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LCRS Year 2 > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

What hormones are produced by the adenohypophysis?

A 
FSH/LH
Prolactin
Growth hormone
Thyroid stimulating hormone
ACTH (Cortisol)
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2
Q

What is a primary endocrine gland disease?

A

Where the gland itself does not work correctly

e.g. the thyroid of the adrenal gland

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3
Q

What is a secondary endocrine gland disease?

A

Where the signal from the pituitary gland doesn’t work so the signal is not sent to the gland

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4
Q

What is a tertiary endocrine gland disease?

A

Where the hypothalamic releasing hormones don’t work: this is not measured clinically

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5
Q

What is panhypopituitarism?

A

A decreased production of all anterior pituitary hormones or of specific hormones
Can be congenital or acquired

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6
Q

What is congenital panhypopituitarism? How common is it? What causes it? What are the symptoms?

A

A deficiency in growth hormones and at least 1 more pituitary hormone. It is rare
Usually due to mutations of transcription factor genes needed for normal pituitary development- e.g. PROP1 mutation
Short stature- plus other features
Hypoplastic anterior pituitry gland on MRI

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7
Q

What are the possible causes of acquired panhypopituitarism?

A 
1) Tumours
hypothalamic, pituitary
2) Radiation
hypothalamic/pituitary damage
3) Infection
e.g. meningitis
4) Traumatic brain injury
5) Infiltrative disease
often involves pituitary stalk e.g. neurosarcoidosis
6) Inflammatory (hypophysitis)
7) Pituitary apoplexy
haemorrhage (or less commonly infarction)
8) Peri-partum infarction (Sheehan's syndrome)
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8
Q

What hormone is deficient in secondary hypogonadism? What are the symptoms?

A

FSH/LH
Reduced libido
Secondary amenorrhoea
Erectile dysfunction

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9
Q

What hormone is deficient in secondary hypoadrenalism? What are the symptoms?

A

ACTH (cortisol deficiency)

Fatigue

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10
Q

What hormone is deficient in secondary hypothyroidism? What are the symptoms?

A

TSH
Fatigue
Weight gain

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11
Q

What is Sheehan’s syndrome? When and why does this occur?

A

Post-partum hypopituitarism secondary to hypotension (post-partum haemorrhage)- happens around delivery of baby
Less common in developed countries
Adenohypophysis enlarges in pregnancy (lactotroph hyperplasia)
Post-partum haemorrhage leads to pituitary infarction

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12
Q

What is the presentation of Sheehan’s syndrome?

A

Lethargy, anorexia, weight loss - TSH/ACTH/(GH) deficiency
Failure of lactation - PRL deficiency
Failure to resume menses post-delivery
Posterior pituitary usually not affected

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13
Q

What is pituitary apoplexy? How does it present?

A

Intra-pituitary haemorrhage or (less commonly) infarction. It is a medical emergency
SEVERE sudden onset headache, visual field defect- compressed optic chiasm (bitemporal hemianopia)
Cavernous sinus involved; may lead to diplopia or ptosis

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14
Q

What properties of the different pituitary hormones makes them difficult to measure?

A

Cortisol varies depending on the time of day
T4 circulating half-life of 6 days
FSH/LH are cyclical
GH/ACTH are pulsatile

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15
Q

What biochemical tests can you perform for hypopituitarism?

A
  • Basal plasma concentrations of pituitary or target endocrine gland hormones
  • Insulin-induced hypoglycaemia stimulates GH and ACTH release
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16
Q

If you are deficient in ACTH what is used as a replacement and what should you check?

A

Replace: Hydrocortisone
Check: Serum cortisol

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17
Q

If you are deficient in TSH what is used as a replacement and what should you check?

A

Replace: Thyroxine
Check: Serum free T4

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18
Q

If a woman is deficient in LH/FSH what is used as a replacement and what should you check?

A

Replace: HRT (E2 plus progestagen)
Check: Symptom improvement, withdrawal bleeds

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19
Q

If a man is deficient in LH/FSH what is used as a replacement and what should you check?

A

Replace: Testosterone
Check: Symptom improvement, serum testosterone

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20
Q

If you are deficient in GH what is used as a replacement and what should you check?

A

Replace: Growth hormone
Check: IGF-1, growth chart (children)

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21
Q

What is the result of growth hormone deficiency in children?

A

Results in short stature

2SD < mean height for children that age and sex

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22
Q

What are the causes of short stature? (7)

A 
1) Genetic
Down's syndrome, Turner's syndrome, Prader-Willi syndrome
2) Emotional deprivation
3) Systemic disease
Cystic fibrosis, Rheumatoid arthritis
4) Malnutrition
5) Malabsorption
Coeliac disease
6) Endocrine disorders
Cushing's syndrome, hypothyroidism, GH deficiency, poorly controlled T1DM
7) Skeletal dysplasias
Achondroplasia, osteogenesis imperfecta
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23
Q

What hormone inhibits the release of growth hormone?

A

Somatostatin

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24
Q

What mutation causes achondroplasia?

A

Mutation in fibroblast growth factor receptor 3 (FGF3)

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25
Q

What is achondroplasia?

A

Abnormality in growth plate chondrocytes causing impaired linear growth
Causes average sized trunk with short arms and legs

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26
Q

What is Laron dwarfism? How can it be treated in children?

A

A mutation in the growth hormone receptor

IGF-1 treatment in childhood can increase height

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27
Q

If a child stays within their predicted height range, but falls off the curve age 11, what is a possible cause of this?

A

Coeliac disease

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28
Q

What are the possible causes of acquired growth hormone deficiency in adults?

A

1) Trauma
2) Pituitary tumour
3) Pituitary surgery
4) Cranial radiotherapy

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29
Q

What methods can be used to induce growth hormone release in a growth hormone provocation test?

A 
1) GHRH + Arginine
(in combination more effective than each alone)
2) Insulin
I.V. via hypoglycaemia
3) Glucagon
I.M.
4) Exercise

Measure plasma GH at specific time-points (before and after)

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30
Q

What is the NICE cut-off for GH secretion during insulin-induced hypoglycaemia to require GH replacement?

A

3μg/L

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31
Q

Somatotrophin is used for growth hormone therapy. How is it administered? When do you get the maximal dose? How is it metabolised and what is the duration of action?

A

Daily subcutaneous injection; monitor clinical response and adjust dose to IGF-1. Maximal plasma concentration in 2-6 hours.
Hepatic/renal metabolism with short (20 min) half-life
Lasts well beyond clearance. Peak IGF-1 levels at approximately 20 hours

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32
Q

What are the signs and symptoms of GH deficiency in adults?

A

Reduced lean mass, increased adiposity, increased waist:hip ratio
Reduced muscle strength and bulk = reduced exercise performance
Decreased plasma HDL-cholesterol (good) and raised LDL-cholesterol (bad
Impaired ‘psychological well being’ and reduced quality of life

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33
Q

What are the potential benefits of GH therapy in adults?

A

Improved body composition- decreased waist circumference, less visceral fat
Improved muscle strength and exercise capacity
More favourable lipid profile (higher HDL and lower LDL)
Increased bone mineral density
Improved psychological well-being and quality of life

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34
Q

What are the potential risks associated with GH therapy in adults?

A

Increased susceptibility to cancer - no data to support this currently
Expensive - NICE estimated cost of lifelong GH treatment in adult = £42k

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35
Q

What is released in the posterior pituitary?

A

Vasopressin (ADH)

Oxytocin

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36
Q

Where is vasopressing produced?

A

In the hypothalamus (released in the neurohypophysis)

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37
Q

What receptor does vasopressin act on?

A

V2 receptor

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38
Q

What does vasopressin cause synthesis of? Where does this product act?

A

Synthesis of AQP2

Inserted into the apical membrane of collecting duct cells

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39
Q

How is vasopressin release regulated?

A

Osmoreceptors in the organum vasculosum are very sensitive to small changes in the osmolarity of the blood, as this area does not have the normal BBB

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40
Q

What happens to the osmoreceptors when there is an increase in the extracellular sodium concentration?

A

Osmoreceptors shrink, which increases osmoreceptor firing, which in turn causes release of vasopressin from PVN and SON neurones

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41
Q

What is the normal response to water deprivation?

A

Increased serum osmolarity
Stimulation of osmoreceptors
Increased vasopressin release (and increased thirst)
Increased water reabsorption from renal collecting ducts
Reduced urine volume, increased urine osmolarity, reduction in serum osmolarity

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42
Q

What is diabetes insipidus?

A

Absence or lack of circulating vasopressin, or end organ resistance to vasopressin

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43
Q

What are the two types of diabetes insipidus?

A

Cranial (or Central)

Nephrogenic

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44
Q

What are the two types of cranial diabetes insipidus? Which one is more common?

A

Acquired (more common)

Congenital (rare)

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45
Q

What are possible causes of acquired diabetes insipidus?

A

1) Traumatic brain injury
2) Pituitary surgery
3) Pituitary tumours, craniopharyngioma
4) Metastasis to the pituitary gland, e.g. breast
5) Granulomatous infiltration of median eminance, e.g. TB, sarcoidosis

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46
Q

What are the possible causes of congenital nephrogenic diabetes insipidus? How common is it?

A

Rare

e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel

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47
Q

What are the possible causes of acquired nephrogenic diabetes insipidus?

A

Drugs

e.g. lithium

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48
Q

What are the signs and symptoms of diabetes insipidus?

A

Polyuria
Hypoosmolar urine
Polydipsia
Dehydration if fluid intake not maintained- can lead to death
Possible disruption to sleep with associated problems

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49
Q

What is the mechanism of diabetes insipidus?

A

1) Inadequate production of/response to VP
2) Large volumes of dilute (hypotonic) urine
3) Increase in plasma osmolarity (and sodium)
4) Reduction in extracellular fluid volume
5) Thirst- polydipsia
6) Extracellular fluid volume expansion

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50
Q

What is psychogenic polydipsia?

A

Most frequently seen in psychiatric patients. Patients told to drink plenty by healthcare professionals
Excess fluid intake and excess urine output- but with ability to secrete vasopressin in response to osmotic stimuli is preserved

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51
Q

What is the mechanism of psychogenic polydipsia?

A

1) Polydipsia
2) Expansion of extracellular fluid volume, reduction in plasma osmolarity
3) Less VP secreted by neurohypophysis
4) Large volumes of dilute (hypotonic) urine
5) Extracellular fluid volume returns to normal

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52
Q

What is the normal (hydrated) range for plasma osmolarity?

A

280-295mOsm/kg H₂O

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53
Q

What is the plasma osmolarity of someone with diabetes insipidus usually over?

A

290mOsm/kg H₂O

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54
Q

What is the urine osmolarity of someone with psychogenic polydipsia usually under?

A

270mOsm/kg H₂O

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55
Q

What is involved in a water deprivation test?

A

Subject deprived of water
Healthy individuals and those with psychogenic polydipsia will start to produce concentrated urine in response. Diabetes insipidus will continue to produce dilute urine
Then administer DDAVP
Cranial DI will start to produce more concentrated urine
Nephrogenic DI will still produce dilute urine

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56
Q

What are the biochemical features of diabetes insipidus? (4)

A

1) Hypernatraemia
2) Raised urea
3) Increased plasma osmolarity
4) Dilute (hypoosmolar) urine- i.e. low urine osmolarity

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57
Q

What are the biochemical features of psychogenic polydipsia?

A

1) Mild hyponatraemia (due to excess water intake)
2) Low plasma osmolarity
3) Dilute (hypo-osmolar) urine

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58
Q

Where are V1 receptors located? (6)

A

1) Vascular smooth muscle
2) Non-vascular smooth muscle
3) Anterior pituitary
4) Liver
5) Platelets
6) CNS

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59
Q

Where are V2 receptors located? (2)

A

1) Kidney

2) Endothelial cells

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60
Q

What selective vasopressin V2 receptor peptidergic agonist is used in diabetes insipidus?

A

Desmopressin (DDAVP)

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61
Q

How is desmopressin administered? What must patients starting this drug ensure?

A 
Administered
- Nasal spray (normally)
- Orally
- Subcutaneous injection
Patients must not continue to drink large amount of fluid- risk of hyponatraemia
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62
Q

What drug is used to treat nephrogenic diabetes insipidus?

A

Thiazides

e.g. bendroflumethiazide

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63
Q

What is the possible mechanism of thiazides?

A

1) Inhibits Na⁺/Cl⁻ transport in distal convoluted tubule (diuretic effect)
2) Volume depletion
3) Compensatory increase in Na⁺ reabsorption from the proximal tubule (plus small decrease in GFR etc)
4) Increased proximal water reabsorption
5) Decreased fluid reaches collecting duct
6) Reduced urine volume

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64
Q

What is SIADH?

A

Syndrome of inappropriate ADH

The plasma vasopressin concentration is inappropriately high for the existing plasma osmolarity

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65
Q

What is the mechanism for SIADH?

