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Endocrinology Flashcards

1
Q

What are some signs of diabetic autonomic neuropathy?

A 
Resting tachycardia 
Gastroparesis
Anhydrosis
Impotence 
Constipation
Urinary retention
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2
Q

Which enzyme is blocked by orlistat?

A

Lipase
Leads to undigested fat passing out as unpleasant oily compound, patients are rapidly self educated as to what appropriate food to eat

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3
Q

Which hormone leads to enhanced insulin release?

A

GLP-1
Produced in small intestine
Leads to slowing of gastric transit time, satiety and enhanced insulin release

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4
Q

Which hormone promotes hyperglycaemia?

A

Glucagon

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5
Q

A 43 year old man with type 2 diabetes is seen in the hepatology clinic with an alt of 189. He denies alcohol consumption. Liver biopsy demonstrates macrovesicular steatosis with centrolobular inflammatory infiltrate and mild fibrosis. What is the most likely diagnosis?

A

Non alcoholic fatty liver disease

Driven by metabolic syndrome in particular central adiposity and insulin resistance

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6
Q

An 88 year old woman has been treated with glibenclamide for 10 years. She has become increasingly confused over last few months in her nursing home and one morning is found unconscious in her soaked bed. Her pupils are dilated and react sluggishly to light. What is the likely complication?

A

Hypoglycaemic coma
Recurrent hypoglycaemic episodes
Occurs more frequently with long acting sulfonylureas such as glibenclamide

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7
Q

76 year old man treated with metformin and glibenclamide for 20 years. He complains of sudden onset diplopia. He has right sided ptosis and is unable to adduct his right eye. Pupils are equal and react normally to light. What is the likely complication?

A

Mononeuropathy affecting the 3rd nerve

Classically painless and pupil is spared

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8
Q

75 year old man treated with insulin for 40 years. Complains of gradually failing vision and difficulty reading the newspaper. Pupils are both small but react equally to light. Visual acuity is 6/18 in both eyes but falls to 6/36 when using a pinhole. Fundoscopy reveals scattered dots, blots and exudates in the peripheral retina. What is the likely complication?

A

Cataracts

He has background retinopathy but this would not account for his visual loss

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9
Q

55 year old woman treated with glibenclamide for 5 years. Complains of severe pain in both feet and legs. Muscle bulk appears normal but tone and power assessment is limited by her pain. Reports subjective loss of light touch sensation. Joint position sense and ankle jerks are impaired. What is the likely complication?

A

Peripheral sensory neuropathy

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10
Q

Where are leydig cells found? What do they do?

A

Between seminiferous tubules

Produce androgens in men: including testosterone

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11
Q

Where are Sertoli cells? What do they do?

A

Arranged into tubular structures with a lumen: seminiferous tubules
Have basal compartment where spermatogonia divide and a luminal compartment where spermatids mature
Testosterone diffuses into Sertoli cells where it is converted to more active form: 5-hydroxytestosterone

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12
Q

What cell type is found in the epididymis?

A

Tall columnar epithelial cells with atypical long microvilli
They phagocytose dead spermatozoa and produce substances which aid in sperm maturation

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13
Q

According to NICE, bariatric surgery is a treatment option for people with obesity if what criteria are fulfilled?

A

All appropriate non-surgical measures have been tried
Person has been receiving or will receive intensive management in a tier 3 service
Person is generally fit for anaesthesia and surgery
Person commits to the need for long-term follow-up
Patients who have recent onset T2DM and a BMI of 35
Patients without co-morbidities and a BMI of 40

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14
Q

What are the categories of obesity?

A 
Healthy weight: 18.5–24.9
Overweight: 25–29.9
Obesity I: 30–34.9
Obesity II: 35–39.9
Obesity III: 40 or more
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15
Q

NICE recommends using different thresholds for BMI to trigger action to prevent type 2 diabetes among Asian (South Asian and Chinese), black African and African-Caribbean populations.
What are the BMI thresholds to identify (a) increased risk, and (b) high risk, in these populations?

A

23-27.4 kg/m2: increased risk

27.5 kg/m2 or higher: high risk of developing chronic health conditions

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16
Q

Orlistat is an approved drug for the treatment of obesity available on prescription. What is its mechanism of action?

A

Orlistat inhibits the action of lipase in the GI tract so 30% less dietary fat is absorbed, resulting in lower calorie intake

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17
Q

What proportion of women were classified as obese in England in 2014 (Health Survey for England)?

