Endocrine Flashcards
fxWhat is primary vs secondary vs congenital hypothyroidism?
primary hypothyroidism: there is a problem with the thyroid gland itself, for example an autoimmune disorder affecting thyroid tissue (see below)
secondary hypothyroidism: usually due to a disorder with the pituitary gland (e.g.pituitary apoplexy) or a lesion compressing the pituitary gland
congenital hypothyroidism: due to a problem with thyroid dysgenesis or thyroid dyshormonogenesis
What is the most common cause of hypothyroidism in the developed vs the devoloping world??
Hashimoto’s thyroiditis
most common cause in the developed world autoimmune disease, associated with type 1 diabetes mellitus, Addison's or pernicious anaemia may cause transient thyrotoxicosis in the acute phase 5-10 times more common in women
Iodine deficiency
the most common cause of hypothyroidism in the developing world
What is hashimotos thyroiditis? what is found o/e? what antibodies are assoc.?
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 (TPO) and also anti-thyroglobulin (Tg) antibodies
What associations are there with hashimotos thyroiditis?
other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo
Hashimoto’s thyroiditis is associated with the development of MALT lymphoma
What diagnosis would be likely if there was a painful goitre and raised ESR with hypothyroidism?
Subacute thyroiditis (de Quervain’s)
associated with a painful goitre and raised ESR
What is subacute thyroiditis? what are the four phases?
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
What are the investigations and management of subacute thyroiditis?
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
What is riedel thyroiditis? What does this cause on examination?
Riedel thyroiditis
fibrous tissue replacing the normal thyroid parenchyma causes a painless goitre
On examination a hard, fixed, painless goitre is noted. It is usually seen in middle-aged women. It is associated with retroperitoneal fibrosis.
How can pregnancy affect thyroid function?
Postpartum thyroiditis - hypothyroidism
What is the most common cause of hyperthyroidism in pregnancy?
What is the management?
Graves’ disease is the most common cause of thyrotoxicosis in pregnancy. It is also recognised that activation of the TSH receptor by HCG may also occur - often termed transient gestational hyperthyroidism. HCG levels will fall in the second and third trimester
Management
propylthiouracil has traditionally been the antithyroid drug of choice however, propylthiouracil is associated with an increased risk of severe hepatic injury therefore NICE Clinical Knowledge Summaries advocate the following: 'Propylthiouracil is used in the first trimester of pregnancy in place of carbimazole, as the latter drug may be associated with an increased risk of congenital abnormalities. At the beginning of the second trimester, the woman should be switched back to carbimazole' maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine the risk of neonatal thyroid problems block-and-replace regimes should not be used in pregnancy radioiodine therapy is contraindicated
How is hypothyroidism managed in pregnancy?
Key points
thyroxine is safe during pregnancy
serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum
women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy
breastfeeding is safe whilst on thyroxine
What drugs can cause thyroid dysfunctions
Drugs
lithium - hypo amiodarone - either
What is the most common cause of hyperthyroidism?
Graves’ disease
most common cause of thyrotoxicosis as well as typically features of thyrotoxicosis other features may be seen including thyroid eye disease It is typically seen in women aged 30-50 years
What 3 features are seen in graves but not in other forms of graves disease?
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
What autoantibodies are found in graves disease? what is found on thyroid scintigraphy?
Autoantibodies
TSH receptor stimulating antibodies (90%) anti-thyroid peroxidase antibodies (75%)
Thyroid scintigraphy
diffuse, homogenous, increased uptake of radioactive iodine
What is the general management of grave’s disease?
Anti-thyroid drugs have emerged as the most popular first-line therapy for Graves’ disease in recent years. Factors that particularly support their use include anti-thyroid drugs significant symptoms of thyrotoxicosis, or patients with a significant risk of hyperthyroid complications (e.g. elderly patients, cardiovascular disease).
Initial treatment to control symptoms
propranolol is used to help block the adrenergic effects
NICE Clinical Knowledge Summaries recommended that patients with Graves’ disease are referred to secondary care for ongoing treatment.
NICE suggest carbimazole should be considered in primary care if patients symptoms are not controlled with propanolol
Describe two regimes of anti-thyroid drug therapy for graves disease?
