is 8 years.

292
Q

Describe the Growth Hormone Axis.

A
  • GHRH released from the arcuate nucleus of the hypothalamus to the anterior pituitary
  • GH released from somatotropic cells of the anterior pituitary
  • ILG-1 released from the liver, negative feedback but promotes somatostatin release
293
Q

What is the major cause of Acromegaly?

A

Pituitary adenomas account for >90% of cases
- Other causes include excess secretion of GH from an ectopic source and hypothalamic dysfunction

294
Q

What are the key clinical features of Acromegaly?

A
  • Headaches
  • Visual changes (bitemporal hemianopia)
  • Large lips and nose
  • Protruding jaw
  • Large hands and feet
  • Hyper-pigmentation

(Acromegaly is typically has an insidious onset and is often diagnosed late)

295
Q

What tests are done for diagnosis of acromegaly and its complications?

A
  • Serum IGF-1 (GH varies, IGF-1 remains constant)
  • Glucose tolerance test (release of GH is linked to blood glucose levels, high glucose inhibits GH secretion)
  • Pituitary MRI (looking for pituitary adenomas)
296
Q

What are the criteria for diagnosing acromegaly?

A
  • Excluded if random GH <0.4ng/ml and normal IGF-1
  • If either are abnormal progress to 75mg glucose tolerance test (GTT)
  • Acromegaly excluded if IGF-1 and GTT lowers GH <1ng/ml
297
Q

What are some common comorbidities of acromegaly?

A
  • Hypertension and heart disease
  • Sleep apnoea
  • Insulin-resistant diabetes
  • Arthritis
  • Cerebrovascular events and headache
298
Q

What types of management can be offered to patients with acromegaly?

A
  • Surgery (first line)
  • Radiotherapy
  • Medical therapy
299
Q

Describe surgical treatment of acromegaly.

A

Surgery to remove the pituitary adenoma
- Microadenomas tend to have better results than macro adenomas (more dangerous to remove)
- Recurrence is common (~10%)

300
Q

Describe radiotherapy treatment of acromegaly.

A

Generally reserved for cases in which surgery fails
- Biochemical response to radiotherapy can be slow (> 10 years)
- Usually combined with medical therapy
- May cause hypopituitarism, therefore avoided in patients of reproductive age

301
Q

Describe medical therapy treatment of acromegaly.

A

Somatostatin receptor agonists (eg. Octreotide or Lanreotide)
- Can be used as primary therapy but usually used as a bridge to surgery
- Somatostatin is a negative regulator of GH
- Other options include dopamine agonists and growth hormone antagonists

302
Q

What cell type is a prolactinoma made up of?

A

Lactotrophs.

303
Q

What condition can prolactinomas lead to?

A

Hyperprolactinemia - excess levels of prolactin in the blood.

304
Q

What else can cause hyperprolactinemia?

A
  • Hypothalamic-pituitary stalk damage
  • Drug-induced eg. anti-psychotics
  • Pregnancy and lactation
  • Systemic disorders eg. CKD
305
Q

What are the key clinical features of prolactinoma?

A

Local effects:
- Headache
- Visual field defect
- CSF leak

Systemic effects of prolactin:
- Menstruation irregularity
- Infertility
- Low libido
- Low testosterone and erectile dysfunction in males
- Hypogonadism

306
Q

How can prolactinoma be diagnosed?

A
  • MRI scan
  • Prolactin levels in the blood (especially in patients with galactorrhea, irregular menses, infertility or impaired sexual function in men)
307
Q

How are prolactinomas managed?

A

Medical therapy > surgery
- Endogenous DA secretion suppresses prolactin secretion
- Dopamine agonists shrink macroadenomas, reducing pressure on the optic chiasma

308
Q

What are the 5 types of radiotherapy?

A
  • Conventional
  • Stereotactic
  • Gamma knife
  • LINAC
  • Proton beam
309
Q

What factors make it difficult for people with diabetes to sustain effective self management?

A
  • Risk of hypoglycaemia
  • Too arduous a treatment
  • Interference with lifestyle
  • Lack of sufficient training from diabetes teams
310
Q

What happens to your patient if you miss a T1DM diagnosis?