A

27%

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18
Q

In which two school years is the National Child Measurement Programme carried out in England?

A

Reception (age 4-5) and Year 6 (age 10-11)

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19
Q

A 43 year old patient with poorly controlled type 1 diabetes mellitus presents with sudden, painful visual loss. He is non compliant with his therapy and has known diabetic nephropathy and peripheral neuropathy. What is the likely cause of his painful visual loss?

A

Neovascular glaucoma - proliferative diabetic neuropathy involves growth of new blood vessels. These can grow over the lens and into the anterior chamber, blocking the trabecular meshwork and causing a type of acute angle closure glaucoma which presents as painful visual loss and a hazy cornea, associated with nausea and vomiting

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20
Q

In what ways does vitamin D lead to raised serum calcium levels?

A

Increases calcium absorption in the small intestine

Increases calcium reabsorption in the renal parenchyma

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21
Q

What effect does hypercalcaemia have on parathyroid hormone levels?

A

Hypercalcaemia inhibits PTH release

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22
Q

What are the effects of parathyroid hormone?

A

Enhances osteoclast activity by binding to osteoblasts which increases their expression of RANKL and inhibits their expression of OPG. RANKL binds to RANK stimulates osteoclast precursors to be activated
Increases calcium reabsorption in kidney but inhibits reabsorption of phosphate
Stimulates conversion of 25hydroxy vitamin D to calcitriol via 25hydroxy vitamin D3, 1 alpha hydroxylase enzyme
Enhances absorption of calcium in intestine by increasing vit D levels

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23
Q

Which vessel does the recurrent laryngeal nerve run close to which means it is at risk of damage in thyroid surgery?

A

Inferior thyroid artery

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24
Q

What is whipples triad?

A

For diagnosis of true Hypoglycaemia:
Presence of hypoglycaemia on a lab sample
Signs/symptoms consistent with hypoglycaemia
Resolution of signs/symptoms when blood glucose normalises

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25
Q

List 5 drugs which are associated with causing pancreatitis

A 
Steroids
Oestrogens
Thiazides
Sodium valproate
Azathioprine 
Chemo with cisplatin/vinca alkaloids 
Radiotherapy: chronic pancreatitis
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26
Q

What is a differential for bilateral facial nerve palsy with bilateral parotid swelling?

A

Sarcoidosis

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27
Q

What clinical feature might be expected in a patient with a deficiency of glycogen synthase?

A

Fasting hypoglycaemia

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28
Q

What are the 2 main stimuli for glycogen formation?

A

Presence of insulin

Rising glucose level in the blood

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29
Q

What enzymes are required for glycogen formation?

A

Phosphoglucomutase
Glucose 1 phosphate uridyltransferase
Glycogen synthase
Branching enzyme

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30
Q

What enzymes are required for glycogen degradation ?

A

Glycogen phosphorylase

Debranching enzyme

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31
Q

What is the difference between cushings disease and Cushing’s syndrome?

A

Disease: pituitary adenoma secreting acth leading to adrenal hyperplasia
Syndrome: anything leading to chronic glucocorticoid excess

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32
Q

What is the typical cushingoid appearance?

A 
Rounded face
Central obesity 
Thin limbs 
Abdominal striae 
Supraclavicular fat deposition
Thin skin
Bruising
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33
Q

What is phaechromocytoma? What symptoms does it produce?

A

Catecholamine producing tumour
Causes secondary hypertension
Palpitations, sweating, headaches particularly during exercise

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34
Q

What symptoms would you expect with acromegaly?

A

Headache
Large hands
Prominent facial features
Bitemporal hemianopia

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35
Q

What is Wemer syndrome?

A

Multiple endocrine neoplasia type 1
Tumours affecting 3 Ps: pituitary, parathyroids and pancreas
Pituitary symptoms: headache, acromegaly and gynaecomastia
Zollinger Ellison syndrome due to gastrin: duodenal ulcers

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36
Q

What is sipple syndrome?

A

Multiple endocrine neoplasia type II

Parathyroid, medullary thyroid and phaechromocytoma

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37
Q

What is lynch syndrome?

A

Hereditary non polyposis colorectal carcinoma

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38
Q

What are pigmented palmar creases a sign of?

A

Addison’s disease

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39
Q

What electrolyte abnormality would you expect in a patient with Addison’s disease?

A

Hyponatraemia and hyperkalaemia

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40
Q

What may be symptoms of Addison’s disease?

