Metabolic Medicine Flashcards
Acromegaly: features
In acromegaly there is excess growth hormone secondary to a pituitary adenoma in over 95% of cases. A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.
Features
coarse facial appearance, spade-like hands, increase in shoe size
large tongue, prognathism, interdental spaces
excessive sweating and oily skin: caused by sweat gland hypertrophy
features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases → galactorrhoea
6% of patients have MEN-1
Complications
hypertension
diabetes (>10%)
cardiomyopathy
colorectal cancer
Addison’s disease
Autoimmune destruction of the adrenal glands is the commonest cause of primary hypoadrenalism in the UK, accounting for 80% of cases. This is termed Addison’s disease and results in reduced cortisol and aldosterone being produced.
Features
lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
hyperpigmentation (especially palmar creases)*, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
Other causes of hypoadrenalism
Primary causes
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
Secondary causes
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
*Primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
Addison’s disease management - hydrocortisone + fludrocortisone
Important for meLess important
Addison’s disease: management
Patients who have Addison’s disease are usually given both glucocorticoid and mineralocorticoid replacement therapy.
This usually means that patients take a combination of:
hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the morning dose
fludrocortisone
Patient education is important:
emphasise the importance of not missing glucocorticoid doses
consider MedicAlert bracelets and steroid cards
discuss how to adjust the glucocorticoid dose during an intercurrent illness (see below)
Management of intercurrent illness
in simple terms the glucocorticoid dose should be doubled
the Addison’s Clinical Advisory Panel have produced guidelines detailing particular scenarios - please see the CKS link for more details
Carbimazole
Carbimazole is used in the management of thyrotoxicosis. It is typically given in high doses for 6 weeks until the patient becomes euthyroid before being reduced.
Mechanism of action
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
in contrast propylthiouracil as well as this central mechanism of action also has a peripheral action by inhibiting 5’-deiodinase which reduces peripheral conversion of T4 to T3
Adverse effects
agranulocytosis
crosses the placenta, but may be used in low doses during pregnancy
Corticosteroids
Corticosteroids are amongst the most commonly prescribed therapies in clinical practice. They are used both systemically (oral or intravenous) or locally (skin creams, inhalers, eye drops, intra-articular). They augment and in some cases replace the natural glucocorticoid and mineralocorticoid activity of endogenous steroids.
The relative glucocorticoid and mineralocorticoid activity of commonly used steroids is shown below:
Fludrocortisone
Minimal glucocorticoid activity, very high mineralocorticoid activity,
Hydrocortisone
Glucocorticoid activity, high mineralocorticoid activity,
Prednisolone
Predominant glucocorticoid activity, low mineralocorticoid activity
Dexamethasone / Betmethasone
Very high glucocorticoid activity, minimal mineralocorticoid activity
Side-effects
The side-effects of corticosteroids are numerous and represent the single greatest limitation on their usage. Side-effects are more common with systemic and prolonged therapy.
Glucocorticoid side-effects
endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia
Cushing’s syndrome: moon face, buffalo hump, striae
musculoskeletal: osteoporosis, proximal myopathy, avascular necrosis of the femoral head
immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis
psychiatric: insomnia, mania, depression, psychosis
gastrointestinal: peptic ulceration, acute pancreatitis
ophthalmic: glaucoma, cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
Mineralocorticoid side-effects
fluid retention
hypertension
Selected points on the use of corticosteroids:
patients on long-term steroids should have their doses doubled during intercurrent illness
the BNF suggests gradual withdrawal of systemic corticosteroids if patients have: received more than 40mg prednisolone daily for more than one week, received more than 3 weeks treatment or recently received repeated courses
Cushing’s syndrome: causes
It should be noted that exogenous causes of Cushing’s syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones.
ACTH dependent causes
Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
ectopic ACTH production (5-10%): e.g. small cell lung cancer
ACTH independent causes
iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
Pseudo-Cushing’s mimics Cushing’s
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
Diabetes mellitus (type 2): diagnosis
The diagnosis of type 2 diabetes mellitus can be made by either a plasma glucose or a HbA1c sample. Diagnostic criteria vary according to whether the patient is symptomatic (polyuria, polydipsia etc) or not.
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 demonstrated on two separate occasions.
Diagram showing the spectrum of diabetes diagnosis
In 2011 WHO released supplementary guidance on the use of HbA1c on the diagnosis of diabetes:
a HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus
a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)
in patients without symptoms, the test must be repeated to confirm the diagnosis
it should be remembered that misleading HbA1c results can be caused by increased red cell turnover (see below)
Conditions where HbA1c may not be used for diagnosis:
haemoglobinopathies
haemolytic anaemia
untreated iron deficiency anaemia
suspected gestational diabetes
children
HIV
chronic kidney disease
people taking medication that may cause hyperglycaemia (for example corticosteroids)
Impaired fasting glucose and impaired glucose tolerance
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
Diabetes UK suggests:
‘People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT.’
