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Clinical Flashcards

1
Q

What is diabetes?

A

Elevation of blood glucose above a diagnostic threshold

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2
Q

what are the thresholds to diagnose someone with diabetes?

A

Fasting glucose= 7mmol/L or 126mg/dl 2hr plasma glucose= 11.1 mmol/L or 200mg/dl - “don’t eat after 10pm the previous night and only drink water”

HbA1c = 48 mmol/mole or 5.8% varies

just think above this value note if patient is asymptomatic then repeat test

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3
Q

what are the thresholds of someone with impaired glucose tolerance “pre-diabetes”?

A

Fasting glucose: 6.1-6.9 mmol/L

2hr plasma glucose: 7.8-11.0 mmol/L

HbA1c - 42-47 mmol/mole or 6-6.4%

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4
Q

what are the thresholds of someone with normal glucose tolerance?

A

Fasting glucose: >6mmol/L2hr

plasma glucose: >7.7 mmol/L

HbA1c: >41mmol/mole

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5
Q

What are the thresholds of Gestational diabetes?

A

Fasting glucose: 5.1 mmol/mole or 92mg/dl2hr

plasma glucose: 8.5 mmol/l

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6
Q

Give examples of disorders of insulin secretion.

A
  1. Type 1 diabetes
  2. Genetic disorders: MODY, NEONATAL diabetes, CF and Haemochromatosis
  3. Pancreatic disease Alcoholic and chronic pancreatitis, acute pancreatitis, Pancreatectomy and pancreatic cancer
  4. Type 2 diabetes
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7
Q

Give examples of disorders of insulin action.

A

pure disorders are rare and mostly genetic.

  1. Type 2 diabetes
  2. Donohue syndrome
  3. Familial partial lipodystrophy
  4. NAFLD
  5. Cushings syndrome
  6. Glucagonoma
  7. steroid induced
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8
Q

what is type 1 diabetes?

A

Autoimmune destruction of the pancreatic beta cells resulting in beta-cell deficiency

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9
Q

what is Type 2 diabetes?

A

disease which ranges from predominantly insulin resistance with relative insulin deficiency to predominantly an insulin secretory defect with insulin resistance patients do not have any other cause for diabetes ( i.e. it is a diagnosis of exclusion)

90% of patients who have diabetes have this form

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10
Q

what is the epidemiology of type 1 diabetes?

A

usually adolescent but can happen at any age

Genetics: associated with HLA D3 and D4 autoimmune diseases. HLA represent 50% familial risk of T1DM. if both parents have T1DM then child is 30% likely to have it

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11
Q

What are the the risk factors type 2 diabetes?

A
  1. Asians
  2. elderly
  3. men
  4. Most people get it over 40 but now becoming more common in teenagers
  5. Obesity
  6. Sedentary lifestyle
  7. calorie and alcohol excess
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12
Q

what are the causes of Diabetes mellitus?

A

T1: insulin deficiency from autoimmune destruction of insulin - secreting pancreatic beta cells

T2 - decrease in insulin secretion with/without increased insulin resistance

other causes: Drugs: steroids, anti HIV drug, new antipsychotics

Pancreas: Pancreatitis, surgery(removal of pancreas), trauma, pancreatic destruction (haemochromatosis,CF) and pancreatic cancer

Cushings disease, acromegaly, hyperthyroidsism and pregnancy

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13
Q

Define impaired glucose tolerance (IGT)?

A

IFG and IGT represent intermediate states of abnormal glucose regulation that exist between normal glucose homeostasis and diabetes

Fasting plasma glucose: <7mmol/L

2hour glucose >7.8mmol/L but <11.1 mmol/L

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14
Q

Define fasting glucose (IFG)?

A

Fasting plasma glucose >6.1mmol/L but <7mmol/L

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15
Q

what are the signs and symptoms of diabetes Mellitus?

A

1.General:

symptoms of hyperglycaemia: e.g.

polyuria (pees more) (osmotic symptom)

polyphagia (more hungry)

polydipsia (more thirsty) (osmotic symptom)

blurred vision

thrush

tiredness

signs of macrovascular and microvascular complications

  1. signs more common in T1:

Acetone breath

weight loss

Kussmaul breathing

nausea, vomiting

ketonuria

Enuresis (in children)

weight loss in Type 1

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16
Q

How do you diagnose Diabetes Mellitus?

A

Remember T2 is a diagnosis of exclusion

  1. Fasting glucose > or equal to 7mmol/l
  2. random glucose >11.1 mmol/L
  3. HbA1c: >48mmol/mol- more efficient in testing for T2
  4. Pancreatic Autoantibodies (T1 mainly) e.g. GAD 65, IAA ,IA2 and ZnT8 - can sometimes have negative but that is rare
  5. Ketones detected (T1 mainly)
  6. C-peptide levels - useful diagnosis for type 1 but should be done much later after diagnosis

Dr Iqbal Malik: to diagnose T1 all you need to do is random blood glucose >11.1 mmol with symptoms is enough

if with symptoms then fasting glucose >7mmol. if they dont have symptoms and you do fasting glucose then must do it twice

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17
Q

How do you manage Type 1 diabetes?

A

General: Education and lifestyle advice Bariatric surgery for some patients

Type 1:

  1. Educate to self adjust doses on the basis of exercise, fingerprick glucose and calorie count.
  2. DAFNE (dose adjusted for normal eating) programme. Use Basal bolus insulin via Multiple daily injections or continuous subcutaneous insulin infusion pump (CSII)
  3. GlucoGel if patient in coma
  4. Regular check HbA1c should be 48 to 58 mmol/mol

Pharmacological:

  1. Subcutaneous insulins: usually 100u/ml very rarely 500u/ml

rapid acting e.g. Humalog, Novorapid, Apidra. Inject at start of meal

short acting(soluble) e.g. Humulin S, Actrapid and Insuman

Rapid medium acting (isofane - NICE favourite) e.g. Insulatard, Humulin I, insuman Basal

Long acting e.g. Lanctus

Rapid acting analogue-intermediate mixture e.g. (novomix 30 = 30% short acting and 70% long acting), Humalog mix25 and Humalog mix50

short acting-intermediate mixture e.g. Humulin M3, Insuman comb 15,25,50

Alternatives:

  1. Can also use insulin pumps now instead of subcutaneous injections
  2. Flash glucose monitoring can be used instead of finger prick test

Surgery:

  1. Kidney-pancreas autotransplantion
  2. Pancreatic islet transplantation - usually reserved for patients with severe hypoglycaemia, severe and progressive long term complications despite maximal therapy.

four steps:

i. Pancreas donation and retireval
ii. islet culture
iii. Islet transplantation
iv. immunosuppression

if patient has acute illness and uses subcutaneous insulin dosing

  1. illness increases insulin requirement
  2. therefore maintain calorie intake
  3. check blood glucose and look for ketonuria
  4. admit if vomiting, dehydrated, ketotic or if they are a child or pregnant
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18
Q

What are the main complications of diabetes mellitus?

A

Macrovascular:

  1. IHD - MI four times more likely in DM and more likely to be silent
  2. Stroke
  3. Hypertension

Microvascular - caused by hyperglycaemia

  1. Retinopathy- any damage to the retina of the eyes, which may cause vision impairment
  2. Nephropathy
  3. Neuropathy
  4. erectile dysfunction

Psychological

  1. Depression
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19
Q

what is the pathophysiology of microvascular complication in Diabetes mellitus?

A
  1. Hyperglycaemia causes excess glucose goes through glycolysis
  2. Mitochondria cannot keep up with rate of excess glucose so other pathways are used. Diabetic patients are associated with mitochondrial impairment whether it be environmental or genetic.
  3. Polyoul pathway converts glucose to solbitol via aldose reductase. Solbitol due to its highly osmotic properties damages tissues which increases reactive oxygen species
  4. Pentose phopshate pathway uses up excess Glucose-6-phosphate in glycolysis causes excess NADPH and thus increase NADH oxidase which also increases reactive oxygen species
  5. Hexomsamine pathway converts Fructose 6 phosphate to produce UDP-glcNAC enzyme which results in inflammation
  6. Glyceral alderhyde 3 phosphate is converted to diacyl glycerol. This activates protein kinase C which leads to inflammation
  7. Glyceral alderhyde 3 phsophate can also be converted to methyl glyoxal. Along with excess glucose can form AGE products which bind to RAGE receptors leading to inflammation
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20
Q

Beside retinopathy what other eye complications can diabetes cause?

A
  1. Maculopathy - macular oedema
  2. Cataract-
  3. Glaucoma-increase in fluid pressure in the eye leading to optic nerve damage
  4. Acute hyperglycaemia - visual blurring but is reversible
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21
Q

What are the main types of diabetic retinopathy?

A
  1. Background (mild non proliferative) retinopathy - blood vessel leak leading to micro-aneurysms (dots), haemorrhages (blots) and hard exudates (lipid deposits)
  2. Pre proliferative retinopathy - signs include cotton wall spots (ischaemic areas) and Intra-retinal microvascular abnormalities (IRMA) as well as venous bleeding.
  3. Proliferative - fragile new vessels (neovascularitsation) form due to lack of oxygen in certain areas of the retina. These weak vessels mean there is a high risk of haemorrhage .
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22
Q

what is the pathophysiology of maculopathy?

A

Maculopathy (or macular oedema)

  1. Macular capillaries undergoes capillary endothelial change due high retinal blood flow from hyperglycaemia
  2. this causes vascular leakage fluid is rich in lipids. lipids are absorbed but leave exduates. Exudates close to the fovea (center of macula) can effect central vision
  3. local hypoxia and ischaemia occurs
  4. new vessels form - risk of detaching the retina if they bleed and fibrose
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23
Q

what are the clinical features of diabetic retinopathy?

A
  1. Blurry vision
  2. floaters
  3. sudden loss of vision
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24
Q

How do you diagnose Diabetic retinopathy?

A

Annual retinal screening is mandatory for diabetic patients

grading:

R0 - No disease - rescreen in 12 months

R1- Mild background diabetic retinopathy:

Microaneurysms, Flame exudates, >4 blot haemorrhages in one or both hemifields, and/or cotton wool blots - rescreen in 12 months

R2 - Moderate background diabetic retinopathy:

> 4 blot haemorrhages in one hemifield - rescreen in 6 months

R3 - pre proliferative diabetic retinopathy:

> 4 blots in both hemifields, IMRA and venous bleeding - refer

R4 - proliferative retinopathy:

NVD,NVE, vitreous haemorrhage, retinal detachment - refer

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25
Q

How do you manage Diabetic retinopathy?

