List I - Core Conditions Flashcards
1
Q
What is type 2 diabetes?
A
- Insulin resistance and a relative insulin deficiency result in persistent hyperglycaemia
2
Q
What are the risk factors for type 2 diabetes?
A
- Obesity and inactivity
- Family history
- Ethinicity - Asian, African and Black communities
- History of gestational diabetes
- Poor dietary habits
- Drug treatments
- Polycystic ovarian syndrome
- Metabolic syndrome
- Low birth weight for gestational age
3
Q
How many people in the UK have type 2 diabetes?
A
- 3.5 million (including 31,500 children and young people under the age of 19 years)
- Estimated there are over half a million people with undiagnosed diabetes
4
Q
What is the prognosis of people with type 2 diabetes?
A
- With optimal management people can participate normally in the usual activities of daily life but are at risk of complications
- Insulin deficiency in type 2 progresses with time and usually worsens over a period of years
- Initial management is with lifestyle (diet and exercise) over time people may need antidiabetic drug treatments
5
Q
What are the macrovascular complications of diabetes?
A
- Cardiovascular disease
- MI, CVD, peripheral arterial disease (e.g. intermittent claudication)
- CVD accounted for 52% of deaths in people with type 2 diabetes
- Twofold increased risk of stroke within the first 5 years of diagnosis compared with the general population
- 20% of hospital admissions for heart failure, MI, and stroke are in people with diabetes (type 1 or 2)
6
Q
What are the microvascular complications of diabetes?
A
- Nephropathy - 3/4 people with diabetes will develop some stage of CKD in their lifetime
- Retinopathy - diabetes is the leading cause of preventable blindness in people of working age in the UK
- Diabetic retinopathy accounts for 7% of people who are registered blind in England and Wales
- Chronic painful neuropathy - estimated to affect up to 26% of people with type 2 diabetes and people with diabetes are up to 30 times more likely to have an amputation compared with the general population
- Autonomic neuropathy - presents in different ways including sweating, blood vessels (postural hypotension), GI (gastroparesis and diarrhoea), heart, bladder and sexual function (35-90% of men with diabetes have erectile dysfunction)
7
Q
What other complications are there from type 2 diabetes?
A
- Psychological - anxiety and depression (incl. children with behavioural and conduct disorders)
- Reduced quality of life - challenges of daily living hyper/hypo and monitoring
- Infections - UTI and skin
- Reduced life expectancy - reduced by an average of 10 years
- Dementia - 1.5 - 2.5 fold increased risk of dementia
8
Q
How should a diagnosis be made of type 2 diabetes in adults?
A
- HbA1c of 40mmol/litre (6.5%) or more
- Or if HbA1c is inappropriate e.g. end stage CKD, diagnosis is made by a fasting blood glucose level of 7.0mmol/l or greater
9
Q
How should diagnosis of type 2 diabetes be made in an asymptomatic person?
A
- Never on a single abnormal HbA1c or fasting glucose level
- At least one additional abnormal HbA1c or plasma glucose level is essential
- If the second test result is normal arrange regular review of the person
10
Q
How should diagnosis of type 2 diabetes be made in a symptomatic person?
A
- Diabetes can be diagnosed with more confidence on the basis of a single abnormal HbA1c or fasting plasma glucose level (a second test would be sensible)
- Be aware that sever hyperglycaemia in people with an acute infection, trauma, or circulatory may be transitory and should not be regarded as diagnostic of diabetes
11
Q
In which groups should diagnosis of type 2 diabetes diagnosis not be made on the basis of HbA1c?
A
- Children and young people <18 years
- Pregnant women or 2 months post partum
- People with diabetes symptoms less than 2 months
- People at high diabetes risk who are acutely ill
- People taking medication that may cause hyperglycaemia (corticosteroids)
- People with acute pancreatic damage, including pancreatic surgery
- People with end stage CKD
- People with HIV infection
12
Q
In which groups should interpretation of HbA1c to diagnose diabetes be made with caution?
A
- Abnormal haemoglobin
- Anaemia
- Altered red cell lifespan (post-splenectomy)
- Recent blood transfusion
13
Q
What is the initial care and support offered to an adult with type 2 diabetes?
A
- Ensure that an individual care plan is set up for all adults with type 2 diabetes
- Offer a structured group education programme (DESMOND)
- Ensure the person and/or their family/carers know how to contact the diabetes team during working hours
- Provide information on government disability benefits
- Manage life style issues such as diet and exercise
- Screen for the complications of type 2 diabetes
- Provide up to date information on diabetes support groups - diabetes UK
14
Q
What is the DESMOND programme?
A
- Diabetes Education for Self-Management for Ongoing and Newly Diagnosed
- Offer at time of diagnosis with annual reinforcement and review
- Explain structured education is an integral part of their diabetes care
15
Q
What is the diet advice you should give to people with type 2 diabetes?
A
- Emphasise the importance of a healthy balanced diet
- Low fibre, fruit, vegetables, wholegrain and pulses, low fat dairy products and oily fish
- Control intake of foods containing saturated and trans fatty acids
- If the person is overweight advise a body weight loss target of 5-10%
- Consider referring to a dietitian
16
Q
What is the advice on exercise and physical activity you should give to people with type 2 diabetes?
A
- Advise that regular exercise may lower blood glucose levels
- All adults aged over 19 years should aim to be active daily
- Over a week should add up to 150 minutes (2.5 hours) of moderate intensity physical activity (such as brisk walking or cycling) in bouts of 10 minutes or more
- Alternatively 75 minutes of vigorous intensity activity (running or playing football) spread through the week or combinations of both
- Adults should take part in muscle strength training on at least 2 days per week
- Time spent sedentary should be minimised
- Older adults with risk of falls should incorporate physical activity to improve balance and coordination on at least 2 days per week
- Advise that regular exercise can
- Reduce their increased cardiovascular risk in the medium and long term
- Help with weight management (combined with a healthy diet)
17
Q
What is the advice to people with diabetes on alcohol intake?
A
- Give information on the maximum alcohol intake
- Advise to avoid drinking on an empty stomach
- Alcohol absorbed faster
- Eat a snack that contains carbohydrate before and after alcohol
- Advise that alcohol may exacerbate or prolong the hypoglycaemic effect or antidiabetic drugs
- Signs of hypoglycaemia may become less clear and delayed hypoglycaemia may occur several hours after alcohol
- Advise on wearing a MedicAlert bracelet or Diabetes ID card
18
Q
What is the advice to people with diabetes regarding smoking?
A
- If they smoke advise to stop
- Advise it is a cardiovascular risk factor
- Explain about the dangers of substance misuse
- Advise young adult non-smokers never to start smoking
19
Q
What are the targets of HbA1c for people with type 2 daibetes to aim for to reduce the risk of long term vascular complications?
A
- Diet and lifestyle - 48mmol/mol (6.5%)
- Diet and lifestyle combined with a single drug not associated with hypoglycaemia (metformin) - 48mmol/mol (6.5%)
- People taking a drug associated with hypoglycaemia (sulphonylurea) - 53mmol/mol (7.0%)
- 58 mmol/mol
20
Q
Following diagnosis of type 2 diabetes, what should the monitoring frequency be?
A
- Measure HbA1c at 3-6 monthly intervals (tailored to individual needs) until the HbA1c is stable on unchanging treatment, then at 6 monthly intervals
- If the person achieves HbA1c lower than their target they should be encouraged to maintain it
- Do not routinely offer self monitoring of blood glucose levels for adults with type 2 diabetes
21
Q
What is the advice to a person with HbA1c not adequately controlled on a single drug and rises to 58mmol/mol or higher (7.5%)?
A
- Reinforce advice on diet and lifestyle and adherence to antidiabetic drug treatment
- Support the person to aim for HbA1c 53mmol/mol (7.0%)
- Intensify drug treatment
22
Q
How should HbA1c control be managed in older and frail people?
A
- Case by case
- Consider relaxing the target if the person is:
- Unlikely to achieve long term risk reduction benefits
- Risk of hypo could risk fall or injury
23
Q
When is there a role for self monitoring blood glucose levels for adults with type 2 diabetes?