A 
Fatigue
Postural hypotension
Anorexia
Nausea and vomiting 
Weight loss
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41
Q

A 22 year old man presents with a short history of thirst, weight loss and polyuria. A random capillary glucose is 32mmol/L. During the examination it is difficult to get an o2 sats reading. What aspect of his management is vital to his immediate survival?

A

IV fluids
DKA can require an enormous amount of rehydration
Patient is shocked which is why it’s difficult to get a sats reading
Insulin administration is the next most crucial intervention

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42
Q

What is background retinopathy?

A

Micro aneurysms
Small dot and blot haemorrhages
Hard exudates

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43
Q

What is pre proliferative retinopathy?

A

Ischaemia on top of background retinopathy

Cotton wool spots

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44
Q

What is maculopathy?

A

Breakdown of blood retina barrier causing central loss of vision

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45
Q

What are symptoms of PCOS?

A

Increasing weight
Irregular periods
Hirstutism

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46
Q

What is a first line treatment for PCOS?

A

Metformin

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47
Q

What are symptoms of primary hyperparathryoidism?

A

Bones: pain/fracture
Stones: renal, polydipsia, polyuria
Groans: peptic ulceration, constipation, pancreatitis
Moans: depression

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48
Q

What is congenital adrenal hyperplasia?

A

Lack of enzyme 21 alpha hydroxylase which leads to an increase in 17 hydroxyprogesterone which is subsequently metabolised to testosterone, leading to hirstutism

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49
Q

What test would you use to look for Cushing’s?

A

Random cortisol

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50
Q

What test would you use to look for Addison’s disease?

A

Synacthen

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51
Q

What is the tensilon test used to diagnose?

A

Myasthenia gravis

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52
Q

What type of respiration is seen in DKA?

A

Kussmaul respiration

Laboured, deep and gasping

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53
Q

What clinical signs would you expect to find in a patient with DKA?

A 
Vomiting
Drowsiness
Kussmaul respiration
Raised blood glucose
Ketonuria 
Metabolic acidosis
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54
Q

State 4 investigations you would do for a patient with a suspected DKA

A 
FBC 
U&Es
LFTs
Calcium and phosphate 
ABGs
Urine cultures
Blood cultures 
Chest X-ray
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55
Q

What are the 2 most important components of your treatment regimen for DKA?

A

0.9% normal saline IV

Soluble insulin IV

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56
Q

What 2 important laboratory measurements apart from blood glucose that you will monitor over the next 6 hours in a patient diagnosed with DKA?

A

Serum potassium

Bicarbonate

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57
Q

What 3 points of advice would you give to a diabetic patient to minimise the risk of long time complications?

A

Keep to a healthy diet
Regular compliance with insulin
Regular self blood glucose monitoring

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58
Q

What can be some precipitating causes of DKA?

A 
Increased levels of stress hormones due to: 
MI
Infection 
Surgical emergency
Errors of insulin administration 
Deliberate omission of insulin
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59
Q

A 68 year old female presents with painful weakness of the upper legs, nocturia and difficulty ascending stairs which has deteriorated over the last 2 months. On examination she has loss of muscle bulk in quads and weakness of flexion bilaterally, right more than left. The knee reflex is lost. What is the likely diagnosis?

A

Diabetic amyotrophy

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60
Q

Which diabetes drugs work to reduce glucose absorption from the gut?

A

Acarbos

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61
Q

Which diabetes drugs act to increase glucose uptake by fat and muscle?

A

Metformin
Pioglitazone
Insulin

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62
Q

Which diabetes drugs act to improve impaired insulin secretion?

A 
Insulin 
Sulphonylureas
Meglitinides 
GLP-1 receptor agonists
DDP-4 inhibitors
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63
Q

Which diabetes drugs are used to reduce glucose production?

A

Metformin
GLP-1 receptor agonists
DDP-4 inhibitors
Insulin

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64
Q

What is the prevalence of T2DM in the uk?

A

6%

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65
Q

What is the most common risk factor for diabetes?

A

Obesity

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66
Q

What impact can T2DM have on a person’s life?

A

Reduced life expectancy (up to 10 years)
Mortality rates from CHD up to five times higher
Leading cause of renal failure
Leading cause of blindness in people of working age
Additional risks in pregnancy

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67
Q

How do you diagnose diabetes?