A

1.Panretinal photocoagulation: removes peripheral retina which reduces oxygen requirements in the retina allowing for there to be less stress on the new vessels

Too much photocoagulation may reduce vision so much so you may not be able to drive

  1. vitrectomy: vitreous haemorrhage leads to profound loss of vision if the macula is obscured
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26
Q

How do you diagnose maculopathy?

A

Annual screening for diabetic patients via optic coherence tomography - assesses oedema

Grading:

MO: no macular findings - 12 months rescreening

M1: hard exudates within 1-2 disc diameters of fovea - 6 months rescreening

M2: blot haemorhage or hard exudate within 1 disc diameter of fovea - refer

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27
Q

How do you manage maculopathy?

A
  1. intravitreal anti vascular enothelial growth factor (VEGF)- stops drive for new blood vessels
  2. grid laser to macula reduces swelling
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28
Q

what is diabetic nephropathy?

A

a progressive kidney disease and most common cause of end stage renal failure

caused by damage to the capillaries in the kidneys’ glomeruli. It is characteriised by proteinuria and diffuse scarring of glomeruli

40% of patients require renal replacement

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29
Q

what are the main signs and symptoms of nephropathy?

A

First sign: Albuminuria

Later: Nodular Glomerulosclerosis and fibrosis with loss of renal function. Hypertension also develops.

Kimmelstiel-wilson nodules

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30
Q

How do you diagnose Diabetic nephropathy?

A
  1. ACR and PCR:

ACR in men >2.5

ACR in women >3.5

for PCR assume daily creatinine excretion is 10mmol, so ratio 100mg/mmol = 1g/day so to convert PCR to protein loss a day multiply by 10

when looking for microalbuminuria mainly use ACR however if patient has overt neropathy then look for proteinuria

Microalbuminuria - (ACR is 3-30 and PCR <50) repeat test. 2/3 tests positive then patient has microalbuminuria (dipstick NEGATIVE)

Proteinuria (overt neuropathy)- ACR >30 and PCR >50
(dipstick POSITIVE)

do random urines for ACR

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31
Q

why do you repeat microalbuminuria tests 3 times?

A

urine albumin excretion rate varies due to numerous factors

e.g. day vs night, different days, exercise, protein load, fluid load

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32
Q

Give examples of conditions which may give false positives for microalbuminuria?

A

Menstruation

Vaginal discharge

UTI

Pregnancy

Non diabetic renal disease

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33
Q

What other conditions should be checked if a patient has microalbuminuria?

A
  1. monitor serum creatine
  2. check for retinopathy
  3. investigate other causes for renal pathology
  4. check for peripheral vascular disease
  5. assess lipid profile
  6. check for IHD
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34
Q

How do you manage Diabetic nephropathy?

A
  1. Extensive diabetes control e.g. get HbA1c <53mmol/mol

Pharmacological

  1. ACE inhibitor or ARB. remember if dry cough occurs with ACE-i then use ARB. Regardless of blood pressure
  2. BP control to 130/80 (NICE guidelines) or 130/70 (SIGN)
  3. sodium restrictions to <2g/d
  4. patients with T2DM should be started of SGLT2i irrespective of HbA1c
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35
Q

How do ACE inhibitors work?

ii. what effect do they have on kidneys?

A
  1. juxtaglomerular apparatus makes renin in kidney
  2. Renin converts angiotensinogen to angiotensin 1
  3. Angiotensin-converting enzyme, or ACE converts angiotensin 1 to angiotensin 2 in the lungs
  4. angiotensin 2 is a vasoconstrictor. and is converted to aldosterone.

ACE i stops vasosconstriction and causes vasodilation

ii.kidneys:

dilation of renal arterioles

decrease filtration pressure

decrease proteinuria

DECREASES GFR

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36
Q

what other drug also acts on the renal arteriole constriction to cause dilation as ACE i/ ARBs?

A

SGLTi

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37
Q

what is diabetic neuropathy?

A

progressive damage to the peripheral nerves seen in some people with long-standing diabetes

different pathophysiology between type 1 and 2

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38
Q

what types of diabetic neuropathy are there?

A
  1. peripheral e.g. pain/loss of feeling in feets, hands (most common)
  2. Proximal: causes amyotrophy which is painful wasting of quadriceps and other pelvifemoral muscles. usually starts with weakness in the thighs, hips or buttocks - difficult to get out of chair
  3. Autonomic: e.g. postural bp drop, decrease in cerbrovascular autoregulation, heart rate , gastroparesis, erectile dysfunction, gustatory sweating and diarrhoea , vomiting
  4. Focal neuropathy: sudden weakness in one weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel syndrome, ulnar mononeuropathy, foot drop and bell palsy and cranial nerve palsy
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39
Q

what are the risk factors of diabetic neuropathy?

A
  1. increased length of diabetes (therefore more common in T1 than T2)
  2. poor glycaemic control
  3. high cholesterol
  4. smoking
  5. alcohol
  6. Genetics
  7. trauma
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40
Q

what are the signs and symptoms of neuropathy?

A

“glove and stocking distribution” of loss of sensation i.e. hands and legs. get it coz of gloves and stockings?

numbness

tingling

sharp pains or cramps

loss of balance

Hypersensitivity

Feet:

  1. absent ankle jerks
  2. neuropathic deformity - charcot foot
  3. claw toe
  4. loss of transverse arch
  5. neuropathic ulcers - lead to cellulitis, abscess and osteomyelitis
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41
Q

what occurs in diabetic feet?

A

combination of Neuropathy and ischaemia

Ischaemia
1. Charcot foot (joint)- refers to progressive degeneration of a weight bearing joint, presents as red hot swollen foot which is confused for DVT and cellulitis

  1. Proximal arterial occulsion
  2. distal gangreen

Neuropathy
4. Ulcer - painless punched out ulcer - in an area of thick callus with or without infection

  1. clawing toes
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42
Q

How do you diagnose neuropathy?

A

Annual screening of feet:

  1. Feel for pulses of feet (dorsalis pedis and posterior tibial)
  2. Feel sensation with a monofilament fibre
  3. check for deformities and breaks in the skin e.g. sign of infection and nail health

Assessment

Low risk:

Sensation unimpaired, foot pulses are present - annual screening by health cares

Moderate risk:

Sensation impaired and foot pulses absent but no skin callus or foot deformity but are unable to self care - annual assessment by podiatrist

High risk:

Sensation impaired and foot pulse absent AND have skin callus or deformity - annual assessment by podiatrist

put into high risk regardless of these symptoms if they had previous foot ulcer or amputation

Active risk:

Current foot ulcer, infection, critical ischaemia, gangrene or red swollen foot - urgent referral to specialist

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43
Q

how do you manage peripheral neuropathy?

A

regular check ups

bed rest and or therapeutic shoes

charcot joints: bed rest/ total contact cast until oedema and local warmth reduce along with bone repair

diabetic amyotrophy: usually self limiting

autonomic neuropathy:

diarrhoea - codeine phosphate

postural hypertension treated with fludrocortisone/ midodrine

Gastroparesis:

Improve glycaemic control.

Dietary - smaller meals

NSAIDs for abdominal pain or fentanyl and anti emitrics

promotility drugs e.g. metoclopramide, domperidone and erthromycin

Botox injections for spasms of pylorus

Gastric pacemakers

Sweat glands: topical glycopyrrolate, clonidine, botox

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44
Q

what is LADA?

A

latent autoimmune diabetes of adults is a form of type 1 DM, with slower progression of insulin dependence in later lifer

usually occurs in males aged 25-40

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45
Q

what does MODY stand for?

A

Maturity Onset Diabetes of the Young - common type of monogenic diabetes

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46
Q

what type of inheritence is Maturity Onset Diabetes of the Young (MODY)?

A

autosomal dominant inheritance

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47
Q

what is the age of onset of Maturity Onset Diabetes of the Young (MODY)?

A

usually before the age of 25

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48
Q

what are the 2 mutations causing Maturity Onset Diabetes of the Young (MODY) that give 2 distinct phenotypes?

A

mutation in transciption factor HNF - MODY 1

mutation in glucokinase - MODY 2

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49
Q

compare MODY glucokinase mutations to transcription factor mutations in terms of onset?

A

glucokinase mutations- onset at birth

transcription factor mutations- young adult onset

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50
Q

compare MODY glucokinase mutations to transcription factor mutations in terms of hyperglycaemia progression?

A

glucokinase mutations- stable hyperglycaemia

transcription factor mutation- progressive hyperglycaemia

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51
Q

compare MODY glucokinase mutations to transcription factor mutations in terms of treatment?

A

glucokinase mutations- diet treatment

transcription factor mutations- 1/3 diet, 1/3 oral hypoglycaemic agents, 1/3 insulin

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52
Q

compare MODY glucokinase mutations to transcription factor mutations in terms of complications?

A

glucokinase mutations- complications rare

transcription factor mutations- complications frequent

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53
Q

what is hypoglycaemia?

A

plasma glucose <4mmol/L

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54
Q

what are the signs and symptoms of hypoglycaemia?

A

can sometimes be asymptomatic

1.Autonomic:
sweating

anxiety

hunger

tremor

palpitations

dizziness

  1. Neuroglycopenic :

confusion

drowsiness

visual trouble

seizures

coma

personality change

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55
Q

What are the main causes for hypoglycaemia?

A

1.Diabetic:

Insulin or SU treatment - increased excercise or overdose

  1. NON- Diabetic - use EXPLAIN

EXogenous drugs e.g. insulin, oral hypoglycaemics, lots of alcohol in take with no food , ACE-i/ARBS, pentamidine

Pituitary insuffiency

Liver failure

Addison’s disease

Islet cell tumours ( insulinoma) and immune hypoglycaemia

Non-pancreatic neoplasms

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56
Q

What does whipples triad consist of?

ii. what does this triad indicate?

A
  1. Hypoglycaemia signs or symptoms
  2. decrease in plasma glucose when symptoms are detected
  3. Relief of symptoms when glucose level is raised
    ii. insulinoma
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57
Q

what is Hyperinsulinemic hypoglycemia (HH)?

A

biochemically characterized by the unregulated secretion of insulin from the pancreatic β-cells in the presence of low blood glucose levels

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58
Q

what are the causes of HH?