A

1) Increased vasopressin
2) Increased H₂O reabsorption from renal collecting ducts
3) Expansion of ECF volume [= 6) Hyponatraemia]
4) Atrial natruiretic peptide (ANP) from right atrium
5) Natriuresis
6) Hyponatraemia and euvolaemia

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66
Q

What are the signs or SIADH?

A

Raised urine osmolarity, decreased urine volume (initially)

Decreases p[NA⁺] (hyponatraemia) mainly due to increased water reabsorption

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67
Q

What are the symptoms of SIADH?

A

Can be symptomless
If p[Na⁺] <120mM: Generalised weakness, poor mental function, nausea
If p[Na⁺] <110mM: Confusion leading to coma and ultimately death

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68
Q

What are the possible causes of SIADH? (5)

A 
1) CNS
Subarachnoid haemorrhage, stroke, tumour, traumatic brain injury
2) Pulmonary disease
Pneumonia, bronchiectasis
3) Malignancy
Lung (small cell)
4) Drug-related
Carbamazepine, SSRIs (selective serotonin reuptake inhibitors)
5) Idiopathic
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69
Q

What treatment is used for SIADH?

A

Appropriate treatment (e.g. surgery for tumour)
To reduce immediate concern (i.e. hyponatraemia)
1) Immediate: fluid restriction
2) Longer-term: use drugs which prevent vasopressin action in kidneys
e.g. Induce nephrogenic DI- demeclocyline; inhibit action of ADH- V2 receptor antagonists

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70
Q

What are Vaptans? How do they work?

A

Non-competitive V2 receptor antagonists
Inhibit AQP2 synthesis and transport to apical membrane, preventing renal water reabsorption
Aquaresis- solute-sparing renal excretion of water
Licensed in the UK for treatment of hyponatraemia associated with SIADH
Very expensive- limits their current use

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71
Q

What is the normal fasting glucose level?

A

4-6mmol/L

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72
Q

What is the diabetic blood glucose level over?

A

7mmol/L

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73
Q

What is the term for an individual with a fasting glucose level of 6-7mmol/L?

A

Impaired fasting glucose

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74
Q

What is the normal oral glucose tolerance test result after 120 mins?

A

7.8mmol/L

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75
Q

What is a diabetic oral glucose tolerance test result over after 120 mins?

A

11.1mmol/L

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76
Q

Why can’t you measure GH? What is measured instead?

A

GH is released in pulses ∼6 times per day.

Measure IGF-1 instead

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77
Q

Why must you perform a water deprivation test rather than measuring ADH levels?

A

ADH breaks down quickly so it cannot be measured accurately

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78
Q

Where is the grey and white matter located in the spinal cord?

A

Grey matter is in the middle surrounded by white matter

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79
Q

What is contained in the grey matter?

A

Cell bodies of interneurones and motor neurones

Neuroglia and unmyelinated axons

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80
Q

How is the grey matter arranged? What is the function of each section?

A

Arranged into dorsal and ventral horns
Dorsal horn receive sensory information from the body via spinal nerves and dorsal roots. This information produces reflex actions or is projected to the brain for processing
Ventral horns contain motor neurones whose axons control muscles of the body.
In the thoracic and upper lumbar region the intermediate horns contain sympathetic preganglionic motor neurones whose axons control visceral functions via the ventral roots and spinal nerves

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81
Q

What does the white matter contain?

A

Short pathways which interconnect adjacent segments of the spinal cord and longer tracts which convey information from the brain
It is mostly myelinated motor and sensory axons

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82
Q

Is damage to grey or white matter likely to result in more serious consequences?

A

White matter

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83
Q

How is the lower end of the spinal cord anchored to the coccygeal vertebrae?

A

The filum terminale (a pial thread)

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84
Q

What consequences result from sacral spine damage?

A

Loss of bladder and bowel function, spina bifida, neural tube defect

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85
Q

What consequences result from thoracic spine damage?

A

Loss of lower limb function and incontinence (paraplegia)

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86
Q

What consequences result from cervical spine damage?

A

Loss of lower limb and upper limb function, incontinence (quadriplegia)
High spinal legion (C1/2) cannot breathe unassisted, as the phrenic nucleus controls the diaphragm which is innervated by C3/4/5

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87
Q

What are the three layers of meninges which cover in the spinal cord? (from outside inwards)

A

Tough outer dura mater
Arachnoid mater
Delicate pia mater (continuous with the spinal cord)

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88
Q

What is found in the extradural space surrounding the spinal cord?

A

Fat and a vanour plexus

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89
Q

What is the name for the lateral projections which extend form the pia mater into the dura mater to help stabilise the spinal cord?

A

Denticulate ligaments

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90
Q

What direction are the tracts found in the dorsal columns in the spinal cord?

A

Ascending tracts (carrying sensory information)

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91
Q

What somatosensory information is found in the dorsal columns pathway?

A

Touch, proprioception and vibration

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92
Q

What somatosensory information is found in the spinothalamic pathway?

A

Pain and temperature

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93
Q

In the dorsal columns pathway if the primary axon enters below spinal level T6 where will it travel? And above?

A

Below: Fasciculus gracilis
Above: Fasciculus cuneatus

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94
Q

In the dorsal columns pathway where do the secondary fibres cross over?

A

In the sensory decussation

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95
Q

In the dorsal columns pathway where do secondary axons terminate?

A

In the ventral posterolateral nucleus (VPL) of the thalamus where they synapse with tertiary neurons

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96
Q

Where do the tertiary neurones of the dorsal columns pathway ascend? Where do they end?

A

Ascends via the posterior limb of the internal capsule

End in the primary sensory cortex

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97
Q

Where do the primary neurons of the spinothalamic pathway synpase?

A

In the substantia gelatinosa

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98
Q

What is Lissauer’s tract?

A

The tract where primary neurones of the spinothalamic pathway ascend before synapsing

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99
Q

Where do the tertiary neurones of the spinothalamic pathway ascend and where do they travel to?

A

Ascend via the posterior limb of the internal capsule to the primary sensory cortex

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100
Q

Which tract is motor organisation in?

A

The corticospinal tract

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101
Q

What is the route of the corticospinal tract?

A

Cortical upper motor neurones descend in the posterior limb of the internal capsule through the crus cerebri, down through the pons and to the medullary pyramids where 95% of the axons cross over at pyramidal decussations.
They then descend as the lateral corticospinal tract

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102
Q

Which spinal tract would result in contralateral loss of sensory information with a mid-thoracic spinal lesion?

A

Spinothalamic pathway

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103
Q

Which spinal tract would result in ipsilateral loss of sensory information with a mid-thoracic spinal lesion?

A

Dorsal columns pathway

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104
Q

Which spinal tract would result in ipsilateral deficits with a mid-thoracic spinal lesion?

A

The corticospinal tract

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105
Q

What determines the degree of deficit following a spinal cord lesion? (3)

A

1) Loss of neural tissue
2) Vertibral level
The higher the level the more severe the disability
3) Transverse plane
Which and how many tracts are affected

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106
Q

What is hyperreflexia?

A

Overactive or over responsive reflexes resultant from injury at T5 level and above

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107
Q

What is syringomyelia?

A

Disorder in which a cyst or cavity forms within the spinal cord. Usually seen in the cervical region, so upper limbs are affected

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108
Q

What is a spinal glioma?

A

A tumour within the spinal cord

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109
Q

What are the usual causes of hyperpituitarism? What symptoms are associated with this?

A

Usually due to isolated pituitary tumours but can also be ectopic in origin
Can be associated with visual field and other (e.g. cranial nerve) defects as well as endocrine-related signs and symptoms

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110
Q

What is bitemporal hemianopia? Why does this occur?

A

A loss of part of the field of vision.
When a suprasellar tumour in the pituitary compresses the optic chiasm so only the fibres which don’t cross over here will provide sensory information

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111
Q

What disorder results from hyperpituitarism where there is excess ACTH?

A

Cushing’s disease

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112
Q

What disorder results from hyperpituitarism where there is excess TSH?

A

Thyrotoxicosis

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113
Q

What disorder results from hyperpituitarism where there are excess gonadotrophins?

A

Precocious puberty in children

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114
Q

What disorder results from hyperpituitarism where there is excess prolactin?

A

Hyperprolactinaemia

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115
Q

What disorder results from hyperpituitarism where there is excess growth hormone?

A

Gigantism or Acromegaly

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116
Q

What is the most common functioning pituitary tumour? What does this suppress?

A

Prolactinoma

Suppresses GnRH pulsatility

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117
Q

What is the pathological cause of hyperprolactinaemia?

A

Prolactinoma

Often microadenomas <10mm in diameter

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118
Q

What are the physiological causes of hyperprolactinaemia?

A

Pregnancy or breastfeeding

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119
Q

What are the symptoms of hyperprolactinaemia due to pituitary adenoma in women?

A

Galactorrhoea (milk production)
Secondary amenorrhoea (or oligomenorrhoea)
Loss of libido
Infertility

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120
Q

What are the symptoms of hyperprolactinaemia due to pituitary adenoma in men?

A 
Galactorrhoea uncommon (since appropriate steroid background is usually inadequate)
Loss of libido
Erectile dysfunction
Infertility
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121
Q

What cell is prolactin secreted from? How is prolactin secretion switched off?

A

Secreted from lactotrophs in the adenohypophysis

Dopamine from hypothalamic dopaminergic neurones binds to D2 receptors which switches off prolactin secretion

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122
Q

What treatment is used for hyperprolactinaemia? Give examples.

A

Dopamine receptor D2 agonists decrease prolactin secretion and reduce tumour size
e.g. Cabergoline (and less frequently Bromocriptine) are given orally

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123
Q

What side effects are associated with dopamine receptor agonists?

A 
Nausea and vomitting
Postural hypotension
Dyskinesias (movement difficulty)
Depression
Pathological gambling
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124
Q

What does excess growth hormone in childhood result in? What usually causes it?

A

Gigantism

Usually due to benign growth hormone secreting pituitary adenoma

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125
Q

What does excess growth hormone in adulthood result in? What usually causes it?

A

Acromegaly

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126
Q

What are the causes of death in Acromegaly?

A

Cardiovascular disease: 60%
Respiratory complications: 25%
Cancer: 15%

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127
Q

What grows in Acromegaly?

A 
Periosteal bone
Cartilage
Fibrous tissue
Connective tissue
Internal organs (cardiomegaly, splenomegaly, hepatomegaly, etc)
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128
Q

What are the clinical features of Acromegaly? (8)

A
  • Excessive sweating (hyperhidrosis)
  • Headache
  • Enlargement of supraorbital ridges, nose, hands and feet, thickening of lips and general coarseness of features
  • Macroglossia
  • Mandible grows causing protrusion of lower jaw (prognathism)
  • Carpal tunnel syndrome (median nerve compression)
  • Barrel chest, kyphosis
  • Spade-shaped hands with doughy palms
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129
Q

What are the metabolic effects of Acromegaly?

A

1) Excess growth hormone (GH)
2) Excess GH inhibits insulin signalling
3) Increased insulin resistance
4) Impaired glucose tolerance
5) Diabetes mellitus

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130
Q

What complications are associated with Acromegaly?

A

1) Obstructive sleep apnea
2) Hypertension
3) Cardiomyopathy
4) Increased risk of cancer

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131
Q

Why is obstructive sleep apnea associated with Acromegaly?

A

Bone and soft tissue changes surrounding the upper airway lead to narrowing and subsequent collapse during sleep

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132
Q

Why is hypertension associated with Acromegaly?

A

Direct effects of GH and/or IGF-1 on the vascular tree

GH-mediated renal sodium reabsorption

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133
Q

Why is cardiomyopathy associated with Acromegaly?

A

Hypertension, diabetes mellitus, direct toxic effects of excess GH on myocardium

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134
Q

Why is an increased risk of cancer associated with Acromegaly?

A

Colonic polyps

Regular screening with colonoscopy

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135
Q

What co-secretion is often associated with acromegaly? What does this cause?

A

Prolactin is often high in acromegaly- may reflect a tumour secreting GH and prolactin
Hyperprolactinaemia will cause secondary hypogonadism

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136
Q

What hormone inhibits GH release from the adenohypophysis?

A

Somatostatin

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137
Q

What effect does growth hormone have on the liver?

A

Induces release of somatomedins (mainly IGF-1)

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138
Q

How is acromegaly diagnosed?

A

GH is pulsatile so random measurement is unhelpful
Instead, measure IGF-1 (will be elevated in Acromegaly)
Failed suppression of GH following oral glucose load (perform oral glucose tolerance test)

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139
Q

What are the treatment options for Acromegaly?

A

1) Surgery (trans-sphenoidal)
- 1st Line
2) Medical
- Somatostatin analogues
- Dopamine agonists
3) Radiotherapy

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140
Q

Give an example of a somatostatin analogue used in the treatment of Acromegaly. Describe the use of these drugs and their side effects?

