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Therapeutic Drug Monitoring (TDM)

A TDM service is provided in the department of Clinical Biochemistry for some of the drugs requiring regular monitoring. Please check the time at which a sample should be collected as failure to collect the blood at the appropriate time will make it impossible to compare the measured concentration with an accepted therapeutic range. Assays are of little use under these conditions.

The monitoring of valproic acid is not recommended because of the poor correlation between plasma levels and therapeutic effect. The duty biochemist must be contacted to discuss its measurement for any other purpose.

Any request for urgent therapeutic drug analysis that is not provided by Clinical Biochemistry must be discussed with the Duty Biochemist, or when out-of-hours with the duty Biomedical Scientist who may ask you to discuss this with the Duty Consultant. In some circumstances additional discussion with a pharmacist is required. Some specimens requiring analysis out-of-hours may need to be sent to the Toxicology unit at City Hospital and if you organise this without consulting the Pharmacy department you will incur charges to the trust that will not be the responsibility of Clinical Biochemistry.

Overdoses/Drug Screens

Samples for a 'Drug Screen' are analysed at the Regional Toxicology Laboratory (RTL) at City Hospital. A request for a "drug screen" or ‘unknown drug’ requires:-

  • At least 10 mL of urine in plain tube (NOT containing boric acid).  A green top (Lithium heparin anticoagulant) tube filled with blood.  Detailed patient information.
  • Clinical condition e.g. coma grade, fitting etc.
  • Current known prescribed drugs.
  • Overdose drug(s) if known.
  • Urine specimen type e.g. voided or catheter.

Blood samples taken for a ‘Drug Screen’ are of little use unless there is prior knowledge of the agent ingested. Discuss whether a blood sample is of use with the duty biochemist or duty consultant (via the out-of-hours Biomedical Scientist). Paracetamol, salicylate and lithium measurements are available on a 24 hr basis. All requests for other ingested drugs must be discussed with the Poisons Unit and Regional Toxicology Laboratory and samples sent only by prior arrangement. Any samples requiring urgent analysis at the Regional Toxicology Laboratory will require direct dispatch to that laboratory and must not be sent to the Clinical Biochemistry department. Charges realised by these analysis will be forwarded to the relevant division.

Antibiotics

Amikacin, gentamycin, tobramycin and vancomycin are measured in Clinical Biochemistry but clinical advice is given from Microbiology. For patients with liver or renal impairment, advice on antibiotic dosage is available from Clinical Microbiology.

Assays for other antimicrobials including flucytosine, teicoplanin and streptomycin are available from Microbiology after prior consultation with the Clinical Microbiologist.

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Diagnosis of Diabetes Mellitus

Conventionally diabetes mellitus was diagnosed by high fasting or random blood glucose concentrations, or an abnormal oral glucose tolerance test (OGTT) whilst haemoglobin A1c (HbA1c) was used to monitor longer term glycaemic control in patients with known diabetes mellitus.

In 2011, the World Health Organisation (WHO 2011) recommended that HbA1c measurements should also be used to diagnose diabetes in the majority of asymptomatic individuals, and this recommendation has been agreed in the UK (NHS Diabetes 2011).

An HbA1c of 48 mmol/mol or more is consistent with diabetes. If the patient has no symptoms then a second HbA1c result must be obtained within 2 weeks, and if it remains ≥48 mmol/mol diabetes mellitus is confirmed.

HbA1c values of 42 to 47 mmol/mol suggest a high risk of future diabetes. Such individuals should be offered structured lifestyle education and support to delay/prevent development of diabetes, and have an annual HbA1c test.

HbA1c must be measured in an accredited laboratory undertaking recommended quality assurance procedures. Near patient testing is not appropriate when HbA1c is used for the diagnosis of diabetes.

HbA1c is now the preferred method to diagnose diabetes, except in the following situations where this test would be unreliable, and in whom the traditional methods of diagnosis with blood glucose concentrations remain the method of choice:

  • Haemoglobinopathies
  • Increased red cell turnover
  • Anaemia (haemoglobin < 80 g/L)
  • ?Type 1 diabetes or acute onset of symptoms of diabetes
  • ?Gestational diabetes
  • Children and adolescents
  • Patients taking steroids and antipsychotic or other medications that cause a rapid rise in blood glucose

Despite this new approach, if an individual has abnormally high random or fasting blood glucose levels or abnormal OGTT, which would be consistent with diabetes on the traditional criteria, then that patient should be considered to have diabetes irrespective of their HbA1c value. Without symptoms of diabetes two abnormal tests of the same type (two high fasting/random blood glucoses or a diabetic OGTT) are required to confirm diabetes mellitus.

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Management of the Menopause

The menopausal transition is best diagnosed on clinical grounds. Endocrine investigation may be helpful where the pattern of age, menstrual history and features of oestrogen deficiency are unusual.

Please indicate the woman’s date of birth, recent menstrual pattern and date of last menstrual period/day of cycle on which the blood sample was collected. A rise in follicle stimulating hormone (FSH) is the earliest sign of the approaching menopause. Measurement of serum FSH is the recommended first investigation if biochemical confirmation is necessary. The measurement of luteinising hormone (LH), oestradiol or progesterone is not appropriate. A serum FSH in the reference range for the follicular phase does not exclude the perimenopause.

Hormone Replacement Therapy

HRT when prescribed (orally or transdermally) for the relief of menopausal symptoms does not require endocrine monitoring. Where there is unexpected failure of treatment, for example due to non-compliance or malabsorption, investigation may be useful. Different formulations of HRT may or may not be detected by oestradiol assays. Please indicate on the request form the HRT preparation prescribed.

The main indication for measuring oestradiol in women on HRT is in those receiving implants containing oestradiol. Early replacement of the implant may result in accumulation of oestradiol. Monitoring of serum oestradiol before the implant is replaced has been recommended to avoid supraphysiological concentrations. Sometimes testosterone implants are used in HRT. Measurement of testosterone in an analogous fashion to oestradiol may help to assess whether a further implant may be necessary.

 

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Thyroid Function Tests

TSH and free thyroxine (fT4) are provided as first-line tests. Since many drugs and treatments affect thyroid function tests, details of all drugs or other treatment must be provided in order that further tests can be initiated by the laboratory as appropriate. Please indicate on request form if patient is on thyroid hormone replacement.

Free T3 is analysed only according to an agreed protocol and full clinical details must be given on the request form.

Thyroid hormone measurements can be misleading in patients with acute and non-thyroid illness. Thyroid status should only be assessed after recovery from acute non-thyroidal illness. 'Screening' of patients in hospital for thyroid illness is not recommended.

Please see the UK Guidelines for the Use of Thyroid Function Tests at: http://www.british-thyroid-association.org/current-bta-guidelines-

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