A
  1. Insulinoma
  2. SUs
  3. Insulin injection
  4. Non-insluninoma pancreatogenous hypglycaemia syndrome
  5. Congenital - mutations in genes in insulin secretion e.g. ABCC8, KCNJ11 and GLUD 1
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59
Q

suggest causes of hypoglycaemia if there low insulin but no excess ketones?

A

Non pancreatic neoplasm

anti-insulin receptor antibodies

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60
Q

suggest causes of hypoglycaemia where there is low insulin but excess ketones?

A

alcohol

Pityutary insuffiency

Addison’s disease?

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61
Q

What is post prandial (reactive) hypoglycaemia?

A

also known as a sugar crash - is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people with and without diabetes.

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62
Q

How do you manage Hypoglycaemia?

A

conscious and able to swallow: 15-20g of quick acting carbohydrate snack

Conscious and unable to swallow: glucose gel between teeth and gums

unconscious or not responding to treatment:

glucose IV (10% at 200mL/h if conscious or 10% at 200mL/15 mins)

or

Glucagon intramuscular injection 1mg

give long acting carbohydrate once blood glucose >4mmol/L

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63
Q

what is the insullin to carb ratio?

A

amount of rapid acting insulin needed to cover a specific amount of carbohydrate

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64
Q

what is the insulin sensitivity factor?

A

used to calculate the drop in glucose for each unit of insulin - also called a correction factor

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65
Q

what is the target blood glucose concentration for a type 1 diabetic pre-meal?

A

4-7mmol/l for children and adults

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66
Q

what is the target blood glucose concentration for a type 1 diabetic after a meal?

A

5-9 mmol/l for children and adults

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67
Q

what is the target blood glucose concentration for a type 2 diabetic pre-meal?

A

4-7 mmol/l

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68
Q

what is the target blood glucose concentration for a type 2 diabetic after a meal?

A

<8.5 mmol/l

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69
Q

what should the fasting glucose levels of a pregnant woman be?

A

<5.3 mmol/l

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70
Q

what should the target glucose concentration for a pregnant woman be for:

1 hour after meal

2 hour after meal

A

i. <7.8mmol/l

ii. <6.4mmol/l

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71
Q

How do you treat different types of MODY based on its genetic aeitiology?

A
  1. GCK MODY - no treatment or follow up required
  2. HNF1A MODY - can transition off insulin into low does SUs
  3. KCNJ11/ABCC8 NDM - can transition off insulin onto SUs
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72
Q

what is diabetic Ketoacidosis? (DKA)

A

disordered metabolic state that usually occurs in the context of an absolute (T1) or relative (T2) deficiency accompanied by an increase in the counter- regulatory hormones i.e glucagon, adrenaline, cortisol and growth hormone

More common in T1 but can happen in T2

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73
Q

what is the pathophysiology of DKA?

A
  1. Absolute or relative insulin deficiency occurs - switches metabolic balance in a catabolic direction
  2. Stress hormone activation

FIRST mechanism - fatty acids

  1. Stress hormones lead to increased lipolysis as glucose is not entering cells so requires fats
  2. more Free fatty acids goes to liver
  3. Increase ketogenesis in liver which forms ketone bodies - produces acetone as a byproduct
  4. Leads to metabolic acidosis as ketone bodies release hydrogen ions

Second mechanism - Amino acids

  1. Stress hormone activation can also use amino acids as a substrate for cells
  2. Muscle is degraded to release protein for gluconeogenesis
  3. Results in Hyperglycaemia
  4. Hyperglycaemia leads to glycosuria
  5. Glycosuria causes osmotic diuresis which leads to dehydration and electrolyte loss
  6. dehydration increases lactate production which in turn causes acidosis

Third mechanism - Glycogen

  1. Stress hormone activation can also promote glycogenolysis
  2. glycogen is converted into glucose
  3. Results in Hyperglycaemia
  4. Hyperglycaemia leads to glycosuria
  5. Glycosuria causes osmotic diuresis which leads to dehydration and electrolyte loss
  6. dehydration increases lactate production which in turn causes acidosis
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74
Q

How do you diagnose DKA?

A

commonly found in patients with known Diabetes however can be found before diagnosis of T1 diabetes

  1. Ketonaemia > 3mmol /L, or significant ketonuria (>2+ on standard urine stick)

blood ketones usually above 5

2.Blood glucose > 11.0 mmol /L or known DM

euglycaemic DKA - where glucose is not elevated. can occur as a rare complication of SGLT2 inhibitors for T2 patients.

3.Acidosis: Bicarbonate < 15 mmol /L or venous pH < 7.3

4.Potassium
Often raised to above 5.5 mmol/L
Beware a low normal reading

5.Creatinine: often raised
Sodium: often low or low N
Raised lactate is common. Normal range is 0.6 to 1.2 mmol/L

6.Amylase often raised
Rarely pancreatitis [i.e. non-surgical]
Origin can be salivary

7.White cell count
Median 25
Does not always equate to infection

if white cell doesnt fall after DKA management then assume infection

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75
Q

what are the complications of DKA?

A

Hypokalaemia- causes cardiac arrest

Aspiration Pneumonia - gas in stomach

ARDS

Co-morbidities

Cerebral oedema

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76
Q

what are the causes of DKA?

A
  1. Insulin deficiency - Type 1 mainly
  2. insulin demand - think of the 5 Is
  3. Infection: Pneumonia, UTIs and cellulitis
  4. Inflammation: Pancreatitis and cholecystitis
  5. Intoxication: Alcohol
  6. Infarction: Acute MI and stroke
  7. Iatrogenic: steroids and surgery
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77
Q

What are the signs and symptoms of DKA?

A

1.Osmotic related:

Polydipsia

polyuria

Dehydration

  1. Ketone body related

Flushed

Vomiting

Abdominal pain

tenderness

Breathless – Kussmaul’s respiration

NB. not all individuals can smell ketones on breath

3.Associated conditions

Underlying sepsis

Gastroenteritis

Large amount of fluid loss - sodium ,potassium and phosphate

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78
Q

How do you manage DKA?

A
  1. IV fluid resuscitation

1000ml NaCl 0.9% in first hour

2000ml NaCl by end of hour 2

3000ml NaCl by end of hour 4

  1. Monitor

Blood for U&E, pH, ketones and bicarbonate and level hour 2

Blood for U&E,pH, ketones and bicarbonate level hour 4

IV potassium replacement as it starts dropping

  1. Insulin

Give IV infusion

Continue patients long acting insulin at usage dosage and time even with infusion

premature end of treatment leads to recurrence

  1. Hypoglycaemia - AVOID

when glucose <14mmol/L start giving 10% glucose at 125ml/h along with the saline

MONITORS:

  1. Blood ketone testing

better as urine ketone gives an idea of levels 2-4 hours before and doesn’t improve straight away due to rate of mobilisation of ketones from fat tissue

Measures beta-hydroxbutyrate

<0.6mmol/L is good

> 3mmol/L significant ketosis

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79
Q

What is Hyperglycaemic Hyperosmolar state (HHS)

A

a complication mainly associated with Type 2 diabetes in which high blood sugar results in high osmolarity WITHOUT significant ketoacidosis

This is because these patients are still able to make insulin so the ketogenesis pathway is not involved

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80
Q

what is the pathophysiology of HHS?

A
  1. Relative insulin defiency causes cortisol and arenaline activation
  2. Stress hormone (cortisol, adrenaline) cause Gluconeogenesis and glycogenolysis
  3. Hyperglycaemia in HHS is much higher in comparison to DKA
  4. Glycosuria causes osmotic diuresis which leads to dehydration and electrolyte loss
  5. Dehydration causes hyperosmolarity
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81
Q

How do you diagnose HHS?

A

Diabetes may be known at presentation – often not

Often presents in Older patients. Young Afro-Caribbean

  1. Hypovolaemia – usually marked
  2. Marked hyperglycaemia > 30mmol/L
  3. No/mild ketonaemia <3 mmol/L
  4. Bicarbonate > 15 mmol /L or venous pH > 7.3
  5. Osmolality >320 mosmol/kg normal is 275- 295
  6. Higher glucose than in DKA – usually above 50 mmol/L
  7. Significant renal impairment
  8. Sodium often high normal or raised

High refined CHO intake pre-presentation

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82
Q

how do you calculate osmolarity?

A

2(Na + K) + glucose + urea

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83
Q

What is the main cause for HHS?

A

Relative insulin deficiency - Type 2 diabetes

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84
Q

How do you manage HHS?

A
  1. Measure or calculate osmolality frequently to monitor progress
  2. Assess severity of dehydration and use 0.9% saline for fluid replacement without insulin. This alone will lower blood glucose which reduce osmality
  3. Monitor and chart BG, osmolality and sodium every 1-2 hours
  4. start low dose IV insulin only if Ketonaemia >1mmol/L or ketonuria >2+ at presenetation or if BG falling at rate less than 5mmol/h
  5. asses for complications of therapy e.g. fluid overload and cerebral oedema
  6. start prophylactic anticoagulation with LMWH (fragmin)
  7. Patient with HHS are at high risk of foot ulceration - check feet daily and protect heels
  8. treat underlying precipitants e.g. sepsis
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85
Q

which type of lactic acidosis is associated with diabetes?

A

Type B- associated with metformin

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86
Q

How is lactate removed from the blood?

A

hepatic uptake and aerobic conversion to pyruvate then glucose

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87
Q

where does lactate orignate from?

A

red cells, skeletal muscle, brain and renal medulla - anaerobic respiation

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88
Q

what is the normal rate of lactate in blood?

A

0.6 to 1.2 mmol/L

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89
Q

what is the ion gap?

A

used to show whether your blood has an imbalance of electrolytes or too much or not enough acid

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90
Q

what is the normal ion gap?

A

10 to 18 mmol/L

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91
Q

how do you calculate the ion gap?

A

[Na+ + K+] – [HCO3- + Cl-]

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92
Q

what is usually associated with type A lactic acidosis?

A

tissue hypoxaemia

infarcted tissue, cardiogenic shock, hypovolaemic shock

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93
Q

what is usually associated with the type B lactic acidosis (diabetes one)

A

Mitochondrial defects

Cyanide toxicity

Beriberi (thiamine deficiency)

Drugs (metformin, salicylates, nucleoside reverse
transcriptase inhibitors)

Liver failure

Ethanol intoxication

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94
Q

what are the main clinical features of lactic acidosis?

A

hyperventilation
mental confusion
stupor/coma

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95
Q

how do you diagnose lactic acidosis?