A

Fasting plasma glucose 7 or more, 2 readings
Random plasma glucose 11.1 or more with symptoms
Oral glucose tolerance test 11.1 or more

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68
Q

How do you diagnose impaired glucose tolerance?

A

Oral glucose tolerance test readings between 7.8 and 11.1

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69
Q

How do you diagnose impaired fasting glycaemia?

A

Fasting plasma glucose between 6.1 and 7

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70
Q

What does glucose bind to in HbA1c?

A

N terminal valine of Hb

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71
Q

What value of HbA1c is diagnostic for diabetes?

A

48 or more

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72
Q

What value of HbA1c is diagnostic for impaired glucose tolerance?

A

42-47

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73
Q

What are some medium vessel effects of diabetes?

A

CAD is 3-4 times more common
Sudden death
Loss of premenopausal protection in females
Triple vessel disease, multiple distal lesions
Fatal stroke, increased 2-3 fold
Morbidity: Non fatal CHD, increased 2-3 fold

74
Q

What are the most common small vessel effects in diabetes?

A

Retinopathy will develop in around 80%
Nephropathy will develop in around 30%
Foot ulcers will develop in around 5%

75
Q

What are some acute complications of diabetes?

A

Hypoglycaemia
DKA
HHS: hyperosmolar hyperglycaemic state

76
Q

What is the ticking clock hypothesis for diabetes?

A

Microvascular complications start to develop at onset of hyperglycaemia
Macrovascular complications start to develop before the diagnosis of hyperglycaemia

77
Q

What is obesity?

A

Lifelong, progressive, life-threatening, genetically-related, costly, multi-factorial disease of excess fat storage with multiple comorbidities

78
Q

What are the classifications of obesity?

A
  1. 0–34.9 class I
  2. 0–39.9 class II
  3. 0 or over class III obesity
79
Q

What proportion of the population are overweight or obese?

A

2/3 adults
1/5 2-10 year olds
1/3 11-15 year olds

80
Q

What negative effects on children can obesity have?

A

Emotional and behavioural: stigmatism, bullying, low self esteem
School absence
Health: high cholesterol, blood pressure, pre diabetes, bone and joint problems, breathing difficulties
Increased risk of becoming obese adult, risk of ill health and premature mortality in adult life

81
Q

What negative effect does obesity have on adults?

A

Less likely to be in employment
Discrimination and stigmatism
Increased risk of hospitalisation
Reduces life expectancy by 3 years or 8-10 if severe

82
Q

Name some major clinical complications of obesity

A

Pulmonary disease: OSA, hypoventilation syndrome
Non alcoholic fatty liver disease: steatosis, steatohepatitis, cirrhosis
Gall bladder disease
Gynaecological abnormalities: abnormal menses, infertility, PCOS
Joint problems: OA, Gout
Neuro: idiopathic intracranial HTN, stroke, cataracts
Metabolic syndrome: CHD, Diabetes, Dyslipidaemia, HTN
Cancer
Phlebitis: venous stasis

83
Q

What effect does obesity have on communities?

A

Less physically active population so reduced productivity
Increased sickness absence
Increased demands on social care services (3x more likely to need help)

84
Q

What factors influence the prevalence of obesity?

A

Food environment: easy availability of processed high fat foods
Workplace
Built environment: less use of bikes/walking
Sport: most people are spectators, don’t do much activity

85
Q

Name some genes which are responsible for causing obesity

A 
Leptin, leptin receptor
MC-4 receptor
POMC
AdipoQ
SIM-1
pPC-1
FTO (fat mass and obesity associated protein)
Insig-2
86
Q

What factors influence eating and exercising behaviours which contribute to obesity?

A

Eating: Strong signals to eat, Weak signals to stop, High availability, Eating is rewarding, No alternative, High status
Exercise: Weak signal -exercise, Strong signals to stop, Reduced availability, Inactivity is rewarding, Inactivity is a viable alternative, Inactivity is high status

87
Q

What are some factors which make up our daily obligatory and facultative energy expenditure?

A

Obligatory: standard metabolic rate, diet induced thermogenesis, physical activity (involuntary, feeding)
Facultative: cold induced shivering thermogenesis, voluntary activity thermogenesis, non exercise activity (fidgeting), cold induced non shivering (brown fat), diet induced

88
Q

What proportion of your daily metabolic rate is made up of basal metabolic rate, physical activity and diet induced thermogenesis?

A

BMR: 55-65%
Activity: 35%
DIT: 10%

89
Q

Why do we become obese?