A
- Person is on insulin therapy
- Evidence of hypoglycaemic episodes
- Drug treatment has a risk of hypo
- Pregnant or planning on becoming pregnant
- When on corticosteroids
- To confirm suspected hypoglycaemia
24
Q
What can lead to worsening hyperglycaemia in adults with type 2 daibetes?
A
- Intercurrent illness or infection
25
How should a person with type 2 diabetes with intercurrent illness be managed?
* Consider the need for hospital admission or seeking specialist advice
* Managing in primary care
- Assess and manage the illness
- Assess how well the blood glucose has been managed
- Warn that the illness may affect blood glucose control
- Consider self monitoring of blood glucose
- Ensure the person has written contact details of their diabetes specialist team
- Ensure the person has sick day food and hydration supplies at home
- Easily digestible food and sugary drinks
- Oral rehydration food and sugary drinks
- Glucose tablets or oral gel
- Equipment for self monitoring
- Additional supplies of insulin (if on insulin therapy)
- A glucagon kit (if appropriate)
26
What are the sick day rules for a person with diabetes type 2?
* If on insulin therapy, they should not stop treatment
* If self monitoring indicated it should be done carefully and frequently
* Consider ketone monitoring
* Maintain normal meal pattern where possible
* Aim to drink at least 3 L of fluid a day to prevent dehydration, seek urgent medical advice if:
- Sick, drowsy or unable to keep fluids down
- Have persistent vomiting or diarrhoea
* When feeling better they should continue to monitor their glucose levels until they return to normal
27
Which drug treatment is first line for type 2 diabetes?
* Metformin - gradually increase the dose over several weeks to minimise the risk of adverse effects such as GI
* Trial of modified release metformin if GI effects are intolerable
28
Which drug is offered if metformin is contraindicated for type 2 diabetes?
One of the following:
* Gliptin
* Pioglitazone
* Sulfonylurea
* SGLT-2i
29
If the first line treatment for type 2 diabetes is contraindicated what can be added?
Metformin plus one of the following:
* Metformin plus a gliptin, or
* Metformin plus pioglitazone, or
* Metformin plus a sulfonylurea.
* Metformin plus an SGLT-2i
For people in whom metformin is contraindicated or not tolerated, consider the following:
* A gliptin plus pioglitazone, or
* A gliptin plus a sulfonylurea, or
* Pioglitazone plus a sulfonylurea.
* An SGLT-2i instead of a gliptin if a sulfonylurea or pioglitazone is not appropriate
30
If the second line treatment for type 2 diabetes is contraindicated what can be added?
For people who can take metformin:
* Triple therapy with metformin, a gliptin, and a sulfonylurea, or
* Triple therapy with metformin, pioglitazone, and a sulfonylurea, or
* Triple therapy with metformin, pioglitazone or a sulfonylurea and an SGLT-2i. (The SGLT-2i dapagliflozin in a triple therapy regimen is recommended as an option for treating type 2 diabetes in adults, only in combination with metformin and a sulfonylurea NOT pioglitazone), or
* Starting insulin-based treatment. See the CKS topic on Insulin therapy in type 2 diabetes for more information.
* For people in whom metformin is contraindicated or not tolerated:
- Consider starting insulin-based treatment.
31
If the third line treatment for type 2 diabetes is contraindicated what can be added?
For people on triple therapy with metformin and two other oral antidiabetic drugs, consider combination treatment with metformin, a sulfonylurea, and a glucagon-like peptide-1(GLP-1) mimetic for:
* Adults who have a body mass index (BMI) of 35 kg/m2 or higher (adjust accordingly for people from Black, Asian and other minority ethnic groups) and specific psychological or other medical problems associated with obesity, or
* Adults who have a BMI lower than 35 kg/m2 and insulin therapy would have significant occupational implications, or weight loss would benefit other significant obesity-related comorbidities.
* Or a combination of metformin, a DPP-4 inhibitor and the sodium glucose co-transporter 2 (SGLT2) inhibitor ertugliflozin for people with diabetes only if the disease is uncontrolled with metformin and a DPP‑4 inhibitor, and a sulfonylurea or pioglitazone is not appropriate.
* For people on insulin-based treatment:
Seek specialist advice (or refer the person to their diabetes team) for consideration of treatment with a GLP-1 mimetic plus insulin.
32
How should screening/review for type 2 diabetes be done?
* At every review appointment
- Measure height, weight and waist circumference and calculate BMI
- Assess for anxiety and depression
- Check smoking status
- Assess for neuropathy
* Every 6 months
- Measure HbA1c
* Once a year screen for:
- Retinopathy
- Diabetic foot problems
- Nephropathy
- Cardiovascular risk factors
- On insulin - check injection sites
33
When is retinopathy screening done for type 2 diabetes?
* At time of diagnosis, annually thereafter
* Emergency review by opthalmologist if there is:
- Sudden loss of vision
- Rubeosis iridis
- Pre-retinal or vitreous haemorrhage
- Retinal detachment
* Urgent review by an opthalmologist if there is:
- Abnormal vessels on the retina
34
What does diabetic foot screening entail for type 2 diabetes?
* At time of diagnosis, annually thereafter
* Advice about foot care, foot wear, persons risk of developing a foot problem, information about blood glucose control
* Examination
- Neuropathy - 10g monofilament for foot sensory examination
- Limb ischaemia - ABPI
- Ulceration
- Callus formation
- Infection and/or inflammation
- Deformity
- Gangrene
- Charcot arthropathy (acute, localised inflammatory condition that may lead to varying degrees of bone destruction, subluxation, dislocation and deformity)
- Categorise on examination findings - low, medium or high risk
* Management - based on foot ulceration risk category
- Low risk - continue annual assessments
- High risk - referral to foot protection service, seen within 2-4 weeks if at high risk or 6-8 weeks if moderate risk
* Dependent on the persons risk of developing a diabetic foot problem, reassessments should be carried out as follows:
- Annually - low risk
- Frequently (3-6 monthly) - moderate risk
- More frequent (1-2 monthly) - high risk with no immediate concern
- Very frequently (1-2 weekly) - high risk with immediate concern
* More frequent assessments for people who are not able to check their own feet
35
What does nephropathy screening entail for type 2 diabetes?
* Perform annually
* Send a first pass early morning specimen for ACR and measure eGFR
* CKD diagnosed when tests show reduction in kidney function or presence of proteinuria (>3 months) eGFR <60mL/min/1.73m2 and/ or ACR persistently >3mg/mmol
36
What does cardiovascular risk factor screening entail for type 2 diabetes?
* Assess annually
* Assess the following
- Age
- Albuminuria
- Smoking status
- Blood glucose control
- Blood pressure
- Full lipid profile (HDL, LDL, cholesterol and triglycerides)
- Family history of CVD
- Waist circumference
37
How should people on anti-hypertensive drug treatment with type 2 diabetes be managed?
* Manage hypertension with antihypertensive medication
* Review BP control and treatments
* For patients under 80 years reduce clinic BP to below 140/90 and maintain that level
For patients aged 80 and over reduce clinic BP to below 150/90 and maintain that level
* Use ABPM or HBPM but be aware that HBPM levels are 5mmHg lower than ABPM
38
How should people with type 2 diabetes without previously diagnosed hypertension or nephropathy be assessed?
* Measure BP at least annually and reinforce lifestyle advice
* Confirm a diagnosis of hypertension in people with:
- Clinical BP of 140/90 mmHg or higher
- ABPM daytime average or HBPM average of 135/85mmHg or higher
* Refer people on the same day for specialist assessment if they have severe hypertension (180/120mmHg) with:
- Retinal haemorrhage or papilloedema (accelerated hypertension)
- Life threatening symptoms such as new onset confusion, chest pain, signs of heart failure or acute kidney injury
- Suspected phaechromocytoma (labile or postural hypotension, headache, palpitations, pallor, abdo pain or diaphoresis)
* Carry out investigations for target organ damage as soon as possible if a person has severe hypertension but no symptoms or signs indicating same day referral
39
How should people with type 2 diabetes without previously diagnosed hypertension or nephropathy be treated?