A

Raised lactate

Reduced bicarbonate

  1. Raised anion gap [(Na+ + K+) – (HCO3 + Cl-)]
    Other causes: dka, starvation, uraemia, alcohol, ethylene glycol, methanol, salicylate or paraldehyde poisoning.
  2. Glucose variable – maybe [often] raised
  3. Absence of ketonaemia
  4. Raised phosphate
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96
Q

how do you manage lactic acidosis?

A

Fluids
Antibiotics

stop drugs which cause it e.g. metformin

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97
Q

what are the 2 classes of neonatal diabetes?

A

transient neonatal diabetes

permanent neonatal diabetes

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98
Q

when is permanent neonatal diabetes usually diagnosed?

A

0-6 weeks

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99
Q

What is Hypothyroidism?

A

Clinical effect of lack of thyroid hormone. Results from any disorder that results in insufficient secretion of the thyroid hormones from the gland.

Primary: due to disease affecting thyroid gland itself. Can occur with or without a goitre

Secondary: No thyroid gland pathology. Most likely problem with either hypothalamus or pituitary gland

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100
Q

How do you diagnose Hypothyroidism?

A

Thyroid function test:

testing with free T3/4 is better then total T3/4 as free forms of these hormones are less affected by TBG. As TBG levels are effected by different conditions (e.g. pregnancy causes increase in TBG whereas is decreased with nephrotic syndrome)

Primary

High TSH

Low Free T4/T3 - T4 would be normal if it was treated hypothyroidism, if there is thyroid resistance, or if it was subclinical hypothyroidism

Increase in PRL - mild

can get:

increase in MCV, CK and LDL cholesterol

Secondary:

Low TSH - due to hypothalamic or pituitary disease

Low Free T4/T3 (or normal)

Thyroid autoantibodies:

Anti TPO antibodies - found in 95%. useful especially for Hashitmoto’s thyroiditis

Anti thyroglobulin antibody - found in 60%

TSH receptor antibody - blocking type only found in 15%

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101
Q

What is Myxoedema?

A

severe hypothyroidism and is a medical emergency

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102
Q

what is pretibial myxoedmea?

A

not associated with hypothyroidism but Hyperthyroidism!

Rare clinical sign of Grave’s disease which is an autoimmune thyroid disease

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103
Q

What are the causes of Hypothyroidism?

A

Primary:

  1. Goitrous
    i. Chronic lymphotic thyroiditis (Hasimoto’s thyroiditis)

ii Iodine defiency

iii. Drug induced e.g. lithium and amiodarone
iv. Maternally transmitted - if women are on antithyroid drugs it can cause neonatal hypothyroidism
v. Hereditary biosynthetic defects
2. Non-goitrous
i. Atrophic thyroiditis
ii. Post-ablative therapy - e.g. radioiodine, surgery
iii. Post- raditotherapy e.g. for lymphoma treatment
iv. congenital developmental defect
3. Self-limiting
i. withdrawal of antithyroid drugs
ii. subacute thyroiditis with transient hypothyroidism
iii. Post- partum thyroiditis
2. Secondary

Infiltrative

infection

Malignant

traumatic

congenital

104
Q

what are the signs and symptoms of Hypothyroidism?

A

Loads of clinical features because almost all our cell nuclei have receptors showing a high affinity for T3. receptors are TRalpha 1, TR alpha 2 and TR beta 1

  1. Hair and skin

dry thin hair and skin

Dull, expressionless face

round puffy face

Pale cool skin

Hypercarotenaemia

  1. Dislikes cold more sensitive to it
  2. Cardiac

Bradycardic

Pericardial effusion

cardiac dilatation

  1. Metabolic

Hyperlipidaemia

Decreased appetite

weight gain

  1. GI

constipation

Megacolon and intestinal obstruction

Ascites - can have non pitting oedema in eye lids and feet

  1. Respiratory

Hoarse voice

Enlarged tongue

obstructive sleep apnoea

  1. CNS

Lethargic

mood/depression, psychosis

Decreased intellectual and motor activities

cramps

Peripheral neuropathy

carpal tunnel syndrome

cerebellar ataxia - signs: seems drunk

memory loss

weakness

  1. reproduction

Menorrhagia

Hyperprolactinaemia - increase TRH causes increase in in prolactin (PRL).

105
Q

How do you manage Hypothyroidism?

A

General: restore metabolic rate to normal

Thyroxine treatment:

THYROXINE NEEDS TO BE TAKEN ON AN EMPTY STOMACH - therefore take before breakfast is best

Thyroxine half life is 7days so wait 4 weeks before checking if needs to adjust. Check TSH 2 months after any dose change

once stabilised TSH should be checked every 12-18months

Young patients: Levothyroxine (T4) 50-100 μg a day.

Elderly or IHD- start at 25-50 μg a day. adjust every 4 weeks according to TSH response

Secondary hypothyroidism:

TSH is unreliable - titrate dose of levothyroxine to the free T4 levels

DO NOT:

Take levothyroxine with PPI, iron tablet and calcium tablets. they affect its absorption

Pregnancy: increase dose by 25-50%

106
Q

What are the sign and symptoms of myxodema coma?

A

Looks hypothyroid

often elderly women

Bradycardia

coma

seizures

Type 2 resp failure - hypoxia, respiratory acidosis and Hypercarbia

107
Q

How do you diagnose Myxodema coma?

A

ECG: bradycardia, Low voltage complexes, varying degrees of heart block, T wave inversion and prolonged QT interval

Goitre

Cyanosis

can have co-existing adrenal failure in 10% of patients

108
Q

How do you manage Myoxdema coma?

A
  1. Check blood for T3,T4, TSH, FBC and U&E. Close cardiac monitoring
  2. High flow O2 if cyanosed
  3. Passively rewarm if hypothermic e.g. blankets and fluid
  4. Rehydrate if needed but watch for cardiac dysfunction
  5. If infection is suspected give antibiotics
  6. Hydrocortisone for pituitary hypothyroidism and adrenal failure
  7. Give Levothyroxine
109
Q

what diseases are associated with hypothyroidism?

A

Autoimmune:

  1. Type 1 dm
  2. Addison’s disease
  3. Genetic:

Down’s syndrome

Turner’s syndrome

cystic fibrosis

  1. others

primary biliary cholangitis (PBC)

110
Q

What is the difference between hyperthyroidism and Thyrotoxicosis?

A

Hyperthyroidism - refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis

Thyrotoxicosis- clinical effect of excess thyroid hormone, usually from gland hyperfunction

111
Q

What are the signs and symptoms of thyrotoxicosis?

A

Cardiac:

  1. Palpitations, pulse fast/irregular (AF)
  2. Cardiac failure - very rare

Sympathetic nervous:

  1. Tremor
  2. sweating - heat intolerance

CNS:

  1. Anxiety
  2. nervousness
  3. Irritability
  4. Sleep disturbance

GI:

  1. Diarrhoea
  2. Weight loss
  3. increase in apeptite

Hair and skin:

  1. thin hair
  2. palmar erythema
  3. rapid finger nail growth

Muscle weakness

Eyes:

  1. Lid lag
  2. Lid retraction
  3. Diplopia- double vision
112
Q

what are the causes of thyrotoxicosis?

A

any condition associated with hyperthyroidism

Excessive thyroid stimulation:

  1. Grave’s disease - 2/3 of cases of hyperthyroidism, more common in 40-60yr old women. Caused by circulating IgG autoantibodies binding to and activating g-protein coupled thyrotropin receptors, which cause smooth thyroid enlargement and increased hormone production
  2. Hashitoxicosis - associated with hashimoto thyroiditis. Early in hashimoto, you get excess TSH which increases release of T3 and T4
  3. Thyrotropinoma
  4. Thyroid cancer - very rarely causes thyrotoxicosis
  5. Choriocarcinoma - trophoblast tumour secreting hCG

Thyroid nodules with autonomous function :

  1. Toxic solitary nodule
  2. Toxic multinodular goitre

Thyroiditis:

  1. Subacute thyroiditis (de Quervain’s) - temporary hypothyroidism after hyperthyroid phase. Associated with painful goitre, pyrexia and raised inflammatory markers. Give NSAIDs
  2. Post-Patrum thyroiditis
  3. Drug induced thyroiditis - amiodarone and lithium

Exogenous thyroid hormones:

  1. Over treatment with Levothyroxine
  2. Thyrotoxicosis factitia

Ectopic thyroid hormones

  1. Metastatic thyroid carcinoma
  2. Struma ovarii
113
Q

what are the specific signs of Grave’s disease?

A
  1. Thyroid eye disease:

occurs in 20% of patients.

can be either unilateral or bilateral. It is mainly mild but can be severe and sight threatening

i. Ophthalmoplegia - paralysis or weakness of eye muscle
ii. Proptosis (exophthalmos) - eyes protrude beyond the orbit
iii. eye discomfort - grittiness
iv. corneal ulceration
v. diplopia - double vision
vi. loss of vision
2. Pretibial myxoedema - swellings above lateral malleoli
3. Thyroid acropachy - clubbing, painful fingers and toe swelling and periosteal reaction in limb bones
4. Thyroid bruit

only associated with large goitres

reflective of hypervascularity of thyroid

ausculate over the thyroid - not heard in other goitrous conditions

Goitre’s associated with Graves’ are smooth

114
Q

What is thyroid eye disease mainly associated with?

A

Smoking

115
Q

How do you diagnose Thyrotoxicosis?

A

TFTs:

Supressed TSH - due to pathological positive feedback

High Free T3/T4

Other:

High ESR

High Calcium ion level - hypercalcaemia. Grave’s is associated with osteoporosis

High LFTs (alkaline phosphatase is high)

Decrease in white cell count (leucopenia) - often mild and related to disease than treatment

Autoantibodies:

TSH receptor antibody (TRAb) - 70-100% people have it in grave’s

Anti TPO -70-80% in graves

Anti thyroglobulin - 30-50% in graves

Isotope scan to detect:

nodular disease: TRAb negative

subacute thyroiditis

116
Q

what is a Hyperthyroid crisis (thyroid storm)?

A

It is severe hyperthyroidism

117
Q

what are the signs and symptoms of a thyroid storm?

A

Agitation

confusion

coma

tachycardia and AF

Hyperthermia

Respiratory and caridc collapse

acute abdomen

thyroid bruit

exaggerated reflexes

Precipitants: hyperthyroid patients with acute infection, recent thyroid surgery or trauma

118
Q

How do you manage a thyroid storm?