A

Inability to balance energy intake and expenditure. Requires an obligatory amount of energy for homeostasis. General average: 2500kcal/day for average 70kg male and 2000kcal/day in adult females. Requirements vary by activity profile
In obesity, homeostatic mechanisms that coordinate storage and use of energy are disturbed leading to exaggerated adipose tissue deposition

90
Q

Why are some obese people metabolically healthy and some unhealthy?

A

Differences in substrate metabolism (genetic & lifestyle)
Ability to store fat in adipose tissue
Propensity to inflammation in adipose tissue

91
Q

What is the IDF criteria for metabolic syndrome?

A

Waist >94 cms in men, >80 in women
Ethnicity specific cut-off ->90 cm in men
Central obesity with 2 of: High BP (>130/85 mmHg), Raised TG (>1.7 mmol), Low HDL cholesterol (5.6 mmol/l

92
Q

What are the steps of medical management of obesity?

A

Assess underlying causes
Look for sequelae of obesity
Formulate a management plan
Involve appropriate professionals
Lifestyle modification for all
Consider drugs for those with complications or at high risk
Surgery for severe obesity after failed medical therapy

93
Q

What screening can be done to check for microvascular complications of diabetes?

A

Microalbuminuria
Retinal screening
Foot check

94
Q

What screening can be done for macrovascular complications of diabetes?

A

High suspicion
Imaging
History and exam

95
Q

What are non pharmacological treatment options for diabetes?

A

Lifestyle: smoking, alcohol
Diet: Type and portion size, carbs awareness
Exercise

96
Q

What are the categories of pharmacological treatment options for diabetes?

A 
Incretins
Gliptins
Glinides
Prandial Insulin
Acarbose
Sulfonylurea
SGLT2
97
Q

Where are SGLT1/2 found?

A

SGLT1: brush border of small intestine
SGLT2: proximal tubule of kidney

98
Q

What multifactorial interventions might be combined to most effectively treat diabetes?

A 
Weight reduction
Diet 
Smoking cessation
Pharmacological 
HTN treatment 
Cholesterol lowering drugs 
Aspirin 
ACE inhibitors
99
Q

What can cause Cushing’s disease or syndrome?

A

Disease: pituitary adenoma
Syndrome: ectopic production of ACTH

100
Q

A 62 year old male presents with an eight hour history of double vision. He has a history of HTN for which he takes amlodipine and atenolol. He has a 4 year hx of diet controlled T2DM. On examination he has water in for the right eye, there is a slight ptosis and the eye is displaced to the right. Pupil size is the same as on the left. What is the likely cause of his symptoms?

A

Diabetes - mononeuritis multiplex, painless 3rd nerve palsy

101
Q

What are clinical features of iodine deficiency?

A

Cretinism in utero: impaired cognitive function, deafness, motor defects
Cognitive impairment and poor growth in children
Confusion, poor concentration and goitre in adults

102
Q

What areas of the population are more at risk of iodine deficiency?

A

Inland areas, iodine is abundant in the sea

103
Q

A 55 year old male presents with a long Hx of headaches and sweats. On examination he has coarse facial features, appears sweaty and has a blood pressure of 168/100. What does he have and how would you treat it?

A

Acromegaly due to GH secreting tumour of the pituitary gland, HTN and diabetes associated
Somatostatin analogue to suppress growth hormone levels, surgery is mainstay of treatment

104
Q

A 33 year old presents with a 3 month Hx of weight loss, sweats and increased anxiety. On examination she has a pulse of 98, a tremor and sweaty palms. What does she have and how do you treat it?

A

She has Thyrotoxicosis

Carbimazole - prevents iodination of tyrosine residues

105
Q

What is a rare but important side effect of carbimazole treatment for Thyrotoxicosis?

A

Agranulocytosis - reduced white cell count making them prone to serious infection

106
Q

A 32 year old female presents with amenorrhoea, flushes and breast milk production. On examination there is little to find but she has galactorrhoea to expression of the breasts. What does she have and what is the treatment?

A

Prolactin secreting pituitary tumour giving rise to galactorrhoea
Bromocriptine - dopamine agonist

107
Q

Describe the different functions of lipoproteins

A

Chylomicrons: transport triglycerides from intestine to tissues
VLDL: transport triglycerides from liver to adipose tissue and muscle
LDL: transport cholesterol from liver to tissues
HDL: transport surplus cholesterol from Torres back to liver

108
Q

What is the major apolipoprotein is present on LDLs?