ATD therapy
carbimazole is started at 40mg and reduced gradually to maintain euthyroidism
typically continued for 12-18 months
the major complication of carbimazole therapy is agranulocytosis
an alternative regime is termed 'block-and-replace'
carbimazole is started at 40mg
thyroxine is added when the patient is euthyroid
treatment typically lasts for 6-9 months
patients following an ATD titration regime have been shown to suffer fewer side-effects than those on a block-and-replace regime
What is the mechanism of action of carbimazole? what adverse effects exist?
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
When is radioiodine treatment used for graves disease? what are contraindications?
Radioiodine treatment
often used in patients who relapse following ATD therapy or are resistant to primary ATD 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
What is a toxic multinodular goitre? does this cause hypo or hyper thyroidism?
Toxic multinodular goitre
autonomously functioning thyroid nodules that secrete excess thyroid hormones
What is sick euthyroid and what TFTs are assoc?
Common in hospital inpatients. Changes are reversible upon recovery from the systemic illness and no treatment is usually needed
T4 - low
TSH - low
What are the 3 main types of thyroid antibody?
A number of thyroid autoantibodies can be tested for (remember the majority of thyroid disorders are autoimmune). The 3 main types are:
Anti-thyroid peroxidase (anti-TPO) antibodies TSH receptor antibodies Thyroglobulin antibodies
Which antibodies are seen in Graves disease? which ones are assoc. with hashimoto?
There is significant overlap between the type of antibodies present and particular diseases, but generally speaking TSH receptor antibodies are present in around 90-100% of patients with Graves’ disease and anti-TPO antibodies are seen in around 90% of patients with Hashimoto’s thyroiditis.
What is seen on nuclear scintigraphy with toxic multinodular goitre?
Other tests include:
nuclear scintigraphy; toxic multinodular goitre reveals patchy uptake
What is the treatment of thyrotoxicosis?
Patients with thyrotoxicosis may be treated with:
propranolol: this is often used at the time of diagnosis to control thyrotoxic symptoms such as tremor carbimazole: blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production. Agranulocytosis is an important adverse effect to be aware of radioiodine treatment
Who is affected by thyroid eye disease and why does this occur?
Thyroid eye disease affects between 25-50% of patients with Graves’ disease.
Pathophysiology
it is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation the inflammation results in glycosaminoglycan and collagen deposition in the muscles
What can be done to prevent thryoid eye disease?
Prevention
smoking is the most important modifiable risk factor for the development of thyroid eye disease radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease. In a recent study of patients with Graves' disease around 15% developed, or had worsening of, eye disease. Prednisolone may help reduce the risk
What features are seen with thyroid eye disease?
Features
the patient may be eu-, hypo- or hyperthyroid at the time of presentation exophthalmos conjunctival oedema optic disc swelling ophthalmoplegia inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy
What symptoms/signs of thyroid eye disease would prompt urgent opthalmologist review?
For patients with established thyroid eye disease the following symptoms/signs should indicate the need for urgent review by an ophthalmologist (see EUGOGO guidelines):
unexplained deterioration in vision awareness of change in intensity or quality of colour vision in one or both eyes history of eye suddenly 'popping out' (globe subluxation) obvious corneal opacity cornea still visible when the eyelids are closed disc swelling
What is the management of thyroid eye disease?
Management
topical lubricants may be needed to help prevent corneal inflammation caused by exposure steroids radiotherapy surgery
What is subclinical hyperthyroidism? how is this managed?
Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as:
normal serum free thyroxine and triiodothyronine levels with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)
Management
TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission
what is the risk of progressing to hypothyroidism in subclinical hypothyroidism?
Significance
risk of progressing to overt hypothyroidism is 2-5% per year (higher in men) risk increased by the presence of thyroid autoantibodies
What is the management of subclinical hypothyroidism?