A
  1. IV access, fluids if dehydrated or NG tube if vomiting
  2. Take blood for TFTs and cultures (infections)
  3. Monitor BP if good cardiac output and if no contraindication give propanolol/ use diltiazem if beta blocker is contraindicated
  4. Digoxin may be needed to slow the heart. Ensure adequately beta blocked, give with cardiac monitoring
  5. Antithyroid drugs : carbimazole, after four hours give Lugols (aqueous iodine) solution
  6. Give hydrocortisone or dexamethasone to prevent peripheral conversion of T4 to T3
  7. Give antibiotics for infection
  8. Cool if hyperthermic
119
Q

How do you manage Hyperthyroidism?

A

Beta blockers

  1. Beta blockers used for rapid control of symptoms - reduces activity of sympathetic nervous system e.g. propanolol
  2. Careful if they are asthmatic as it can cause bronchospasm
  3. Can use CBB instead e.g. diltiazem

Anti thyroid drugs - inhibits TPO thereby blocking thyroid hormone synthesis:

  1. Carbimazole
    i. 1st line drug
    ii. Once daily dosing
    iii. lower rate of side effect than PTU
    iv. risk of aplasia cutis in early pregnancy
  2. Propylthiouracil (PTU)
    i. 1st line only in trimester of pregnancy
    ii. twice daily dosing
    iii. Inhibits DIo1 (stops conversion of T4 to T3)

Graves disease:

two strategies:

Dose titration: e.g. carbimazole (12-18 months)

Block and replace: e.g. carbimazole and levothyroxine simultaneously (6 months)

RADIOIODINE

1st line IF Graves disease relapse or nodular thyroid disease

no increased risk of thyroid cancer

risk of hypothyroidism if the patient has grave’s disease

dont use if patient is pregnant

Thyroidectomy: usually total

Used if radioiodine is contraindicated

scar

Sugrical/anaesthetic risks:

recurrent laryngeal nerve palsy

Hypothyroidism

Hypoparathyroidism

120
Q

What are the types of thyroiditis?

A

Hashimoto’s thyroiditis

De Quervain’s/ subacute - viral

Post partum

Drug-induced (amiodarone, lithium)

radiation induced thyroiditis

Acute suppurative thyroiditis (bacterial)

121
Q

What is subclinical thyroid disease

ii. what are its readings?

A

Abnormal TSH with normal thyroid hormone levels

ii. Subclinical hypothyroidism:

TSH is high but normal level of free T4 and T3

treat if TSH >10 mu/L and positive thyroid autoantibodies. Also if patient previously had Grave’s disease

Always treat in pregnancy to maintain normal TSH

Subclinical hyperthyroidism:

Low TSH and normal level of free T4 and T3

associated with AF and osteoporosis

treat if TSH <0.1 mu/L or if they have co existing osteoporosis or AF

122
Q

What is sick euthyroid syndrome?

A

non -thyroidal illness which causes TSH levels to be secreted due to severe illness

TSH will rise to normal when patient recovers from illness

123
Q

what are the five types of thyroid cancer?

A
  1. Papillary - most common
  2. Follicular - second most common
  3. Medullary -
  4. Anaplastic - extremely invasive and difficult to treat
  5. Hurthle cell
124
Q

What is differentiated thyroid cancer ? (DTC)

A

Refers to two types of thyroid cancer: papillary and follicular

Has histological appearance which is similar to normal thyroid cells

“differentiated” features means good prognosis

Best prognosis only second to non melanoma skin cancer.

125
Q

How can you separate differentiated thyroid cancer from other forms of thyroid cancer?

A

they take up radioactive iodine

they secrete TSH - they are TSH driven

126
Q

what is the incidence and prevalence of differentiated thyroid cancer?

A

1: 100,000 men
2: 100,000 in women

non existent in childhood

Females rates increase 15-40 but then plateau

Male rates increase steadily

127
Q

what is the epidemiology of Differentiated thyroid cancer?

A

More common in women

Lower incidence with Afro carribeans

Risk factor :Radiation exposure

No association with diet, family history, smoking or other lifestyle factors

128
Q

what are the clinical features of differentiated thyroid cancer?

A

Palpable nodules - move on swallowing

Hoarse voice - could lead to vocal cord palsy

swollen glands in the neck

pain in neck is uncommon

5% present with local or disseminated metastases

Papillary thyroid cancer:

have Psammoma bodies

Tends to spread via lymphatics

Haematogenous spreads to lungs, bone, liver and brain

Follicular carcinoma:

Tends to spread via haematogenous

Lymphatic spread and lymph node enlargement relatively rare

equal prognosis with Papillary cancer

129
Q

How do you diagnose Differentiated thyroid cancer?

A

Ultrasound guided FNA of the lesion

Can involve excision of lymph node

No need for:

isotope thyroid scan

CT/MRI

130
Q

How do you manage differentiated thyroid cancer?

A
  1. surgery treatment of choice:

thyroid lobectomy with isthmusectomy

Used for patients in AMES low risk group

For:

Papillary microcarcinoma (<1cm diameter)

Minimally invasive follicular carcinoma with capsurlar invasion only

subtotal thyroidectomy - safest option

Used for patients in AMES high risk group

for:

DTC with extra-thyroidal spread

Bilateral/multifocal DTC

DTC with distant metastases

DTC with nodal involvement

Total thyroidectomy - quiet difficult as thyroid is deep in the neck

used for patient in AMES high risk group

for:

DTC with extra-thyroidal spread

Bilateral/multifocal DTC

DTC with distant metastases

DTC with nodal involvement

  1. Whole body iodine scanning

Given Iodine 131 - 2-4 mCi given as a capsule

Used after patients who have undergone subtotal or total thyroidectomy

occurs 3-6 months post op

Make TSH levels elevated: Administer recombinant human TSH (rhTSH) means you dont need to stop T3/T4 medication. Injection twice a week. This makes the cancer cells “hungry” for iodine. This makes it easier to see them in scan

  1. Thyroid remnant ablation:

used if evidence of metastatic disease is found in whole body iodine scanning

Pre-treated with rhTSH as before

given a much HIGHER dosage of Iodine 131 (3.3 GBq)

Few side effects: Sialadenitis (inflammation of salivary glands) and sore throat. No link to causing tumours or effect infertility/ genetic abnormalities in foetus

  1. Follow up after TRA

80% of radioactive iodine is excreted in first 24 hours

patient maintained on T4 - causes TSH suppression. But must not have Free T4 at too high of a level

Use thyroglobulin as a tumour marker - if differentiated thyroid cancer recurs, thyroglobulin is made only by this type of cancer and healthy thyroid cells. Therefore it is very specific

High Thyroglobulin levels can only be used if TSH levels are low. TSH levels if raised is associated with high Tg therefore can lead to misdiagnosis

  1. Systemic Anti- cancer therapy

Patients with DTC refractory to radioactive iodine therapy use this

biological agents: types of Tyrosine kinase inhibitors

Lenavatinib

Sorafenib

131
Q

How do you define Pituitary tumours?

A

Microadenomas <1cm

Macroadenomas >1cm - more aggresive

99.5% of pituitary tumours are benign

132
Q

What are the main issues of non functioning adenomas?

A

They can grow too big:

Compresses optic chiasma

Compresses cranial nerves 3,4,6

They can squeeze out other hormone production:

Hypoadrenalism

Hypothyroidism

Hypogonadism

GH defiency

Can effect post pituitary gland too- vasopressin deficiency = Diabetes Insipidus

133
Q

How do you manage a non functioning adenoma?

A

Transphenoidal surgery

Replace hormones

134
Q

What are the cause for raised prolactin?

A

Physiological:

Breastfeeding

Pregnancy

Stress

Sleep

Pharmacological:

Dopamine antagonists e.g. metoclopramide

Antipsychotics e.g. Phenothiazines - mainly older antipsychotic drugs

Antidepressants e.g. TCA, SSRIs

oestrogens e.g. contraceptive pill

Cocaine

Pathological:

Hypothyroidism

Stalk lesions

Prolactinoma - prolactin secreting tumour

135
Q

If the prolactin level is over 5000 mu/L what does this suggest?

A

prolactin secreting tumour

136
Q

What are the signs and symptoms of Prolactinoma?

A

Female:

Early presentation

Galactorrhoea

30-80%

Menstrual irregularity

Amenorrhoea

Infertility

137
Q

define what AMES low risk group is.

A

Younger patients ( men <40, women <50) with no evidence of metastases

Older patients with intrathyroidal papillary lesion or minimally invasive follicular lesion and primary tumour < 5cm and no distant metastases

138
Q

Define what AMES high risk group is.

A

All patients with distant metastases

Extrathyroidal disease in patients with papillary cancer

Significant capsular invasion with follicular carcinoma

Primary tumour > 5cm in older patients

139
Q

What is type 3 diabetes?

A

diabetes secondary to a disease/syndrome/drug/monogenic cause

140
Q

what are the 3 main pancreatic causes of type 3 diabetes?

A

chronic/recurrent pancreatitis
haemochromatosis
cystic fibrosis

141
Q

what are the 4 main endocrine causes of type 3 diabetes?

A

cushings syndrome
acromegaly
phaechromocytoma
glucagonoma

142
Q

what are the 3 main drug-induced causes of type 3 diabetes?

A

glucocorticoids
diuretics
b-blockers

143
Q

what are the 3 main genetic causes of type 3 diabetes?

A

CF
myotonic dystrophy
turner’s syndrome

144
Q

will C-peptide be positive or negative in monogenic diabetes?

A

positive

145
Q

what is type 4 diabetes?

A

gestational diabetes:

any degree of glucose intolerance arising or diagnosed during pregnancy

146
Q

what are the main causes of Primary Hyperparathyroidism (PHPT)?

A
  1. Adenomas: (80%)
  2. Hyperplasia of all four parathyroid glands (20%)
  3. Carcinoma (0.5%) - parathyroid cancer
147
Q

What are the signs and symptoms of Primary hyperparathyroidism?

A

Asymptomatic

  1. Hypertension
  2. Hypercalcaemia - weak, tired, depressed, thirsty, dehydrated-but-polyuric, renal stones, abdominal pain, pancreatitis and ulcers
  3. Bone resorption: Bone pain, fractures, and osteoporosis
148
Q

How do you diagnose primary hyperparathyroidism?