A

Octreotide
Injection: Subcutaneous (short-acting) or monthly depot
Side effects: Nausea, diarrhoea, gallstones (GI)
Reduces GH secretion and tumour size
Pretreatment before surgery may make resection easier
Used post-op if not cured or whilst waiting for radiotherapy

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141
Q

Give an example of a dopamine agonist used in the treatment of Acromegaly.

A

Cabergoline

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142
Q

What is thyroxine?

A

Prohormone T4

Converted into the active metabolite T3

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143
Q

What drug is used in thyroid hormone replacement therapy?

A

1) Levothyroxine sodium (T4)
Usually the drug of choice
2) Liothyronine sodium (T3)
Less commonly used

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144
Q

What is the clinical use of Levothyroxine sodium in primary hypothyroidism? How is it administered and how is the correct dose given?

A

1) Autoimmune primary hypothyroidism
2) Iatrogenic primary hypothyroidism (e.g. post-thyroidectomy, post-radioactive iodine)
Oral administration
TSH used as a guide for thyroxine dose- suppress TSH into reference range

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145
Q

What is the clinical use of Levothyroxine sodium in secondary hypothyroidism? How is it administered and how is the correct dose given?

A

e.g. pituitary tumour, post-pituitary surgery or radiotherapy
Oral administration
TSH low due to anterior pituitary failure, so can’t use TSH as a guide to dose. Instead aim for fT4 in the middle of the reference range

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146
Q

What is the clinical use of Liothyronine? How is it administered?

A

Myxoedema coma- a very rare complication of hypothyroidism
IV administration
Onset of action faster than T4 (then oral when possible)

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147
Q

What symptoms occur with combined thyroid hormone replacement?

A

Combination T3/T4- some reported improvement in well-being

Complicated by symptoms of ‘toxicity’- palpitations, tremor, anxiety- often combination treatment suppresses TSH

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148
Q

What are the adverse effects of thyroid hormone over-replacement?

A

Usually associated with low/suppressed TSH

1) Skeletal- increased bone turnover, reduction in bone mineral density, risk of osteoporosis
2) Cardiac- tachycardia, risk of dysrhythmia, particularly atrial fibrillation
3) Metabolism- increased energy expenditure, weight loss
4) Increased β-adrengergic sensitivity- tremor, nervousness

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149
Q

What is the half-life of Levothyroxine?

A

6 days

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150
Q

What is the half-life of Liothyroxine

A

2.5 days

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151
Q

What percentage of circulating T4 and T3 are bound to plasma proteins? Which plasma protein mainly binds to these?

A

Thyroxine binding globulin
∼99.97% of T4
∼99.7% of circulating T3

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152
Q

What conditions increase the amount of plasma binding proteins?

A

Pregnancy

Patients on prolonged treatment with oestrogens and phenothiazines

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153
Q

What conditions decrease the amount of plasma binding proteins?

A

Malnutrition
Liver disease
Certain drug treatments

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154
Q

Give examples of co-administered drugs that compete for protein binding sites.

A

Phenytoin

Salicylates

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155
Q

How much more T4 is in the plasma compared with T3?

A

10 times

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156
Q

How is free and conjugated T3 and T4 secreted? How long does it take to be cleared?

A

Secreted in the bile and urine
T3 is cleared in hours
T4 takes 6 days

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157
Q

What are the different classes of drugs used in the treatment of hyperthyroidism?

A

1) The thionamides (anti-thyroid drugs)
- propylthiouracil (PTU)
- carbimazole (CBZ)
2) Potassium iodide
3) Radioiodine
4) β-blockers
- help with symptoms, don’t help with thyroid hormone function

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158
Q

What are the uses of thionamides?

A

1) Daily treatments of hyperthyroid conditions
2) Treatment prior to surgery
3) Reduction of symptoms while waiting for radioactive iodine to act

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159
Q

What is the mechanism of action of thionamides?

A

1) They inhibit thyroperoxidase and peroxidase transaminase which inhibits T3/4 synthesis and secretion
2) May also suppress antibody production in Graves’ disease
3) Reduces conversion of T4 to T3 in peripheral tissue (PTU)

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160
Q

What are the unwanted actions of thionamides?

A

1) Agranulocytosis/granulocytopenia (reduction or absence of granular leukocytes)- rare and reversible on withdrawal of the drug
2) Rashes (relatively common)- normally associated with one drug, so swapping drug type relieves this

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161
Q

Describe the pharmacokinetics of thionamides.

A

Orally active
Carbimazole is a prodrug which has to be converted to methimazole
Plasma half-life of 6-15 hours
Crosses placenta and is secreted in breastmilk
Metabolised in the liver and secreted in the urine

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162
Q

Which thionamide crosses the placenta and is secreted in breastmilk less?

A

Propylthiouracil

PTU

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163
Q

How long is anti-thyroid drug treatment used before it is aimed to stop?

A

18 months

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164
Q

Why would β-blockers be used in thyrotoxicosis?

A

Thionamides take several weeks to have clinical effects e.g. reduce tremor, slow heart rate, less anxiety etc
β-blockers (e.g. propranolol) will achieve these effects in the interim

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165
Q

When is potassium iodide used?

A

1) Preparation of hyperthyroid patients for surgery

2) Severe thyrotoxic crisis

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166
Q

What is the mechanism of action of potassium iodide?

A

1) Inhibits iodination of thyroglobulin

2) Inhibits H₂O₂ generation

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167
Q

How long does it take for the effects of potassium iodide to be seen?

A

Hyperthyroid symptoms reduced withing 1-2 days

Vascularity and size of gland reduced within 10-14 days

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168
Q

What are the unwanted effects of potassium iodide?

A

Allergic reactions

e.g. rashes, fever, angiooedema

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169
Q

How is potassium iodide administered? When are the maximum effects seen?

A

Oral administration

Maximal effects seen after 10 days continuous administration

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170
Q

What is radioiodine used to treat?

A

Treats hyperthyroidism

Graves, toxic nodular disease, thyroid cancers

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171
Q

How does radioiodine work?

A

Accumulates in the colloid; emits β particles, destroying follicular cells

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172
Q

What are the pharmacokinetics of radioiodine?

A

Discontinue anti-thyroid drugs 7-10 days prior to radioiodine treatment
Administer as a single oral dose
Radioactive half-life of 8 days
Radioactivity negligible after 2 months

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173
Q

What risks are associated with radioiodine treatment?

A

Must avoid close contact with small children for several weeks after receiving radioiodine
Contra-indicated in pregnancy and breast feeding

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174
Q

What are the symptoms of hypothyroidism?

A

Hair dry and brittle

  • Lethargy, memory impairment, depression
  • Oedema of face and eyes
  • Thick tongue, slow speech
  • Deepening voice
  • Cold intolerance, diminished perspiration
  • Cardiomegaly, poor heart sounds, hypertension
  • Weight gain with reduced appetite and ascites
  • Constipation
  • Eventually myxodema coma
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175
Q

What is bilateral exophthalmos?

A

Seen in Graves’ disease, where the antibodies bind to muscles in the back of the eye, causing them to swell

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176
Q

What are the symptoms of hyperthyroidism?

A
  • Fatigue or muscle weakness
  • Hand tremors
  • Mood swings
  • Nervousness or anxiety
  • Rapid heartbeat
  • Heart palpitations or irregular heartbeat
  • Skin dryness
  • Trouble sleeping
  • Weight loss
  • Increased frequency of bowel movements
  • Light periods or skipping periods
  • Exophthalmos and lid lag (corneal scarring)
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177
Q

What disorder is associated with excess cortisol? Give two examples of drugs used to inhibit steroid biosynthesis.

A

Cushing’s syndrome

  • Metyrapone
  • Ketoconazole
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178
Q

What disorder is associated with excess aldosterone? Give two examples of drugs used as an mineralocorticoid receptor antagonist.

A

Conn’s syndrome

  • Spironolactone
  • Epleronone
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179
Q

What is metyrapone used to treat? What is it’s action and mechanism?

A

Used to treat Cushing’s syndrome
- Cortisol synthesis blocked
- ACTH secretion increased
- Plasma deoxycortisol increased
Causes inhibition of 11β-hydroxylase
Steroid synthesis in the zona fasciculata (and reticularis) is arrested at the 11-deoxycortisol stage
11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland

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180
Q

When is metyrapone used?

A

In the control of Cushing’s syndrome prior to surgery
- to get serum cortisol between (150-300nmol/L)
- improves patient’s symptoms and promotes better post-op recovery
Used to control Cushing’s symptoms after radiotherapy

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181
Q

What are the side effects of metyrapone?

A

Hypertension on long administration
- deoxycorticosterone accumulates in the zona glomerulosa and has aldosterone-like activity, leading to salt retention
Hirsutism
(excessive hair growth)

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182
Q

What is ketoconazole used to treat? What is it’s action and mechanism?

A

Used to treat Cushing’s syndrome
Main use as an antifungal agent (withdrawn in 2013 due to hepatotoxicity)
At higher concentrations, inhibits steroidogenesis - off label use
- Blocks action of glucocorticoids, mineralocorticoids and sex steroids

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183
Q

What are the side effects of ketoconazole?

A

Liver damage- possibly fatal

Monitor liver function weekly, clinically and biochemically

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184
Q

What is spironolactone used to treat? What is it’s action and mechanism?

A 
Primary hyperaldosteronism (Conn's syndrome)
It is converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptor
Blocks Na⁺ reabsorption and K⁺ excretion in the kidney tubules (K⁺ sparing diuretic)
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185
Q

Where is spironolactone metabolised?

A

In the liver

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186
Q

What are the side effects of spironolactone?

A 
Menstrual irregularities (+ progesterone receptor)
Gynaecomastia (- androgen receptor)
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187
Q

What is epleronone used to treat?

A

Conn’s syndrome (a mineralocorticoid receptor antagonist

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188
Q

Why is epleronone preferable to spironolactone?

A

Similar affinity to the mineralocorticoid receptor compared to spironolactone
Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated

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189
Q

What are the symptoms of Cushing’s syndrome?

A

Too much cortisol

  • Centripetal obesity
  • Moon face
  • Osteoporosis
  • Diabetes
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190
Q

What are the possible causes of Cushing’s syndrome?

A

1) Taking too many steroids
2) A pituitary tumour
3) Ectopic tumour secreting ACTH
4) Adrenal adenoma

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191
Q

How does a dexamethasone suppression test diagnose Cushing’s syndrome?

A

Dexamethasone is an artificial steroid
Low dose- it is administered every 6 hours for 48 hours in a 0.5mg dose
-Normal patients will respond by suppressing their cortisol levels to zero but Cushing’s patients will fail to suppress their cortisol levels.
High dose determines the type of pituitary Cushing’s disease
- Only pituitary Cushing’s will suppress their cortisol to 50%; ectopic ACTH and adrenal tumours will not suppress at all

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192
Q

What is Conn’s syndrome?

A

A benign adrenal cortical tumour in the zona glomerulosa, which causes excessive aldosterone release, leading to hypertension and hypokalaemia

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193
Q

What are the possible causes of adrenocortical failure?

A

1) Adrenal glands destroyed
- Tuberculous Addison’s disease
- Autoimmune Addison’s disease
2) Congenital adrenal hyperplasia

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194
Q

What are the consequences of adrenocortical failure?

A
  • Fall in blood pressure
  • Loss of salt in the urine
  • Increased plasma potassium
  • Fall in glucose due to glucocorticoid deficiency
  • High ACTH resulting in increased pigmentation
  • eventual death due to severe hypotension
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195
Q

Why do you get skin pigmentation in Addison’s disease?

A

As cortisol is not being produced ACTH is increased.
ACTH is produced from a large precursor molecule POMC. POMC is cleaved into ACTH and MSH
MSH = Melanocyte-stimulating hormone which causes increased skin pigmentation

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196
Q

How do you test for Addison’s disease?

A

FBC = ↑↑↑ K⁺, ↓Na⁺
Meausre cortisol at 9am = low
ACTH = high

Cortisol at time 0 (270-900)
Short synATCHen test (I.M. injection)
Measure cortisol at time 30 and 60 (>600)
In Addison’s flattened response to ACTH

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197
Q

What is the most common cause of Congenital Adrenal Hyperplasia?

A

21-hydroxylase deficiency

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198
Q

What are the different types of Congenital Adrenal Hyperplasia? What is it?

A

Complete or Partial

Large adrenal glands with poor function. Inability to synthesise one hormone

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199
Q

What results from Congenital Adrenal Hyperplasia with 21-hydroxylase deficiency?

A

Deficiency in aldosterone and cortisol
BUT not sex steroids

Causes sex steroids to be made in excess due to increased precursors that get converted into sex steroids (↑ ACTH)
Excess testosterone

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200
Q

What age will someone present with Congenital Adrenal Hyperplasia with 21-hydroxylase deficiency?

A

Usually by 1 week old
Before birth foetus gets steroids across the placenta
Girls might have ambiguous genitalia

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201
Q

How will a patient present with partial Congenital Adrenal Hyperplasia with 21-hydroxylase deficiency? What are the main problems?