* If target end organ damage is identified, consider starting anti-hypertensive drug treatment immediately without waiting for the results of ABPM or HBPM
* If no target end organ damage, repeat BP measurement within 7 days
* Offer anti-hypertensive drug treatment in addition to lifetsyle advice to adults of any age with persistent stage 1 or 2 hypertension
- Stage 1 BP 140/90 - 159/99
- Stage 2 BP 160/100 - 180/120
* Discuss with the person their individual CVD risk and preferences for treatment including no treatment, explain the risks and benefits before starting treatment
* Consider anti-hypertensive medication for adults under 60 with stage 1 hypertension and a QRISK <10%
* For adults aged <40 years with hypertension - consider specialist evaluation of secondary causes of hypertension and a more detailed assessment of the long term balance of treatment benefit and risks
40
If anti-hypertensive treatment is required in type 2 diabetes, what should be offered?
* ACEi or ARB to all adults
* For black African or African-Caribean, consider ARB in preference to ACEi
* Do not combine ACEi and ARB
* Offer CCB next step or
* Thiazide like diuretic in addition to ACEi or ARB
* If not controlled after 3 medications, consider adding a fourth antihypertensive drug - measure BP again and assess for postural hypotension
* Consider adding a fourth medication for people with confirmed resistant hypertension
- Consider further diuretic therapy with low-dose spironolactone for adults who have a blood potassium level of 4.5mmol/L or less
- Consider an alpha-blocker or beta-blocker for adults who have a blood pressure level of >4.5mmol/L
* For women who are considering pregnancy, pregnant or breast feeding manage in line with pregnancy and hypertension guidelines
41
Which medications should not be offered to manage the primary prevention of cardiovascular disease in adults with type 2 diabetes?
* Do not offer antiplatelet treatment (aspirin or clopidogrel)
42
How should lipid modification be managed for people with type 2 diabetes (without established CVD)?
* Offer statin treatment with 20mg atorvastatin for the primary prevention of CVD if the person is aged 84 years and younger and their estimated 10-year risk of developing CVD using the QRISK2 assessment tool is 10% or more
* Consider offering statin treatment of atorvastatin 20mg for patients who are 85 years of age or older - formal risk assessment not needed
43
How should lipid modification be managed for people with type 2 diabetes (with established CVD)?
* Advise statin treatment with atorvastatin 80 mg for the secondary prevention of CVD - formal risk assessment not needed
* Ensure regular protocol is followed before initiating statin treatment (see coronary heart disease notes)
44
How should neuropathy be managed for people with type 2 diabetes?
* Erectile dysfunction - consider prescribing a phosphodiesterase-5 inhibitor (sildenafil, etc)
* Autonomic neuropathy - advise small particle size diet, involve gastroenterologist for consideration of a prokinetic drug such as erythromycin, metoclopramide or domperidone
* Be aware of increased risks of postural hypotension for adults taking tricyclic antidepressants or antihypertensive medications
45
What is the recommended dosing of metformin stardard release for type 2 diabetes?
* 500 mg with breakfast for at least 1 week, then 500 mg with breakfast and evening meal for at least 1 week, then 500 mg with breakfast, lunch, and evening meal thereafter; the usual maximum dose is 2 g daily in divided doses
46
What is the recommended dosing of metformin modified release for type 2 diabetes?
* 500 mg once daily, increased every 10-15 days on the basis of blood glucose measurements, maximum recommended dose is 2 g once daily with evening meal
* If control is not achieved, 1 g twice daily with meals should be tried
47
How should metformin be initiated and managed?
* Check eGFR - do not start if eGFR <30mL/min/1.73m2
During treatment
* Monitor renal function
- At least once per year for people with normal renal function
- At least twice a year for people with impairment or risks such as elderly
* Review the dose of metformin if eGFR <45mL/min/1.73m2
* Stop treatment with metformin if eGFR <30 or those at risk of sudden renal function deterioration
48
What are the contraindications for metformin?
* Do not prescribe to people at risk of lactic acidosis including people with:
* DKA
* eGFR <30 standard release or <45 for modified release
* Acute conditions with potential to alter renal function - dehydration, prolonged fasting, severe infection or shock
* Hepatic insufficiency, acute alcohol intoxication or alcohol addiction
* People about to undergo elective surgery - discontinue 48 hours before, restart no earlier than 48 hours following surgery or resumption of oral nutrition if normal renal function has been established
* Prescribe in caution to people with mild to moderate CKD
49
What are the adverse effects associated with metformin?
* Gastrointestional - nausea, vomiting, diarrhoea, abdominal pain and loss of appetite - common at the start of treatment and resolve on their own in most cases - therefore gradual increase when starting is recommended
* Lactic acidosis - rare but potentially fatal adverse effect that can occur due to accumulation
- Insidious onset - abdo pain, anorexia, hypothermia, lethargy, nausea, respiratory distress and vomiting
- Stop if eGFR <30
* Vitamin B12 deficiency - long term and can be a cause of megaloblastic anaemia
* Hypoglycaemia - metformin alone does not cause hypoglycaemia but caution is advised when it is used in combination with other drugs
* Taste disturbance - common
* Skin reactions (rare) - erythema, pruritis and uticaria
50
What are the drug interactions with metformin?
* Alcohol - increased risk of lactic acidosis
* Beta blockers - can mask the warning signs of a hypo such as tremor
* Ketotifen - platelet count may be depressed when meformin is given with ketotifen
* Topiramate - may increase plasma concentration of metformin
* Caution advised when taken with other anti-diabetic drugs such as sulfonylurea (risk hypo)
51
What are gliptins?
* Inhibitors of the enzyme dipeptidyl peptidase (DPP-4)
* Plays a major role in glucose metabolism by rapidly degrading the incretins (glucose-dependent insulinotropic polypeptide) (GIP) and glucagon like peptide 1 (GLP-1) which stimulate postprandial insulin secretion and suppress glucagon secretion
* Inhibition of DPP-4 results in increased circulating levels of GIP and GLP-1 following the ingestion of food and to increase insulin secretion and reduced glucagon secretion
52
What are the gliptins available in the UK?
* Sitagliptin
* Saxagliptin
* Vildagliptin
* Linagliptin
* Alogliptin
53
When would a lower dose of gliptin be required?
* Impaired eGFR
| * In combination with a sulphonylurea to reduce the risk of hypoglycaemia
54
How should gliptins be initiated and monitored?
* Check LFT and U and E's
55
What are the contraindications and cautions for gliptins?
Do not prescribe gliptins to people with:
* Keto-acidosis
Avoid in people with:
* Renal impairment - end stage
* Hepatic impairment - avoid in people with ALT or AST greater than 3 times the upper limit of normal
* People with moderate to severe heart failure
56
What are the adverse effects of gliptins?
* GI disturbance
* Acute pancreatitis - uncommon but serious
* Bullous pemphigoid
* Hypoglycaemia - may occur in combination with other drugs
* Nervous system disorders
* Skin and subcutaneous disorders
* MSK and connective tissue disorders
* Infections
* Hepatic dysfunction
* Hypersensitivity reactions
57
What drug interactions are associated with gliptins?
* Beta blockers - may mask hypoglycaemia signs
* ACEi - may increase risk of angioedema
* Digoxin - sitagliptin increases plasma concentration of digoxin (no dose adjustment required but monitor)
* Ketoconazole - may increase plasma levels
* Rifampicin - possibly reduced effects
* Blood glucose lowering effects may be enhanced by:
- Alcohol
- Anabolic steroids
- MAOI's
- Testosterone
* Blood glucose lowering effects may be impaired by:
- Corticosteroids
- Diuretics
- Oestrogens and progestogens
58
How does pioglitazone work?
* Reduces peripheral insulin resistance thereby leading to a reduction in blood glucose concentration (does not stimulate insulin secretion)
59
How should treatment with pioglitazone be initiated and monitored?
* Check LFT - if ALT is more than 2.5 times the upper limit of normal or there is any other evidence of disease, do not start treatment
* Measure FBC
* BMI
* Check for a history of bladder cancer or blood in the urine which has not been investigated - do not start if so
Following initiation of treatment with pioglitazone:
* Measure ALT
* Signs of fluid retention
* Assess the safety and efficacy of pioglitazone 3-6 months after treatment is initiated and regularly afterwards
60
What is the recommended dose of pioglitazone?