TSH is > 10mU/L and the free thyroxine level is within the normal range
consider offering levothyroxine if the TSH level is > 10 mU/L on 2 separate occasions 3 months apart
TSH is between 5.5 - 10mU/L and the free thyroxine level is within the normal range
if < 65 years consider offering a 6-month trial of levothyroxine if:
the TSH level is 5.5 - 10mU/L on 2 separate occasions 3 months apart,and
there are symptoms of hypothyroidism
in older people (especially those aged over 80 years) follow a 'watch and wait' strategy is often used
if asymptomatic people, observe and repeat thyroid function in 6 months
What is the management of hypothyroidism? What is the therapeutic goal? How to manage pregnant ladies with established hypothyroidism?
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
What are the side effects of thyroxine therapy? What interactions exist?
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
What investigations are indicated when considering T1DM? 4. Is HbA1c useful?
urine should be dipped for glucose and ketones
fasting glucose and random glucose
HbA1c is not as useful for patients with a possible or suspected diagnosis of T1DM as it may not accurately reflect a recent rapid rise in serum glucose
C-peptide levels are typically low in patients with T1DM
diabetes-specific autoantibodies are useful to distinguish between type 1 and type 2 diabetes
What is HbA1c?
glycosylated haemoglobin HbA1c - reflects glucose over 3mths
What causes lower than expected HbA1c levels?
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
Haemodialysis
What causes higher than expected HbA1c levels?
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
What 4 antibodies are tested when considering T1DM? what are the association?
Antibodies to glutamic acid decarboxylase (anti-GAD) - Present in around 80% of patients with T1DM
Islet cell antibodies (ICA, against cytoplasmic proteins in the beta cell) - Present in around 70-80% of patients with T1DM
Insulin autoantibodies (IAA) - Presence in T1DM correlates strongly with age, found in over 90% of young children with T1DM but only 60% of older patients
Insulinoma-associated-2 autoantibodies (IA-2A)
What is the diagnostic criteria for T1DM if symptomatic? what if asymptomatic?
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.
Do all patient suspected of T2DM need to get antibody levels checked?
patients suspected of type 2 diabetes, if they over the age of 40 years and respond well to oral hypoglycaemic agents do not need to undergo further testing for type 1 diabetes. For those in whom there is a doubt, C-peptide levels and diabetes-specific autoantibodies are the investigations of choice.
How often is HbA1c checked in T1DM?
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
Describe self-monitoring of BMs and the target levels of patients with T1DM?
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
What types of insulin is used in T1DM? when is metformin added?
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
What is diagnostic criteria for T2DM?
If the patient is symptomatic: CKS
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.
When HbA1c is used for 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)
What is impaired fasting glucose? what is impaired glucose tolerance? what causes this?
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.'
Causes:
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
What is pre-diabetes?
Fasting glucose - 6.1-6.9
HbA1c - 42-47
or impaired glucose tolerance
What is the management of pre-diabetes?
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'
What dietary advice is recommended for patients with T2DM?
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 the use of foods marketed specifically at people with diabetes initial target weight loss in an overweight person is 5-10%
What are HbA1c targets for patients on lifestyle measures or single drug therapy?
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%)
When would you add another drug to a patient with T2DM and what is the HbA1c target?
HbA1c rises to 58
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%), aim for HbA1c 53 mmol/mol (7.0%)
Describe the first line management of T2DM?
Metformin
Add SGLT2 inhibitor if have high risk CVD (QRisk >10) / Established CVD or Chronic heart failure
metformin should be established and titrated up before introducing the SGLT-2 inhibitor
SGLT-2 inhibitors should also be started at any point if a patient develops CVD (e.g. is diagnosed with ischaemic heart disease), a QRISK ≥ 10% or chronic heart failure
What is the first line therapy for T2DM if there is contraindications to metformin?
If metformin is contraindicated
if the patient has a risk of CVD, established CVD or chronic heart failure:
SGLT-2 monotherapy
if the patient doesn't have a risk of CVD, established CVD or chronic heart failure:
DPP‑4 inhibitor or pioglitazone or a sulfonylurea
SGLT-2 may be used if certain NICE criteria are met
What is the second line treatment of T2DM?
Dual therapy - add one of the following:
metformin + DPP-4 inhibitor metformin + pioglitazone metformin + sulfonylurea metformin + SGLT-2 inhibitor (if NICE criteria met)
What is the third line treatment of T2DM?