A

ApoB100

109
Q

Describe the process of LDL metabolism

A

LDL receptors are made in the endoplasmic reticulum, processed in the Golgi apparatus and transported to the cell surface in vesicles
LDL binds the receptors via ApoB100 in clathrin coated pits
These are endocytosed and then fuse with a lysosome which degrades the LDL into cholesterol and amino acids

110
Q

What are some potential risks of having high cholesterol levels?

A

Atherosclerosis
Heart attack
Stroke
TIA

111
Q

What is hyperlipidaemia?

A 
Raised serum levels of: 
Total cholesterol
LDL cholesterol 
Triglycerides or
Both total cholesterol and triglycerides
112
Q

What is dyslipidaemia?

A 
Raised serum levels of:
Total cholesterol 
LDL cholesterol
Triglycerides or
Both total cholesterol and triglycerides 
Low serum levels of: HDL cholesterol
113
Q

What lifestyle factors can contribute to high blood cholesterol?

A 
Unhealthy diet: saturated fat 
Lack of exercise 
Obesity 
Excess alcohol 
Smoking
114
Q

What underlying conditions can contribute to high levels of cholesterol?

A 
HTN 
Diabetes 
Kidney disease 
Liver disease 
Underactive thyroid
115
Q

What fixed factors are associated with high levels of cholesterol?

A 
FH of early heart disease or stroke 
FH of a cholesterol related condition 
Age
Ethnic group: Indian, Pakistani, Bangladeshi, Sri Lankan 
Genetics
116
Q

What is the friedewald formula?

A

LDL cholesterol = total - HDL - triglycerides/2.2

117
Q

What is the inheritance pattern of familial hypercholesterolaemia?

A

Autosomal dominant

118
Q

What are major clinical features of familial hypercholesterolaemia?

A

Onset at all ages
Xanthomas
Accelerated atherosclerosis

119
Q

What plasma lipid levels will be altered in familial hypercholesterolaemia?

A

Increased cholesterol

Triglycerides normal

120
Q

When should a diagnosis of familial hypercholesterolaemia be considered?

A

Total cholesterol concentration more than 7.5mmol/L

Family history of premature coronary heart disease

121
Q

At what level of total cholesterol concentration should an arrangement for specialist assessment be made?

A

More than 9mmol/L or non HDL concentration of more than 7.5 even in absence of first degree family history of premature CHD

122
Q

What is the risk of a triglyceride concentration >20mmol/L that is not as a result of excess alcohol or poor glycaemic control?

A

Pancreatitis

123
Q

What should you do for a patient with with triglyceride levels between 10 and 20mmol/L

A

Repeat measurement with a fasting test
Review for potential secondary causes of hyperlipidaemia
Seek specialise advice if the concentration remains above 10

124
Q

What are side effects of statins?

A

Myositis
Myalgia
Elevated hepatic transaminases

125
Q

What drugs can be used to lower cholesterol?

A

Bile acid binding resins
Nicotinic acid
Fibric acid analogues
HMG Co A reductase inhibitors

126
Q

What is the Simon broom diagnostic criteria for diagnosing familial hypercholesterolaemia?

A

Definite: Total cholesterol >7.5 and LDL > 4.9
Tendon xanthomata or evidence of these in a first degree relative
DNA evidence of an LDL receptor mutation, familial defective apo B 100 or a PCSK9 mutation
Possible: total cholesterol >7.5 LDL >4.9
Family history of MI in second degree relative aged 50 or younger, first degree relative aged 60 years or younger
Family history of raised total cholesterol greater than 7.5 in adult or 6.7 in a child

127
Q

What nice guidance is there on clinical diagnosis of familial hypercholesterolaemia?

A

Exclusion of secondary causes of hypercholesterolaemia
2 measurements of LDL concentration
Assessment against Simon broome criteria

128
Q

What 4 genes can be mutated in familial hypercholesterolaemia?

A

LDL receptor
Apo B
PCSK9 (degrades LDL receptors)
LDL RAP1 (mediates internalisation via clathrin coated pits)

129
Q

In which patients should pioglitazone not be used?

A

Hx of bladder cancer
Unexplained macroscopic haematuria
High risk of developing bladder cancer

130
Q

What are side effects of sulphonylureas?

A

Hypoglycaemia
Weight gain
Hyponatraemia

131
Q

What is the mechanism of action of sulphonylureas?