Diabetes mellitus (type 2): management
NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2015. Key points are listed below:
HbA1c targets have changed. They are now dependent on what antidiabetic drugs a patient is receiving and other factors such as frailty
there is more flexibility in the second stage of treating patients (i.e. after metformin has been started) - you now have a choice of 4 oral antidiabetic agents
It’s worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)
Dietary advice
encourage high fibre, low glycaemic index sources of carbohydrates
include low-fat dairy products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
discourage use of foods marketed specifically at people with diabetes
initial target weight loss in an overweight person is 5-10%
HbA1c targets
This is area which has changed in 2015
individual targets should be agreed with patients to encourage motivation
HbA1c should be checked every 3-6 months until stable, then 6 monthly
NICE encourage us to consider relaxing targets on ‘a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes’
in 2015 the guidelines changed so HbA1c targets are now dependent on treatment:
Lifestyle or single drug treatment
Management of T2DM
HbA1c target
Lifestyle - 48 mmol/mol (6.5%)
Lifestyle + metformin - 48 mmol/mol (6.5%)
Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) - 53 mmol/mol (7.0%)
Practical examples
a patient is newly diagnosed with HbA1c and wants to try lifestyle treatment first. You agree a target of 48 mmol/mol (6.5%)
you review a patient 6 months after starting metformin. His HbA1c is 51 mmol/mol (6.8%). You increase his metformin from 500mg bd to 500mg tds and reinforce lifestyle factors
Patient already on treatment
Management of T2DM
HbA1c target
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%)
53 mmol/mol (7.0%)
Diabetes Mellitus - Beyond metformin
Tolerates metformin:
metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions
if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list:
→ sulfonylurea
→ gliptin
→ pioglitazone
→ SGLT-2 inhibitor
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:
→ metformin + gliptin + sulfonylurea
→ metformin + pioglitazone + sulfonylurea
→ metformin + sulfonylurea + SGLT-2 inhibitor
→ metformin + pioglitazone + SGLT-2 inhibitor
→ OR insulin therapy should be considered
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)
if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if:
→ BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
→ BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or
weight loss would benefit other significant obesityrelated comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
Cannot tolerate metformin or contraindicated
if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions, consider one of the following:
→ sulfonylurea
→ gliptin
→ pioglitazone
if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
→ gliptin + pioglitazone
→ gliptin + sulfonylurea
→ pioglitazone + sulfonylurea
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy
Starting insulin
metformin should be continued. In terms of other drugs NICE advice: ‘Review the continued need for other blood glucose lowering therapies’
NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bed-time or twice daily according to need
Risk factor modification
Blood pressure
target is < 140/80 mmHg (or < 130/80 mmHg if end-organ damage is present)
ACE inhibitors are first-line
Antiplatelets
should not be offered unless a patient has existing cardiovascular disease
Lipids
following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on
Thiazolidinediones
Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.
The PPAR-gamma receptor is an intracellular nuclear receptor. It’s natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function.
Adverse effects
weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
Diabetes mellitus DM1
The long-term management of type 1 diabetics is an important and complex process requiring the input of many different clinical specialties and members of the healthcare team. A diagnosis of type 1 diabetes can still reduce the life expectancy of patients by 13 years and the micro and macrovascular complications are well documented.
NICE released guidelines on the diagnosis and management of type 1 diabetes in 2015. We’ve only highlighted a very select amount of the guidance here which will be useful for any clinician looking after a patient with type 1 diabetes.
HbA1c
should be monitored every 3-6 months
adults should have a target of HbA1c level of 48 mmol/mol (6.5%) or lower. NICE do however recommend taking into account factors such as the person’s daily activities, aspirations, likelihood of complications, comorbidities, occupation and history of hypoglycaemia
Self-monitoring of blood glucose
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 breastfeeding
Blood glucose targets
5-7 mmol/l on waking and
4-7 mmol/l before meals at other times of the day
Type of insulin
offer multiple daily injection basal–bolus insulin regimens, rather than twice‑daily mixed insulin regimens, as the insulin injection regimen of choice for all adults
twice‑daily insulin detemir is the regime of choice. Once-daily insulin glargine or insulin detemir is an alternative
offer rapid‑acting insulin analogues injected before meals, rather than rapid‑acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes
Metformin
NICE recommend considering adding metformin if the BMI >= 25 kg/m²
Diabetic foot disease
Diabetic foot disease is an important complication of diabetes mellitus which should be screen for on a regular basis. NICE produced guidelines relating to diabetic foot disease in 2015.