* 15-30 mg daily, increased to 45 mg according to response
61
What are the contraindications and cautions for pioglitazone?
Do not prescribe in people with the following:
* Heart failure (NYHA stages I to IV)
- In caution people at risk of developing congestive heart failure
* DKA
* Macroscopic haematuria
* Previous or active bladder cancer
* Hepatic impairment
* Start with lowest available dose
62
What are the possible adverse effects of pioglitazone?
* Fluid retention
* Bladder cancer
* Increased risk of bone fractures
* Weight gain
* Decreased visual acuity
* Hypoglycaemia risk increased
* Liver toxicity
* GI disturbance, anaemia, headaches, dizziness, arthralgia, hypoaesthesia, haematuria, impotence
63
What are the drug interactions associated with pioglitazone?
* Beta blockers
* Gemfibrozil
* Ketoconazole
* Lanreotide and octreotide
* NSAID's
* Liver enzyme inducing drugs
* Blood glucose lowering effects may be enhanced by:
- Alcohol
- Anabolic steroids
- MAOI's
- Testosterone
* Blood glucose lowering effects may be impaired by:
- Corticosteroids
- Diuretics
- Oestrogens and progestogens
64
How do sulfonylureas work?
* They are insulin secretagogues - act by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present
* Five available in the UK
- Glibenclamide
- Gliclazide
- Glimepiride
- Glipizide
- Tolbutamide
65
What are the contraindications and cautions of sulfonylureas?
Do not prescribe a sulfonylurea to people with:
* Acute porphoria
* Ketoacidosis
* Severe renal impairment
Prescribe sulphonylurea's with caution in:
* People with severe hepatic impairment - increased risk of hypo
* People with mild to moderate renal impairment - risk of hypo
* Elderly - risk hypo
* People with G6PD deficiency
66
What are the adverse effects of sulfonylureas?
Generally mild and infrequent
* GI disturbances
* Disturbance in liver function
* Hypersensitivity reactions - occur in the first 6-8 weeks of treatment and consist mainly of allergic skin reactions which progress rarely to erythema multiforme and exfoliative dermatitis, fever and jaundice
* Skin and subcutaneous tissue disorders - rare
* Blood disorders
* Hyponatraemia
* Dizziness and drowsiness
* Headaches and tinnitus
67
When should insulin therapy be considered in type 2 diabetes?
* Blood glucose levels are inadequately controlled despite dual therapy with metformin and another oral anti-diabetic drug
* Oral anti-diabetic drugs are contraindicated or not tolerated
68
What are the reasons for not initiating insulin therapy in type 2 diabetes?
* Obesity - can lead to further weight gain
* Physical and mental health - potential benefits of insulin therapy may not outweigh the potential risks
* Anxiety about needles
* Personal preference
* Concerns regarding group 2 vehicles
69
How do GLP-1 medications work?
* Glucagon-like peptide 1 (GLP-1) mimetics bind to and activate the GLP-1 receptor to increase insulin secretion, suppress glucagon secretion and slow gastric emptying
* There are 3 GLP-1 mimetics available in the UK
- Exenatide
- Liraglutide
- Lixisenatide
70
How should treatment with a GLP-1 be initiated and monitored?
* NICE recommends that combination treatment with metformin, sulfonylurea and a GLP-1 mimetic should only be considered if triple therapy with metformin and two other oral anti-diabetic drugs is not effective
* After 6 months of treatment with a GLP-1 mimetic - check the persons body weight and HbA1c level
- Only continue treatment if the person has had a beneficial metabolic response (reduction of at least 11 mmol/mol (1%) in HbA1c and a weight loss of at least 3% of initial body weight
71
What is the mode of action of SGLT-2i?
* Reversible inhibition of sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convuluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
72
What are the 3 licensed SGLT-2i medicines?
* Canagliflozin
* Dapagliflozin
* Empagliflozin
73
What are SGLT-2i medicines indicated for?
* Type 2 diabetes as monotherapy (if metformin inappropriate) or in combination with insulin or other anti-diabetic drugs (if existing treatment fails to achieve adequate glycaemic control)
* Dapagliflozin in a triple therapy is recommended as an option for treating type 2 diabetes in adults only in combination with metformin and a sulphonylurea
74
What are the contraindications for using SGLT-2i medicines?
* Serious risk of DKA
- Test for raised ketones in patients presenting with symptoms of DKA, even if plasma glucose levels are near normal, omitting this test could delay a diagnosis of DKA
- Stop if DKA is suspected
- Treat the DKA is confirmed
* Not recommended for patients with moderate to severe renal impairment <60 eGFR
* Increased risk of volume depletion
* Lactose intolerance - tablets contain lactose
75
What are the adverse effects of SGLT-2i medicines?
* Vulvovaginitis, balanitis, UTI
* Hypoglycaemia
* Pruritus
* Frequency of micturation
* Raised serum lipids
* Raised haematocrit
* Fourniers gangrene
* Dapagliflozin - angioedema - rare
76
Which drugs interact with SGLT-2i?
* Thiazide and loop diuretics
* Insulin and insulin secretagogues
* Enzyme inducers
* Digoxin
* Dabigatran
* Cholestyramine
77
What is type 1 diabetes mellitus?
* Autoimmune disorder
* Insulin producing islet cells of Langerhans in the pancreas are destroyed by the immune system
* Results in absolute deficiency of insulin, results in raised glucose levels in the blood
* Patients tend to develop T1DBM in childhood/early adult life and typically present unwell, possibly in DKA
78
What are the presenting features of T1DBM?
* Weight loss
* Polydipsia
* Polyuria
May present with diabetic ketoacidosis
* Abdominal pain
* Vomiting
* Reduced consciousness level
79
What is the WHO diagnostic criteria for DBMT1?
* If the patient is symptomatic:
- Fasting glucose greater than or equal to 7.0 mmol/L
- Random glucose greater than or equal to 11.1 mmol/L (or after 75g oral glucose tolerance test)
* If the patient is asymptomatic, the above criteria apply but must be present on two separate occasions.
80
What is the approach to the management of T1DBM?
* Patients always require insulin to control the blood sugar levels
* This is because there is an absolute deficiency of insulin with no pancreatic tissue left to stimulate with drugs
* Different types of insulin are available according to their duration of action
* Requires input of many different specialties and members of the healthcare team
* Diagnosis of type 1 DBM can still reduce the life expectancy of patients by 13 years
* Micro and macrovascular complications
81
What are the insulin regimes for T1DBM?
* Offer daily multiple injection basal-bolus insulin regimes, rather than twice-daily mixed insulin regimes as the insulin injection regime of choice for all adults
* Twice daily insulin determir is the regime of choice
* Once daily glargine or insulin determir is an alternative
* Offer rapid acting insulin (Novorapid/Actrapid) analogues injected before meals, rather than rapid acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 DBM
* If basal bolus not working - use the pump
82
When is metformin recommended as an addition to the insulin regime?
* NICE recommend considering adding metformin if the BMI >=25 kg/m2
83
What is the frequency of monitoring HbA1c for patients with T1DBM?
* Every 3-6 months
| * Adults should have a target of HbA1c level of 48 mmol/mol (6.5%) or lower
84
What is the recommended self monitoring frequency of blood glucose for patients with T1DBM?
* Recommend testing at least 4 times a day, including before each meal and before bed
* More frequent monitoring is recommended if frequency of hypoglycaemic episodes increases, during periods of illness, before, during and after sport, when planning pregnancy, during pregnancy and while breast feeding
85
What are the blood glucose target ranges for people with T1DBM?
* 5-7 mmol/L on waking
* 4-7 mmol/L before meals at other times of the day
* 5-9 mmol/L after meals
* No driving <5 mmol
86
What is the guidance for the management of hypertension in patients with diabetes?
* Type 1
- Intervention should be at 135/85 mmHg unless the adult with type 1 diabetes has albuminuria or 2 or more features of metabolic syndrome, in which case it should be 130/80 mmHg
* Type 2
- <140/90
* ACEi are first line due to renoprotective effect in diabetes
* Autonomic neuropathy may result in more postural symptoms in patients taking antihypertensive therapy
* Avoid beta-blockers, particularly with thiazide diuretics as they may cause insulin resistance, impair insulin secretion and alter the autonomic response to hypoglycaemia
87
What are the risks to the feet in people with DBM?