A

Can make enough aldosterone and cortisol to survive, but they are deficient
Produce excess sex steroids and testosterone
Can present at any age
In girls: Hirsuitism and virilisation
In boys: Precocious puberty

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202
Q

What results from Congenital Adrenal Hyperplasia with 11β-hydroxylase deficiency?

A

Patient will produce lots of 11-deoxycorticosterone which is a mineralocorticoid and behaves like aldosterone.
It is produced in excess as it does not provide negative feedback so produces hypertension (excess water retention) and hypokalaemia (excess excretion)
Deficient in cortisol and aldosterone
Excess 11-deoxycorticosteron, sex steroids and testosterone
Problems with virilisation

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203
Q

What results from Congenital Adrenal Hyperplasia with 17-hydroxylase deficiency?

A

Deficient in cortisol and sex steroids
Excess 11-deoxycorticosterone and aldosterone
Problems with hypertension, low K⁺, sex steroid deficiency and glucocorticoid deficiency (low glucose)

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204
Q

What stimulates the hypothalamus to release corticotrophin-releasing hormone?

A

Circadian rhythm

Stress

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205
Q

What regulates the release of aldosterone?

A

The Renin-Angiotensin system

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206
Q

In adrenocortical failure what hormones need to be replaced?

A

Cortisol and aldosterone must be replaced

Androgens do not need to be replaced as the gonads are the main source and they can take over sufficiently

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207
Q

What hormone binds to the glucocorticoid receptor?

A

Cortisol

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208
Q

What hormone binds to the mineralocorticoid receptor?

A

Aldosterone and cortisol

Cortisol has higher affinity

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209
Q

Where are glucocorticoid receptors located?

A

Wide distribution in the body

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210
Q

Where are mineralocorticoid receptors located?

A

In the kidney

discrete distribution

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211
Q

How is cortisol prevented from binding to aldosterone receptors?

A

11β-hydroxysteroid dehydrogenase 2 converts cortisol to cortisone which is inactive

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212
Q

Why do patients with Cushing’s syndrome have hypertension and hyperkalaemia?

A

High cortisol, eventually 11β-HSD becomes saturated and can’t convert any more cholesterol so the cholesterol binds to the mineralocorticoid receptors
= ↑ Na⁺ resorption, ↑ water resorption, ↑ K⁺ excretion
= hypertension, hypokalaemia

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213
Q

What is the receptor selectivity of hydrocortisone?

A

Glucocorticoid with mineralocorticoid activity at high doses

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214
Q

What is the receptor selectivity of prednisolone?

A

Glucocorticoid with weak mineralocortiocid activity

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215
Q

What is the receptor selectivity of dexamethasone?

A

Synthetic glucocorticoid with no mineralocorticoid activity

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216
Q

What is the receptor selectivity of fludrocortisone?

A

Aldosterone analogue

Used as an aldosterone substitute

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217
Q

What are the routes of administration of corticosteroids?

A 
Oral
- Hydrocortisone
- Prednisolone
- Dexamethasone
- Fludrocortisone
Parenteral (I.V. or I.M.)
- Hydrocortisone
- Dexamethasone
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218
Q

What plasma proteins bind corticosteroids?

A

Cortisol Binding Globulin

Albumins

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219
Q

What is the duration of action of hydrocortisone?

A

∼8 hours

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220
Q

What is the duration of action of prednisolone?

A

∼12 hours

221
Q

What is the duration of action of dexamethasone?

A

∼40 hours

222
Q

What drugs are used to treat Addison’s disease?

A

Patients lack cortisol and aldosterone

Treat with hydrocortisone (replaces cortisol) and fludrocortisone (replaces aldosterone) by mouth

223
Q

What drugs are used to treat patients with ACTH deficiency

A

Patients lack cortisol but aldosterone is normal (RAAS)

Treat with hydrocortisone

224
Q

What is the treatment for Addisonian crisis?

A

First therapeutic step- I.V. saline (0.9% sodium chloride) to rehydrate patient
High dose hydrocortisone
- I.V. infusion or I.M. every 6 hours
- Has mineralocorticoid effect at high dose (11β-HSD overwhelmed) so no need to replace aldosterone
5% dextrose if hypoglycaemic

225
Q

What are the objectives of therapy in a patient with Congenital Adrenal Hyperplasia?

A
  • Replace cortisol
  • Suppress ACTH and thus, adrenal androgen production
  • Replace aldosterone in salt wasting forms
226
Q

What is the therapy used for Congenital Adrenal Hyperplasia? How is therapy monitored? What are the side effects?

A

Given cortisol replacement at very high doses compared to Addison’s to reduce ACTH
Measure 17 OH progesterone (high ACTH = high 17 OH prog)
Cushingoid - Glucocorticoid dose is too high
Hirsuitism - Glucocorticoid dose is too low

227
Q

When do patient’s with glucocorticoid replacement need to increase their dose?

A

In minor illness double the dose

During surgery- hydrocortisone I.M. with pre-med and at 6-8 hour intervals. oral once eating and drinking

228
Q

What hormone suppresses GnRH to prevent the release of testosterone?

A

Inhibin

229
Q

How long is a menstrual cycle? What are the phases of the cycle?

A

28 days

  • Follicular phase
  • Ovulation
  • Luteal phase
230
Q

What happens in the follicular phase of the menstrual cycle?

A

Low level of LH and FSH stimulate development of follicles. These develop and start to produce oestradiol, progesterone and inhibin. Inhibin gives negative feedback to the hypothalamus

231
Q

What hormones spike in ovulation?

A

Oestradiol

Progesterone

232
Q

What occurs in the luteal phase of the menstrual cycle?

A

If implantation does not occur the endometrium is shed
If implantation does occur = pregnancy
Luteal phase is the release of an egg and the subsequent hormonal change. Large progesterone spike (plus oestradiol and inhibin) peaking at the middle of the Luteal phase. As progesterone release decreases it initiates menstration

233
Q

What is infertility?

A

The inability to conceive after 1 year of regular unprotected sex

234
Q

What hormone levels would be found in a patient with primary gonadal failure?

A

High GnRH
High LH
High FSH
Low testosterone/oestradiol

235
Q

What hormone levels would be found in a patient with hypopituitary disease?

A

Low LH
Low FSH
Low testosterone/oestradiol

236
Q

What are the clinical features of male hypogonadism?

A 
Loss of libido
Impotence
Small testes
Decrease muscle bulk
Osteoporosis
237
Q

What are the causes of male hypogonadism? (4)

A

1) Hypothalamic-pituitary disease
- Hypopituitarism
- Kallman’s syndrome (anosmia + low GnRH)
- Illness/underweight
2) Primary gonadal disease
- Congenital: Klinefelter’s syndrome (XXY)
- Acquired: Testicular torsion, Chemotherapy
3) Hyperprolactinaemia
4) Androgen receptor deficiency

238
Q

What investigations are conducted if male hypogonadism is suspected?

A

1) LH, FSH, testosterone
- if all low MRI pituitary
2) Prolactin
3) Sperm count
- Azoospermia = absence of sperm in ejaculate
- Oligospermia = reduced numbers of sperm in ejaculate
4) Chromosomal analysis (Klinefelter’s XXY)

239
Q

What is the treatment for male hypogonadism?

A

Replacement testosterone for all patients
For fertility: if hypo/pit disease
- subcutaneous gonadotrophins
Hyperprolactinaemia- dopamine agonist

240
Q

What are the endogenous sites of androgen production?

A

1) Interstitial Leydig cells of the testes
2) Adrenal cortex (males and females)
3) Ovaries
4) Placenta
5) Tumours

241
Q

What are the main actions of testosterone?

A

1) Development of the male genital tract
2) Maintains fertility in adulthood
3) Control of secondary sexual characteristics
4) Anabolic effects (muscle, bone)

242
Q

How much of circulating testosterone is protein bound?

A

98%

243
Q

What are the products of tissue-specific processing of testosterone? What receptor do these products act on?

A

1) Dihydrotestosterone (DHT)
acts via the androgen receptor
2) 17β-oestradiol
acts via the oestrogen receptor

244
Q

What are the different types of amenorrhoea?

A

1) Primary amenorrhoea
failure to begin spontaneous menstruation by age 16 years
2) Secondary amenorrhoea
absence of menstruation for 3 months in a woman who has previously had cycles
3) Oligomenorrhoea
irregular long cycles

245
Q

What are the possible causes of amenorrhoea?

A

1) Pregnancy / lactation
2) Ovarian failure
- premature ovarian failure
- ovariectomy / chemotherapy
- ovarian dysgenesis (Turner’s 45 X)
3) Gonadotrophin failure
- Hypo / pit disease
- Kallmann’s syndrome (anosmia, low GnRH)
- Low BMI
- Post pill amenorrhoea
4) Hyperprolactinaemia
5) Androgen excess: gonadal tumour

246
Q

What investigations are conducted in a patient with amenorrhoea?

A 
Pregnancy test
LH, FSH, oestradiol
Day 21 progesterone
Prolactin, thyroid function tests
Androgens (testosterone, androstenedione, DHEAS)
Chromosomal analysis (Turner's 45 X)
Ultrasound scan ovaries / uterus
247
Q

What is the treatment for amenorrhoea?

A

1) Treat the cause (e.g. low weight)
2) Primary ovarian failure - infertile, HRT
3) Hypothalamic / pituitary disease
- HRT for oestrogen replacement
- Fertility: gonadotrophins (LH and FSH) - part of IVF treatment

248
Q

What diseases have an increased risk in polycystic ovarian syndrome?

A

Increased cardiovascular risk

Increased insulin resistance ( >diabetes)

249
Q

What is the criteria to diagnose PCOS?

A

Need 2 of the following:

  • polycystic ovaries on ultrasound scan
  • oligo- / anovulation
  • clinical / biochemical androgen excess
250
Q

What are the clinical features of PCOS?

A

1) Hirsuitism
2) Menstrual cycle disturbance
3) Increased BMI

251
Q

What is the treatment for PCOS with regard to fertility?

A

Metformin
Clomiphene
Gonadotrophin therapy as part of IVF treatment

252
Q

What is the mechanism of clomiphene?

A

An anti-oestrogenic in the hypothalamo-pituitary axis
Binds to oestrogen receptors in the hypothalamus thereby blocking the normal negative feedback, resulting in an increase in the secretion of GnRH and gonadotrophins

253
Q

How is prolactin secretion controlled?

A

Thyrotrophin-releasing hormone stimulates the pituitary to release prolactin
Dopamine inhibits the release of prolactin
Prolactin has negative feedback on the hypothalamus (inhibits GnRH pulsatility) and on LH actions on ovary / testes

254
Q

What are the causes of hyperprolactinaemia?

A

1) Dopamine antagonist drugs
- Anti-emetics (metoclopramide)
- Anti-psychotics (phenothiazines)
2) Prolactinoma
3) Stalk compression due to pituitary adenoma
4) PCOS
5) Hypothyroidism
6) Oestrogens (OCP), pregnancy, lactation
7) Idiopathic

255
Q

What are the clinical features of hyperprolactinaemia?

A 
Galactorrhoea
Reduced GnRH secretion / LH action - hypogonadism
Prolactinoma
- headache
- visual field defect
256
Q

What is the treatment of hyperprolactinaemia?

A

1) Treat the cause - stop drugs
2) Dopamine agonist
- Bromocriptine
- Cabergoline
3) Prolactinoma
- Dopamine agonist therapy
- Pituitary surgery rarely needed

257
Q

A male presents to endocrine clinic who has had bilateral orchidectomy. What would you expect his blood results to show?

A

Low testosterone
High LH
High FSH

258
Q

A young woman presents to endocrine clinic who complains of secondary amenorrhoea and galactorrhoea. Her GP measured her prolactin at 4500 (high). What would you expect her blood results to show?

A

Low LH
Low FSH
Low oestradiol

259
Q

What is the mechanism of cabergoline? How is it used to treat a prolactinoma?

A

It is a dopamine agonist. It inhibits prolactin which brings down the prolactin levels and shrinks the tumour

260
Q

What causes hypothalamic amenorrhoea? Why?

A

Over-exercising
Severe weight loss
Anorexia
Less fat = less leptin. Leptin produced from adipose tissue linked to amenorrhoea

261
Q

If you are prescribed cabergoline to treat a prolactinoma when would it be necessary to continue treatment prior to conceiving and when would it be possible to stop taking it? Can you stop taking it indefinitely?

A

Depends on the size of the prolactinoma
If it is a macroprolactinoma that is touching the optic chiasm then continue cabergoline
If it is a microprolactinoma stop taking cabergoline and monitor headaches and visual field every trimester

262
Q

How does cabergoline affect a woman who wants to breastfeed? How is cabergoline managed in a woman who wants to breastfeed?

A

If you are taking cabergoline you cannot breastfeed.
Take cabergoline until 34 weeks then monitor the visual field and headaches to see if the prolactinoma is growing or compressing the optic chiasm

263
Q

What investigations would be performed on a woman of 30 who has not had a period for 3 months and has a BMI of 18?