It occurs secondary to two main factors:
neuropathy: resulting in loss of protective sensation (e.g. not noticing a stone in the shoe), Charcot’s arthropathy, dry skin
peripheral arterial disease: diabetes is a risk factor for both macro and microvascular ischaemia
Presentations
neuropathy: loss of sensation
ischaemia: absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication
complications: calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, gangrene
All patients with diabetes should be screened for diabetic foot disease on at least an annual basis
screening for ischaemia: done by palpating for both the dorsalis pedis pulse and posterial tibial artery pulse
screening for neuropathy: a 10 g monofilament is used on various parts of the sole of the foot
NICE recommend that we risk stratify patients:
Low risk
• no risk factors except callus alone
Moderate risk
- deformity or
- neuropathy or
- non-critical limb ischaemia.
High risk
- previous ulceration or
- previous amputation or
- on renal replacement therapy or
- neuropathy and non-critical limb ischaemia together or
- neuropathy in combination with callus and/or deformity or
- non-critical limb ischaemia in combination with callus and/or deformity.
All patients who are moderate or high risk (I.e. any problems other than simple calluses) should be followed up regularly by the local diabetic foot centre.
Diabetic neuropathy
Diabetes typically leads to sensory loss and not motor loss in peripheral neuropathy. Painful diabetic neuropathy is a common problem in clinical practice.
NICE updated it’s guidance on the management of neuropathic pain in 2013. Diabetic neuropathy is now managed in the same way as other forms of neuropathic pain:
first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
pain management clinics may be useful in patients with resistant problems
Gastrointestinal autonomic neuropathy
Gastroparesis
symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)
Chronic diarrhoea
often occurs at night
Gastro-oesophageal reflux disease
caused by decreased lower esophageal sphincter (LES) pressure
Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) may be a complication existing type 1 diabetes mellitus or be the first presentation, accounting for around 6% of cases. Rarely, under conditions of extreme stress, patients with type 2 diabetes mellitus may also develop DKA.
Whilst DKA remains a serious condition mortality rates have decreased from 8% to under 1% in the past 20 years.
Pathophysiology
DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
The most common precipitating factors of DKA are infection, missed insulin doses and myocardial infarction.
Features
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drops’ smell)
Diagnostic criteria
American Diabetes Association (2009)
Joint British Diabetes Societies (2013)
Key points
glucose > 13.8 mmol/l
pH < 7.30
serum bicarbonate <18 mmol/l
anion gap > 10
ketonaemia
Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick
Management
fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially. Please see an example fluid regime below.
insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started
correction of hypokalaemia
long-acting insulin should be continued, short-acting insulin should be stopped
Glycosylated haemoglobin
Glycosylated haemoglobin (HbA1c) is the most widely used measure of long-term glycaemic control in diabetes mellitus. HbA1c is produced by the glycosylation of haemoglobin at a rate proportional to the glucose concentration. The level of HbA1c therefore is dependant on
red blood cell lifespan
average blood glucose concentration
A number of conditions can interfere with accurate HbA1c interpretation:
Lower-than-expected levels of HbA1c (due to reduced red blood cell lifespan)
Higher-than-expected levels of HbA1c (due to increased red blood cell lifespan)
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
HbA1c is generally thought to reflect the blood glucose over the previous ‘3 months’ although there is some evidence it is weighed more strongly to glucose levels of the past 2-4 weeks. NICE recommend ‘HbA1c should be checked every 3-6 months until stable, then 6 monthly’.
The relationship between HbA1c and average blood glucose is complex but has been studied by the Diabetes Control and Complications Trial (DCCT). A new internationally standardised method for reporting HbA1c has been developed by the International Federation of Clinical Chemistry (IFCC). This will report HbA1c in mmol per mol of haemoglobin without glucose attached.