* Neuropathy
* Infections
* Charcot joint
* Gangrene
* Amputation
88
How does foot disease occur in DBM?
* Macrovascular - PVD
| * Microvascular - neuropathy
89
What are the signs of ischaemia in the foot?
* ABPI <0.5, cold, pale, absent pulse
90
What are the signs of neuropathy in the foot?
* Glove/stocking distribution of sensory neuropathy
* Reduced vibration sense
* Absent ankle jerks
* Deformity - pes cavus/claw toes, loss of transverse arch, rocker bottom feet
91
What is the conservative measures to manage diabetic foot?
* Podiatrist (regular foot exam)
* Chiropodist (remove calluses)
* Patient education - daily foot inspection, comfortable shoes with cushioning, no barefoot walking
* Bed rest if high pressure areas
92
What is the medical management of diabetic foot?
* Antifungals
* Sympathetic sensory polyneuropathy
- Aspirin/paracetamol
- Amytryptyline 10-25mg/24hr
- Gabapentin
- Carbamazepine
* Cellulitis
- Tazocin 4.5g/6h IV (DBM)
* Charcot joints
- Rest
- Immobilise (total contact cast for 2-3 months to allow for bony repair)
- Bisphosphonates
93
What is the surgical management of diabetic foot?
* Indicated for deep abscess/infection
* Spreading anaerobic infection
* Severe ischaemia (gangrene/rest pain)
* Suppurative arthritis
94
What is the normal physiology of the thyroid gland?
* Hypothalamus - TRH
* Anterior pituitary - TSH
* Thyroid gland - thyroxine (T4) and triiodothyronine (T3)
* Negative feedback loop - low T3/T4 = release more TRH/TSH
95
What type of problem with the thyroid does Graves disease cause (Graves is most common hyperthyroidism cause)?
* Hyperthyroidism (thyrotoxicosis)
| * Typically affecting women aged 30-50 years
96
What is the mechanism of Graves disease?
* Autoantibodies to TSH (90%)
| * Anti-thyroid peroxidase antibodies (75%)
97
What are the clinical features in thyrotoxicosis specific to Graves disease? (but not other causes of thyrotoxicosis)
* Eye signs
- Exophthalmos
- Ophthalmoplegia
* Pretibial myxoedema
* Thyroid acropachy
- Digital clubbing
- Soft tissue swelling of the hands and feet
- Periosteal new bone formation
98
What other causes of hyperthyroidism are there?
* Toxic multinodular goitre
- Autonomously functioning thyroid nodules that secrete excess thyroid hormones
* Drugs
- Amiodarone
99
What are the less specific signs and symptoms of thyrotoxicosis?
* General
- Weight loss
- Manic - restlessness
- Heat intolerance
* Cardiac
- Palpitations, may even provoke arrythmias e.g. AF
* Skin
- Increased sweating
- Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
- Thyroid acropachy: clubbing
* GI
- Diarrhoea
* Gynaecological
- Oligomenorrhea
* Neurological
- Anxiety
- Tremor
100
What is a thyrotoxic storm?
* Excess of endogenous thyroid hormones leading to the following clinical features
- Fever >38.5c
- Tachycardia
- Confusion and agitation
- Nausea and vomiting
- Hypertension
- Heart failure
- Abnormal LFT - jaundice
101
What are the triggers for a thyrotoxic storm?
* Recent treatment - radio-iodine
* Infection
* MI
* Trauma
Risk factors:
* Smoking
102
What are the differential diagnoses for hyperthyroidism?
* Neck lump causes
- Midline
- Submandibular
- Anterior
- Posterior
* Goitre causes
- Physiological
- Inflammatory
- Autoimmune
- Multinodular goitre
- Adenoma/carcinoma
- Immunological/thyroglossal cyst
103
What are the types of midline neck lump?
* Dermoid cyst (<20yrs)
* Thyroglossal cyst - moves on tongue protrusion
* Thyroid goitre (>20yrs)
* Chrondroma (hard)
104
What are the types of submandibular neck lump?
* Lymphadenopathy
- <20yrs self limiting
- >20yrs malignant - firm/non tender Hodgkin's/NHL
- TB
- Salivary stone/gland tumour
- Sialodenitis
105
What are the types of anterior triangle neck lump?
* Branchial cyst <20 yrs between upper-middle 1/3 of sternomastoid from non-disappearance of cervical sinus
* Parotid tumour >40 yrs - superoposterior part
* Laryngocele - painless, worse on blowing
* Carotid - pulsatile, aneurysm, tortuous body tumour
106
What are the types of posterior triangle neck lump?
* Cervical rib (enlarged C7 costal elements - Raynaud's/wasted 1st dorsal interosseus
* Pharyngeal pouch on swallow - often on left
* Cystic hygroma - infants, jugular lymph sac
* Pancost tumour
* Subclavian aneurysm (pulsatile)
107
What are the reasons for a physiological goitre (moves on swallowing)?
* Puberty
* Pregnancy
* Iodine deficiency
108
What are the reasons for an inflammatory goitre (De Quervain's thyroiditis)?
* Streptococcal
| - May be tender with +/- TFT's
109
What are the auto-imune reasons for a Goitre?
* Grave's
| * Hashimoto's thyroiditis
110
What are the types of malignant neck lumps?
* Adenoma/carcinoma
- Papillary 70%
- Follicular 15%
- Medullary 5-10%
- Anaplastic
- Toxic multi-nodular goitre - needs fine needle aspiration (10% are cancerous)
* Features
- Solitary
- Hard
- Irregular
- Painless
- Lyphadenopathy
111
What are the blood investigations for hyperthyroidism?
* FBC - Hb low, MCV normal
- Graves - mild neutropenia
* Raised ESR
* TFT's
- Hyperthyroidism
- High T3/T4
- Low TSH
- Subclinical hyperthyroidism
- Low TSH
- Normal free T4
* Raised LFT's
* Raised Ca2+
* Anti-thyroglobulin antibodies present (Graves)
112
What further tests can be done to investigate hyperthyroidism?
* ECG - AF
* USS-guided fine needle aspiration - if solitary/dominant nodule in multinodular goitre to exclude malignancy
* Radio-isotope scan (iodine/technetium) - to determine if hot nodules are malignant (20% cold are malignant) or thyrotoxic storm
113
What is the acute management of a thyrotoxic storm?
* B - 15L/min O2 via NRBM (ITU/HDU)
* C - ECG/BP - IV access - bloods
- 0.9% NaCl 500 ml/4h IV (NG tube if vomiting)
- Chlorpromazine 50mg po (if sedation needed)
- Propanolol 40mg/8hr po (NOT if asthmatic)
- Digoxin 1 mg over 2 hrs IVI (if HR high)
- Carbimazole 15-25mg/6h po and after 4 h
- Lugol's solution 0.3ml/8h for 1 wk
- Hydrocortisone sodium succinate 100mg/6h IV (or dexamethasone 4mg/6h po)
- Cefuroxime 1.5 g/8h IV (if infection)
- Cool with tepid sponging +/- paracetamol
- After 5 days reduce carbimazole to 15mg/8 h po
114
What are the medical treatments for hyperthyroidism?
* Beta blockers - propanolol 40mg/6 hr po for rapid symptom relief
* Carbimazole
- SE agranulocytosis due to reduced neutrophils
- CI in pregnancy - use propylthiouracil - still risk of agranulocytosis
* Titration
- 20-40mg/24h po - titrate down according to TFT/1-2 months, maintain for 18 months
* Block and replace
- Plus levothyroxine 100ng/24h po (less risk of iatrogenic hypothyroidism)
- Maintain for 12 months - then attempt withdrawal (50% relapse so try radio-iodine/surgery)
- Radio-iodine - mode: taken up/concentrates in thyroid - radiation destroys it - 50% become hypothyroid post treatment
- SE - may initially worsen eye disease but transient
- CI - pregnancy/lactation
- Caution in active hyperthyroidism - as risk of thyrotoxic storm
- Referral to ENT surgeon if eye disease
115
What are the surgical treatment options for hyperthyroidism?