A

1.Bloods:

Hypercalcaemia - incidental Ca ≥ 2.6 mmol/litre

Increase in PTH and Low PO43-

  1. Increased ALP from bone activity
  2. 24 hr urinary Ca2+

imaging:

Sesatimbi scan: osteitis fibrosa cystica - subperiosteal erosions, cysts or brown tumours of phalanges

Dexa for osteoporosis

149
Q

How do you manage Primary hyperparathyroidism?

A
  1. Mild PHPT

increase fluid intake to prevent stones

avoid thiazides and High Ca2+/ Vit D intake

  1. Surgery:

Excision of adenoma or all parathyroid glands

this prevents peptic ulcers and fractures

Complications:

Hypoparathyroidism, recurrent laryngeal nerve damage (hoarse voice), hypocalcaemia

150
Q

What are the indications of Primary hyperthyroidism?

A
  1. Hypercalcaemia
  2. Normal U&E
  3. High urine calcium
  4. Not on lithium or thiazide
  5. <50 years old
151
Q

compare primary and secondary causes of hypothyroidism in terms of goitre (enlarged thyroid)?

A

primary gland failure- may have a goitre

secondary to TRH or TSH- no goitre

152
Q

compare primary hyperthyroidism to pituitary disease causing secondary hyperthyroidism in terms of levels of T3/4 and TSH?

A

primary: low TSH, high T3/4
secondary: high TSH, high T3/4

153
Q

compare primary hypothyroidism to pituitary disease causing secondary hypothyroidism in terms of levels of T3/4 and TSH?

A

primary: high TSH, low T3/4
secondary: low TSH, low T3/4

154
Q

compare primary and secondary hypothyroidism in the use of TSH levels as an indicator for if thyroxine treatment is working?

A

primary: TSH is a good indicator- will be low when T4 treatment is successful

secondary: TSH is not a good indicator, will be low regardless of if the treatment is successful
(in this case montor T4 levels)

155
Q

what is primary hyperparathyroidism?

A

overactive parathyroid glands: PTH is produced irrespective of calcium levels

156
Q

what is secondary parathyroidism?

A

physiological high PTH in response to low calcium.

The release of PTH is appropriate

157
Q

what is tertiary hyperparathyroidism?

A

parathyroid becomes autonomously overactive having undergone hyperplastic or adenomatous change this occurs after many years of secondary parathyroidism.

The release of PTH is inappropriate (i.e. too high)

158
Q

what are the cause of Secondary and tertiary hyperparathyroidism?

A

Vitamin D deficiency

Chronic Kidney disease

159
Q

How do you diagnose between Secondary and tertiary hyperparathyroidism?

A

Secondary:

Low Ca

High PTH

High PO4

Tertiary:

High Ca

Very high PTH

Low PO4

160
Q

How do you manage Secondary and tertiary hyperparathyroidism?

A

Treat underlying cause

Renal disease: diet restriction, phosphate binders

Vitamin D

Cinacalcet if PTH >85pmol/L (secondary)

161
Q

What is malignant Hyperparathyroidism?

A

Parathyroid related protein ( PTHrP) is produced by the following types of cancer:

  1. some squamous cell lung cancers
  2. breast and renal cell carcinomas

this mimics PTH resulting in increased Ca 2+

162
Q

which MEN type are parathyroid neoplasms associated with?

A

both 1 and 2

163
Q

what is primary hypoparathyroidism?

A

Low PTH secretion due to gland failure

164
Q

What are the causes of primary hypoparathyroidism?

A

Autoimmune

Di george syndrome

Haemochromatosis/ wilsons

Iatrogenic: removal or accidental injury of parathyroid glands in surgery or radio ablation

165
Q

What are the signs and symptoms of Primary hypoparathyroidism?

A

Hypocalcaemia: perioral numbness, cramps, carpopedal spasm, laryngospasm, seizures, wheeze and anxiety

166
Q

How do you diagnose Primary hypoparathyroidism?

A

Bloods: Low ca, Low PTH and high PO4

167
Q

How do you manage Primary hypoparathyroidism?

A

Treatment of underlying cause

calcium and vitamin D supplements

168
Q

what is pseudohypoparathyroidism?

A

a genetic defect causing PTH resistance

169
Q

what are the levels of PTH in pseudohypoparathyroidism?

A

high

170
Q

What are the causes of secondary hypoparathyroidism?

A

Radiation

Surgery - thyroidectomy, parathyroidectomy

Hypomagnesaemia

171
Q

what are the signs and symptoms of pseudohypoparathyroidism?

A

Short metacarpals ( 4th and 5th especially)

round face

short stature

calcified basal ganglia

Low IQ

obesity

172
Q

How do you diagnose pseudohypoparathyroidism?

A

Low Ca2+

High PTH/PO4

High ALP

173
Q

How do you manage Pseudohypoparathyroidism?

A

Calcium and vitamin D supplements

174
Q

what is pseudo-pseudohypoparathyroidism?

A

a genetic defect causing PTH resistance

calcium is normal because PTH is high

175
Q

compare calcium, phosphate and PTH levels in a patient with:

  1. Hypoparathyroidism
  2. pseudohypoparathyroidism
  3. pseudo-pseudohypoparathyroidism
A

Calcium Phosphate PTH

  1. Low high Low
  2. Low high High
  3. Normal Normal High
176
Q

what is cushing’s syndrome?

A

the clinical state produced by chronic glucorticoid excess

177
Q

What are the causes of cushing’s syndrome?

A
  1. Exogenous - prolonged use of oral steroid ( main cause)
  2. Endogenous:
    i. ACTH-dependent (Increase in ACTH):

Cushing’s disease - bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma

Ectopic ACTH production - occurs especially in small cell lung cancer and carcinoid tumours

ii. ACTH-independent ( Decrease in ACTH due to -ve feedback):

Iatrogenic: Pharmacological doses of steroids

Adrenal adenoma/ cancer

Adrenal nodular hyperplasia

178
Q

what are the signs and symptoms of cushings syndrome?

A
  1. Psychology

Euphoria - though sometimes depression or psychotic symptoms and emotional lability

increased appetite

  1. Head:
    Benign intracranial hypertension

Cataracts

Moon face with red plethoric cheeks

  1. Body:

Hirsutism

Obesity

Osteoporosis

Increased abdominal fat

thin arms and legs - muscle wasting

osteoporosis

Poor wound healing

Easy bruising

thinning of skin

abdominal striae

  1. Legs

recurring Achilles tendon rupture

other:

Tendency to hyperglycaemia

negative nitrogen balance

infection-prone

Hypertension

Hyperglycaemia

179
Q

How do you diagnose Cushing’s syndrome?

A

First line:

  1. Overnight 1mg dexamethasone suppression test (oral) - dexamethasone makes ACTH low which in turn makes Cortisol low if normal

If cortisol <50 nmol/L next morning then normal

if Cortisol >130 nmol/L next morning then abnormal

  1. 24hr urine free cortisol

If total <250 then normal

or

if cortisol/creatinine ratio <25 then normal

2nd line:

  1. 48 hr dexamethasone suppression test 0.5mg/6hr (oral) - diagnostic

measure at 0hr and 48hr

there is a failure to suppress cortisol

  1. Diurnal cortisol variation (midnight/8am)

Loss of diurnal variation suggests cushing’s

(cortisol lowest at midnight and highest in early morning)

Imaging:

CT/MRI head

CT CAP

others:

blood glucose : hyperglycaemia

180
Q

How do you manage Cushing’s syndrome?

A
  1. Pharmacological:

Ketoconazole may have a direct effect on corticotropic tumour cells in patients with Cushing’s disease.

Metyrapone in controlling the symptoms of the disease

Adrenal enzyme inhibitors

  1. Cushing’s disease

selective removal of pituitary adenoma

  1. Adrenal adenoma or carcinoma
    adrenalectomy. Radiotherapy and adrenolytic drugs follow if carcinoma
  2. Ectopic ACTH: surgery if tumour is located and and hasn’t spread
  3. Iatrogenic:

stop medication

181
Q

what is primary hyperaldosteronism?

A

excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high water retention and sodium levels. This independent of the functions of the RAAS system.

182
Q

What are the causes of primary hyperaldosteronism?

A
  1. Conn’s syndrome - solitary aldosterone producing adenoma
  2. Bilateral adrenocortical hyperplasia (BAH)

other causes: adrenal carcinoma, glucorticoid-remediable aldosteronism

183
Q

What are the signs and symptoms of Primary Hyperaldosteronism?

A

Often asymptomatic

Hypokalaemia

Polyuria

Polydipsia

headaches

weakness

cramps

parasthesia

muscle spasms

Hypertension- young onset and treatment resistant

184
Q

How do you diagnose primary hyperaldosteronism?

A

Bloods:

U&Es

low Renin and high aldosterone levels

Sodium high

potassium low

Diagnostics

Plasma aldosterone: renin ratio >750

Saline suppression test - failure to suppress aldosterone production by 50% following consumption of water.

imaging:

CT abdomen - to identify adenoma

185
Q

how do you manage primary hyperaldosteronism?

A

Conn’s syndrome:

  1. Medical management first: aldosterone antagonists - eg, spironolactone
  2. Surgery: Laparoscopic adrenalectomy

BAH:

treatment is medical with aldosterone antagonists:

Amiloride- potassium-sparing diuretic

Spironolactone - nonselective aldosterone antagonist

Eplerenone - relatively new selective aldosterone antagonist and therefore does not have the same troublesome side-effects as spironolactone.

GRA:

Dexamethasone for four weeks. if the patient is still hypertensive then use spironolactone

186
Q

What is primary adrenal insufficiency (Addison’s disease)

A

destruction of the adrenal cortex leads to glucocorticoids and mineralocorticoids deficiency

187
Q

What are the causes of primary adrenocortical insufficiency?

A
  1. TB - most common cause in the world
  2. Autoimmune - most common cause in UK
  3. Adrenal metastasis: Lung, breats, renal and lymphoma
  4. Opportunistic infection in HIV
  5. Waterhouse Friderichsens syndrome: bilateral adrenal haemorrhage due to sepsis
188
Q

what are the signs and symptoms of primary adrenocortical insufficiency?

A

Anorexia

weight loss

fatigue/lethargy

dizziness

hypotension

abdominal pain

vomiting/ diarrhoea

hyperpigmentation of skin especially of palmar creases

myalgia and arthralgia

can have vitiligo and goitres

189
Q

How do you diagnose primary adrenocortical insufficiency?