A

Pregnancy test
Blood test (prolactin, LH, FSH, oestrogen, hyper/hypothyroid, androgens- PCOS)
High prolactin- pituitary MRI
Low oestrogen, high LH and FSH = something wrong with ovaries

264
Q

If a woman presents with the following results what is the interpretation?
High oestrogen
Low LH
Low FSH

A

Pregnancy

265
Q

If a woman presents with the following results what is the interpretation?
Low oestrogen
Low LH
Low FSH

A

High prolactin

Prolactinoma / pituitary tumour

266
Q

If a woman presents with the following results what is the interpretation?
Low oestrogen
High LH
High FSH

A

Damage to the gonads

267
Q

Why must oestradiol be given in higher doses if administered orally? How can this be avoided?

A

It undergoes extensive first pass metabolism

Can be avoided by administering it intramuscularly or as a transdermal patch

268
Q

How much of circulating oestrogen is plasma protein bound? What proteins bind oestrogen?

A

70%

Sex hormone binding globulin or albumin

269
Q

What are the different types of contraceptive?

A

1) Combined oral contraceptives
2) Progesterone only contraceptive
3) “Emergency” contraceptive

270
Q

How does a combined oral contraceptive work to prevent pregnancy?

A
  • Feedback actions of progesterone in the hypothalamus and pituitary
  • Progesterone thickens cervical mucus which provides hostile environment to sperm
  • Oestrogen up-regulates progesterone receptors, enhancing sensitivity to progesterone
  • Oestrogen counteracts the androgenic effects of synthetic progesterone, preventing masculinisation
  • Oestrogen contributes to negative feedback at hypothalamus and pituitary, by synergising with progesterone
271
Q

What are the different types of combined oral contraceptive?

A

Monophasic: one concentration taken throughout
Triphasic: 3 step-wise changes in oestrogen/progesterone ratio

272
Q

What are the side effects of oestrogen?

A

Increased clotting factors (increased thromboembolic disease)
Increased proliferation of endometrium (increased risk of cancer)
Breast discomfort
Increased water and salt retention may cause oedema, increased hypertension)
Nausea (triggering vomiting centre of the brain)
Headaches
Increased weight gain (fat deposition and oedema)

273
Q

What is the effectiveness of the emergency contraception?

A

75-85%

274
Q

What is menopause?

A

Permanent cessation of menstruation resulting from the loss of ovarian follicular activity and 12 months of amenorrhoea at the time of midlife (arounf 50, range 45-55)

275
Q

What are the symptoms of menopause?

A
  • Irregular cycles and hot flushes (inc. at night- insomnia)
  • Psychosocial symptoms (e.g. depression, mood swings, loss of energy)
  • Translucent thin skin
  • Decreased libido
  • Urogenital atrophy
276
Q

What complications are associated with menopause?

A

Osteoporosis: oestrogen deficiency- loss of bone matrix, decrease in bone mass and increased fracture risk
Cardiovascular disease: women are protected against CVD before menopause, but have the same risk as men by 70 years

277
Q

What are the different types of HRT? When are they used? Give an example of each drug.

A

Oestrogen-only: Used for women who have had a hysterectomy.
e.g. Premarin
Combined: Used to prevent endometrial hyperplasia in all other women.
e.g. PremPro, CEEs and medroxyprogesterone

278
Q

What hormone controls tubular fluid reabsorption?

A

Oestrogen

279
Q

What hormone controls nutrients and glycoprotein secretion into epididymal fluid?

A

Androgens

280
Q

What enzyme converts androgens to oestrogens?

A

Aromatase

281
Q

What does the semen contain? How many spermatozoa in the semen?

A

Semen:

  • Spermatozoa (15-120 x 10⁶/ml)
  • Seminal fluid (2-5ml)
  • Leucocytes
  • Potentially viruses (e.g. hepatitis B, HIV)
282
Q

What percentage of spermatozoa in the ejaculate enter the cervix?

A

1%

283
Q

Where is seminal fluid produced?

A 
Small contribution from
- Epididymis/testis
Mainly from accessory sex glands
- Seminal vesicle
- Prostate
- also bulbourethral glands
284
Q

What is capacitation of the sperm? What is the process?

A

Maturation of the sperm so it can achieve fertilising capability

  • Loss of glycoprotein coat
  • Change in the surface membrane characteristics
  • Whiplash movements of the tail
285
Q

What hormone is capacitation of sperm dependent on? Where does it occur?

A

Oestrogen-dependent
Takes place in ionic and proteolytic environment of the fallopian tube
Ca²⁺ dependent mechanism

286
Q

What is the acrosome reaction?

A

1) Sperm binds to the ZP3 receptors on the glycoprotein coating of the ovum (zona pellucida)
2) This causes a Ca²⁺ influx into the sperm (stimulated by progesterone)
3) The sperm then releases hyaluronidase and proteolytic enzymes
4) Sperm then penetrates the zona pellucida

287
Q

What does hyaluronidase do?

A

Breaks polysaccharides

288
Q

What happens when fertilisation occurs? What is the process?

A

Triggers a cortical reaction
Cortical granules are located in the cortex (underneath the plasma membrane of the ovum) and these fuse with the membrane once a sperm has entered and release their contents into zona pellucida which causes if to degrade ZP2 and ZP3 which prevents sperm from binding

289
Q

Where does fertilisation occur?

A

In the fallopian tube

290
Q

What are polar bodies?

A

Produced from unequal division of the ovum; contains only genetic material, no cytoplasm

291
Q

How long can a fertilised ovum survive before implantation as it travels down the fallopian tube? How does it receive nutrients?

A

Can last around 9-10 days

Receives nutrients from uterine secretions

292
Q

How does implantation of a blastocyst occur?

A

Attachment phase: outer trophoblast cells contact uterine surfece epithelium
Decidualization of underlying stromal tissue (within a few hours)

293
Q

What hormones are requires for implantation of a blastocyst to occur?

A

Requires progesterone domination in the presence of oestrogen

294
Q

What hormones are secreted from the secretory glands in the endometrial lining that promotes adhesion of the blastocyst?

A

LIF (leukaemia inhibitory factor)

IL11

295
Q

What is decidualisation? What changes occur?

A

Endometrial changes due to progesterone

  • Glandular epithelial secretion
  • Glycogen accumulation in stromal cell cytoplasm
  • Growth of capillaries
  • Increased vascular permeability (oedema)
296
Q

What is the first hormone to peak during pregnancy (<10 weeks)

A

hCG

human chorionic gonadotrophin

297
Q

What happens to the hormones in the first 5-6 weeks of pregnancy?

A

Rising circulating progesterone and oestradiol
Essential for developing fetoplacental unit
Inhibits maternal LH and FSH (-ve feedback)

298
Q

Where is hCG produced?

A

Produced by the developing blastocyst

299
Q

At what point during pregnancy does the fetoplacental unit take over oestrogen production?

A

From day 40

300
Q

How does the placenta produce oestrogen?

A

The fetus and mother produce DHEAS which the placenta then converts to oestrogen

301
Q

What maternal hormones increase during pregnancy?

A
  • ACTH
  • Prolactin
  • Iodothyronines
  • Adrenal steroids
  • PTHrp (lactation)
302
Q

What maternal hormones decrease during pregnancy?

A
  • Gonadotrophins
  • TSH
  • hGH decreases as the placental hGH-variant increases towards term
303
Q

What effect does high ACTH have during pregnancy?

A

Would cause high cortisol, so normal pregnant women can be diagnosed with Cushing’s

304
Q

Why does prolactin increase during pregnancy? What impact does this have clinically?

A

High prolactin shuts off the HPG axis so you can’t become pregnant.
Clinically this means you can’t use prolactin levels to monitor a pituitary adenoma. Instead check visual field detects and headache symptoms

305
Q

What happens to thyroid hormones during pregnancy?

A

Thyroxine production (and T3 and T4) increases driven by hCG
TSH decreases due to negative feedback
Parathyroid related hormone (PTHrp) is produced by breast tissue and is involved in lactation increases during pregnancy and can cause hypercalcaemia

306
Q

What happens to gonadotrophins during pregnancy?

A

Levels decrease due to excess levels of oestrogen

307
Q

What happens to hGH (growth hormone) during pregnancy?

A

Decreases as the placental hGH increases towards term

308
Q

How does oxytocin cause contraction of breast tissue?

A

Stimulates an influx of calcium

309
Q

What hormones are involved in lactation?

A

Suckling stimulates the hypothalamus→pituitary to produce prolactin which stimulates milk synthesis and oxytocin which causes milk ejection

310
Q

If a patient has low Na⁺ and high K⁺ what does this mean?

A

They are dehydrated

311
Q

What is congenital adrenal hyperplasia?

A

Where a baby does not produce cortisol and aldosterone; less negative feedback so increased ACTH which drives hyperplasia of adrenals

312
Q

What is the commonest enzyme to be deficient in with congenital adrenal hyperplasia?

A

21 hydroxylase

313
Q

Why does virilisation occur with 21 hydroxylase deficiency?

A

21 hydroxylase deficiency prevents production of cortisol and aldosterone from cholesterol, so all reagents get pushed into testosterone production which causes virilisation

314
Q

How would you test for 21 hydroxylase insufficiency?

A
  • Would perform a blood test for 17 hydroxyprogesterone (which is proximal to block so expect it to be high- continuing feedback and not being converted)
  • High androgens and ACTH
  • Low aldosterone
315
Q

What treatment is used for 21 hydroxylase insufficiency?

A

Give hydrocortisone (or prednisolone which is longer lasting)

316
Q

What steroid replacement is needed peri-operatively for pituitary tumour removal surgery?

A

Need to give hydrocortisone (IV or intermittent IM following natural cycle) then taper dose down gradually
- done in case natural cells are removed
Aldosterone not under control of ACTH so doesn’t need replacement

317
Q

What advice is given to patients on cortisol replacement?

A
  • Need to double dose if you get ill (cold) for two days

- If you vomit you need to inject or go to A&E- FATAL

318
Q

How do you assess whether a patient needs long term steroid replacement?

A

Assess HPA axis when dose has been tapered down

- Insulin tolerence test (administer insulin to make them hypoglycaemic, then see if cortisol levels go up)

319
Q

How much of the body’s calcium is stored in bone?

A

> 95%

320
Q

What is the inorganic mineral component of bone? How much of bone is composed of this?

A

Calcium hydroxyapatite crystals fill the space between collagen fibrils
65% bone mass

321
Q

What are the organic components of bone? What percentage of bone is made up of this?

A

Osteoid- unmineralised bone (35% bone mass)

Type 1 collagen fibres (95%)

322
Q

What is the function of osteoblasts?

A

Synthesise osteoid and participate in mineralisation/calcification of osteoid
(Bone deposition)

323
Q

What is the function of osteoclasts?

A

Release lysosomal enzymes which break down bone

Bone resorption

324
Q

What is the function of osteocytes?

A

Make type I collagen and other extracellular matrix components

325
Q

How does the differentiation of osteoclasts occur from osteoblasts?

A

RANKL is expressed on the surface of osteoblasts

RANKL binds to RANK-R to stimulate osteoclast formation and activity

326
Q

What is osteoprotegerin?

A

A protein which is a decoy receptor for RANKL; inhibits osteoclast differentiation

327
Q

What are the two key hormones that regulate bone remodelling and calcium balance?

A 
Parathyroid hormone (PTH)
Calcitriol
328
Q

What stimulates PTH release?

A

Hypocalcaemia

329
Q

How is calcitriol produced?

A

Inactive vitamin D is synthesised in the skin
Converted to calcidiol in the liver
Converted to calcitriol in the kidney

330
Q

How does hypercalcaemia affect nerve and skeletal muscle excitability?

A

Ca²⁺ blocks Na⁺ influx, so less membrane excitability

331
Q

How does hypocalcaemia affect nerve and skeletal muscle excitability?

A

Enables greater Na⁺ influx, so more membrane excitability

332
Q

What are the signs and symptoms of hypocalcaemia?

A
  • Parasthesia (hands, mouth, feet, lips)
  • Convulsions
  • Arrhythmias
  • Tetany
333
Q

What is Chvostek’s Sign? What does this indicate?

A

The facial nerve is tapped just below the zygomatic arch
Positive response= twitching of facial muscles

Indicates neuromuscular irritability due to hypocalcaemia

334
Q

What is Trousseau’s sign? What does this indicate?

A

Inflation of blood pressure cuff for several minutes induces carpopedal spasm (painful spasm)

Neuromuscular irritability due to hypocalcaemia

335
Q

What are the possible causes of hypocalcaemia?

A

1) Vitamin D deficiency
2) Low PTH levels = hypoparathyroidism
- Surgical- neck surgery
- Autoimmune
3) PTH resistance
(e. g. Pseudohypoparathyroidism)
4) Renal
- Impaired 1α hydroxylation → decreased production of 1, 25(OH)₂D₃

336
Q

What are the signs and symptoms of hypercalcaemia?