A

Fat metabolism and formation of ketones
- Reduced insulin leads to fat breakdown and formation of glycerol and FFA
- FFAs impair glucose uptake and are oxidised to form ketone bodies

311
Q

How does ketoacidosis manifest and how does the body respond?

A
  1. Absence of insulin and rising counterregulatory hormones = increased hyperglycaemia and rising ketones
  2. Glucose and ketones escape in the urine, leading to osmotic diuresis
  3. Ketones cause anorexia and vomiting
  4. Vicious cycle of increasing dehydration, hyperglycaemia and increasing acidosis (eventually leading to circulatory collapse)
312
Q

Summarise Diabetic Ketoacidosis.

A

DKA is caused by uncontrolled lipolysis which results in an excess of free fatty acids that are ultimately converted to ketone bodies.

313
Q

What are the common causes of DKA?

A
  • Infection (20-30%)
  • Missed insulin doses (10-15%)
  • Previously undiagnosed diabetes (10%)
  • Myocardial infarction (1%)
  • Unknown (40-50%)
314
Q

What is the diagnostic criteria for DKA?

A
  • Blood ketones are >3.0 mmol/L or there is ketonuria
  • Blood glucose in >11.1 mmol/L or known diabetes
  • Bicarbonate (HCO3) is <15.0 mmol/L and/or venous pH is <7.3

(All 3 are required for diagnosis of DKA)

315
Q

What are the symptoms of DKA?

A
  • Abdominal pain
  • Drowsiness/confusion
  • Polyuria and polydipsia
  • Dehydration
  • Hypotension and tachycardia
  • Kussmaul respiration
  • Acetone-smelling breath
316
Q

How is DKA managed?

A
  • Fluid replacement (isotonic saline)
  • Insulin (IV infusion 0.1unit/kg/hour)
  • Correction of hypokalaemia
  • Long-acting insulin should be continued, short-acting should be stopped
  • Treat the underlying cause (eg. infection or MI)
317
Q

What are some complications of DKA?

A
  • Gastric stasis
  • Thromboembolism
  • Arrhythmias
  • Iatrogenic due to incorrect fluid therapy (eg. cerebral oedema)
  • Acute respiratory distress syndrome
  • Acute kidney injury
  • Aspiration pneumonia
318
Q

What are some symptoms of hypoglycaemia?

A
  • Loss of concentration, confusion and coma (acute deprivation of glucose leading to cerebral dysfunction)
  • Sweating, tremors, palpitations and hunger (release of glucagon and adrenaline)
319
Q

What is the hormonal response to hypoglycaemia?

A

The first response of the body is decreased insulin secretion, followed by increased glucagon secretion.

GH and cortisol are also released but later.

320
Q

What does MODY stand for?

A

Maturity-Onset Diabetes of the Young

321
Q

What specific gene mutations give rise to the different types of MODY?

A
  • Transcription factor MODY
  • Glucokinase (GCK) gene mutation (MODY 2)
322
Q

When is “Permanent Neonatal Diabetes (PNDB)” diagnosed?

A

< 6 months
Neonates may present with:
- Small size
- Epilepsy
- Muscle weakness

323
Q

What causes Maternally Inherited Diabetes and Deafness (MIDD)?

A

A mutation in mitochondrial DNA.

324
Q

What are the features of MIDD?

A
  • Loss of beta cell mass
  • Overweight
  • Sensorineural hearing loss
  • Similar presentation to T2DM
325
Q

What is lipodystrophy?

A
  • An abnormal distribution of sat in the body, usually due to a selective loss of adipose tissue
  • Associated with severe insulin resistance, dyslipidemia, hepatic stenosis etc
  • Often missed diagnosis in men (may appear more muscular)
326
Q

Why can acute pancreatitis result in hyperglycaemia?

A

Inflammation of the pancreas may cause transient hyperglycaemia due to increased glucagon secretion.

327
Q

What commonly causes chronic pancreatitis?

A

Chronic use of alcohol - alters secretions and forms proteinaceous pugs that block ducts

Treat by stopping alcohol intake and starting insulin.

328
Q

What disease is described as an accumulation of iron in various organs (eg. liver, pituitary and pancreas)?