From the above we can see that average plasma glucose = (2 * HbA1c) - 4.5
Graves’ disease: management
Despite many trials there is no clear guidance on the optimal management of Graves’ disease. Treatment options include titration of anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace regimes, radioiodine treatment and surgery. Propranolol is often given initially to block adrenergic effects
ATD titration
carbimazole is started at 40mg and reduced gradually to maintain euthyroidism
typically continued for 12-18 months
patients following an ATD titration regime have been shown to suffer fewer side-effects than those on a block-and-replace regime
Block-and-replace
carbimazole is started at 40mg
thyroxine is added when the patient is euthyroid
treatment typically lasts for 6-9 months
The major complication of carbimazole therapy is agranulocytosis
Radioiodine treatment
contraindications include pregnancy (should be avoided for 4-6 months following treatment) and age < 16 years. Thyroid eye disease is a relative contraindication, as it may worsen the condition
the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years
Gynaecomastia
Gynaecomastia describes an abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia
Causes of gynaecomastia
physiological: normal in puberty
syndromes with androgen deficiency: Kallman’s, Klinefelter’s
testicular failure: e.g. mumps
liver disease
testicular cancer e.g. seminoma secreting hCG
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs: see below
Drug causes of gynaecomastia
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
gonadorelin analogues e.g. Goserelin, buserelin
oestrogens, anabolic steroids
Very rare drug causes of gynaecomastia
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa
Hashimoto’s thyroiditis
Hashimoto’s thyroiditis (chronic autoimmune thyroiditis) is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women
Features
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase and also anti-Tg antibodies
Hypercalcaemia causes
Two conditions account for 90% of cases of hypercalcaemia:
- Primary hyperparathyroidism: commonest cause in non-hospitalised patients
- Malignancy: the commonest cause in hospitalised patients. This may be due to number of processes, including; bone metastases, myeloma, PTHrP from squamous cell lung cancer
Other causes include
sarcoidosis*
vitamin D intoxication
acromegaly
thyrotoxicosis
Milk-alkali syndrome
drugs: thiazides, calcium containing antacids
dehydration
Addison’s disease
Paget’s disease of the bone**
*other causes of granulomas may lead to hypercalcaemia e.g. Tuberculosis and histoplasmosis
**usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
Hyperosmolar hyperglycaemic state
Hyperosmolar hyperglycaemic state (HHS) is a medical emergency which is extremely difficult to manage and has a significant associated mortality. Hyperglycaemia results in osmotic diuresis, severe dehydration, and electrolyte deficiencies. HHS typically presents in the elderly with type 2 diabetes mellitus (T2DM), however the incidence in younger adults is increasing. It can be the initial presentation of T2DM.
It is extremely important to differentiate HHS from diabetic ketoacidosis (DKA) as the management is different, and treatment of HHS with insulin (e.g. as part of a DKA protocol) can result in adverse outcomes. The first 24 hours of treatment is very labour intensive so these patients are best managed in either a medical high dependency unit.
HHS has a higher mortality than DKA and may be complicated by vascular complications such as myocardial infarction, stroke or peripheral arterial thrombosis. Seizures, cerebral oedema and central pontine myelinolysis (CPM) are uncommon but documented complications of HHS. Whilst DKA presents within hours of onset, HHS comes on over many days, and consequently the dehydration and metabolic disturbances are more extreme.
Pathophysiology
Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
Clinical features
General: fatigue, lethargy, nausea and vomiting
Neurological: altered level of consciousness, headaches, papilloedema, weakness
Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
Cardiovascular: dehydration, hypotension, tachycardia
Diagnosis
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- Significantly raised serum osmolarity (> 320 mosmol/kg)
Note: A precise definition of HHS does not exist, however the above 3 criteria are helpful in distinguishing between HHS and DKA. It is also important to remember that a mixed HHS / DKA picture can occur.
Management
The goals of management of HHS can be summarised as follows:
- Normalise the osmolality (gradually)
- Replace fluid and electrolyte losses
- Normalise blood glucose (gradually)
Fluid replacement
Fluid losses in HHS are estimated to be between 100 - 220 ml/kg (e.g. 10-22 litres in an individual weighing 100 kg).
The rate of rehydration will be determined by assessing the combination of initial severity and any pre-existing co-morbidities (e.g. heart failure and chronic kidney disease). Caution is needed, particularly in the elderly, where too rapid rehydration may precipitate heart failure but insufficient may fail to reverse an acute kidney injury.
Intravenous (IV) 0.9% sodium chloride solution is the first line fluid for restoring total body fluid.
It is important to remember that isotonic 0.9% sodium chloride solution is already relatively hypotonic compared to the serum in someone with HHS. Therefore in most cases it is very effective at restoring normal serum osmolarity.
If the serum osmolarity is not declining despite positive balance with 0.9% sodium chloride, then the fluid should be switched to 0.45% sodium chloride solution which is more hypotonic relative to the HHS patients serum osmolarity
IV fluid replacement should aim to achieve a positive balance of 3-6 litres by 12 hours and the remaining replacement of estimated fluid losses within the next 12 hours.
Existing guidelines encourage vigorous initial fluid replacement and this alone (without insulin) will result in a gradual decline in plasma glucose and serum osmolarity. A rapid decline is potentially harmful (see below) therefore insulin should NOT be used in the first instance unless there is significant ketonaemia or acidosis
The aim of treatment should be to replace approximately 50% of estimated fluid loss within the first 12 hours and the remainder in the following 12 hours. However this is just a guide, and clinical judgement should be applied, particularly in patient with co-morbidities such as heart failure and chronic kidney disease (which may limit the speed of correction).