A

1) Kidney stones
- polyurea and thirst
- nephrocalcinosis, renal colic, chronic renal failure
2) Abdominal moans - G.I. Effects
- anorexia, nausea, dyspepsia, constipation, pancreatitis
3) Psychic groans
- fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)

337
Q

What are the causes of hypercalcaemia?

A

1) Primary hyperparathyroidism
2) Malignancy- tumours/metastases
(often secrete a PTH-like peptide)
3) Conditions with a high bone turnover
(hyperthyroidism, Paget’s disease of bone- immobilised patient)
4) Vitamin D excess (rare)

338
Q

What causes hypercalcaemia and high PTH? Why are they both high?

A

Primary hyperparathyroidism
(adenoma secreting PTH)
PTH increases serum Ca²⁺ which provides negative feedback to parathyroid, ineffective due to autonomous PTH secretion

339
Q

What Ca²⁺ and PTH levels would you expect to see in hypercalcaemia of malignancy? Why?

A

High Ca²⁺
Low PTH
Malignancy causes release of PTH-related peptide which behaves exactly like PTH causing increase of serum Ca²⁺
Normal PTH is low because of negative feedback from Ca²⁺

340
Q

What are the effects of calcitriol?

A

1) Stimulates intestinal absorption of Ca²⁺ (and Mg²⁺) and PO₄³⁻. This provides the ions necessary for normal bone mineralisation
2) Regulates osteoblast differentiation
3) Increases renal Ca²⁺ reabsorption, decreases PO₄³⁻ reabsorption via FGF23- a hormone produced by bone which increases urine PO₄³⁻ excretion

341
Q

What does vitamin D deficiency result in, in adults and children? What are the symptoms?

A

In children: Rickets
In adults: Osteomalacia
Results in softening of bone, bone deformities, bone pain and severe proximal myopathy

342
Q

Where is vitamin D synthesised?

A

In the skin by converting UVB light

343
Q

What part of the process of production of active vitamin D occurs in the liver?

A

25 hydroxylation

Vitamin D → 25 OH-D

344
Q

What part of the process of production of vitamin D occurs in the kidneys? What enzyme catalyses this reaction?

A

1 hydroxylation catalysed by 1α-hydroxylase (stimulated by PTH)
25 OH-D → 1, 25 (OH)₂D

345
Q

What are the causes of vitamin D deficiency?

A

1) Diet
2) Lack of sunlight
3) G.I. malabsorption
e. g. coeliac disease, inflammatory bowel disease
4) Renal failure, liver failure
5) Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment

346
Q

What causes secondary hyperparathyroidism?

A

Low Ca²⁺due to vitamin D deficiency. PTH increases appropriately to try to normalise serum calcium

347
Q

How do you diagnose a vitamin D deficiency?

A
  • Plasma [25(OH)D₃] usually low
  • Plasma [Ca²⁺] low (may be normal if secondary hyperparathyroidism has developed)
  • Plasma [PO₄³⁻] low (as vitamin D required to absorb it in the gut)
  • [PTH] high (secondary hyperparathyroidism)
  • Radiological findings (variable)
    e. g. widened osteoid seams
348
Q

Where is 1α hydroxylase produced?

A

In the kidney

349
Q

How does renal failure contribute to hypocalcaemia?

A

1) Cannot produce 1α hydroxylase, so there is decreased Ca²⁺ absorption causing hypocalcaemia
2) As renal function decreases PO₄³⁻ excretion decreases which causes elevated PO₄³⁻ in the plasma. PO₄³⁻ binds calcium which decreases serum Ca²⁺ further

350
Q

What are Brown tumours?

A

Radiolucent bone lesions.

They reflect excessive osteoclastic bone resorption secondary to high PTH

351
Q

What is 25 hydroxy vitamin D₂?

A

Ergocalciferol

352
Q

What is 25 hydroxy vitamin D₃?

A

Cholecalciferol

353
Q

What treatment is given to patients with vitamin D deficiency if they have normal renal function?

A

Give 25 hydroxy vitamin D (25 (OH) D)

Patient can convert this to 1, 25 (OH)₂ D via 1α hydroxylase

354
Q

What treatment is given to patients with vitamin D deficiency if they have renal failure?

A

Patient will have inadequate 1α hydroxylase so they cannot activate 25 (OH) D
They must be given Alfacalcidol- 1α hydroxycholecalciferol

355
Q

What can result from vitamin D excess (intoxication)?

A

Can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium

356
Q

What can cause vitamin D intoxication?

A

1) Excessive treatment with active metabolites of vitamin D
e. g. Alfacalcidol
2) Granulomatous disease
e. g. sarcoidosis, leprosy and tuberculosis (macrophages in the granuloma produce 1α hydroxylase to convert 25(OH)D to the active metabolite 1, 25(OH)₂D

357
Q

What is osteoporosis? How is it measured?

A

Defined as having a bone mineral density (BMD) that is 2.5 standard deviations or more below the average value for young healthy adults.
Measured by Dual Energy X-ray Absorptiometry (DEXA)

358
Q

What are the pre-disposing conditions for osteoporosis?

A

1) Post-menopausal oestrogen deficiency
2) Age-related deficiency in bone homeostasis (men and women)
e. g. osteoblast senescence
3) Hypogonadism in young women and in men
4) Endocrine conditions
- Cushing’s syndrome
- Hyperthyroidism
- Primary hyperparathyroidism
5) Iatrogenic
- Prolonged cause of glucocorticoids
- Heparin

359
Q

What are the treatment options for osteoporosis?

A

1) Oestrogen/selective oestrogen receptor modulators
2) Bisphosphonates
3) Denosumab
4) Teriparatide

360
Q

What are the effects of treating post-menopausal women with pharmacological doses of oestrogen?

A
  • Antiresorptive effects on the skeleton

- Prevents bone loss

361
Q

Why do post-menopausal women with an intact uterus need additional progesterone when on HRT?

A

To induce a bleed to prevent endometrial hyperplasia

362
Q

Why is the use of HRT limited?

A
  • Increased risk of breast cancer

- Venous thromboembolism

363
Q

What are the different types of SERMs? What do they do? Give examples.

A

Selective oEstrogen Receptor Modulators:

1) Tissue-selective ER antagonist
e. g. tamoxifen
- Antagonises ERs in breast but has oestrogenic activity in bone
- Oestrogenic effects on endometrium limit it’s use in osteoporosis management
2) Tissue selective ER agonist
e. g. raloxifen (further developed for it’s selectivity on bone)
- Oestrogenic activity in bone. Anti-oestrogenic at breast and uterus
- Risks include venous thromboembolism and stroke

364
Q

What do bisphosphonates do?

A
  • Bind avidly to hydroxyapatite and ingested by osteoclasts - impair ability of osteoclasts to reabsorb bone
  • Decrease osteoclast progenitor development and recruitment
  • Promote osteoclast apoptosis
    NET RESULT: Reduced bone turnover
365
Q

What conditions are bisphosphonates used for?

A

1) Osteoporosis- first line treatment
2) Malignancy
- Associated hypercalcaemia
- Reduce bone pain from metastases
3) Paget’s disease- reduce bony pain
4) Severe hypercalcaemic emergency- I.V. initially (rehydration first)

366
Q

What are the unwanted actions of bisphosphonates?

A

1) Oesophagitis
- may require switch from oral to IV preparation
2) Flu-like symptoms (IV)
- often limited to first dose
3) Osteonecrosis of the jaw
- greatest risk in cancer patients receiving IV bisphosphonates
4) Atypical fractures
- may reflect over-suppression of bone remodelling in prolonged bisphosphonate use

367
Q

How does denosumab inhibit bone resorption? How is it administered?

A

It is a human monoclonal antibody
- Binds RANKL inhibiting osteoclast formation and activity
- Hence inhibits osteoclast-mediated bone resorption
Administered as a subcutaneous injection every 6 months. 2nd option following bisphosphonates

368
Q

What is teriparatide?

A

Recombinant PTH fragment- amino-terminal 34 amino acids of native PTH
Increases bone formation and bone resorption, but formation outweighs resorption
Subcutaneous injection

369
Q

What are the options for treatment of osteoporosis in the order that they would be given?

A

1) Bisphosphonates
2) Denosumab
3) Teriparatide

370
Q

What is Paget’s disease?

A

Accelerated, localised but disorganised bone remodelling
Excessive bone resorption (↑ osteoclast activity) followed by a compensatory increase in bone formation leads to a formation of woven bone (structurally disorganised)- mechanically weaker than normal adult lamellar bone
Results in:
- Bone fragility
- Bone hypertrophy and deformity

371
Q

What is the presentation of Paget’s disease?

A

Most patients are asymptomatic

Characterised by abnormal, large osteoclasts- excessive in number

372
Q

What are the clinical features of Paget’s disease?

A
  • Skull, thoracolumbar spine, pelvis, femur and tibia most commonly affected
  • Arthritis
  • Fracture
  • Pain
  • Bone deformity
  • Increased vascularity (warmth over affected bone)
  • Deafness- cochlear involvement
  • Radiculopathy- due to nerve compression
373
Q

How is Paget’s disease of bone diagnosed?

A
  • Plasma [Ca²⁺] normal
  • Plasma [alkaline phosphatase] usually increased
  • Plain xrays:
    • Lytic lesions (early)
    • Thickened, enlarged, deformed bones (later)
  • Radionuclide bone scan demonstrates extent and locations of skeletal involvement
374
Q

What are the treatment options for Paget’s disease?

A

1) Bisphosphonates
- very helpful for reducing boney pain and disease activity
2) Simple analgesia

375
Q

If a patient has high calcium and low phosphate with high PTH what would the diagnosis be?

A

Primary hypoparathyroidism

376
Q

What is the definitive treatment of primary hyperparathyroidism?

A

Remove parathyroid with adenoma

377
Q

What is the likely diagnosis if a patient has high calcium and low PTH?

A

Malignancy producing PTHrp

378
Q

What is the treatment for a patient who has a malignancy producing PTHrp resulting in high calcium and low PTH?

A

Treat with bisphosphonates

379
Q

What is the key brain area involved in the regulation of food intake?

A

The arcuate nucleus

380
Q

How is the arcuate nucleus able to monitor food intake?

A

Has an incomplete blood-brain barrier which allows access to peripheral hormones. It integrates peripheral and central feeding signals

381
Q

What are the two neural populations in the arcuate nucleus?

A

1) Stimulatory
(NPY/Agrp neurons)
2) Inhibitory
(POMC neuron)

382
Q

What is the role of NPY/Agrp neurons in the arcuate nucleus?

A

Increase appetite

383
Q

What is the role of POMC neurons in the arcuate nucleus?

A

Decrease appetite

384
Q

How does POMC decrease appetite?

A

POMC is cleaved to produce α-MSH, an agonist of MC4R.

α-MSH activates MC4R which decreases food intake

385
Q

Where is the melanocortin 4 receptor located?

A

MC4R is located in the paraventricular nucleus

386
Q

How does Agrp work to increase appetite?

A

It is an endogenous antagonist. It blocks the MC4R receptor and blocks α-MSH signalling which increases food intake

387
Q

What do POMC and MC4R mutations result in?

A

Obesity

388
Q

How does a POMC mutation present?

A

Hungry all the time
No cortisol regulation
Pale skin and red hair

389
Q

What was the presentation of the ob/ob mouse?

A 
Similar to a starved animal (minus diabetes and obesity)
Recessive mutation
- Profoundly obese
- Diabetic
- Infertile
- Stunted linear growth
- Decreased body temperature
- Decreased energy expenditure
- Decreased immune function
Missing leptin!
390
Q

What leptin level will a person with low body fat have?

A

Low

391
Q

What effect does central or peripheral administration of leptin have?

A
  • Decreases food intake

- Increases thermogenesis

392
Q

What effect does leptin have on the arcuate nucleus?

A

Activates POMC

Inhibits NPY/ Agrp neurons

393
Q

What leptin level will a person with high body fat have?

A

High

394
Q

The presence of leptin tells the brain what?

A

That the body has sufficient fat reserves for normal functioning

395
Q

Insulin circulates at levels proportional to what?

A

Body fat

396
Q

Ghrelin regulates food intake when combined with what enzyme?

A

Ghrelin O-acyltransferase

GOAT

397
Q

What effect does ghrelin have on neurons in the arcuate nucleus?

A
  • Stimulates NPY/Agrp neurons
  • Inhibits POMC neurons
  • Increases appetite
398
Q

What do L cells secrete?

A

L cells sense what is going on in the gut. They cause a wave of Ca²⁺ down the gut and exocytosis of gut hormones
L cells secrete PYY and GLP-1

399
Q

How big is Peptide YY? What amino acids are in the active form?

A

36 amino acids long

Cleaved to 3-36 AA in the active form

400
Q

What effect does PYY have on neurons in the arcuate nucleus?

