The glucose sample must be collected in a fluoride oxalate tube as glucose measurements on serum samples are unstable.
If asymptomatic, two elevated concentrations are required to make the diagnosis (for HbA1c the repeat test should be collected two weeks after the first raised measurement).
Please note that HbA1c is not appropriate for the diagnosis of diabetes in the following populations (information taken from Diabetes UK):
All children and young people
Patients of any age suspected of having Type 1 diabetes
Patients with symptoms of diabetes for less than 2 months
Patients at high risk who are acutely ill (e.g. those requiring hospital admission)
Patients taking medication that may cause rapid glucose rise e.g. steroids, antipsychotics
Patients with acute pancreatic damage, including pancreatic surgery
Presence of genetic, haematologic and illness-related factors that influence HbA1c and its measurement (see reference: Use of Glycated Haemoglobin (HbA1c) in the diagnosis of Diabetes Mellitus WHO 2011)
Please refer to the NICE Guidelines for the management of type 1 and type 2 diabetes if you require information on the frequency of monitoring.
Short synacthen test for suspected adrenal failure
This is performed for the investigation of adrenal insufficiency.
Cortisol secretion is stimulated by ACTH from the anterior pituitary. This test evaluates the ability of the adrenal glands to produce cortisol in response to stimulation by a synthetic ACTH preparation (Synacthen).
Hypersensitivity to Synacthen has been reported
The test should ideally be performed in the morning.
Take a basal serum blood sample for measurement of cortisol (gold-topped tube). Inject Synacthen 250 µg iv or im (children 36 µg/kg body weight). Take blood for cortisol after 30 and 60 minutes
There are different protocols and cut-offs in place around the UK due to variation in assay platforms used. A cut-off of >440nmol/L is used in the Derriford protocol, and a rise in cortisol above this concentration will usually exclude adrenal insufficiency.
The diagnosis of primary hyperaldosteronism (frequently due to adrenal aldosterone-producing adenomas) should be considered in hypertensive patients with spontaneous or diuretic-induced hypokalaemia. However, a number of patients with aldosterone secreting adenomas are normokalaemic.
The renin-aldosterone axis is primarily regulated by renal blood flow. Patients under investigation should therefore be normally hydrated, have an adequate sodium intake and be normokalaemic. Any potassium replacement should be stopped on the day of the test.
There are a number of medications that can falsely alter the aldosterone:renin ratio. Therefore, if safe to do so, all drugs should be discontinued for at least two weeks prior to sample collection. See the table below for minimum length of withdrawal for specific medications. The β-blockers prazosin or doxazosin have minimal effect on the renin-aldosterone system and therefore can be used at the time of sampling. If there are medications that cannot be withdrawn then a list of all such medications must be provided with the request to aid interpretation of results.
|Drug||Minimum length of withdrawal|
|• spironolactone||6 weeks|
|• oestrogen preparations||6 weeks|
|• ACE inhibitors||2 weeks|
|• angiotensin II receptor blockers||2 weeks|
|• direct renin inhibitors||2 weeks|
|• calcium channel blockers||2 weeks|
|• β-blockers (for exclusions see above)||2 weeks|
|• diuretics||2 weeks|
|• NSAIDs||2 weeks|
A plasma EDTA sample (lavender top) for renin and a serum SST (gold top) for aldosterone and potassium are required for analysis. Samples must be taken to the laboratory immediately to allow the sample to be separated promptly, hence samples cannot be collected in Primary Care. If the test is required by a GP, then the samples can be collected in the venepuncture suite in Derriford (please contact the Duty Biochemist for more information).
The patient should remain seated for five minutes prior to venepuncture.
High aldosterone and suppressed renin activity indicate primary hyperaldosteronism. Similar results may sometimes be seen in renal disease. In the case of equivocal results, repeat after withdrawal of all interfering medications (as listed above) may be indicated.
Clinical Biochemistry Guidelines
Thyroid function testing
Thyroid disease is associated with significant morbidity. It can present with non-specific symptoms hence thyroid function tests (TFTs) are frequently requested. As the results of TFTs can themselves by affected by intercurrent illness it is important that they are interpreted correctly and thyroid pathology is not assumed and treatment commenced inappropriately.
What should I do about a marginally raised TSH?
If a marginally raised TSH (4.9 –10 mIU/L) is found on a screening blood test and the fT4 is normal, measurement should be repeated in 3-6 months after excluding non-thyroidal illness and drug interference.
If TSH remains marginally elevated the patient’s thyroid autoantibody status should be determined. If thyroid autoantibodies are negative TFTs should be repeated every three years, unless symptoms develop (or the patient is pregnant/contemplating pregnancy). If thyroid auto-antibodies are positive TFTs should be repeated annually.
There is no evidence to support the benefit of routine early treatment with thyroxine in non-pregnant patients with a serum TSH between 4.9-10 mIU/L and a normal FT4, but physicians may wish to consider the suitability of a therapeutic trial of thyroxine on an individual patient basis and in patients who are pregnant/seeking fertility, children and those with a goitre.
How often should I check TFTs in a patient on thyroxine replacement for primary hypothyroidism?
In stable patients annual measurement is sufficient. After a change in dose two months should generally elapse before repeat measurement of TFTs to allow TSH to stabilise.
How do I know from TFT results that the dose of thyroxine is appropriate?
In uncomplicated primary hypothyroidism the biochemical target is a TSH within the reference range, however clinical and biochemical findings need to be taken into consideration.
Should I measure TFTs routinely in patients with diabetes mellitus?
Patients with Type 1 should have a check included in their annual review. Patients with Type 2 should have TFTs checked at diagnosis but routine annual testing is not necessary.
What do I do about a marginally low TSH?
Causes include non-thyroidal illness, medication and subclinical hyperthyroidism. Suggest repeat in 1-2 months, after excluding non-thyroidal illness and drug effects. With subclinical hyperthyroidism, AF is a strong indicator to treat the condition. In the presence of sinus rhythm, individuals with persistent TSH <0.1 mIU/L with symptoms of hyperthyroidism, goitre or osteoporosis should also be considered for referral to one of the endocrinologists and annual follow-up is certainly appropriate to ensure overt hyperthyroidism does not develop.
Is it necessary to check TFTs in patients presenting with hypertension?
This is no longer considered necessary.
How do I monitor TFTs in patients on amiodarone?
TFTs before commencing amiodarone and every 6 months during and for a year after treatment.
How do I monitor TFTs in patient on lithium?
TFTs before commencing and every 6 months whilst on treatment.
Patients who have cholesterol and LDL-C concentrations as per Simon Broome criteria (see table below) need to have further assessment and be referred to specialist lipid clinic if they have:
*Premature CHD younger than 60 years.
*Family history of raised total cholesterol: as in the table below.
*Lipid stigmata mainly Tendon Xanthomata or juvenile corneal arcus.
|Child||> 6.7 mmol/l||> 4.0 mmol/l|
|Adult||> 7.5 mmol/l||> 4.9 mmol/l|
*Or access the Dutch Lipid Clinic Network criteria on:
www.fhscore.eu to determine the patients FH score.