* Subtotal thyroidectomy
- Pre-surgery
- TFT's should be in normal range
- Lugol's iodine beforehand to reduce vascularity of the thyroid
- Procedure
- Collar incision - remove enough tissue to make euthyroid only (normally 5-8g left)
- Complications
- Recurrent laryngeal nerve damage
- Hypoparathyroidism (accidental removal)
- Haemorrhage
116
What are the causes of hypothyroidism?
* Auto-immune
- Atrophic
- Hashimoto's thyroiditis
* Acquired
- Iodine deficiency (commonest cause worldwide)
- Post thyroidectomy/radioiodine
- Drug induced (anti-thyroid medications, amiodarone, lithium, iodine)
- Infiltration (sarcoidosis, amyloidosis)
* Hypopituitarism
- Defect of the hypothalamus/pituitary stalk/pituitary gland
117
What are the triggers of a myxoedema coma?
* Sedatives - especially elderly with undiagnosed hypothyroidism and overlying hypothermia
118
What are the symptoms of hypothyroidism?
General
* Fatigue
* Cold intolerance
* Dry/thick skin
* Carpal tunnel syndrome
* Coarse hair
* Alopecia
* Anaemia
Cardiac
* SOB
* Cough +/- pink frothy sputum
GI
* Reduced appetite
* Increased weight
* Constipation (ileus)
MSK
* Arthralgia/myalgia
Neuro
* Depression
* Reduced memory/cognition
Reproductive
* Menorrhagia
* Infertility
* Impotence
PMH
* Autoimmune conditions
119
What are the signs of hypothyroidism?
* Obesity
* Brittle nails
* Bradycardia
* Carpal tunnel syndrome (Phalens/Tinnels +ve)
* Dry skin
* Flaky hair
* +/- loss of outer 1/3 of the eyebrow
* Peaches/cream or toad faces
* Cerebellar ataxia
* Rarely goitre +/- hoarse voice/stridor/snoring/dysphagia, Pemberton's sign
* Bibasal lung crepitations (HF)
* Peri-orbital oedema
* Slow relaxing reflexes
120
What are the clinical signs of a myoedema coma?
* Hypothyroidism signs
* Altered mental status
* Hypothermic
* Hyporeflexia
* Hypoglycaemia
* Bradycardia
* Seizures/coma
121
What are the investigations for hypothyroidism?
* FBC - low Hb, normal MCV
* TFT - low free T4, high TSH
* Secondary - normal/low TSH
* Subclinical - high TSH, normal free T4
* Increased cholesterol/triglycerides
* Anti-thyroid perioxidase antibodies
* High TPO
122
What is the management of a myxoedema coma?
* B - 15L via NRBM
* C - ECG IV access - bloods
- Tri-ioothyronine (T3) 5-20ng
- IV hydrocortisone 100mg/8h IV
- 0.9% NaCl IV
- Cefuroxime 1.5g/8 h IV (if infection related)
123
What is the medical management of hypothyroidism?
* Levothyroxine 50-100ng/24h po
- 25ng if elderly/IHD - may precipitate angina/MI
- Review at 12 weeks
- Adjust dose/6 weeks until TSH >0.5mU/L and clinically stable
- Check annually
- If subclinical hypothyroidism - yearly monitoring but can try course of levothyroxine
- NB enzyme inducers increase metabolism of levothyroxine
124
What are the complications of hypothyroidism?
* Cardiovascular disease
* Dementia
* Myxoedema coma (30% mortality)
125
What is Addison's disease/adrenocortical insufficiency?
* 1 Addison's disease
| * 2 Long term steroids causing suppression of pituitary adrenal axis
126
Which pathways are involved in ACI?
* Hypothalamus - CRF
* Anterior pituitary - ACTH
* Adrenal - cortisol
* Physiological effect (and negative feedback to pituitary and hypothalamus)
127
What are the causes of Addison's disease?
* Autoimmune 80%
* Congenital adrenal hyperplasia
* TB 10% - but most common world wide
* Hypopituitarism - low ACTH
* Bleeding (haemorrhage) - antiphospholipid syndrome, SLE, Water-House Friederichsen syndrome (bilateral haemorrhage from meningococcal septicaemia)
* Infection - opportunistic in HIV (CMV, mycobacterium avium)
* Neoplasia - metastatic cancer to adrenal (lung/breast/renal), lymphoma
128
What are the triggers of an Addisonian crisis?
* Stress
* Infection
* Trauma
* Surgery
129
What is the pathological process of adrenocortical insufficiency?
* Adrenal cortex destruction
* Low glucocorticoid (cortisol - low glucose)
* Low mineralocorticoid (aldosterone - low Na+, low H2O, high K+)
* Low testosterone - hypovolaemia (increased urea/creatinine)
130
What are the presenting symptoms of ACI?
* General
- Fatigue
- Weakness
* MSK
- Myalgia
- Arthralgia
* Neuro
- Dizzy
- Faint
- Depression
- Psychosis
- Low self esteem
* GI
- Anorexia
- Weight loss
* Adrenal crisis
- Vomiting
- Abdominal pain
- Shock
- Fever
- Coma
- Low glucose
* PMH
- Type 1 DBM
- Hashimoto's thyroiditis
- Pernicious anaemia
- Grave's
- Premature ovarian failure
- Vitiligo
131
What are the signs of ACI?
* Hyperpigmentation
* Postural drop in BP
* Vitiligo
132
What are the differentials for ACI?
* Viral infection
* Anorexia nervosa (but low K+ here)
* DBM
133
What are the appropriate investigations for an Addisonian crisis?
* Plasma glucose
* Cortisol
* ACTH
* Cultures - blood/urine/sputum
Don't delay treatment
134
What are the blood investigations for ACI?
* FBC - low Hb, increased eosinophils
* U and E's - low Na+, high K+, high urea/creatinine
* Low cortisol
* Increased ACTH (at 9am)
* Low glucose
* Increased Ca2+
* Increased renin/low aldosterone
* 21-hydroxylase adrenal auto-antibodies
135
How is the short Synacthen test used for ACI?
* 2nd cortisol reading >550mmol/L excludes Addison's
1) Measure plasma cortisol
2) Give tetracosactide 250ng (synacthen: synthetic ACTH)
3) Measure cortisol 30 and 60 mins later
136
What others tests are important to include in the investigation of someone with ACI?
* Exclude other autoimmune disease
- TFT
- OGTT
- Coeliac Abs (alpha-gliadin, anti-endomysial Abs)
137
What imaging can be done to investigate ACI?
* Chest x-ray - exclude old TB
* Abdominal x-ray - exclude adrenal calcifications
* CT adrenals - exclude calcifications/haemorrhage
138
What is the approach to the management of an Addisonian crisis?
* ABC
* B - 15L NRBM O2
* C - ECG, IV access - bloods
- Hydrocortisone sodium succinate 100mg IV stat
- Haemaccel then 0.9% NaCl IV stat (then hourly)
- Cefuroxime 1.5g/8h IV
- 100ml 20% dextrose IV glucose (if low)
- Continue hydrocortisone and fluids
- Change to oral steroids after 72 hrs if stable
139
What is the conservative approach to management of a patient with ACI?
* Patient education - steroid counselling
1) Carry steroid card/bracelet
2) Don't stop abruptly
3) Tell doctors about them
4) Double dose if febrile illness/injury
5) Increase by 5-10mg before stenuous exercise
6) Keep IM hydrocortisone (show how to inject in case of vomiting and cannot take orally)
140
What is the medical management of a patient with ACI?
* Steroid replacement
- Hydrocortisone 15-25mg/24h po (divided doses: 10mg on waking, 5mg lunchtime - give early in day to avoid insomnia)
- Fludrocortisone 50-200ng/24 h po if needed (postural hypotension, U and E abnormality, increased plasma renin)
141
What are the risks of ACI?
* Addison crisis can be fatal
| * Hypovolaemic shock
142
What is the difference between Cushing's syndrome and disease?