A

Blood:

Low sodium

high potassium

signs of hypoglycaemia

Very high ACTH levels - causes ksin pigmentation

Very high renin

low Aldosterone and low cortisol

  1. Short SYNACTHEN Test: diagnostic marker

Measure plasma cortisol before and 30 minutes after IV/IM ACTH injection

Normal results are:

baseline: > 250 nmol/L

30 min result post ACTH > 550 nmol/L

  1. Adrenal autoantibodies:

21-hydroxylase and 17 alpha hydroxylase

Imaging:

CXR

CT CAP

190
Q

How do you manage primary adrenocortical insufficiency?

A

Pharmacological:

  1. cortisol replacement — hydrocortisone:

Glucocorticoid replacement should resemble the natural cycle of corticosteroid release

15–25 mg in divided doses

  1. Aldosterone replacement — fludrocortisone:

50–200 micrograms

careful monitoring of BP and K

Sick days:

they should double their usual dose of hydrocortisone until recovered.

if vomiting replace oral with IM

191
Q

what is secondary adrenal insufficiency?

A

condition where there is a failure to produce adequate steroids as a result of ACTH deficiency

192
Q

What are the causes of secondary adrenal insuffiency?

A
  1. Long term steroid therapy
  2. Pituitary disease
  3. Tumours - surgery and radiotherapy
193
Q

what are the signs and symptoms of secondary adrenal insuffiency?

A

Same as primary except for:

No hyperpigmentation ( skin pale) due to no increase in ACTH

Aldosterone production intact - regulated with RAS

194
Q

How do you diagnose secondary adrenal insufficiency?

A

Blood:

Low sodium

high potassium

signs of hypoglycaemia

Low Cortisol and normal aldosterone

  1. Short SYNACTHEN Test: diagnostic marker

Measure plasma cortisol before and 30 minutes after IV/IM ACTH injection

Normal results are:

baseline: > 250 nmol/L

30 min result post ACTH > 550 nmol/L

  1. Adrenal autoantibodies:

21-hydroxylase and 17 alpha hydroxylase

Imaging:

CXR

CT CAP

195
Q

how do you manage secondary adrenal insufficiency?

A

Hydrocortisone replacement

196
Q

What are the causes of an acute adrenal crisis (Addisonian crisis)?

A

Bilateral adrenal haemorrhage

Patient on long term steroids who suddenly doesn’t take them

Illness, trauma or surgery in those with primary adrenal failure

197
Q

what are the signs and symptoms of an acute adrenal crisis?

A

Shock:

increased Heart rate

vasoconstriction

postural hypotension

oliguria

weak

confused

comatose

Hypoglycaemia

198
Q

How do you diagnose acute adrenal crisis?

A

FBC

U&E

Glucose

Cortisol

ACTH

Lactase

cultures

199
Q

How do you manage acute adrenal crisis?

A

ABCDE

Hydrocortisone 100mg IV

IV fluid bolus Resuscitation

monitor blood glucose: Glucose IV needed if hypoglycaemic

200
Q

What are Phaeochromocytoma?

A

They are rare catecholamine-producing tumours of the adrenal medulla . They arise from sympathetic paraganglia cells (phaeochrome bodies) which are collections of chromaffin cells.

201
Q

What is the 10% rule for phaeochromocytomas?

A

They roughly follows this rule

10% are malignant:

extra adrenal lesions (20-40%)

tend to be large and nectrotic

10% are extra-adrenal:

Called paraglangliomas

organs of zuckerkandl, carotid

10% are familial:

germline mutations

10% bilateral:

Up to 50% in familial cases

202
Q

what are the signs and symptoms of phaeochromocytomas?

A

Classic triad:

Episodic headache

Sweating

tachycardia

Hypertension

CNS: Headache, visual disorder, dizziness, tremor, numbness, fits and encephalopathy

Psychological: anxiety, panic, hyperactivity, confusion; episodic psychosis

203
Q

What are the associated conditions with phaeochromocytomas?

A

MEN2A - sipple syndrome

MEN2B

neurofibromatosis

von- Hippel Lindau syndrome

204
Q

How do you diagnose phaeochromocytomas?

A

Detection of urinary excretion of catecholamines and metabolites

increased White cell count

MIBG scan - uses a chromaffin seeking isotope

205
Q

How do you manage Phaeochromocytomas?

A

alpha blockage : phenoxybenzamine
then use

Beta blocker e.g. atenolol to avoid crisis from unopposed alpha adrenergic stimulation

206
Q

what is hypopituitarism?

A

decrease in secretion of one type of pituitary hormones

Panhypopituitarism - deficiency of anterior hormones

it involves problems in the hypothalamus, the pituitary stalk or the pituitary gland itself

207
Q

What are the causes of hypopituitarism?

A

Hypothalamus causes:

Kallman’s syndrome

tumour

inflammation

Infection ( TB and meningitis)

ischaemia

Pituitary stalk:

Trauma

surgery

mass lesion

meningioma

carotid artery aneurysm

Pituitary gland:

Tumour

irradiation

inflammation

autoimmune - may be triggered by pregnancy

infiltration: haemochromatosis , amyloid, sarcoid

Ischaemia: Sheehan syndrome, pituitary apoplexy

Sheehan syndrome: pan hypopituitarism due to pituitary ischaemia and necrosis following a post partum haemorrhage. commonly presents with failure to produce breast milk

Pituitary apoplexy: ischaemia due to bleeding of pituitary tumours

208
Q

What are the signs and symptoms of hypopituitarism?

A

Lack of of GH: Central obesity, atherosclerosis, dry wrinkly skin, weakness, loss of balance, osteoporosis, hypoglycaemia

Absent TSH: hypothyroidism

Lack of corticotropin: adrenal insufficiency

Lack of GRH:

Women: amenorrhoea, decrease in fertility, decrease in libido, breast atrophy, dyspareunia

Men: erectile dysfunction, decrease in muscle bulk, decrease in libido, hypogonadism

lack of prolactin: absent lactation ( rare)

209
Q

how do you diagnose hypopituitarism?

A

Basal testing:

LH, FSH, testosterone or oestradiol, TSH, T4, prolactin, IGF1

Dynamic tests:

short synacthen test : used for adrenal axis

Insulin tolerance test: used for adrenal and GH axes

both will rise in the presence of hypoglycaemia induced by giving insulin

210
Q

How do you manage hypopituitarism?

A

Hydrocortisone for adrenal failure

thyroxine if hypothyroidism

Hypogonadism:

males: testosterone enanthate 250mg IM every three weeks

topical gels can also be used on the daily

females: transdermal oestradiol patches or contraceptive pill

Growth hormone deficiency:

somatotropin

211
Q

what is Diabetes Insidpidus? (DI)

A

The passage of large volumes ( >3L/day) of dilute urine due to impaired water resorption by kidney

Either because of reduced ADH secretion from the posterior pituitary (central DI)

or

impaired response of the kidney to ADH ( nephrogenic DI)

212
Q

what are the causes of DI?

A

Central DI:

  1. Idiopathic - most common
  2. Genetic - e.g. DIDMOAD
  3. Tumour - may present with DI and hypopituitarism
  4. Sarcoidosis
  5. Trauma to the pituitary stalk

Nephrogenic DI:

  1. Genetic
  2. Metabolic - Low potassium/ high calcium
  3. CKD
  4. Drugs - Lithium, demeclocycline
213
Q

What are the signs and symptoms of DI?

A

Polyuria

Polydipsia

dehydration

214
Q

How do you diagnose DI?

A

Gold test standard

Water deprivation tests: Tests the ability of kidneys to concentrate urine ( dilute urine in spite of dehydration) - must check calcium to exclude hypercalcaemia

osmolality >600 is normal

Can distinguish between the two types of DI via water deprivation test by giving desmopressin (ADH):

Cranial DI: will rise to >600 after desmopressin

Nephrogenic DI: will NOT rise >600 after desmopressin

215
Q

How do you manage DI?

A

Cranial DI: Desmopressin

Nephrogenic:

Treat the cause

if it persists give Bendroflumethiazide - generate hyponatremia and drive water reabsorption

216
Q

What is acromegaly?

A

abnormal growth of the hands, feet, and face, caused by overproduction of growth hormone by the pituitary gland.

217
Q

What are the causes of acromegaly?

A

GH secreting pituitary tumours associated with MEN - 1

218
Q

What are the signs and symptoms of acromegaly?

A

Symptoms:

Acroparaethesia (pins and needles)

amenorrhoea

decrease in libido

headache

increase in sweating

snoring

backache

signs:

Growth of hands, lower jaw, brow and tongue

coarsening face, wide nose

big supraorbital ridges

macroglossia

widely space teeth

puffy eyelids/ lips

skin darkening

goitre

obstructive sleep apnoea

signs of any pituitary mass

carpal tunnel syndrome

219
Q

How do you diagnose Acromegaly?

A

high IGF1 levels - First line

bloods:

High glucose

High calcium and Phosphate

high GH - dont rely on random GH as secretion is pulsatile and during peaks acromegalic and normal levels overlap.

Tests:

Glucose tolerance tests: if OGTT is above 1mcg/L then acromegaly is confirmed

imaging:

MRI of pituitary

220
Q

how do you manage acromegaly?

A

1st line: Trans-sphenoidal surgery is the treatment of choice

2nd line: pharmacology

carried out if surgery not possible or fails to correct growth hormone levels

Somatostatin analogues (somatostatin receptor ligands) are the first-choice medical treatments e.g. Octreotide and lanreotide

Side-effects are frequent and include abdominal discomfort and gallstones or gallbladder sludge

Dopamine agonists:

Bromocriptine, cabergoline and quinagolide are effective but are less effective than somatostatin analogues

Cabergoline is the most effective dopamine agonist

Pegvisomant (PEG):

This is a genetically modified analogue of human GH and a highly selective GH receptor antagonist which blocks the peripheral synthesis of IGF-1.

doesnt shrink tumour

Pregnancy

Medical therapy is withheld during pregnancy.
Short-acting octreotide may be used as needed when attempting to conceive.

221
Q

What is Hyperprolactinaemia?

A

prolactin fasting levels of above 20 ng/ml in men and above 25 ng/ml in women at least 2 hours after waking up.

222
Q

what are the causes of hyperprolactinaemia?

A

Drugs (most common):

metoclopramide

haloperidol

methyldopa

oestrogens

MDMA

antipsychotics

Physiological: pregnancy, breastfeeding, stress

Pathological:

Pituitary tumour (prolactinoma)

Stalk damage: pituitary adenoma, surgery, trauma

Hypothalamic disease: craniophayngioma

Hypothyroidism

chronic renal failure

223
Q

What are the signs and symptoms of hyperprolactinaemia?