A

Hereditary haemochromatosis (HH)
- Autosomal recessive
- A triad of cirrhosis, diabetes and bronzed hyperpigmentation
- Treat with insulin

329
Q

What other deposition disease can cause diabetes?

A
  • Amyloidosis
  • Cystinosis
330
Q

What is a common cause of death relating to the pancreas?

A

Pancreatic Neoplasia
- Patients can get their pancreas removed but will require sub-cutaneous insulin
- Prone to hypoglycaemia due to loss of glucagon

331
Q

How can cystic fibrosis lead to diabetes?

A
  • Defective CFTR gene leads to thick mucus secretions which can block ducts and lead to pancreatic fibrosis
  • 25-50% of CF patients will have diabetes
  • Treated with insulin
  • Ketoacidosis is rare
332
Q

How might insulin benefit a CF patient (other than treating diabetes)?

A
  • Improve body weight
  • Reduce infections
  • Improve lung function
  • Improval in quality of life and potentially survival
333
Q

How can acromegaly cause diabetes?

A
  • Insulin resistance rises
  • Impairs insulin action in the liver and peripheral tissue
  • Presents similar to T2DM
334
Q

How can Cushing’s syndrome cause diabetes?

A
  • Increased insulin resistance and reduced glucose uptake into peripheral tissues
  • Hepatic glucose production is increased through stimulation of gluconeogenesis
335
Q

Name some drugs that can induce diabetes.

A
  • Steroids
  • Thiazides
  • Protease inhibitors (HIV)
  • Antipsychotics
336
Q

What makes up there HPA axis?

A
  • Hypothalamus
  • Pituitary
  • Adrenal glands
337
Q

What are the hormones involved in the HPA axis?

A
  • Cortisol (released from adrenal glands, acts on pituitary and hypothalamus)
  • Corticotrophin-releasing hormone (released from hypothalamus, acts on pituitary)
  • Adrenocorticotrophic hormone (release from pituitary and acts on adrenal glands)
338
Q

When do you get peaks of cortisol?

A
  • On waking up
  • Lunchtime
  • Dinnertime
339
Q

What resets the circadian rhythm clock?

A

Light.

340
Q

What is the secondary messenger from central to peripheral clocks?

A

Glucocorticoids.

341
Q

Give a cause of primary adrenal insufficiency.

A

Addison’s disease (autoimmune).

342
Q

Give a cause of secondary adrenal insufficiency.

A

Hypopituitarism.

343
Q

Give a cause of tertiary adrenal insufficiency.

A

Suppression of HPA axis (may be due to steroids).

344
Q

What are the symptoms of adrenal insufficiency?

A
  • Fatigue
  • Weight loss
  • Poor recovery from illness
  • Adrenal crisis
  • Headache
345
Q

What past medical history is associated with adrenal insufficiency?

A
  • TB
  • Post partum bleed
  • Cancer
346
Q

What family history is associated with adrenal insufficiency?

A
  • Autoimmunity
  • Congenital disease
347
Q

What drug history is associated with adrenal insufficiency?

A
  • Steroid use
  • Etomidate
  • Ketoconazole
348
Q

What are the clinical signs of adrenal insufficiency?

A
  • Pigmentation
  • Pallor
  • Hypotension
349
Q

Describe the biochemistry of a patient with adrenal insufficiency.

A
  • Low sodium
  • High potassium
  • Eosinophilia
  • Borderline elevated TSH
350
Q

What investigations are done to diagnose adrenal insufficiency?

A
  • 09:00 Cortisol and ACTH
  • Renin/aldosterone (elevated in Primary AI)
  • Synacthen test
351
Q

Describe the results of 09:00 cortisol and ACTH test.

A
  • Cortisol > 450-500 mol/L - Insufficiency unlikely
  • Cortisol < 100 mol/L - High likelihood of insufficiency
  • ACTH >22 pmol/L - Primary adrenal insufficiency
  • ACTH < 5 pmol/L - Secondary adrenal insufficiency
352
Q

Describe the Synacthen test.

A
  • Stimulation test
  • Synacthen is synthetic ACTH
  • 250 micrograms IV measure at 0 and 30 mins
  • Cortisol > 450-550 nmol/L - AI unlikely
353
Q

What are the common causes of Primary Adrenal Insufficiency?