If a patient does not achieve control on dual therapy then the following options are possible:
metformin + DPP-4 inhibitor + sulfonylurea metformin + pioglitazone + sulfonylurea metformin + (pioglitazone or sulfonylurea or DPP-4 inhibitor) + SGLT-2 if certain NICE criteria are met insulin-based treatment
When would you offer DPP4 inhibitor to treat T2DM?
NICE guidelines on DPP-4 inhibitors
NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione (pioglitazone) if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione
Describe common adverse effects of sulfonylureas? (gliclazide) What are rarer adverse effects?
Common adverse effects
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide) weight gain
Rarer adverse effects
hyponatraemia secondary to syndrome of inappropriate ADH secretion bone marrow suppression hepatotoxicity (typically cholestatic) peripheral neuropathy
Sulfonylureas should be avoided in breastfeeding and pregnancy.
When is a GLP-1 mimetic added?
If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic:
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 obesity-related 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
What are adverse effects of pioglitazone? thiazolidinedione
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)
What are meglitinides?
Meglitinides (e.g. repaglinide, nateglinide)
increase pancreatic insulin secretion like sulfonylureas they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells often used for patients with an erratic lifestyle adverse effects include weight gain and hypoglycaemia (less so than sulfonylureas)
What insulin is used first line for T2DM?
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
Describe T2DM advice for ramadan?
If a patient with type 2 diabetes mellitus does decide to fast:
they should try and and eat a meal containing long-acting carbohydrates prior to sunrise (Suhoor) patients should be given a blood glucose monitor to allow them to check their glucose levels, particularly if they feel unwell for patients taking metformin the expert consensus is that the dose should be split one-third before sunrise (Suhoor) and two-thirds after sunset (Iftar) expert consensus also recommends switching once-daily sulfonylureas to after sunset. For patients taking twice-daily preparations such as gliclazide it is recommended that a larger proportion of the dose is taken after after sunset no adjustment is needed for patients taking pioglitazone
What are sick day rules for T1DM?
Patients with type 1 diabetes CKS
if a patient is on insulin, they must not stop it due to the risk of diabetic ketoacidosis
check blood glucose more frequently, for example, every 1–2 hours including through the night
consider checking blood or urine ketone levels regularly
maintain normal meal pattern if possible
if appetite is reduced meals could be replaced with carbohydrate-containing drinks (such as milk, milkshakes, fruit juices, and sugary drinks)
aim to drink at least 3 L of fluid (5 pints) a day to prevent dehydration
Describe sick day rules for T2DM?
Patients with type 2 diabetes CKS
advise the patient to temporarily stop some oral hypoglycaemics during an acute illness
medication may be restarted once the person is feeling better and eating and drinking for 24-48 hours
metformin: stop treatment if there is a risk of dehydration, to reduce the risk of lactic acidosis.
sulfonylureas: may increase the risk of hypoglycaemia
SGLT-2 inhibitors: check for ketones and stop treatment if acutely unwell and/or at risk of dehydration, due to the risk of euglycaemic DKA
GLP-1 receptor agonists: stop treatment if there is a risk of dehydration, to reduce the risk of AKI
if on insulin therapy, do not stop treatment, as above
monitor blood glucose more frequently as necessary
Describe diabetic foot screening?
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
What would indicate a low risk in diabetic foot disease?
- no risk factors except callus alone
What indicates a moderate risk in diabetic foot disease?
- deformity or
- neuropathy or
- non-critical limb ischaemia
What indicates a high risk in diabetic foot disease?
- 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.
What is the first line treatment for diabetic neuropathy?
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
What can be used for gastroparesis in T2DM? What other GI upset can be caused due to T2DM?
