Investigating Thyroid Function
Which test should be used?
| Key Point | |
| TSH is the best test for the routine assessment of thyroid function |
In most situations use TSH as the sole test of thyroid function. It is the most sensitive test of thyroid function and adding other tests is only of value in specific circumstances.
In normal patients, when the TSH is within the reference range, there is a 99% likelihood that the FT4 will also be within the reference range. Furthermore, in a recent study of 1392 patients,7 in which both TSH and FT4 were performed, both test results were found to be consistent with euthyroidism, hypothyroidism, or hyperthyroidism in 96% of cases. Another 3.8% of patients were found to have results consistent with subclinical thyroid dysfunction. The study determined that using TSH alone as an initial test is adequate for testing patients on 99.6% of occasions.
When is it inappropriate to test only TSH?
Central (secondary) hypothyroidism - This is the most significant condition in which an incorrect diagnosis of euthyroidism could be made, based on TSH alone.8 When a patient is suspected of having pituitary failure both TSH and FT4 should be requested, as typically the patient has a normal TSH with a decreased FT4. Symptoms which may alert you to this rare, but significant condition include: menstrual disturbance, loss of sex drive, galactorrhoea, unexplained weight gain, skin changes, headaches/visual disturbances, and symptoms of hypoadrenalism, such as lethargy and dizziness.
Non compliance with replacement therapy - In hypothyroid patients suspected of intermittent use or non-adherence with their thyroxine replacement regimen, both TSH and FT4 should be used for monitoring. Non-adherent patients may exhibit discordant serum TSH and FT4 values (eg high TSH/high FT4) because of disequilibrium between TSH and FT4.
Early stages of therapy - During the first 2 months of treatment for hypo- or hyper-thyroidism, patients will have unstable thyroid status because TSH will not have reached equilibrium. Early in thyroid replacement therapy, FT4 is the more reliable test, but testing should preferably be deferred for 2 months after a dose alteration. With anti-thyroid therapy, both TSH and FT4 are required for early monitoring (see later section)
Acutely ill patients - TSH is altered independent of thyroid status. As a result, testing should only be performed when it is likely to have an effect on acute management.
Pregnant patients on replacement - See later section.
Reflex testing
Laboratories retain blood samples for varying lengths of time, making it possible to add additional tests without the need for another blood sample.
If further testing is indicated by the result of the TSH test some laboratories will add FT4, FT3 and thyroid antibodies (this is called ‘reflex testing’). However, we do not recommend GPs rely on the laboratory to add extra tests.
Order of testing
| Perform TSH | ||||||||||||||||||
| TSH elevated | TSH decreased | |||||||||||||||||
| Add FT4 | Add FT4 + FT3 | |||||||||||||||||
| Normal FT4 | Low FT4 | Elevated FT4 &/or FT3 |
Normal FT4 & FT3 |
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| Consider autoantibodies to assess further risk |
Hypothyroidism, Consider thyroxine therapy |
Hyperthyroidism, Consider antithyroid therapy |
Clinical review and consider repeat in 6 months |
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| If you receive an abnormal thyroid result on a patient it is important you reconsider the clinical picture. Particularly if there are small variations from normal the best approach may to retest the patient in 4-6 months. Some results may show variation as a result of resolving non-thyroid illness, or biological and analytical variation. |
Possible explanations for various result combinations
| High T4 | Normal T4 | Low T4 | |
| High TSH | Irregular use of thyroxine Amiodarone Pituitary hyperthyroidism (TSH-producing pituitary tumour - rare) Thyroid hormone resistance (very rare) |
Subclinical hypothyroidism T4 under replacement |
Primary hypothyroidism |
| Normal TSH |
As above Some drugs (steroids, beta-blockers, NSAIDS) Non-thyroidal illness T4 replacement (sometimes stablises with normal TSH and  FT4) |
Normal | Some drugs (anticonvulsants,anti-T3, anti-T4) Pituitary or hypothalamic hypothyroidism, Severe non-thyroidal illness |
| Low TSH | Primary hyperthyroidism | Subclinical hyperthyroidism Subtle T4 over replacement Non-thyroidal illness |
Pituitary or hypothalamic hypothyroidism, Severe non-thyroidal illness |
| Adapted from: Topliss DJ, MJA 2004;180:186-93. | |||
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