Monitoring response to treatment
The key parameter in managing HHS is the osmolality to which glucose and sodium are the main contributors. Rapid changes of serum osmolarity are dangerous and can result in cardiovascular collapse and central pontine myelinolysis (CPM).
Guidelines suggest that serum osmolarity, sodium and glucose levels should be plotted on a graph to permit appreciation of the rate of change. They should be plotted hourly initially.
Not all laboratories have readily available access to serum osmolarity measurements. If not available then a calculated osmolarity can be estimated with 2Na + glucose + urea
Fluid replacement alone (without insulin) will gradually lower blood glucose which will reduce osmolality
A reduction of serum osmolarity will cause a shift of water into the intracellular space. This inevitably results in a rise in serum sodium (a fall in blood glucose of 5.5 mmol/L will result in a 2.4 mmol/L rise in sodium). This is not necessarily an indication to give hypotonic solutions. If the inevitable rise in serum Na+ is much greater than 2.4 mmol/L for each 5.5 mmol/L fall in blood glucose this would suggest insufficient fluid replacement. Rising sodium is only a concern if the osmolality is NOT declining concurrently.
Rapid changes must be avoided. A safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. The rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours.
A target blood glucose of between 10 and 15 mmol/L is a reasonable goal.
Complete normalisation of electrolytes and osmolality may take up to 72 hours.
Insulin
Fluid replacement alone with 0.9% sodium chloride solution will result in a gradual decline of blood glucose and osmolarity
Because most patients with HHS are insulin sensitive (e.g. it usually occurs in T2DM), administration of insulin can result in a rapid decline of serum glucose and thus osmolarity.
Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse as the water moves out of the intravascular space, with a resulting decline in intravascular volume.
A steep decline in serum osmolarity may also precipitate CPM.
Measurement of ketones is essential for determining if insulin is required.
If significant ketonaemia is present (3β-hydroxy butyrate is more than 1 mmol/L) this indicates relative hypoinsulinaemia and insulin should be started at time zero (e.g. mixed DKA / HHS picture). The recommended insulin dose is a fixed rate intravenous insulin infusion given at 0.05 units per kg per hour.
If significant ketonaemia is not present (3β-hydroxy butyrate is less than 1 mmol/L) then do NOT start insulin.
Potassium
Patients with HHS are potassium deplete but less acidotic than those with DKA so potassium shifts are less pronounced
Hyperkalaemia can be present with acute kidney injury
Patients on diuretics may be profoundly hypokalaemic
Potassium should be replaced or omitted as required
Hypothyroidism: causes
Hypothyroidism affects around 1-2% of women in the UK and is around 5-10 times more common in females than males.
Primary hypothyroidism
Hashimoto’s thyroiditis
most common cause
autoimmune disease, associated with IDDM, Addison’s or pernicious anaemia
may cause transient thyrotoxicosis in the acute phase
5-10 times more common in women
Subacute thyroiditis (de Quervain's) Riedel thyroiditis After thyroidectomy or radioiodine treatment Drug therapy (e.g. lithium, amiodarone or anti-thyroid drugs such as carbimazole) Dietary iodine deficiency
Secondary hypothyroidism (rare)
From pituitary failure
Other associated conditions
Down’s syndrome
Turner’s syndrome
coeliac disease
Hypothyroidism management
Key points
initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od
following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks
the therapeutic goal is ‘normalisation’ of the thyroid stimulating hormone (TSH) level. As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range
women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value
there is no evidence to support combination therapy with levothyroxine and liothyronine
Side-effects of thyroxine therapy
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
Interactions
iron, calcium carbonate
absorption of levothyroxine reduced, give at least 4 hours apart
Prediabetes and impaired glucose regulation
Prediabetes is a term which is increasingly used where there is impaired glucose levels which are above the normal range but not high enough for a diagnosis of diabetes mellitus. The term includes patients who have been labelled as having either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Diabetes UK estimate that around 1 in 7 adults in the UK have prediabetes. Many individuals with prediabetes will progress on to developing type 2 diabetes mellitus (T2DM) and they are therefore at greater risk of microvascular and macrovascular complications.
Terminology
Diabetes UK currently recommend using the term prediabetes when talking to patients and impaired glucose regulation when talking to other healthcare professionals
research has shown that the term ‘prediabetes’ has the most impact and is most easily understood
Identification of patients with prediabetes
NICE recommend using a validated computer based risk assessment tool for all adults aged 40 and over, people of South Asian and Chinese descent aged 25-39, and adults with conditions that increase the risk of type 2 diabetes
patients identified at high risk should have a blood sample taken
a fasting plasma glucose of 6.1-6.9 mmol/l or an HbA1c level of 42-47 mmol/mol (6.0-6.4%) indicates high risk
Management
lifestyle modification: weight loss, increased exercise, change in diet
at least yearly follow-up with blood tests is recommended
NICE recommend metformin for adults at high risk ‘whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme’
Impaired fasting glucose and impaired glucose tolerance
There are two main types of IGR:
impaired fasting glucose (IFG) - due to hepatic insulin resistance
impaired glucose tolerance (IGT) - due to muscle insulin resistance
patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG
Definitions
a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
people with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT
Conns - Primary hyperaldosteronism
Primary hyperaldosteronism was previously thought to be most commonly caused by an adrenal adenoma, termed Conn’s syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases. Differentiating between the two is important as this determines treatment. Adrenal carcinoma is an extremely rare cause of primary hyperaldosteronism.