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
What are the rules for HGV drivers with diabetes?
there has not been any severe hypoglycaemic event in the previous 12 months
the driver has full hypoglycaemic awareness
the driver must show adequate control of the condition by regular blood glucose monitoring*, at least twice daily and at times relevant to driving
the driver must demonstrate an understanding of the risks of hypoglycaemia
here are no other debarring complications of diabetes
What are the rules for group 1 drivers with diabete?
if on insulin then patient can drive a car as long as they have hypoglycaemic awareness, not more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months and no relevant visual impairment. Drivers are normally contacted by DVLA
if on tablets or exenatide no need to notify DVLA. If tablets may induce hypoglycaemia (e.g. sulfonylureas) then there must not have been more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months
if diet controlled alone then no requirement to inform DVLA
Describe onset/peak/duration of rapid acting insulin analogues
Onset Peak Duration
5 mins 1 hour 3-5 hours
insulin aspart: NovoRapid
insulin lispro: Humalog
Describe onset/peak/duration of short acting insulin analogues
Onset Peak Duration
30 mins 3 hours 6-8 hours
Actrapid (human, pyr), Humulin S (human, prb)
Describe onset/peak/duration of intermediate acting insulin analogues
Onset Peak Duration
2 hours 5-8 hours 12-18 hours
isophane insulin (many use this in a mix with long acting)
Describe onset/peak/duration of long acting insulin analogues
1-2 hours Flat profile Up to 24 hours
insulin determir (Levemir): given once or twice daily insulin glargine (Lantus): given once daily
Hypoglycaemia
-What are the signs
-How can you fix this in conscious patient?
Hypoglycaemia
patients should be taught the signs of hypoglycaemia: sweating, anxiety, blurred vision, confusion, aggression conscious patients should take 10-20g of a short-acting carbohydrate (e.g. a glass of Lucozade or non-diet drink, three or more glucose tablets, glucose gel) every person treated with insulin should have a glucagon kit for emergencies where the patient is not able to orally ingest a short-acting carbohydrate patients who have frequent hypoglycaemic episodes may develop reduced awareness. If this develops then allowing glycaemic control to slip for a period of time may restore their awareness beta-blockers reduce hypoglycaemic awareness
What can cause hypoglycaemia? 6
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison’s disease
alcohol
causes exaggerated insulin secretion
mechanism is thought to be due to the effect of alcohol on the pancreatic microcirculation → redistribution of pancreatic blood flow from the exocrine into the endocrine parts → increased insulin secretion
nesidioblastosis - beta cell hyperplasia
What is the management of hypoglycaemia?
Management of hypoglycaemia
the following guidelines are based on the BNF hypoglycaemia treatment summary.
in the community (for example, diabetes mellitus patients who inject insulin):
Initially, oral glucose 10-20g should be given in liquid, gel or tablet form
Alternatively, a propriety quick-acting carbohydrate may be given: GlucoGel or Dextrogel.
A 'HypoKit' may be prescribed which contains a syringe and vial of glucagon for IM or SC injection at home
in a hospital setting:
If the patient is alert, a quick-acting carbohydrate may be given (as above)
If the patient is unconscious or unable to swallow, subcutaneous or intramuscular injection glucagon may be given.
Alternatively, intravenous 20% glucose solution may be given through a large vein
What is MODY? and how is this inherited?
Maturity-Onset Diabetes of the Young (MODY) is a form of monogenic diabetes, typically characterized by an autosomal dominant inheritance pattern, onset usually before 25 years of age, and impairment in insulin secretion with minimal or no defects in insulin action. Unlike more common forms of diabetes, such as Type 1 and Type 2, MODY is not primarily driven by lifestyle factors.
It is thought that around 1-2% of patients with diabetes mellitus have MODY, and around 90% are misclassified as having either type 1 or type 2 diabetes mellitus.
What are the clinical features of MODY?
Patients with MODY often present with mild non-ketotic hyperglycemia that is often detected incidentally or during routine screening. It may also be discovered during pregnancy. Unlike Type 1 diabetes, patients with MODY usually do not present with diabetic ketoacidosis except under severe stress conditions, and unlike Type 2 diabetes, they are often of normal weight and do not exhibit signs of insulin resistance.
The specific clinical manifestations and complications can vary depending on the subtype of MODY. For example, individuals with MODY2 generally have mild, stable fasting hyperglycemia and rarely develop severe complications, whereas those with MODY3 or MODY1 may have progressive hyperglycemia and are at higher risk for complications typically associated with diabetes, such as retinopathy, nephropathy, and cardiovascular disease.
How is MODY diagnosed and treated?
Genetic testing, the treatment depends on the type
What is acromegaly and what causes it?
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.
What are features of acromegaly?
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
What are 4 complications of acromegaly?