* Syndrome - any cause of increased glucocorticoid
| * Disease - bilateral adrenal hyperplasia from pituitary adenoma (increased ACTH)
143
Which pathways are involved in Cushing's disease?
* Hypothalamus - CRF
* Anterior pituitary - ACTH
* Adrenal cortex
- Glucocorticoid: cortisol
- Mineralocorticoid: aldosterone
- Androgen: testosterone
* Adrenal medulla
- Catecholamine: adrenaline
* Physiological effect (and negative feedback to pituitary and hypothalamus)
* Cortisol excreted as free urinary cortisol
144
What are the causes of Cushing's disease / syndrome?
* Iatrogenic - glucocorticoids (most common)
* ACTH dependent
- Pituitary adenoma - Cushing's disease - most common 70%
- Ectopic ACTH 14% - from small cell lung cancer, renal cancer, or carcinoid (lung, GIT, thymus)
- Ectopic CRH - some thyroid (medullary) and prostate cancer
* ACTH independent
- Adrenal adenoma (10%)
- Adrenal cancer (5%)
- Adrenal hyperplasia (1%)
- McCune Albright syndrome (rare)
145
What are the symptoms of Cushing's?
* Neuro
- Mood change (depression, psychosis, lethargy, irritability)
- Visual field defects
* Skin
- Thin hair
- Moon face
- Acne
- Hirsutism
* Reproductive
- Dys-oligomenorrhoea
- Impotence
* GI
- Weight gain
* PMH
- Fracture
- Osteoporosis
- PUD
- Hypertension
- DBM
146
What are the signs of Cushing's disease/syndrome?
* ACTH dependent
- Thin skin
- Bruising
- HTN
- Hirsuitism
- Infection (tinea)
- Proximal myopathy
- Moon face
- Acne
* * Bitemporal hemianopia
* * Papilloedema
- Purple striae (weight gain)
- Supraclavicular fat pad (buffalo hump)
- Centripetal obesity (lemon on a stick)
* ACTH independent
- Hyperpigmented (from increased ACTH)
147
What are the differential diagnoses for Cushing's?
* Pseudo-Cusing's (due to alcohol, depression)
148
What are the investigations required for Cushing's ?
1) Overnight dexamethasone suppression test 1st line
- Check cortisol
- Give dexamethasone 1mg po midnight
- Check cortisol at 8am (fail to suppress to <50nmol/L)
2) Plasma ACTH
- If undetectable (ACTH independent) - do bilateral CT of adrenals
- If detectable (ACTH dependent) - do high dose dexamethasone suppression test
3) 48hr high dose dexamethasone suppression test (2nd line diagnostic)
- Check cortisol
- Give dexamethasone 0.5mg/6h po (8mg high dose)
- Check cortisol level at 48hr, 6hr after last dose
- ACTH dependent - fail to suppress but pituitary source suppresses partially unlike with ectopic ACTH
4) CRH test
- Check cortisol
- Give 100mcg ovine/human CRH IV
- Check again at 120 minutes (if pituitary not ectopic ACTH)
* Urine - 24 hr urine (2nd line screen - exclude 1st void on AM collection of urine, include it AM after)
- Free cortisol - normal = <280nmol/L
* Radiology
- CT adrenals - if adrenal source suspected (if no mass seen, do adrenal vein sampling/adrenal scintigraphy)
- MRI pituitary - if pituitary source suspected (and no mass seen on bilateral inferior petrosal sinus sampling: excludes ectopic ACTH production)
- CT +/- MRI neck, thorax, abdomen if ectopic source likely
149
What is the approach to management of Cushing's syndrome?
* Iatrogenic steroids - stop the steroids!
* Cushing's disease
- Medical - adrenal radiotherapy (to prevent Nelson's syndrome post surgery: increased skin pigmentation due to increased ACTH)
- Surgical - transphenoidal resection of pituitary adenoma (or bilateral adrenalectomy if source not found)
* Adrenal tumour
- Medical - radiotherapy and adrenolytics (mitotan) post-surgery
- Surgical - adrenalectomy (curative for adenoma, rarely for Ca so must follow with adrenolytics)
* Ectopic ACTH
- Medical - metryrapone, ketoconazole (reduce cortisol: if unfit for surgery/radiotherapy or pre-op)
- Surgical - depending on source
150
What are the risks/complications of Cushing's?
* Premature IHD
* Osteoporosis +/- #
* HTN
* Impaired glucose tolerance/DBM (30%)
* Predisposed to infection
* Poor wound healing
151
What is hyperaldosteronism/Conn's syndrome?
* Primary - mainly Conn's (increased aldosterone independent of RAAS system)
* Secondary - suppressed pituitary adrenal axis
152
What are the causes of hyperaldosteronism?
Primary
* Conn's syndrome 66%
- Solitary aldosterone producing adenoma
* Bilateral adrenocortical hyperplasia 33%
- Adrenal carcinoma
- Glucocorticoid-remedial aldosteronism
Secondary
* Steroids
- Long term
* Renal artery stenosis
153
Who is affected by Conn's syndrome?
* F>M
154
What is the pathology of Conn's syndrome?
* Increased aldosterone
| - Increased Na+/H2O reabsorption, increased K+ excretion, reduced renin release
155
What is the pathology of renal artery stenosis?
* Causes increased renin initially
* Activation of RAAS
* Increased aldosterone
* Refractory increase in BP and reduced K+
156
What are the signs and symptoms of Conn's syndrome?
* U and E's - increased Na+, decreased or normal K+
* Aldosterone: Renin
- Patient sits upright for at least 2h withhold antihypertensives/diuretics for 2 weeks
- Increased aldosterone:renin ratio
* Fludrocortisone/saline suppression test in some centres
157
What is the approach to the management of Conn's syndrome?
Medical
* Aldosterone antagonists
- Indications - bilateral hyperplasia or Conn's pre-op
- Types - spironolactone 300mg/24 hrs po max (for 4 weeks pre-op), amiloride, eplenerone
- SE - gynaecomastia (except eplenerone as more selective)
Surgical
* Laproscopic adrenalectomy: Conn's syndrome
* 6 monthly imaging post surgery detects recurrence
158
What are the risks of Conn's syndrome?
* Increases BP
159
What are the different types of hyperparathyroidism?
1. Hyperplasia
2. Appropriate response
3. Autonomous PTH production (from hyperplastic/adenomatous change)
160
Which pathways are involved in hyperparathyroidism?
1. Dehydrocholesterol - sunlight-skin - cholecalciferol
* Liver - 25-hyroxycalciferol
2. Parathyroids - PTH - axial skeletal bone (increased osteoclast activity - increased Ca2+/PO4
* Kidney (activates 1a-hydroxylase to convert 25-hydroxycholecalciferol to 1,25-dihydroxycalciferol - i.e. calcitriol/a-calcitrol - increased Ca2+/reduced PO4 reabsorption in the kidneys
161
What are the reference ranges for Ca2+ and PTH?
* Ca2+
- Total (2.12-2.65mmol/L)
- Ionized (1.0-1.25mmol/L)
* PTH
- <0.8-8.5pmol/L
162
What are the causes of hyperparathyroidism?
Primary
- Solitary parathyroid adenoma 80%
- Hyperplasia 15-20%
- MEN
- Parathyroid adenocarcinoma
- Ectopic PTH related peptide (squamous cell lung cancer, breast/renal cancer)
Secondary
- Persistently low Ca2+ (vitamin D deficiency, renal failure, osteomalacia)
Tertiary
- Prolonged secondary hyperparathyroidism (chronic renal failure
163
How common is hyperparathyroidism?
* M
164
What is the pathology of hyperparathyroidism?
* Increased PTH can lead to increased bone resorption - osteoporosis - pathological #
165
What are the signs/symptoms of hyperparathyroidism?
* Often asymptomatic (high Ca2+ on bloods)
* Hypercalcaemia
- Stones (renal 10-15%, nephrocalcinosis, metastatic calcification)
- Bones (pain, pathological #, osteoporosis/osteopenia
- Moans (lethargy, depression, dehydration, polyuria)
- Abdominal groans (abdominal pain, constipation, ulcers, pancreatitis)
166
What are the differential diagnoses for hyperparathyroidism?