Features
hypertension
hypokalaemia
e.g. muscle weakness
this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients
alkalosis
Investigations
the 2016 Endocrine Society recommend that a plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism
should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone)
following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
Adrenal Venous Sampling (AVS) can be done to identify the gland secreting excess hormone in primary hyperaldosteronism
Management
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
Primary hyperparathyroidism
In exams, primary hyperparathyroidism is stereotypically seen in elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma
Causes of primary hyperparathyroidism
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
Features - ‘bones, stones, abdominal groans and psychic moans’
polydipsia, polyuria
peptic ulceration/constipation/pancreatitis
bone pain/fracture
renal stones
depression
hypertension
Associations
hypertension
multiple endocrine neoplasia: MEN I and II
Investigations
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
pepperpot skull is a characteristic X-ray finding of hyperparathyroidism
Treatment
the definitive management is total parathyroidectomy
conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage
calcimimetic agents such as cinacalcet are sometimes used in patients who are unsuitable for surgery
The PTH level in primary hyperparathyroidism may be normal
Prolactinoma
Prolactinomas are a type of pituitary adenoma, a benign tumour of the pituitary gland.
Pituitary adenomas can be classified according to:
size (a microadenoma is <1cm and a macroadenoma is >1cm)
hormonal status (a secretory/functioning adenoma produces and excess of a particular hormone and a non-secretory/functioning adenoma does not produce a hormone to excess)
Prolactinomas are the most common type and they produce an excess of prolactin.
Features of excess prolactin
men: impotence, loss of libido, galactorrhoea
women: amenorrhoea, infertility, galactorrhoea, osteoporosis
Diagnosis
MRI
Management
in the majority of cases, symptomatic patients are treated medically with dopamine agonists (e.g. cabergoline, bromocriptine) which inhibit the release of prolactin from the pituitary gland
surgery is performed for patients who cannot tolerate or fail to respond to medical therapy. A trans-sphenoidal approach is generally preferred unless there is a significant extra-pituitary extension
Each of the other four drugs may be associated with gynaecomastia rather than galactorrhoea
Prolactin and galactorrhoea
Prolactin is secreted by the anterior pituitary gland with release being controlled by a wide variety of physiological factors. Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia
Features of excess prolactin
men: impotence, loss of libido, galactorrhoea
women: amenorrhoea, galactorrhoea
Causes of raised prolactin
prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
Drug causes of raised prolactin
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
Sick euthyroid syndrome
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
Subacute (De Quervain’s) thyroiditis
Subacute thyroiditis (also known as De Quervain’s thyroiditis and subacute granulomatous thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism.
There are typically 4 phases;
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal
Investigations
thyroid scintigraphy: globally reduced uptake of iodine-131
Management
usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops
Thyrotoxicosis: causes and investigation
Graves’ disease accounts for around 50-60% of cases of thyrotoxicosis.
Causes
Graves’ disease
toxic nodular goitre
acute phase of subacute (de Quervain’s) thyroiditis
acute phase of post-partum thyroiditis
acute phase of Hashimoto’s thyroiditis (later results in hypothyroidism)
amiodarone therapy
Investigation
TSH down, T4 and T3 up
thyroid autoantibodies
other investigations are not routinely done but includes isotope scanning
Graves’ disease: features
Graves’ disease is the most common cause of thyrotoxicosis. It is typically seen in women aged 30-50 years.
Features
typical features of thyrotoxicosis
specific signs limited to Grave’s (see below)
Features seen in Graves’ but not in other causes of thyrotoxicosis
eye signs (30% of patients)
exophthalmos
ophthalmoplegia
pretibial myxoedema
thyroid acropachy, a triad of:
digital clubbing
soft tissue swelling of the hands and feet
periosteal new bone formation
Autoantibodies
TSH receptor stimulating antibodies (90%)
anti-thyroid peroxidase antibodies (75%)
Acute phase proteins
Acute phase proteins
CRP*
procalcitonin
ferritin
fibrinogen
alpha-1 antitrypsin
caeruloplasmin
serum amyloid A
serum amyloid P component**
haptoglobin
complement
During the acute phase response the liver decreases the production of other proteins (sometimes referred to as negative acute phase proteins). Examples include:
albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein
*Levels of CRP are commonly measured in acutely unwell patients. CRP is a protein synthesised in the liver and binds to phosphocholine in bacterial cells and on those cells undergoing apoptosis. In binding to these cells it is then able to activate the complement system. CRP levels are known to rise in patients following surgery. However, levels of greater than 150 at 48 hours post operatively are suggestive of evolving complications.