A
  • Adrenal antibodies
  • Very long chain fatty acids
  • 17-OHP
  • Imaging
  • Genetic
354
Q

What are the common causes of Secondary Adrenal Insufficiency?

A
  • Using steroids
  • Imaging
  • Genetic
355
Q

What is the treatment for an adrenal crisis?

A
  • Take bloods to test for ACTH and cortisol
  • Immediate hydrocortisone (100mg IV, IM)
  • Fluid resuscitation (1L N/saline 1 hour)
  • Hydrocortisone (50-100mg IV/IM 6 hourly)
  • When stable, wean to normal replacement
  • If Primary, give fludocortisone
356
Q

What should patients with adrenal sufficiency carry with them?

A

10x 10mg tablets hydrocortisone

357
Q

When ill, what should patients with adrenal insufficiency do to their steroid dose?

A
  • If unwell with fever or flu-like symptoms - double dose
  • If in doubt - double dose
358
Q

What should patients with adrenal insufficiency do if they’re vomiting and cannot take their medication?

A

Emergency injection of hydrocortisone 100mg IM.

If unable to inject, 20mg of hydrocortisone 6 hourly and repeat if vomited. Go to A&E.

359
Q

Why should hydrocortisone be administered without prejudice to patients with adrenal insufficiency?

A

It can’t harm the patient but can be life-saving.

360
Q

What is the recommended glucocorticoid replacement therapy?

A

Hydrocortisone 15-25mg in 2-3 divided doses.

361
Q

When should glucocorticoid replacement therapy be taken?

A
  • First on waking
  • Second at midday
  • Third at 17:00
362
Q

When should prednisolone be administered? (Glucocorticoid replacement therapy)

A
  • 3-5mg/day orally once or twice a day
  • Patients with reduced compliance
363
Q

When should cortisol levels be checked? (Glucocorticoid replacement therapy)

A

Suspected malabsorption or rapid clearance.

364
Q

Why should a dose be adjusted? (Glucocorticoid replacement therapy)

A

According to symptoms of under or over replacement.

365
Q

What’s the usual dose for mineralocorticoid treatment?

A
  • 50-300 micrograms once or twice daily
  • Start with 100-150 micrograms
366
Q

What is the aim of mineralocorticoid treatment?

A

Renin should be in the upper half of the normal range.

367
Q

What is monitored during mineralocorticoid treatment?

A
  • Urea and Electrolytes
  • Blood pressure
  • Salt craving
368
Q

When would you change the dose of mineralocorticoid treatment?

A

Increase - sweating due to hot climate or exercise

Decrease - Hypotension

369
Q

When is DHEA given and what is the dose?

A

Women with low libido and low energy levels (25-50mg daily).

370
Q

What does DHEA do?

A

Provides normal body hair in young women with adrenal insufficiency.

371
Q

What is measured and monitored as part of androgen replacement therapy?

A
  • DHEA levels
  • Watch out for signs and symptoms of excess androgens
372
Q

A high HbA1c % increases your risk of developing which conditions?

A
  • Diabetic retinopathy (DR)
  • Nephropathy
  • Severe non-proliferative or proliferative DR
  • Neuropathy
  • Microalbuminuria
373
Q

What are the 3 main objectives of T2DM treatment?

A
  1. Reducing blood glucose
  2. Reduce the risk of CVD morbidity and mortality, CKD and microvascular complications
  3. Weight reduction, increase in physical activity and decreasing dietary fat
374
Q

What is the mechanism of action for metformin?

A
  1. ↑ insulin sensitivity by enhancing peripheral glucose uptake through inducing phosphorylation of GLUT-4 enhancer factor
  2. ↓ hepatic gluconeogenesis (via a complex cell signalling pathway)
375
Q

What effect does metformin have on weight?

A

Slight decrease in weight, usually weight neutral.

376
Q

Are there any notable side effects of metformin?

A
  1. Gestational upset
  2. Lactic acidosis
377
Q

Why are we starting to move away from sulphonylureas as 2nd line treatment for T2DM?

A

Patients experiencing increased weight gain.