* Increased calcium
- Iatrogenic from blood from IV drip arm, thiazides/vitamin D
* Hypercalcaemia of malignancy
* Others
- Sarcoidosis
- DBM
- MEN I - Multiple-Endocrine-Neoplasia I gene is a tumour suppressor gene
- Parathyroid hyperplasia/adenoma, pancreatic (gastrinoma/insulinoma, somatostatinoma, VIPoma)
- Pituitary prolactinoma
- MEN II gene is a ret proto-oncogene
- MEN IIa - parathyroid hyperplasia, adrenal phaeochromocytoma, thyroid medullary carcinoma
- MEN IIb - like IIa but no hyperparathyroidism (instead mucosal neuromas/Marfinoid appearance)
167
What is the blood picture for primary hyperparathyroidism?
* Ca2+ high
* PO4 low
* PTH high
168
What is the blood picture for secondary hyperparathyroidism?
* Ca2+ low
* PO4 low
* PTH high
169
What is the blood picture for tertiary hyperparathyroidism?
* Ca2+ high
* PO4 low
* PTH high ++
170
What is the blood picture for hypoparathyroidism?
* Ca2+ low
* PO4 high
* PTH low
171
How is ALP affected by hyperparathyroidism?
* Increased if there is a fracture
172
What are the appropriate blood investigations for hyperparathyroidism?
* U and E's
* LFT's
* ALP
* PTH
* Ca2+
* PO4
173
What is the urine test for hyperparathyroidism?
* 24 hr urine collection - Ca2+
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What imaging can be done for hyperparathyroidism?
* Abdominal x-ray - renal calculi, nephrocalcinosis
* DEXA scan - osteoporosis
* X-ray - sub-periosteal resorption (hands), pepperpot skull
* USS - pre-op surgery for adenomas
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What is the approach to the management of hyperparathyroidism - primary?
* Conservative (mild)
- Encourage fluids (prevent stones)
- Avoid thiazides
- Reduce calcium/vitamin D intake
* Medical
- Cinacalcet (increases sensitivity of parathyroids to Ca2+ so reduces PTH production)
* Surgical
- Excision if complications and >50 yrs
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What is the approach to the management of hyperparathyroidism - secondary?
* Medical
- Treat the underlying cause once known
- Supplements
- Ca2+ (Calcichew or 10ml 10% calcium gluconate IVI over 30mins if severe)
- Vitamin D3 - cholecalciferol or alfa-calcidol if renal failure
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What is the approach to the management of hyperparathyroidism - tertiary?
* Medical (treatment for hypercalcaemia)
- 0.9% NaCl IV - frusemide 40 mg/4h po/IV
- Bisphosphonates
* Surgical
- Parathyroidectomy
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What are the risks and complications of hyperparathyroidism?
* Risk of surgery
- Hypoparathyroidism, recurrent laryngeal nerve damage/palsy, post op hypocalcaemia
* Prognosis
- 8% adenomas recur in 10 yrs
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What are the different types of hypoparathyroidism?
1. Gland failure
2. Appropriate
- Pseudohypoparathyroidism (PH): failure of target cell response to PTH
- PseudoPH (PPH): morphologically identical to PH but normal biochemistry
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What are the causes of hypoparathyroidism?
1. Autoimmune, congenital (Di George syndrome)
2. Radiation/surgery (parathyroidectomy/thyroidectomy), hypomagnesaemia (Mg2+ needed for PTH secretion)
- PH/PPH - genetic (types I: autosomal recessive and 2: polygenetic)
181
What are the symptoms and signs of hypoparathyroidism?
* Hypocalcaemia - tetany, depression, perioral paraesthesia
* Trousseau's sign (carpopedal spasm): wrist/fingers flex and draw together (on inflating BP cuff)
* Chvostek's sign (neuromuscular excitability): corner of mouth twitches if tap facial nerve over parotid
* PH/PPH: short 4th and 5th metacarpals, mental retardation, round face, short stature
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What are the differential diagnoses for hypoparathyroidism?
* Low Ca2+
- Vitamin D deficiency - Asians, Africans, CRF
* Hypoparathyroidism
* Acute pancreatitis
* Alkalosis
* Mg2+ deficiency
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What are the appropriate blood investigations for hypoparathyroidism?
* U and E's
* LFT's (ALP)
* PTH
* Ca2+
* PO4
* Mg2+
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What are the urine investigations for hypoparathyroidism?
* 24 hr urine - Ca2+
185
What are the imaging investigations for hypoparathyroidism?
* CT head - calcified basal ganglia in PH
186
What is the blood picture for hypoparathyroidism?
* Ca2+ low
* PO4 high or normal
* PTH low
* ALP normal
187
What is the blood picture for pseudohypoparathyroidism?
* Ca2+ low
* PO4 high
* PTH high
* ALP normal or high
188
What is the medical management of hypoparathyroidism?
* Ca2+ supplements and activated vitamin D3 (alfa-calcidol/calcitriol) or synthetic PTH/12h SC (prevents hypercalciuria)
189
What is hypercalcaemia of malignancy?
* Increased blood calcium levels due to:
1. Primary malignancy
- Myeloma (increased osteoclast activating factors)
- Squamous cell lung cancer (increased PTH related peptide)
2. Secondary malignancy (bone metastases)
- Breast
- Bronchus
- Prostate
- Thyroid
- Kidney
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How common is hypercalcaemia of malignancy?
* 10-20% of those with malignancy
* 40% with myeloma - raised ESR, raised Ca2+, normal ALP
* Others - breast, lung, renal
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What are the symptoms of hypercalcaemia?
* Stones (renal 10-15%, nephrocalcinosis: metastatic calcification)
* Bones (pain, pathological #, osteopenia/osteoporosis)
* Moans (lethargy, depression, confusion, dehydration, polyuria, polydipsia)
* Abdominal groans (abdominal pain, constipation, ulcers, pancreatitis, anorexia, nausea, vomiting, weight loss)
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What are the signs of hypercalcaemia?
* Hypertension
* Arrhythmias
* Dehydration (shock if severe)
* Cachexia
* Bony tenderness secondary to local lesion (especially along spine)
Worrying features
* Reduced GCS
* Chest pain
* Palpitations
* Tacycardia
* Hypotension
* Abnormal ECG
193
What are the differential diagnoses for hypercalcaemia?
* Raised Ca2+
- Iatrogenic - blood from IV drip arm, increased thiazides/vitamin D
- Hypercalcaemia of malignancy
- Others - sarcoidosis, DBM
194
What are the appropriate investigations for hypercalcaemia?
* Bloods - FBC, ESR, U and E's (low K+, low Cl-), LFT (low albumin), high Ca2+, low PO4, high ALP (bone), low Mg2+, serum electrophoresis (myeloma)
* Urine - MSU dipstick, consider urine electrophoresis (myeloma)
* Radiology - chest x-ray - exclude malignancy
* Special tests - ECG - short QT interval, arrythmias
195
What is the approach to management of hypercalcaemia of malignancy?
* Depends on the level of Ca2+
- <3 treat if symptomatic, monitor others
- 3-4 treatment usually needed
- >4 see urgent advice
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What is the conservative treatment for hypercalcaemia of malignancy?
* Conservative - avoid certain medications such as thiazide diuretics
* Treat the underlying cause
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What is the medical treatment for hypercalcaemia of malignancy?
* Catheterise if anuric >4hrs, CVP monitoring
* IV access - bloods
* 0.9% NaCl 1L/4-8 hrs IV for 4-5 days
* Correct low K+ and low Mg2+
* Furosemide 40 mg/12 hr po/IV
* Pamidronate 30mg/300mL 0.9% NaCl IVI over 3 hrs or zolendronic acid 4 mg IVI over 2 hrs (inhibit osteoclast activity/bone resorption: takes 3-5 days to work)
* Then oral bisphosphonates for maintenance
* Monitoring (U and E's, Ca2+, Mg2+, daily, then after 5-7 days) - consider calcitonin of still low
198
What are the risks of hypercalcaemia?
* RAPPOR
* Renal failure
* Arrhythmia
* Peptic ulcer
* Pancreatitis
* Osteopenia
* Renal stones