**plays a more significant role in other mammals such as mice
Body mass index
Body mass index (BMI) is calculated by dividing the weight (in kilograms) by the height (in metres) squared
BMI
Old classification
NICE classification
< 18.5
Underweight
Underweight
18.5 - 24.9
Normal
Normal
25 - 29.9
Overweight
Overweight
30 - 34.9
Obese
Obese I
35 - 39.9
Clinically obese
Obese II
> 40
Morbidly obese
Obese III
Familial hypercholesterolaemia
Familial hypercholesterolaemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the gene which encodes the LDL-receptor protein.
Case finding:
NICE suggest that we should suspect FH as a possible diagnosis in adults with:
a total cholesterol level greater than 7.5 mmol/l and/or
a personal or family history of premature coronary heart disease (an event before 60 years in an index individual or first-degree relative)
children of affected parents:
if one parent is affected by familial hypercholesterolaemia, arrange testing in children by age 10
if both parents are affected by familial hypercholesterolaemia, arrange testing in children by age 5
Clinical diagnosis is now based on the Simon Broome criteria:
in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus:
for definite FH: tendon xanthoma in patients or 1st or 2nd degree relatives or DNA-based evidence of FH
for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels
Management
the use of CVD risk estimation using standard tables is not appropriate in FH as they do not accurately reflect the risk of CVD
referral to a specialist lipid clinic is usually required
high-dose statins are usually used first-line
first-degree relatives have a 50% chance of having the disorder and should therefore be offered screening. This includes children who should be screened by the age of 10 years if there is one affected parent
statins should be discontinued in women 3 months before conception due to the risk of congenital defects
Hypercalcaemia management
The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days
Other options include:
calcitonin - quicker effect than bisphosphonates
steroids in sarcoidosis
Loop diuretics such as furosemide are sometimes used in hypercalcaemia, particularly in patients
Hyperkalaemia
Plasma potassium levels are regulated by a number of factors including aldosterone, acid-base balance and insulin levels. Metabolic acidosis is associated with hyperkalaemia as hydrogen and potassium ions compete with each other for exchange with sodium ions across cell membranes and in the distal tubule. ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRS leading to a sinusoidal pattern and asystole
Causes of hyperkalaemia:
acute kidney injury
drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers, spironolactone, ciclosporin, heparin**
metabolic acidosis
Addison’s disease
rhabdomyolysis
massive blood transfusion
Foods that are high in potassium:
salt substitutes (i.e. Contain potassium rather than sodium)
bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
*beta-blockers interfere with potassium transport into cells and can potentially cause hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are sometimes used as emergency treatment
**both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is thought to be caused by inhibition of aldosterone secretion
Hypocalcaemia: causes and management
The clinical history combined with parathyroid hormone levels will reveal the cause of hypocalcaemia in the majority of cases
Causes
vitamin D deficiency (osteomalacia)
chronic kidney disease
hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
pseudohypoparathyroidism (target cells insensitive to PTH)
rhabdomyolysis (initial stages)
magnesium deficiency (due to end organ PTH resistance)
massive blood transfusion
Acute pancreatitis may also cause hypocalcaemia. Contamination of blood samples with EDTA may also give falsely low calcium levels
Management
acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying cause
As extracellular calcium concentrations are important for muscle and nerve function many of the features seen in hypocalcaemia seen a result of neuromuscular excitability
Features
tetany: muscle twitching, cramping and spasm
perioral paraesthesia
if chronic: depression, cataracts
ECG: prolonged QT interval
Trousseau’s sign
carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
wrist flexion and fingers drawn together
seen in around 95% of patients with hypocalcaemia and around 1% of normocalcaemic people
Chvostek’s sign
tapping over parotid causes facial muscles to twitch
seen in around 70% of patients with hypocalcaemia and around 10% of normocalcaemic people
QRISK
Measuring lipid levels
When measuring lipids both the total cholesterol and HDL should be checking to provide the most accurate risk of CVD. A full lipid profile should also be checked (i.e. including triglycerides) before starting a statin. The samples does not need to be fasting.