A

Works by stimulating pancreatic beta cells to secrete insulin

132
Q

What is the mechanism of action of GLP1 agonists?

A

Incretin mimetic which inhibits glucagon secretion

133
Q

What is the difference between Cushing’s disease and syndrome?

A

Disease: pituitary adenoma
Syndrome: corticosteroid Immunosuppression

134
Q

What is Conns syndrome?

A

Increased aldosterone production from a tumour, hyperplasia of the adrenal gland or elevated angiotensin (secondary)
Hypertension in presence of hypokalaemia

135
Q

What is the treatment for Conns syndrome?

A

Laparoscopic adrenalectomy after raising potassium levels to normal with Spironolactone

136
Q

In which patients should a diagnosis of zollinger Ellison syndrome be considered?

A

Recurrent ulceration despite optimal medical therapy

137
Q

How do you diagnose zollinger Ellison syndrome?

A

Measure fasting gastrin levels

138
Q

Where are the tumours usually located in zollinger Ellison syndrome?

A

Pancreas and duodenum - gastrin secreting

139
Q

What is the embryological origin of the thyroid gland?

A

Base of the tongue and descends to middle of neck

140
Q

What is the daily iodine recommended intake?

A

140 micrograms

141
Q

What are some problems in interpretation of thyroid function tests?

A

Serious acute or chronic illness: reduced concentration and affinity of binding proteins, decreased peripheral conversion of T4 to T3, reduced hypothalamic pituitary TSH production
Pregnancy and oral contraceptives: increased thyroid binding globulins so high T4
Drugs: amiodarone decreases T4 to T3 conversion

142
Q

What are some causes of hypothyroidism?

A

Congenital: agenesis
Defects of synthesis: iodine deficiency, lithium, amiodarone
Autoimmune: atrophic thyroiditis, Hashimoto’s thyroiditis, post partum thyroiditis
Post surgery
Post irradiation: radioactive iodine therapy, external neck irradiation
Infiltration: tumour
Secondary: hypopituitarism
Peripheral resistance to thyroid hormone

143
Q

What antibodies are present in Hashimoto’s thyroiditis?

A

Thyroid peroxidase

144
Q

What is myxoedema?

A

Accumulation of mucopolysaccharide in subcutaneous tissue associated with hypothyroidism

145
Q

What are symptoms of hypothyroidism?

A 
Bradycardia 
Constipation 
Cold intolerance
Weight gain
Thick skin
Dry hair
Deep voice
Slow 
Tiredness 
Amenorrhoea 
Menorrhagia
146
Q

What are some causes of hyperthyroidism?

A 
Graves' disease 
Toxic multinodular goitre 
Solitary toxic nodule/ adenoma
Acute thyroiditis: viral (de quervains), autoimmune, post irradiation, post partum
Gestational thyrotoxicosis 
Exogenous iodine
Drugs: amiodarone 
TSH secreting pituitary tumours
147
Q

Name 2 antithyroid drugs

A

Carbimazole

Propylthiouracil

148
Q

What is a major side effect of antithyroid medication?

A

Agranulocytosis

149
Q

What are some complications of thyroidectomy surgery?

A

Post op bleeding: tracheal compression and asphyxia
Laryngeal nerve palsy: check vocal cord movement post op
Transient hypocalcaemia/permanent hypoparathyroidism
Recurrent hyperthyroidism

150
Q

What causes thyroid eye disease?

A

Retro orbital inflammation

Swelling and oedema of extraocular muscles lead to limitation of movement and proptosis

151
Q

What are obese patients at risk of dying of?

A

Diabetes
Coronary heart disease
Cerebrovascular disease

152
Q

Where should a skinfold thickness measurement be taken? What are normal values?

A

Middle of triceps
20mm in a man
30mm in a woman

153
Q

What waist/hip circumference ratio is associated with increase risk of morbidity?

A

> 1 in men and >0.9 in women

154
Q

What conditions and complications are associated with obesity?

A 
Psychological 
Osteoarthritis of knees and hips
Varicose veins
Hiatus hernia
Gallstones 
Post op problems
Back strain
Obstructive sleep apnoea
HTN
Breathlessness
Ischaemic heart disease
Stroke
T2DM
Hyperlipidaemia 
Menstrual abnormalities
Cancer risk 
Heart failure
155
Q

How do you define metabolic syndrome?