Complications
hypertension diabetes (>10%) cardiomyopathy colorectal cancer
What is addisons 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.
What are features of addisons?
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
What are other primary causes of hypo-adrenalism?
Primary causes
tuberculosis metastases (e.g. bronchial carcinoma) meningococcal septicaemia (Waterhouse-Friderichsen syndrome) HIV antiphospholipid syndrome
What are secondary causes of hypo-adrenalism?
Secondary causes
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
What is the definite investigation for addisions? What is a useful first line ix?
In a patient with suspected Addison’s disease the definite investigation is an ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
If an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:
> 500 nmol/l makes Addison's very unlikely < 100 nmol/l is definitely abnormal 100-500 nmol/l should prompt a ACTH stimulation test to be performed
What electrolyte abnormalities are assoc. with addisons disease?
Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients:
hyperkalaemia hyponatraemia hypoglycaemia metabolic acidosis
What is the management of addisons disease?
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 first half of the day fludrocortisone
What should patients do who are on steroids and become unwell? what indicates a gradual withdrawal of systemic steroids?
Selected points on the use of corticosteroids:
patients on long-term steroids should have their doses doubled during intercurrent illness
longer-term systemic corticosteroids suppress the natural production of endogenous steroids. They should therefore not be withdrawn abruptly, as this may precipitate an Addisonian crisis
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 of treatment
recently received repeated courses
What are some ACTH dependant causes of cushings syndrome?
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 is the most common causes
What are 5 ACTH independant causes of cushings syndrome?
ACTH independent causes
iatrogenic: steroids adrenal adenoma (5-10%) adrenal carcinoma (rare) Carney complex: syndrome including cardiac myxoma micronodular adrenal dysplasia (very rare)
What is pseudo-cushings? how to differentiate this and cushings?
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
What is phaeochromocytoma? what is the 10% rule?
Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
Basics
bilateral in 10% malignant in 10% extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
What are the features of phaechromocytoma?
Features are typically episodic
hypertension (around 90% of cases, may be sustained) headaches palpitations sweating anxiety
What is the test for phaechromocytoma?
Tests
24 hr urinary collection of metanephrines (sensitivity 97%*) this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)
What is the management of phaechromocytoma?
Surgery is the definitive management. The patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a beta-blocker (e.g. propranolol)
How are pituitary adenomas classified? What is the most commonest pituitary adenoma?
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.
What are the features of excess prolactin in women?
excess prolactin in women
amenorrhoea infertility galactorrhoea osteoporosis
What are the features of excess prolactin in men?
excess prolactin in men
impotence loss of libido galactorrhoea
What are the signs of a macroadenoma?
other symptoms may be seen with macroadenomas
headache.
visual disturbances (classically, a bitemporal hemianopia (lateral visual fields) or upper temporal quadrantanopia)
symptoms and signs of hypopituitarism
What is the diagnosis and treatment of prolactinoma?
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
What are other causes of raised prolactin in addition to prolactinoma?
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)
What are 4 drug causes of raised prolactin?
Drug causes of raised prolactin
metoclopramide, domperidone phenothiazines haloperidol very rare: SSRIs, opioids
What is bartters syndrome?
Bartter’s syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn’s, Cushing’s and Liddle’s syndrome which are associated with hypertension).
Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide
What are the features of bartters syndroms?
Features
usually presents in childhood, e.g. Failure to thrive polyuria, polydipsia hypokalaemia normotension weakness
What is Androgen insensitivity syndrome? What is the karyotype?
46 XY X-linked recessive condition.
Defect in androgen receptor results in end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Rudimentary vagina and testes present but no uterus. Testosterone, oestrogen and LH levels are elevated
What is 5-α reductase deficiency? what is the karyotype?
46 XY Autosomal recessive condition.
Results in the inability of males to convert testosterone to dihydrotestosterone (DHT). Individuals have ambiguous genitalia in the newborn period. Hypospadias is common. Virilization at puberty.
What is male Male pseudohermaphroditism? What is the karyotype?
46 XY
Individual has testes but external genitalia are female or ambiguous. may be secondary to androgen insensitivity syndrome
What is female pseudohermaphroditism? what is the karyotype?