A

presents earlier in women than men

Females:

Amenorrhoea

infertility

galactorrhoea

decrease in libido

increase in weight

dry vagina

Male:

erectile dysfunction

reduced facial hair

galactorrhoea - less prominent in comparison to females

224
Q

How do you diagnose hyperprolactinaemia?

A

Bloods: TFT, U&E, prolactin

pregnancy test if other causes are ruled out

imaging - MRI

225
Q

How do you manage hyperprolactinaemia?

A

1st line - dopamine agonists e.g. bromocriptine or cabergoline

2nd - surgical excision of the tumour

226
Q

What is a microprolactinoma?

A

A tumour <10mm on MRI

227
Q

what is a macroprolactinoma?

A

a tumour >10mm on MRI

228
Q

where are craniopharyngiomas found?

A

the pituitary and 3rd ventricle floor

a tumour of rathke’s pouch

229
Q

what are the clinical features of craniopharyngioma’s?

A

most common intracranial tumour

Childhood growth failure

adults:

amenorrhoea

libido decrease

hypothalamic symptoms e.g. DI

230
Q

How do you treat craniopharyngioma’s?

A

Surgery and post op radiation

imaging: CT/ MRI

231
Q

what is the presentation of a thyroglossal cyst?

A

Lesion usually in the midline

moves upwards on protrusion of the tongue

not painful

232
Q

what is osteoporosis?

A

progressive systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture

if trabecular bone is affected, crush fractures of vertebrae are common

if cortical bone is affected, long bone fractures are more likely

233
Q

what are risk factors of osteoporosis?

A
  1. risk factors Reducing Bone material density include:

Endocrine disease including Diabetes mellitus,

Hyperthyroidism, and hyperparathyroidism.

Gastrointestinal conditions that cause malabsorption such as Crohn’s disease, Ulcerative colitis, Coeliac disease, and Pancreatitis - chronic.

Chronic kidney disease.

Chronic liver disease.

Chronic obstructive pulmonary disease.

untreated Menopause.

Immobility.

Body mass index of less than 18.5 kg/m²

  1. Risk factors which Do not reduce BMD include:

Age - risk increases with age and is at least partly independent of BMD.

Oral corticosteroids (dependent on the dose and duration of treatment).

Smoking.

Alcohol (3 or more units daily).

Previous fragility fracture (risk increases with increasing
number of fractures). Risk is highest for previous hip fractures and lowest for previous vertebral fractures.

rheumatoid arthritis, and other inflammatory arthropathies.

Parental history of hip fracture.

234
Q

what are the signs and symptoms of osteoporosis?

A

asymptomatic until minimal trauma fractures occur

common fracture sites:

neck of femur

vertebral body

distal radius

humeral neck

domino fracture effect: one Vertebral Compression Fracture increases risk of another

235
Q

how do you diagnose osteoporosis?

A

1.DEXA scan used to measure bone mass density:

T -score - the number of standard deviations the BMD is from the youthful average

T score > 0 -:Good BMD

T score 0 to -1 : normal BMD

T score -1 to -2.5: osteopenia. risk of later osteoporotic fracture

  • 2.5 or worse: osteoporosis
    2. Bloods:

Ca2+ : normal

Po43- : normal

ALP : normal

  1. For all other people with risk factors for osteoporosis, calculate the 10-year fragility fracture risk prior to arranging a DXA scan to measure BMD. e.g. FRAX or Q fracture
236
Q

Who do you refer for DEXA scans?

A

patients over 50 years with low trauma fracture - often identified through fracture liaison service

Patients at increased risk of fracture based on risk factors - calculated with risk assessment tools e.g. FRAX or Q fracture >10% risk of fracture over 10 years

237
Q

how do you manage Osteoporosis?

A

Lifestyle:

Fall prevention

avoidance of smoking and alcohol

Low impact weight-bearing exercise may increase BMD e.g. standing, one foot always on the floor

Diet: high in calcium and Vitamin D. Reference nutrition intake = 700mg calcium

Pharmacological:

  1. Bisphosphonates:
    e. g. alendronate and risedronate.

prevent bone loss at all sites vulnerable to osteoporosis. reduce risk of hip and spine fractures . it prevents bone resorption

use in patients of T score <2.5

use zoledronic acid if intolerant to oral bisphosphonates or unable to comply with dosing regime

  1. calcium and vitamin D supplements: rarely used alone for prophylaxis. used to reduce risk of non-vertebral fractures in patients who are at risk of deficiency due to insufficient dietary intake
  2. Denosumab - fully human monoclonal antibody to RANKL ( receptor activator of nuclear factor - kB ligand)

prevents activation of its receptor RANK which inhibits development and activity of osteoclasts which decreases bone resorption and increases bone density

sub cutaneous injection 6 monthly

adverse effects: cellulitis and eczema and hypocalcaemia

  1. Teriparatide

recombinant PTH

stimulates bone growth

consider for severe osteoporosis- especially in high risk of vertebral fracture

when to treat
= -2.5 - no steroids and with anti resorptive therapy

  1. 5mg prednisolone for three months)
  2. corticosteroids

directly - reduce osteoblast activity and lifespan

reduces calcium absorption

indirectly - inhibits gonadal and adrenal steroid production

238
Q

what is the pathogenesis of osteoporosis?

A

caused by increase in bone turnover due to an imbalance in bone turnover

three is a shift towards increased resorption which reduces BMD and causes micro architectural changes

239
Q

what is metabolic bone disease ?

e.g. osteomalacia and rickets

A

there is a normal amount of bone but its mineral content is low.

it is a reverse of osteoporosis

240
Q

what is the difference between osteomalacia and rickets?

A
  1. rickets is the result of abnormal bone mineralisation occurring during the period of bone growth
  2. osteomalacia - is the result if it occurs after fusion of epiphyses
241
Q

what are the causes of osteomalacia and rickets?

A

vitamin D deficiency - due to malabsorption, poor diet or lack of sunlight

Renal osteodystrophy - renal failure leads to 1,25 dihydroxy-cholecalciferol deficiency

vitamin D resistance

liver disease - due to reduce hydroxylation of vitamin D to 25 hydroxy-cholecalciferol deficiency e.g. cirrhosis

tumour induced osteomalacia

drugs: anticonvulsants

242
Q

what are the signs and symptoms of osteomalacia and rickets?

A

1.Rickets:

growth retardation

hypotonia

apathy in infants

signs of hypocalcaemia

ii. when walking: knock kneed, bow legged and deformities of the metaphyseal-epiphyseal junction
2. osteomalacia

Bone pain and tenderness

fractures

proximal myopathy due to fall in PO43-

vitamin D deficiency

243
Q

how do you diagnose osteomalacia and rickets?

A

hypocalcaemia with profile being particular to cause:

  1. Vitamin D deficiency:

fall in Po43-

fall in vitamin D

increase in ALP

increase in PTH

  1. Renal bone disease

increase in PO43-

increase in PTH

increase in ALP

may have high 25-OH Vitamin D

biopsy- shows incomplete mineralisation

x-ray:

osteomalacia - loss of cortical bone and looser’s zones ( partial fractures without displacement )

rickets- cupped, ragged metaphyseal surfaces are seen in rickets

244
Q

how do you manage osteomalacia and rickets?

A
  1. Vitamin D deficiency - give Vitamin D e.g. calcium D3
  2. renal disease or vitamin D resistance - give alfacalcidol or calctirol and adjust dose to plasma ca2+. they both cause severe hypercalcaemia
245
Q

what are the two forms of vitamin D -resistant rickets?

A

type 1 - low renal 1alpha hydroxy-lase activity

type 2 - end-organ resistance to 1,25 dihydroxy-vitamin D3

give calcitriol for both

due to FGF23 gene mutation - regukates phosphate levels

246
Q

what is x linked hypophosphataemic rickets?

A

dominantly inherited due to PHEX gene mutation

plasma PO43- is low

ALP is high

phosphaturia occurs

treatment - oral phosphate and vitamin D supplements

247
Q

what is pagets disease?

A

increased bone turnover associated with increased number of osteoblasts and osteoclasts with resultant remodelling, bone enlargement deformity and weakness

rare in the under-40s

248
Q

what are the signs and symptoms of pagets disease?

A

primarily affects: long bones, pelvis, lumbar spine and skull - bone enlargement and deformity

asymptomatic in majority of cases

deep, boring pain

deafness

compression neuropathies e.g. nerve entrapment syndrome

headaches

large joint OA

complications: osteosarcoma

249
Q

how do you diagnose paget disease?

A

imaging:
X-ray:

early - lytic lesions (mixed lytic and sclerotic appearance too)

late disease: cortical thickening, deformity

skull disease: cotton wool appearance

isoptope bone scan shows distribution of disease

Biochemistry:

ALP raised

ca2+ is normal

PO43- is normal

250
Q

how do you manage Paget’s disease?

A

mild: analgesia e.g. NSAIDs
severe: bisphosphonates e.g. pamidronate

251
Q

what is a goitre?

A

a thyroid lump normally found on the midline of the neck

normally rises on swallowing

252
Q

what is a branchial cyst?

A

a lump in the neck which is smooth and round normally located on the anterior border of the upper third of the sternocleidomastoid muscle

presentation:

in young adults

painless and smooth swelling

surgical excision is management

253
Q

what is an acute parotitis?

A

a recent swelling of the salivary glands

associated with painful pre-auricular swelling

254
Q

What is MEN 1 defined as?

A

a group of inherited syndromes that are characterised by groups of tumours of the endocrine glands

MEN 1 is defined as tumours occurring with any two of the following:

parathyroid hyperplasia

Pituitary adenoma

pancreatic islet cell tumours

255
Q

what is MEN 2 defined as?

A

MEN 1 is defined as tumours occurring with any two of the following:

medullary thyroid carcinoma

phaeochromocytoma

parathyroid tumour

256
Q

what causes blue sclera in children?

A

ostegenesis imperfecta (brittle bone disease)

257
Q

what are the four types of osteogenesis imperfecta?

A

Type 1 - mildest and most common form - multiple fractures, discoloured teeth, blue scerae, aortic root dilatation, aortic regurigitation Mitral valve prolapse

Type 2 - lethal form

Type 3 - severely progressive and deforming form

Type 4 - moderately progressive form

Endocrine (7 decks)

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