In the vast majority of patient the cholesterol measurements will be fed into the QRISK2 tool. If however the patient’s cholesterol is very high we should consider familial hyperlipidaemia. NICE recommend the following that we should consider the possibility of familial hypercholesterolaemia and investigate further if the total cholesterol concentration is > 7.5 mmol/l and there is a family history of premature coronary heart disease. They also recommend referring people with a total cholesterol > 9.0 mmol/l or a non-HDL cholesterol (i.e. LDL) of > 7.5 mmol/l even in the absence of a first-degree family history of premature coronary heart disease.
Interpreting the QRISK2 result
Probably the headline changes in the 2014 guidelines was the new, lower cut-off of 10-year CVD risk cut-off of 10%.
NICE now recommend we offer a statin to people with a QRISK2 10-year risk of >= 10%
Lifestyle factors are of course important and NICE recommend that we give patients the option of having their CVD risk reassessed after a period of time before starting a statin.
Atorvastatin 20mg should be offered first-line.
Special situations
Type 1 diabetes mellitus
NICE recommend that we ‘consider statin treatment for the primary prevention of CVD in all adults with type 1 diabetes’
atorvastatin 20 mg should be offered if type 1 diabetics who are:
→ older than 40 years, or
→ have had diabetes for more than 10 years or
→ have established nephropathy or
→ have other CVD risk factors
Chronic kidney disease (CKD)
atorvastatin 20mg should be offered to patients with CKD
increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved and the eGFR > 30 ml/min. If the eGFR is < 30 ml/min a renal specialist should be consulted before increasing the dose
Secondary prevention
All patients with CVD should be taking a statin in the absence of any contraindication.
Atorvastatin 80mg should be offered first-line.
Follow-up of people started on statins
NICE recommend we follow-up patients at 3 months
repeat a full lipid profile
if the non-HDL cholesterol has not fallen by at least 40% concordance and lifestyle changes should be discussed with the patient
NICE recommend we consider increasing the dose of atorvastatin up to 80mg
Lifestyle modifications
These are in many ways predictable but NICE make a number of specific points:
Cardioprotective diet
total fat intake should be <= 30% of total energy intake
saturated fats should be <= 7% of total energy intake
intake of dietary cholesterol should be < 300 mg/day
saturated fats should be replaced by monounsaturated and polyunsaturated fats where possible
replace saturated and monounsaturated fat intake with olive oil, rapeseed oil or spreads based on these oils
choose wholegrain varieties of starchy food
reduce their intake of sugar and food products containing refined sugars including fructose
eat at least 5 portions of fruit and vegetables per day
eat at least 2 portions of fish per week, including a portion of oily fish
eat at least 4 to 5 portions of unsalted nuts, seeds and legumes per week
Physical activity
each week aim for at least 150 minutes of moderate intensity aerobic activity or 75 minutes of vigorous intensity aerobic activity or a mix of moderate and vigorous aerobic activity
do musclestrengthening activities on 2 or more days a week that work all major muscle groups (legs, hips, back, abdomen, chest, shoulders and arms) in line with national guidance for the general population
Weight management
no specific advice is given, overweight patients should be managed in keeping with relevant NICE guidance
Alcohol intake
again no specific advice, other than the general recommendation that males drink no more than 3-4 units/day and females no more than 2-3 units/day
Smoking cessation
smokers should be encouraged to quit
SIADH causes
The syndrome of inappropriate ADH secretion (SIADH) is characterised by hyponatraemia secondary to the dilutional effects of excessive water retention.
Causes of SIADH
Category
Examples
Malignancy
small cell lung cancer
also: pancreas, prostate
Neurological
stroke
subarachnoid haemorrhage
subdural haemorrhage
meningitis/encephalitis/abscess
Infections
tuberculosis
pneumonia
Drugs
sulfonylureas*
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
Other causes
positive end-expiratory pressure (PEEP)
porphyrias
Management
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
*the BNF states this has been reported with glimepiride and glipizide.
Vitamin deficiency
The table below summarises vitamin deficiency states
Vitamin
Chemical name
Deficiency state
A
Retinoids
Night-blindness (nyctalopia)
B1
Thiamine
Beriberi
polyneuropathy, Wernicke-Korsakoff syndrome
heart failure
B3
Niacin
Pellagra
dermatitis
diarrhoea
dementia
B6
Pyridoxine
Anaemia, irritability, seizures
B7
Biotin
Dermatitis, seborrhoea
B9
Folic acid
Megaloblastic anaemia, deficiency during pregnancy - neural tube defects
B12
Cyanocobalamin
Megaloblastic anaemia, peripheral neuropathy
C
Ascorbic acid
Scurvy
gingivitis
bleeding
D
Ergocalciferol, cholecalciferol
Rickets, osteomalacia
E
Tocopherol, tocotrienol
Mild haemolytic anaemia in newborn infants, ataxia, peripheral neuropathy
K
Naphthoquinone
Haemorrhagic disease of the newborn, bleeding diathesis