A
  • Inhibits NPY release
  • Stimulates POMC
  • Decreases appetite
401
Q

What does glucagon-like peptide-1 do?

A

Important in stimulating glucose-stimulated insulin release (incretin role) and also reduces food intake

402
Q

Why is GLP-1 not used as a treatment for obesity?

A

Poor half-life

Effective but it is inactivated very easily

403
Q

What is Saxenda?

A

A long-acting glucagon-like peptide-1 receptor agonist

404
Q

What are the limitations of using PYY as a drug target?

A

It has a narrow therapeutic window:
- Above the correct dose causes nausea
- Below has no effect on appetite
Different people respond to the drug differently. It also has a short half life

405
Q

What comorbidities are associated with obesity?

A
  • Depression
  • Sleep apnoea
  • Bowel cancer
  • Osteoarthritis
  • Gout
  • Stroke
  • Myocardial infarction
  • Hypertension
  • Diabetes
  • Peripheral vascular disease
406
Q

As a percentage how likely is obesity inherited?

A

60-80%

407
Q

What is the “Thrifty Gene Hypothesis”?

A

Suggests specific genes were selected to increase metabolic efficiency and fat storage.
It was evolutionary sensible to put on weight
Thin humans didn’t survive famines, so they didn’t pass on their genes to modern humans

408
Q

What is the “Adaptive Drift Hypothesis”?

A

Normal distribution of body weight:
- The fat are eaten
- The thin starve
When humans learned to defend against predators obesity was not selected against. Putting on body fat then a neutral change (genetic drift). In current context, the inheritors of these genes become obese

409
Q

What is cachexia? What type of diabetes is it associated with?

A

Weakness and wasting of the body die to a chronic condition.

Associated with type 1 diabetes

410
Q

What type of type I diabetes occurs when a patient is over 40?

A

Latent autoimmune diabetes in adults (LADA)

411
Q

What is the mechanism of Maturity Onset Diabetes of the Young?

A

Single gene mutation in the insulin receptor; presents at a young age phenotypically as Type I or type II
Mutations of transcription factor genes, glucokinase gene

412
Q

What type of diabetes has a maternal predisposition?

A

Mitochondrial diabetes

413
Q

What causes type I diabetes onset?

A

An environmental trigger initiates autoimmune destruction of islets

414
Q

What causes type II diabetes onset?

A

Genetic predisposition and obesity lead to insulin resistance causing hyperglycaemia.

415
Q

Why do patients with type II diabetes get β-cell failure?

A

Because they become resistant to insulin the pancreas has to produce so much that the cells start to fail.

416
Q

What peptide is released with insulin, that is used to detect low insulin release?

A

C-peptide

417
Q

What is the Honeymoon phase in type I diabetes?

A

Where the pancreas produces the last amount of insulin before it completely fails; then the patient permanently has type I diabetes

418
Q

Which HLA-DR alleles significantly increase the genetic susceptibility to type I diabetes?

A

HLA-DR3

HLA-DR4

419
Q

What environmental factors increase the prevalence of type I diabetes?

A

Season. Onset is more common in autumn and winter. Suggests this could be due to infection

420
Q

What markers are typically used to measure diabetes?

A

Islet cell antibodies (ICA)- group O human pancreas

Glutamic acid decarboxylase (GADA) - widespread neurotransmitter

421
Q

What are the signs and symptoms of type I diabetes?

A

Symptoms

  • Polyuria
  • Nocturia
  • Polydispia
  • Blurred vision
  • ‘Thrush’
  • Weight loss
  • Fatigue

Signs

  • Dehydration
  • Cachexia
  • Hyperventilation
  • Smell of ketones
  • Glycosuria
  • Ketonuria
422
Q

How is fat stored in adipocytes? What is this fat broken down into?

A

Triglyceride, broken down into glycerol + fatty acids

423
Q

What happens to glycerol from adipocytes when triglycerides have been broken down? What hormones stimulate this?

A

It is transported to the liver where it enters the Kreb’s cycle to produce glucose.
Stimulate by catecholamines and growth hormone

424
Q

What happens to fatty acids from adipocytes once glycerol has been broken down?

A

The fatty acids are transported to the liver where they produce ketones

425
Q

What are ketones used as a marker for?

A

Insulin deficiency

426
Q

What are the long term complications associated with diabetes?

A
  • Retinopathy
  • Nephropathy
  • Neuropathy
  • Vascular disease
427
Q

What is the recommended diet in a type I diabetes patient?

A
  • Reduce calories as fat
  • Reduce calories as refined carbohydrate
  • Increase calories as complex carbohydrate
  • Increase soluble fibre
  • Balanced distribution of food over the course of the day with regular meals and snacks
428
Q

When is insulin treatment administered and how long does it last?

A 
With Meals:
- Short acting
- Human insulin
- Insulin analogue (e.g. Lispro, Aspart, Glulisine)
Background
- Long acting
- Non-c bound to zinc or protamine
- Insulin analogue (e.g. Glargine, Determir, Degludec)
429
Q

How does HbA1c indicate glucose levels? What is this measure used for?

A

HbA1c red cells reacts with glucose irreversibly. This gives a good long-term measure of glycaemic control and is related to the risk of complications
Lowering HbA1c is associated with a lower risk of complication particularly microvascular complications

430
Q

What are the acute complications of type I diabetes?

A

Ketoacidosis

1) Hyperglycaemia
- reduced tissue glucose utilisation
- increased hepatic glucose production
2) Metabolic acidosis
- circulating acetoacetate and hydroxybutyrate
- Exacerbated by osmotic dehydration and poor tissue perfusion

431
Q

What plasma glucose level defines hypoglycaemia?

A

<3.6mmol/L

432
Q

What is severe hypoglycaemia?

A

Any hypo requiring help of another person to treat

433
Q

At what glucose level are mental processes impaired?

A

<3mmol/L

434
Q

At what glucose level is consciousness impaired?

A

<2mmol/L

435
Q

What are the signs and symptoms of increased autonomic activation caused by hypoglycaemia?

A
  • Palpitations (tachycardia)
  • Tremor
  • Sweating
  • Pallor/cold extremities
  • Anxiety
436
Q

What are the signs and symptoms of impaired CNS function caused by hypoglycaemia?

A
  • Drowsiness
  • Confusion
  • Altered behaviour
  • Focal neurology
  • Coma
437
Q

How is hypoglycaemia treated in a conscious patient?

A

Oral

  • Food
  • Glucose (solution or tablets)
  • complex carbohydrate (to maintain blood glucose after initial treatment)
438
Q

How is hypoglycaemia treated in an unconscious patient?

A
  • IV dextrose
    (e. g. 10% glucose infusion)
  • 1mg glucagon IM
  • Avoid concentrated solutions if possible
    (e. g. 50% glucose)
439
Q

What type of diabetes is ketosis prone?

A

Type I diabetes mellitus

Although can occur in type II

440
Q

What fasting blood glucose level is diagnostic of diabetes? What does this increase to following glucose administration?

A

Fasted: >7.0mmol/L

2 hours: >11.1mmol/L

441
Q

What are a normal fasting glucose and 2 hour reading following glucose administration?

A

Fasted: 4-6mmol/L

2 hours: <7.8mmol/L

442
Q

What range is diagnostic of impaired glucose tolerance for both fasting and 2 hours following glucose administration?

A

Fasted: 6.1-6.9mmol/L

2 hours: 7.9-11mmol/L

443
Q

What result would indicate diabetes following a random blood test?

A

> 11.1mmol/L

444
Q

In what country is type II diabetes most common?

A

India

445
Q

What factors are thought to predispose patients to MODY?

A

Maturity Onset Diabetes of the Young

  • Genetics
  • Intrauterine calorie restriction
  • Low birth weight
  • Some fatty acids damage insulin secretion
446
Q

What is the inheritance pattern of MODY?

A

Autosomal dominant

447
Q

What type of diabetes is more genetic?

A

Type II diabetes

448
Q

How many type II diabetes patients are obese?

A

80%

449
Q

What happens to cholesterol in type II diabetes?

A

Patients get dyslipidaemia

450
Q

How does insulin release usually occur in a healthy patient?

A

First phase response after eating a meal- regulated by GLP-1 (stored insulin), then gradual release as β-cells produce insulin

451
Q

What is glucose converted into in muscle?

A

Glycogen

452
Q

What process converts glycerol into glucose?

A

Gluconeogenesis

453
Q

Where does the liver get most of it’s fatty acids from?

A

Omental fat

454
Q

What protein is thought to be responsible for the mechanism of type II diabetes?

A

Adiponectin

455
Q

What type of obesity drives changes to metabolism which predispose to type II diabetes?

A

Central or omental obesity

456
Q

What is a common side effect of diabetes treatments?

A

Weight gain

457
Q

What is the presentation of type II diabetes?

A
  • Osmotic symptoms
  • Infections
  • Screening test
  • Presentation with complications
    Acute; hyperosmolar coma
    Chronic; ischaemic heart disease, retinopathy
458
Q

What are the complications of type II diabetes?

A

1) Microvascular
- retinopathy
- nephropathy
- neuropathy
2) Macrovascular
- Ischaemic heart disease
- Cerebrovascular
- Renal artery stenosis
- PVD
3) Metabolic
- Lactic acidosis
- Hyperosmolar
4) Treatment
- Hypoglycaemia

459
Q

What is the basic management of type II diabetes mellitus?

A

1) Education
2) Diet
3) Pharmacological treatment
4) Complication screening

460
Q

What diet is recommended in type II diabetes mellitus?

A
  • Control total calories/increase exercise (weight)
  • Reduce refined carbohydrate (less sugar)
  • Increase complex carbohydrate (more rice etc)
  • Reduce fat as proportion of calories (less IR)
  • Increase unsaturated fat as proportion of fat (IHDL)
  • Increase soluble fibre (longer to absorb carbohydrate)
461
Q

What is monitored during type II diabetes?

A
  • Weight
  • Glycaemia
  • Blood pressure
  • Dyslipidaemia
462
Q

What is the most effective drug to treat diabetes mellitus?

A

Metformin

463
Q

What patients are prescribed metformin? How does metformin work? Give examples.

A

Overweight patients with type II diabetes where diet alone has not succeeded
Reduces insulin resistance
- Reduced hepatic glucose output
- Increases peripheral glucose disposal
GI side effects
Do not use if severe liver, severe cardiac or mild renal failure
e.g. biguanide

464
Q

What is the mechanism of action of glibenclamide?

A

Enters β-cells and blocks K⁺ channel (like glucose); voltage change activates Ca⁺ channel which causes an influx of Ca⁺ which stimulates the release of insulin (mimics and increases the insulin response)

465
Q

What patients are prescribed sulphonylurea? What are the side effects? Give examples.

A

Lean patients with type II diabetes where diet alone has not succeeded
Side effects: hypoglycaemia, weight gain
e.g. Glibenclamide

466
Q

How does arbose work? What are the side effects?

A

Alpha glucosidase inhibitor
Prolongs absorption of oligosaccharides. Allows insulin secretion to cope, following defective first phase insulin
As effective as metformin
Side effects flatus

467
Q

How do thiazolidinediones work? What are the side effects? Give an example

A

Peroxisome proliferator-activated receptor agonists PPAR-Y
Insulin sensitizer, mainly peripheral
Adipocyte differentiation modified, weight gain but peripheral not central
Improvement in glycaemia and lipids
Side effects: older types of hepatitis and heart failure

468
Q

What hormone is responsible for an increased response to insulin if it is taken orally compared to if it is administered intravenously? What else does this hormone do?

A

GLP-1 is secreted in response to nutrients which stimulates insulin and suppresses glucagon
Increases satiety
Restores β-cell glucose sensitivity

469
Q

Why can GLP-1 not be used as a drug to treat diabetes?

A

It has a short half-life, and is rapidly degraded by enzyme dipeptidyl peptidase-4 (DPPG-4)

470
Q

How do GLP-1 agonists work? Give examples?

A

Injectable; long-acting
Decrease [glucagon] and [glucose]
Weight loss
e.g. Exenatide, liraglutide

471
Q

How do gliptins work?

A 
DPPG-4 inhibitor
Increase the half life of exogenous GLP-1
Increase [GLP-1]
Decrease [glucagon] and [glucose]
Neutral on weight
472
Q

How does empagliflozin work?

A

Inhibits Na-Glu transporter, increases glycosuria

Side effects: UTIs

473
Q

Other than glycaemia what other factors need to be controlled in type II diabetes petients?

A

Blood pressure
- In possibly 90% of patients
Diabetic dyslipidaemia
- causes ↑ cholesterol; ↑ triglyceride; ↓HDL

474
Q

What is the most effective method for reduction of incidence in type II diabetes?

A

Lifestyle changes

475
Q

What type of diabetes is more prevalent?

A

Type II

476
Q

What type of diabetes has acute onset?

A

Type I

477
Q

What type of diabetes has gradual onset?