378
Q

What is the mechanism of action for sulphonylureas?

A
  1. Stimulate the release of insulin by pancreatic beta cells
  2. Inititates cellular depolarisation to cause an influx of Ca2+ into the cell
  3. Increased fusion of insulin granulae with cell membrane = release of insulin
379
Q

Are there any notable side effects of sulphonylureas?

A
  1. Hypoglycaemia
  2. Weight gain
  3. Hyponatraemia
380
Q

Give 2 examples of sulphonylureas.

A
  1. Gliclazide
  2. Glimepiride
381
Q

What is the mechanism of action SGLT-2 inhibitors?

A

Inhibit Na/Glu cotransporters (SGLT-2) to inhibit reabsorption of glucose by the kidney (PCT).

382
Q

What effect do SGLT-2 inhibitors have on weight?

A

Typically result in weight loss.

383
Q

Are there any notable side effects of SGLT-2 inhibitors?

A
  1. Increased risk of UTI
  2. Increased risk of candidiasis (thrush)
384
Q

Give some examples of SGLT-2 inhibitors.

A
  1. Canagliflozin
  2. Dapagliflozin
  3. Empagliflozin
385
Q

What is the mechanism of action of GLP-1 analogues?

A
  1. GLP-1 is excreted by L-cells upon ingestion of food
  2. GLP-1 inhibits glucagon release, stimulating insulin release and decreasing blood glucose
  3. GLP-1has a short half-life so GLP-1 analogues can be administered to mimic its action
  4. Induces a delay in gastric emptying
386
Q

Effects of GLP-1 analogues are mediated by which receptor?

A

GLP-1 receptor.

387
Q

What effect to GLP-1 analogues have on weight?

A

Typically result in weight loss.

388
Q

How are GLP-1 analogues administered?

A

S.C injection only.

389
Q

Are there any notable side effects of GLP-1 analogues?

A
  1. Induces nausea and vomiting
  2. Increased risk of pancreatitis
390
Q

Give some examples of GLP-1 analogues?

A
  1. Exenatide (S.C injection within 60 minutes before meals)
  2. Liraglutide (only needs to be given once daily)
391
Q

What is the mechanism of actions of DPP-4 inhibitors?

A
  1. Dipeptidyl-peptidase 4 is an enzyme present in vascular endothelial lining
  2. It inactivates GIP and GLP-1
  3. DPP-4 inhibitors are competitive antagonists of DPP-4, enhancing the effects of GIP and GLP-1
  4. Little effect of gastric emptying
392
Q

Effects of DPP-4 inhibitors are mediated via which receptor?

A

Multiple types of receptors.

393
Q

What effect do DPP-4 inhibitors have on weight?

A

Very little effect (weight neutral).

394
Q

Are there any notable side effects of DPP-4 inhibitors?

A

Generally well tolerated, less likely to cause nausea and vomiting, but increases risk of pancreatitis.

395
Q

Give 2 examples of DPP-4 inhibitors.

A
  1. Vildagliptin
  2. Sitagliptin
396
Q

What is the mechanism of action of Thiazolidinones (TZD)

A
  1. Increased adipogenesis and fatty acid uptake
  2. Leads to altered gene expression = increased storage of FFA
  3. Other cells become more dependent on glucose for respiration and increase their uptake of glucose
397
Q

What effect to TZD have on weight?

A

Induce weight gain.

398
Q

Are there any notable side effects of TZD?

A
  1. Weight gain
  2. Fluid retention
  3. Contraindicated in congestive cardiac failure, fracture risk and macula oedema
  4. Increased CV risk
399
Q

What is the only licensed TZD?

A

Pioglitazone.

400
Q

What are the two types of bariatric surgery and which is more common?

A

Roux-en-Y bypass and sleeve gastrectomy - bypass is more effective and more widely used.

401
Q

How does Diabetes Mellitus cause morbidity and mortality?

A
  • Acute hyperglycaemia which can lead to hyperglycaemic hyperosmotic state or DKA
  • Chronic hyperglycaemia can cause tissue damage and complications
  • Side effects of treatment (hypoglycaemia)
402
Q

What are the macrovascular complications of Diabetes Mellitus?