46 XX
Individual has ovaries but external genitalia are male (virilized) or ambiguous. May be secondary to congenital adrenal hyperplasia
What is true hermaphroditism?
46 XX or 47 XXY
Very rare, both ovarian and testicular tissue are present
What is gynaecomastia?
Gynaecomastia describes an abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio.
What are 9 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
What are 6 common drug causes of gynaecomastia?
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
what are 6 very rare drug cause of gynaecomastia?
Very rare drug causes of gynaecomastia
tricyclics isoniazid calcium channel blockers heroin busulfan methyldopa
What is Kallman’s syndrome? How is it inherited? what is the clue in many questions?
Kallmann’s syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann’s syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.
The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.
What are 6 features of kallman’s syndrome?
Features
'delayed puberty' hypogonadism, cryptorchidism anosmia sex hormone levels are low LH, FSH levels are inappropriately low/normal patients are typically of normal or above-average height
Cleft lip/palate and visual/hearing defects are also seen in some patients
What is the management of kallman’s syndrome?
Management
testosterone supplementation gonadotrophin supplementation may result in sperm production if fertility is desired later in life
What is klinefelter’s syndrome?
Klinefelter’s syndrome is associated with karyotype 47, XXY.
What are the features of klinefelters syndrome?
Features
often taller than average lack of secondary sexual characteristics small, firm testes infertile gynaecomastia - increased incidence of breast cancer elevated gonadotrophin levels but low testosterone
Diagnosis is by karyotype (chromosomal analysis).
How is metabolic syndrome diagnosed?
SIGN recommend using criteria similar to those from the American Heart Association. The similarity of the International Diabetes Federation criteria should be noted. For a diagnosis of metabolic syndrome at least 3 of the following should be identified:
elevated waist circumference: men > 102 cm, women > 88 cm elevated triglycerides: > 1.7 mmol/L reduced HDL: < 1.03 mmol/L in males and < 1.29 mmol/L in females raised blood pressure: > 130/85 mmHg, or active treatment of hypertension raised fasting plasma glucose > 5.6 mmol/L, or previously diagnosed type 2 diabetes
What is the management of diabetes?
The management of obesity consists of a step-wise approach:
conservative: diet, exercise
medical
orlistat
liraglutide
surgical
What is orlistat? who can get it?
Orlistat is a pancreatic lipase inhibitor used in the management of obesity. Adverse effects include faecal urgency/incontinence and flatulence. A lower dose version is now available without prescription (‘Alli’). NICE have defined criteria for the use of orlistat. It should only be prescribed as part of an overall plan for managing obesity in adults who have:
BMI of 28 kg/m^2 or more with associated risk factors, or BMI of 30 kg/m^2 or more continued weight loss e.g. 5% at 3 months orlistat is normally used for < 1 year
Who can get Liraglutide for obesity (GLP1 mimetic)
Liraglutide
a glucagon-like peptide-1 (GLP-1) mimetic that is used in the management of type 2 diabetes mellitus (T2DM)
given as a once daily subcutaneous injection
when used in the management of T2DM it was noted to cause weight loss in a significant proportion leading to research interest in its use in obesity
current NICE criteria for use (see link for full criteria):
person has a BMI of at least 35 kg/m²
prediabetic hyperglycaemia (e.g. HbA1c 42 - 47 mmol/mol)
What two of the commonest conditions that can cause hypercalcaemia?
Two conditions account for 90% of cases of hypercalcaemia:
1. Primary hyperparathyroidism: commonest cause in non-hospitalised patients
2. Malignancy: the commonest cause in hospitalised patients. This may be due to a number of processes, including;
PTHrP from the tumour e.g. squamous cell lung cancer
bone metastases
myeloma,: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
for this reason, measuring parathyroid hormone levels is the key investigation for patients with hypercalcaemia
What other causes that arent cancer or primary hyperparathyroidism, for hypercalcaemia? 10
Other causes include
sarcoidosis
other causes of granulomas may lead to hypercalcaemia e.g. tuberculosis and histoplasmosis
vitamin D intoxication
acromegaly
thyrotoxicosis
Milk-alkali syndrome
drugs:
thiazides
calcium-containing antacids
dehydration
Addison's disease
Paget's disease of the bone
usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
What is primary hyperparathyroidism? What are the different causes of this?