A

Type II

478
Q

What type of diabetes is more common in caucaseans?

A

Type I

479
Q

What could precipitate diabetic ketoacidosis?

A
  • New diagnosis of type I diabetes mellitus
  • Not taking insulin
  • Incurrent stress (e.g. pneumonia, heart attack)
  • Fasting and not taking enough insulin
480
Q

What will happen if there is deficient [insulin]?

A

High hepatic glucose output and deficient muscle glucose uptake

481
Q

What causes hyperglycaemia?

A

Insulin deficiency

Stress hormone

482
Q

What causes ketosis?

A

Insulin deficiency
Stress hormone
Fasting

483
Q

Why does HCO₃⁻ concentration decrease with diabetic ketoacidosis?

A
  • Impaired production from the pancreas

- Increased H⁺ buffering

484
Q

What are the clinical features of diabetic ketoacidosis?

A
  • Dehydration
  • Insulin deficiency
  • Total body K⁺ deficiency, although plasma [K⁺] high
  • Acidotic
  • Risk of arrhythmia, infection and dilated stomach
  • Polyuria and polydipsia due to osmotic diuresis
  • Hyperventilation (Kussmaul)
  • Abdominal pain, vomiting
  • Coma
  • Glycosuria and ketonuria
485
Q

What investigations are conducted for diabetic ketoacidosis?

A
  • Capillary glucose
  • Plasma glucose
  • Creatinine, K⁺, Na⁺
  • FBC
  • Arterial blood gases
  • Amylase (triglyceride)
  • ECG
  • CXR (chest X-ray)
  • Septic screen
486
Q

What is the treatment for diabetic ketoacidosis?

A 
1) Fluid
(H₂O 100ml/kg; Na⁺ 8mmol/kg in 24 hours)
2) Insulin
3) Potassium
4) Bicarbonate
5) Other measures
- Cardiac monitor (arrhythmias)
- Catheterise
- Antibiotics
- Nasogastric tube (gastroparesis)
- Consider heparin
- Consider arterial line (very acidotic) and central line (elderly or when cardiac failure)
487
Q

What are the dangers associated with acidaemia?

A
  • Negative inotropism
  • Peripheral vasodilation
  • Hypotension
  • Cerebral inhibition
488
Q

What are the dangers associated with bicarbonate?

A
  • Hypokalaemia
  • Hypernatraemia
  • Rebound alkalosis
  • CSF acidosis
  • Impaired oxyHb dissociation
489
Q

How do you prevent diabetic ketoacidosis?

A
  • Education
  • Never stop insulin
  • Check glucose and modify insulin if ill
  • Admit if vomiting
490
Q

What stimulates and inhibits proteolysis?

A

Stimulates: Cortisol
Inhibits: Insulin

491
Q

What stimulates protein synthesis?

A 
Insulin
Growth hormone (IGF-1)
492
Q

What is the hepatic glucose output after a 10 hour fast?

A

25%

493
Q

What sites are affected by microvascular complications of diabetes?

A

1) Retinal arteries
2) Glomerular arterioles (kidney)
3) Vasa nervorum (tiny blood vessels that supply nerves)

494
Q

What percentage HbA1c is indicative of type II diabetes?

A

> 6.5%

495
Q

What factors increase the risk of microvascular complications?

A

1) Severity of hyperglycaemia
2) Hypertension
3) Genetic
4) Hyperglycaemic memory
5) Tissue damage through originally reversible and later irreversible alterations in proteins

496
Q

What are the clinical features of background diabetic retinopathy?

A
  • Hard exudates (cheese colour, lipid)
  • Microaneurysms (“dots”)
  • Blot haemorrhages
497
Q

What are the clinical features of pre-proliferative diabetic retinopathy?

A
  • Cotton wool spots also called soft exudates

- Represent retinal ischaemia

498
Q

What are the clinical features of proliferative diabetic retinopathy?

A
  • Visible new vessels

- On disk or elsewhere in retina

499
Q

What are the clinical features of maculopathy?

A
  • Hard exudates near the macula
  • Same disease as background, but happens to be near the macula
  • Changes around the macula affect colour vision
  • This can threaten direct vision
500
Q

What is the management procedure for background diabetic retinopathy?

A
  • Improve control of blood glucose

- Warn patient that warning signs are present

501
Q

What is the management procedure for pre-proliferative diabetic retinopathy?

A

Suggests general ischaemia; if left alone new vessels will grow
Treated with pan retinal photocoagulation
Also used for proliferative diabetic retinopathy

502
Q

What is the management procedure for maculopathy?

A

Needs only a grid of photocoagulation

503
Q

What are the clinical features of diabetic nephropathy?

A
  • Hypertension
  • Progressively increasing proteinuria
  • Progressively deteriorating kidney function
  • Classic histological features
504
Q

What histological glomerular changes occur in diabetic nephropathy?

A
  • Mesangial expansion
  • Basement membrane thickening
  • Glomerulosclerosis
505
Q

What is the prevalence of diabetic nephropathy in type I diabetes?

A

20-40%

506
Q

What are the strategies for intervention in diabetic nephropathy?

A

1) Hyperglycaemia control
2) Blood pressure control
3) Inhibition of the activity of RAS system
4) Stop smoking
5) Dyslipidaemia control
6) Education

507
Q

What receptors does Angiotensin 2 act on?

A

AT₁ and AT₂ receptor

508
Q

What causes diabetic neuropathy?

A

The small vessels supplying the nerves, called the vasa nervorum, become blocked

509
Q

What are the different types of diabetic neuropathy?

A

1) Peripheral polyneuropathy
2) Mononeuropathy
3) Mononeuritis multiplex
4) Radiculopathy
5) Autonomic neuropathy
6) Diabetic amyotrophy

510
Q

What is peripheral neuropathy? Who is most likely to get it?

A
  • Longest nerves supply feet
  • Loss of sensation
  • More common in tall people and patients with poor glucose control
  • Danger is that patients will not sense an injury to the foot (e.g. stepping on a nail)
511
Q

What are the clinical features of peripheral neuropathy?

A
  • Loss of ankle jerks
  • Loss of vibration sense (using tuning fork)
  • Multiple fractures on foot X-ray (Charcot’s joint)
512
Q

What is mononeuropathy?

A
  • Usually sudden motor loss
  • Wrist drop, foot drop
  • Cranial nerve palsy:
    • most commonly double vision due to 3rd nerve palsy
513
Q

What is pupil sparing third nerve palsy?

A

Eye is usually “down and out” (6th nerve pulls eye out and 4th nerve pulls it down)
Pupil does respond to light

514
Q

What would cause a third nerve palsy with a fixed dilated pupil?

A

Could be an aneurysm pressing on the parasympathetic fibres

Patients need a CT as they could have a tumour

515
Q

What is mononeuritis multiplex?

A

A random combination of peripheral nerve lesions

516
Q

What is radiculopathy?

A

Pain over spinal nerves, usually affecting a dermatome on the abdomen or chest wall

517
Q

What is an autonomic neuropathy?

A

Loss of sympathetic and parasympathetic nerves to the GI tract, bladder and cardiovascular system
Difficult to treat

518
Q

What effect does autonomic neuropathy have on the GI tract?

A
  • Difficulty swallowing
  • Delayed gastric emptying
  • Constipation/nocternal diarrhoea
  • Bladder dysfunction
519
Q

What effect does autonomic neuropathy have on the cardiovascular system?

A
  • Postural hypotension (can be disabling)
  • Cardiac autonomic supply
    (case reports of sudden cardiac death)
520
Q

What are the clinical signs of autonomic neuropathy?

A
  • Measure changes in heart rate in response to Valsalva manoeuvre
  • Normally there is a change in heart rate
  • Look at ECG and compare R-R intervals
521
Q

What complications are associated with macrovascular disease?

A
  • Early widespread atherosclerosis
  • Ischaemic heart disease
  • Cerebrovascular disease
  • Peripheral vascular disease
  • Renal artery stenosis
522
Q

What are the stages in atheroma formation?

A

1) Initial lesion
2) Fatty streak
3) Intermediate
4) Atheroma
5) Fibroatheroma
6) Complicated

523
Q

What factors increase the risk of macrovascular complications?

A
  • Fasting glucose >6mmol/L
  • Waist circumference
    Men: >102
    Women: >88
  • HDL
    Men: <1.0
    Women: <1.3
  • Hypertension >135/80
  • Insulin resistance
  • Inflammation
  • Adipocytokines
  • Urine Microalbumin
524
Q

What effect does hyperglycaemia have on life expectancy?

A

Significantly reduces life expectancy

Microvascular disease causes morbidity; macrovascular disease causes morbidity and mortality

525
Q

What is the biggest cause of morbidity and mortality in diabetics?

A

Ischaemic heart disease

526
Q

How is cerebrovascular disease different in diabetics?

A

It occurs earlier than without diabetes and is more widespread

527
Q

What complications associated with diabetes are caused by peripheral vascular disease?

A

Diabetic foot and problems with neuropathy

528
Q

What complications associated with diabetes does renal artery stenosis contribute to?

A

Hypertension

Renal failure

529
Q

Why is hyperglycaemia alone not treated in diabetes?

A

Hyperglycaemia alone has a minor effect on increased risk of cardiovascular disease. Must aggressively treat multiple risk factors (e.g. BP and cholesterol)

530
Q

What are the non-modifiable risk factors for macrovascular disease?

A
  • Age
  • Sex
  • Birth weight
  • FH/Genes
531
Q

What are the modifiable risk factors for macrovascular disease?

A
  • Dyslipidaemia
  • High blood pressure
  • Smoking
  • Diabetes
532
Q

What is the name of the systemic disease of multiple arterial beds?

A

Macrovascular disease

533
Q

What is the pathway to foot ulceration in diabetes?

A

1) Sensory neuropathy
2) Motor neuropathy
3) Limited to joint mobility
4) Autonomic neuropathy
5) Peripheral vascular disease
6) Trauma- repeated minor/discrete episode
7) Reduced resistance to infection
8) Other diabetic complications e.g. retinopathy

534
Q

What tool is used to predict neuropathy and ulceration in the feet? How does it work?

A

Nylon microfilament

Bends when you have applied 10g of pressure to the skin

535
Q

What is used as a marker for joint adjustment in diabetic neuropathy?

A

Loss of vibration sense

536
Q

What is used to improve peripheral vascualr disease?

A

Angioplasty

537
Q

Describe the neuropathic foot.

A

Numb, warm, dry, palpable foot pulses, ulcers at points of high pressure loading

538
Q

Describe the ischaemic foot.

A

Cold, pulseless, ulcers at the foot margins

539
Q

Describe the neuro-ischaemic foot.

A

Numb, cold, dry, pulseless, ulcers at points of high pressure loading and at foot margins

540
Q

How do you assess the foot of a diabetic patient?

A 
1) Appearance
(deformity, callus)
2) Feel
(hot/cold, dry)
3) Foot pulses
(dorsalis pedis / posterior tibial pulse)
4) Neuropathy
(vibration sensation, temperature, ankle jerk reflex, fine touch sensation)
541
Q

What is the preventative management of diabetic foot?

A

1) Control diabetes
2) Inspect feet daily
3) Have feet measured when buying shoes
4) Buy shoes with laces and square toe box
5) Inspect inside of shoes for foreign objects
6) Attend chiropodist
7) Cut nails straight across
7) Care with heat
8) Never walk barefoot

542
Q

What is the management procedure of foot ulceration in a diabetic patient?

A

1) Relief of pressure
- bed rest (risk of DVT, heel ulceration)
- redistribution of pressure / total contact cast
2) Antibiotics, possibly long term
3) Debridement
4) Revascularisation
- angioplasty
- arterial bypass surgery
5) Amputation

543
Q

What are the symptoms of osteomyelitis in the diabetic foot?

A
  • Hot red foot with ulcer
  • Forefoot: MTP’s IPs
  • Hindfoot: calcaneus
  • MRI: marrow oedema in forefoot and hindfoot near ulcer
544
Q

What are the symptoms of active Charcot’s in the diabetic foot?

A
  • Hot red foot with no ulcer
  • Midfoot: subarticular
  • MRI: marrow oedema in midfoot subchondral
545
Q

When you eat a meal insulin binds to a receptor on adipocytes. What is then taken into the cell?

A

Glucose via GLUT4
Potassium
Phosphate

546
Q

What symptoms presents in diabetic ketoacidosis to compensate for acidic blood?

A

Air hunger

blow off carbon dioxide

547
Q

Why is it impossible that a patient with type II diabetes is not ketotic?

A

Because they produce high levels of insulin because they are resistant, which turns off ketogenesis

548
Q

What is the diagnosis if a patient has
Fasting glucose: 7.4mM
Following GTT, 2 hour value: 7.7mM

A

Type II diabetes

549
Q

What treatment has been proven to prevent diabetes in the diabetes prevention programme?

A 
Metformin (Biguanide)
Lifestyle changes (diet and exercise)

LCRS Year 2 (6 decks)

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