A
  • Stroke
  • CVD (leading cause of mortality)
  • Peripheral vascular disease
403
Q

What percentage of diabetes patients experience diabetic neuropathy?

A

30-50%

404
Q

What are the symptoms and signs of diabetic neuropathy?

A
  • Paraesthesia (abnormal sensation due to peripheral nerve damage)
  • Allodynia (abnormal pain response)
  • Orthostatic hypotension (postural)
  • Cardiac autonomic neuropathy
  • Charcot foot (weakening of the bones)
405
Q

What is the treatment for diabetic neuropathy?

A

DN is a non-reversible condition therefore treatment is symptomatic.

406
Q

Describe the progression of diabetic neuropathy.

A
  • Glows and stocking sensory loss
  • Starts in the tips of fingers and toes and works its way up
407
Q

What are the risk factors for diabetic neuropathy?

A
  • Hypertension
  • Smoking
  • Poor glycaemic control
  • Diabetic duration
  • BMI
  • Triglycerides
  • Total cholesterol
408
Q

What is the treatment for painful diabetic neuropathy?

A
  • Good glycemic control
  • Tricyclic antidepressants/SSRIs
  • Anticonvulsants
  • Opioids
  • Transcutaneous nerve stimulation
  • Psychological interventions (hypnosis)
409
Q

What screening tests are available for diabetic neuropathy?

A
  • Test sensation (10gm monofilament)
  • Vibration perception (tuning fork, biothesiometer)
  • Ankle reflexes
410
Q

What percentage of patients with diabetes experience foot ulceration?

A

15%

411
Q

What is the risk associated with diabetic foot ulceration?

A
  • Amputations
  • 15 fold increase in risk of amputation
412
Q

What are the stages in the disease process that lead to amputation in diabetic foot ulceration?

A
  1. Neuropathy
  2. Trauma
  3. Ulcer
  4. Failure to heal
  5. Infection
  6. Amputation
413
Q

What are the signs of a ‘high-risk foot’?

A
  • Peripheral neuropathy (painless and dry)
  • Peripheral vascular disease
  • Deformity (increases pressure on the foot)
414
Q

Where is peripheral vascular disease most common?

A

Distal sites.

415
Q

What causes peripheral vascular disease in diabetes?

A

Macrovascular disease.

416
Q

What are the symptoms and signs associated with peripheral vascular disease?

A
  • Intermittent claudication
  • Rest pain
  • Diminished or absent pedal pulses
  • Coolness of feet or toes
  • Poor skin and nails
  • Absence of hair on feet and legs
417
Q

What is the treatment for peripheral vascular disease?

A
  • Quit smoking (more effective than surgical intervention)
  • Walk through the pain (distance before claudication can increase)
  • Surgical intervention
418
Q

What are the risk factors for diabetic retinopathy?

A
  • Long duration of diabetes
  • Poor glycaemic control
  • Hypertension
  • Insulin treatment
  • Pregnancy
419
Q

Who’s eligible for retinopathy screening?

A

Patients with diabetes over the age of 11.

420
Q

How does diabetic retinopathy get graded?

A

R0 - None detected
R1 - Background changes (screened annually)
R2 - Pre-proliferative (screened 6-monthly)
R3 - Proliferative (interventions to protect vision)
M - Maculopathy
P - Photocoagulation (laser treatment has been done)
U - Unclassifiable

421
Q

What is the treatment for diabetic retinopathy?

A
  • Laser therapy
  • Aim is to stabilise the changes
  • Target abnormal blood vessels to stop them bleeding
  • Does not improve sight
422
Q

What are the risks of treatment for diabetic retinopathy?

A
  • Difficulty with night vision
  • Loss of peripheral vision
  • Temporary drop in acuity
  • Vitreous haemorrhage (very rare)
  • Benefits far outweigh the risks
423
Q

How successful is the treatment for diabetic retinopathy?

A

Very effective - 90% of severe eye sight loss is prevented by early treatment.

424
Q

What is the hallmark of diabetic nephropathy?

A

Proteinuria.

425
Q

What is diabetic nephropathy a major risk for?

A

Cardiovascular Disease.

426
Q

What does diabetic nephropathy lead to?