Primary hyperparathyroidism is caused by excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration. In 85% of cases a parathyroid adenoma is responsible.
Causes of primary hyperparathyroidism
85%: solitary adenoma 10%: hyperplasia 4%: multiple adenoma 1%: carcinoma
What are the features of primary hypeparathyroidism?
Around 80% of patients are asymptomatic and are diagnosed on routine blood tests. The symptomatic features of primary hyperparathyroidism may be remembered by the mnemonic: ‘bones, stones, abdominal groans and psychic moans’:
polydipsia, polyuria depression anorexia, nausea, constipation peptic ulceration pancreatitis bone pain/fracture renal stones hypertension
What are the 2 assoc. with primary hyperparathyroidism?
Associations
hypertension multiple endocrine neoplasia: MEN I and II
What are the investigations for primary hyperparathyroidism?
Investigations
bloods
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
x-ray findings
pepperpot skull
osteitis fibrosa cystica
what is the treatment 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
patients not suitable for surgery may be treated with cinacalcet, a calcimimetic
a calcimimetic 'mimics' the action of calcium on tissues by allosteric activation of the calcium-sensing receptor
What is primary hypoparathyroidism?
Primary hypoparathyroidism
decrease PTH secretion e.g. secondary to thyroid surgery* low calcium, high phosphate treated with alfacalcidol
What are the symptoms of hypoparathyroidism? 4 . what is seen on ECG?
The main symptoms of hypoparathyroidism are secondary to hypocalcaemia:
tetany: muscle twitching, cramping and spasm perioral paraesthesia Trousseau's sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic Chvostek's sign: tapping over parotid causes facial muscles to twitch if chronic: depression, cataracts ECG: prolonged QT interval
What is pseudohypoparathyroidism?
Pseudohypoparathyroidism
target cells being insensitive to PTH due to abnormality in a G protein associated with low IQ, short stature, shortened 4th and 5th metacarpals low calcium, high phosphate, high PTH diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
What is primary hyperaldosteronism? what are the causes?
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 most common cause. Differentiating between the two is important as this determines treatment.
Causes
bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases adrenal adenoma: 20-30% of cases unilateral hyperplasia familial hyperaldosteronism adrenal carcinoma
What are the features of primary hyperaldosteronism?
Features
hypertension
increasingly recognised but still underdiagnosed cause of 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, and is more common with adrenal adenomas
metabolic alkalosis
What are the investigations for hyperaldosteronism?
Investigations
guidelines vary but certain patients should be screened for primary hyperaldosteronism, e.g.
hypertension with hypokalemia
treatment-resistant hypertension
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
if the CT is normal adrenal venous sampling (AVS) can be used to distinguish between unilateral adenoma and bilateral hyperplasia
What is the management of hyperaldosteronism?
Management
adrenal adenoma: surgery (laparoscopic adrenalectomy) bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
How is MEN inherited?
MEN is inherited as an autosomal dominant disorder.
What are the three P’s of MEN type 1? What gene is found? what is the most common presentation?
MEN type I
3 P’s
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
Also: adrenal and thyroid Medullary thyroid cancer (70%)
MEN1 gene
Most common presentation = hypercalcaemia
What neoplasm is seen in MEN IIa? Which gene is found?
2 P’s
Parathyroid (60%)
Phaeochromocytoma
Medullary thyroid cancer
RET oncogen
What cancer is seen in MEN IIb? which gene is found? what are features?
Medullary thyroid cancer
1 P
Phaeochromocytoma
Marfanoid body habitus
Neuromas
RET oncogen
What is a neuroblastoma? when does this occur?
Neuroblastoma is one of the top five causes of cancer in children, accounting for around 7-8% of childhood malignancies. The tumour arises from neural crest tissue of the adrenal medulla (the most common site) and sympathetic nervous system.
Median age of onset is around 20 months
what are 6 features of neuroblastoma?
Features
abdominal mass pallor, weight loss bone pain, limp hepatomegaly paraplegia proptosis
What are the investigations for neuroblastoma?
Investigation
raised urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels calcification may be seen on abdominal x-ray biopsy