A

Waist circumference men >94cm, women >80cm
Triglycerides >1.7
HDL cholesterol men 130/85
Fasting glucose >5.6

156
Q

What is the most common cause of an impaired adrenal response?

A

Suppression of the HPA axis by exogenous glucocorticoid treatment

157
Q

What is Waterhouse friderichsen syndrome?

A

Meningococcal sepsis syndrome

Bilateral adrenal haemorrhage

158
Q

what is a synacthen test?

A

ACTH stimulation test

Assess functioning of adrenal glands stress response by measuring cortisol

159
Q

What are likely causes of fluid overloaded hyponatraemia?

A

Cirrhosis of liver

CCF

160
Q

What is a likely cause for normovolaemic hyponatraemia?

A

SIADH

161
Q

What are likely causes for a hyponatraemic patient who is dehydrated and has a low urine sodium?

A

Vomiting and diarrhoea
Burns
Pancreatitis
Sodium depletion after diuretics

162
Q

What are likely causes for hyponatraemia in a patient who is dehydrated and has a high urinary sodium?

A

Diuretics
Addison’s
Cerebral salt wasting
Salt wasting nephropathy

163
Q

What happens if glucocorticoids are stopped abruptly?

A

No acth so no cortisol being produced

Leads to adrenal crisis

164
Q

What is the management of adrenal insufficiency?

A

Acute: samples for cortisol and acth, IV normal saline, hydrocortisone 100mg IM 6 hourly until eating and drinking, treat precipitant
Resolving: hydrocortisone 20mg PO TDS
Maintenance: hydrocortisone 10/5/5mg and fludrocortisone 0.1-0.2mg/day (if primary insufficiency)

165
Q

What level of urine osmolality suggests ADH excess?

A

> 100mOsm/kg

166
Q

What is hyperosmolar hyponatraemia?

A

Hyperglycaemia causes osmotic trranslocation of water from Intracellular compartment to extracellular fluid which results in decrease in serum sodium level

167
Q

What factors are required for diagnosis of SIADH?

A

Decreased serum osmolality (100 during hypotonicity
Clinical euvolaemia
Urinary sodium >40 with normal dietary salt intake
Normal thyroid and adrenal function
No recent use of diuretics

168
Q

What is Trouseau’s sign?

A

Carpo pedal spasm associated with hypocalcaemia when sphygmomanometer cuff is inflated above systolic pressures

169
Q

A 54 year old woman presents with generalised muscle aches and weakness. She seems a little depressed and has been very thirsty lately. What is the likely diagnosis?

A

Primary hyperparathryoidism

170
Q

A 35 year old woman presents with episodes of sweating headache and palpitations. She gets episodes of pallor and a feeling of impending doom. On examination she seems well but has a BP of 174/88 and a pulse of 92. What is the likely diagnosis?

A

Phaechromocytoma

171
Q

What test results would suggest a phaechromocytoma?

A

Elevated urinary catecholamines, metanephrines and vanillyl mandelic acid (VMA)

172
Q

A 36 year old woman presents with weight loss, lethargy and oligomenorrhoea. On examination she is tanned and has pigmentation of a recent appendix scar. She has a pulse of 80 and a BP of 96/70. What is the likely diagnosis?

A

Addison’s disease

173
Q

How can you diagnose adrenal insufficiency?

A

ACTH stimulation test

174
Q

A 42 year old woman presents with weight gain and thirst. On examination she has a plethoric complexion, marked central obesity, bitemporal visual field loss, a pulse of 88 and a BP of 166/92. What is the likely diagnosis?

A

Cushing’s disease

175
Q

What drugs are associated with pancreatitis?

A 
Steroids
Oestrogens
Thiazides
Valproate 
Azathioprine
176
Q

Why does Addison’s lead to increased pigmentation?

A

Stimulation of melanocytes

177
Q

In which patients is exanatide recommended to treat their diabetes?

A

BMI over 35

BMI less than 35 but significant weight related comorbidity

178
Q

What are potential side effects of sulphonylurea diabetic medication?

A

Hypoglycaemia
Weight gain
Hyponatraemia

179
Q

What are the effects of cortisol?

A

Increases blood pressure
Inhibits bone formation
Increases insulin resistance
Increases gluconeogenesis, lipolysis and proteolysis
Inhibits inflammatory and immune response
Maintains function of skeletal and cardiac muscle

180
Q

What 3 things stimulate aldosterone release?

A

Angiotensin II
Hyperkalaemia
Elevated ACTH levels

CCE (20 decks)

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