A

Progressive decline in renal function.

427
Q

What are the risk factors for diabetic nephropathy?

A

Poor blood pressure and blood glucose control.

428
Q

What is the pathophysiology of diabetic nephropathy?

A
  • Glomerulus changes
  • Increased injury of glomerulus
  • Filtration of proteins
  • Diabetic nephropathy
429
Q

How is diabetic nephropathy classified?

A

Monitor levels of albumin excreted in urine:
- Normoalbuminuria
- Microalbuminuria
- Macroalbuminuria

430
Q

What can lead to a false positive in a diabetic nephropathy test (spot collection)?

A
  • Exercise
  • Infection
  • Fever
  • Congestive heart failure
  • Marked hypertension
  • Pregnancy or menstruation
  • UTI
  • Haematuria
431
Q

How is diabetic nephropathy graded?

A

Chronic kidney disease classification:
- Grade 1 = Kidney damage with reduced eGFR
- Grade 2 = Mild CKD
- Grade 3 = Moderate CKD
- Grade 4 = Severe CKD
- Grade 5 = End-stage renal failure

432
Q

When does diabetic nephropathy develop in T1DM?

A

Around 10 years after diagnosis.

433
Q

When does diabetic nephropathy develop in T2DM?

A

Can be present when diagnosed.

434
Q

What is the treatment for diabetic nephropathy?

A
  • Blood pressure control
  • Glycaemic control
  • Angiotensin recepotr blockers (ARBs)
  • ACE inhibitors (ACEi)
  • Proteinuria control
  • Cholesterol control
435
Q

Where does glucose come from in the fasting state?

A

The liver (and a bit from the kidneys).

436
Q

What are the insulin levels in the fasting state like?

A

Low.

437
Q

What do muscles use for fuel in the fasting state?

A

Free fatty acids.

438
Q

What do rising glucose levels in the post-prandial state lead to?

A
  • Inhibition of glucagon secretion
  • Stimulation of insulin release
439
Q

What happens to glucose in the post-prandial state?

A

40% goes to the liver, 60% to the periphery (mostly to muscle).

440
Q

What does a high level of insulin and glucose in the post-prandial state promote?

A

Inhibition of lipolysis and the levels of free fatty acids decrease.

441
Q

What is the site of insulin and glucagon secretion?

A

Islets of Langerhans in the pancreas.

442
Q

Which cells are responsible for insulin and glucagon release?

A

Alpha cells - glucagon
Beta cells - insulin

443
Q

What is important about the paracrine function of insulin?

A

The release of insulin acts on ⍺-cells, inhibiting the release of further glucagon - this is often lost in diabetes.

444
Q

What is the action of insulin on fat and muscle cells?

A
  • Stimulates the mobilisation of GLUT4 channels to the cell membrane
  • Allows entry of glucose into the cell
445
Q

What is the action of insulin?

A
  • Suppresses hepatic glucose output (decreases glycogenolysis and gluconeogenesis)
  • Increased glucose uptake into insulin-sensitive tissues (eg. muscle and fat)
  • Suppresses lipolysis and breakdown of muscle
446
Q

What is the action of glucagon?

A
  • Counterregulatory hormone
  • Increases hepatic glucose output (increased glycogenolysis and gluconeogenesis)
  • Reduce peripheral glucose uptake
  • Stimulates peripheral release of gluconeogenic precursors
447
Q

What is the pathogenesis of Type 1 DM?

A
  • Autoimmune destruction of pancreatic beta-cells leading to an insulin deficiency
  • Beta-cells express HLA antigens on MHC in response to an environmental event
  • Activates a chronic cell-mediated immune response leading to chronic insulitis
448
Q

What happens to insulin metabolism in T1DM?

A
  • Loss of beta-cells means insulin secretion is compromised
  • Leads to continued glycogenolysis in the liver etc
  • Glucose concentration increases, leading to excretion of glucose in urine as renal reuptake routes are saturated
449
Q

Failure to treat T1DM with insulin leads to what?

A
  • Increase in circulating glucagon (increasing glucose)
  • Perceived stress leads to increase in cortisol and adrenaline
  • Progressive catabolic state and increased levels of ketones

Phase 2a (11 decks)

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