Hormone Tests Requirements

Interpretation of Thyroid function tests

Reference Ranges

It should be remembered that different testing laboratories may have different reference ranges.  These are the reference ranges used by the Leeds and Bradford Department of Chemical Pathology & Immunology.

TSH 0.2 - 4.0 miu/L
free T4 10 - 20 pmol/L
total T3 0.9 - 2.5 nmol/L

These references ranges are used in all the evaluations shown above.

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The Euthyroid Patient

In the Euthyroid patient the free T4 is within the range 10 - 20 pmol/L and the TSH is within the range 0.2 - 4.0 miu/L .

However in sick euthyroidism T4 and or TSH may be lowered during the non-thyroidal illness. TSH may be transiently elevated during recovery from non-thyroidal illness but almost any combination of thyroid tests can be seen in sick patients.

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TSH Low or Normal TSH Elevated
If T4 is normal then Thyroid status is Normal
  • If T4 is normal, sublinical hypothyroidism exists.
  • Consider T4 replacement if TSH > 12 miu/L.
  • When the TSH is mildly elevated ie 4 - 12 miu/L, positive TPO antibodies indicate an increased risk of future hypothyroidism of 5% per year.
If T4 is low consider secondary hypothyroidism (but more commonly Sick Euthyroid)
  • If T4 is low, primary hypothyrodism.
  • A normal or low TSH level usually excludes primary hypothyroidism. However, the rare diagnosis of secondary (pituitary) hypothyroidism should be considered if T4 is also low. The commonest cause of this pattern is sick euthyroid syndrome.
  • A TSH level between 10-16 miu/L indicates hypothyroidism, and usually indicates that replacement therapy should be commenced.
  • A TSH level between 6-12 miu/L with normal T4 may represent subclinical or compensated hypothyroidism. 
  • Anti-thyroid peroxidase autoantibodies (TPO Ab) are recommended as their presence predicts the development of hypothyroidism at va rate of approx 5% per year.

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Sick Euthyroid Syndrome

During severe illness or starvation, the metabolic drive on the human body by the thyroid is reduced. The term 'sick euthyroid' is used in this condition since it represents a state of thyroid function appropriate for a sick individual; and it returns to normal with the return of good health.

The most active thyroid hormone tri-iodothyronine, T3, is largely produced by peripheral ie non-thyroidal conversion of thyroxine, T4. In the typical sick euthyroid, circulating T3 is usually low but the total T4 may be normal or even raised since there is reduced conversion to T3. Conversely, T4 may be low since the majority is carried on serum binding proteins and their synthesis may be suppressed by severe illness. The absence of a raised TSH excludes primary hypothyroidism. However, almost any pattern of thyroid hormones may be seen in an unwell patient!!

Suppressed TSH may be seen in elderly patients who do not have thyrotoxicosis (since the T3 is low or normal). TSH may also be suppressed in depression.

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Interference with TFT interpretation due to committant drug therapy

Amiodarone interferes both with the synthesis of TSH, with iodine uptake by the thyroid gland and with conversion of T4 to T3. It may be impossible to interpret TFTs in isolation and decisions may need to be taken on clinical grounds or on the pattern of change in TFTs over a period of time. Overt hypo- or hyperthyroidism probably occurs in 4% (2% each) of patients treated with amiodarone but the exact proportion is strongly affected by iodine intake. Minor abnormalities may be seen in approximately 50% of patients.

Beta-blockers interfere with conversion of T4 to T3 but this does not cause hypothyroidism.

Lithium interferes with thyroid hormone synthesis and inhibits their release from the gland. Long term lithium treatment results in goitre in up to 50% of patients, subclinical hypothyroidism occurs in 20% and overt hypo-thyroidism in a further 20%. The presence of thyroid peroxidase antibodies may be useful to predict the future development of hypothyroidism in long- term treated patients.

Cortisol (or hydrocortisone or prednisolone) given orally transiently suppresses TSH secretion for a few hours. Patients taking corticosteroids should have blood taken for TFTs before the morning steroid medication is taken.

Antiepileptics, NSAIDS & aspirin all interfere with the binding of thyroxine and its binding proteins resulting in lowish free T4 in the presence of normal thyroid binding globulin. It is most marked with carbamazepine; there appears to be no interference by valproate.

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  • TSH is the most useful parameter in screening for thyroid dysfunction in most non critically ill patients since TSH is almost always suppressed in hyperthyroidism.
  • A raised T4 and T3 with suppressed TSH and an elevated TSH receptor antibody level confirms the diagnosis of Grave's disease.
  • A proportion of cases have normal T4 with suppressed TSH and represent T3 toxicosis and T3 measurements may be necessary. This is usually performed automatically by the laboratory.
  • A raised T4 with normal or raised TSH usually indicates T4 -> T3 conversion defect, or analytical artefacts.
  • A rare cause is secondary hyperthyroidism (TSH resistance or secreting pituitary tumours). 

Thyroxine Replacement Therapy in Primary Hypothyroidism

Replacement Therapy
TSH Level This Indicates
< 0.05 miu/L Over Replacement
0.05 - 0.2 miu/L Indicates Possible Over Replacement
0.2 - 2.0 miu/L Sufficient Replacement
> 2.0 miu/L Likely under Replacement
  • Clinical symptomatology and TSH are the major parameters used in assessing the adequacy of replacement therapy.
  • T4 level is an index of recent patient compliance.
  • TSH may take up to 4-6 weeks to stabilise. Thus, repeat TFT following alteration of dose should only be performed after this period.
  • PAtients with Throid Cncer should have their TSH suppressed to inhibit regrowth of malignant thyroid cells.

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  Medications interfering with thyroxine replacement

Treatment with iron and calcium salts, proton pump inhibitors and oestrogens is associated with reduced therapeutic efficacy and rises in TSH. The effect with iron and calcium is due to impaired absorption and these agents should be taken at a different time of day than the thyroxine.

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Thyroxine Replacement Therapy for Secondary Hypothyroidism

Replacement Therapy
freeT4 Level This Indicates
< 17 pmol/L Likely under replacement
17-25 pmol/L Sufficient replacement
>25 nmol/L Likely over replacement
  • Clinical symptoms and T4 are used to monitor the adequacy of therapy in hypopituitarism as TSH is not representative of thyroid function.
  • Results should always be interpreted in combination with clinical status.

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Suggested monitoring schemes

Thyroxine Therapy

Newly commenced

  • Measure TFT ~ 6-8 weeks post commencement of thyroxine therapy and adjust the dose accordingly in order to bring TSH into the range of 0.2 - 2.0 miu/L
  • Repeat TFT ~ 6 months after normalisation as metabolic clearance of T4 may increase with correction of hypothyroidism.
  • Note that TFT should not be repeated until at least 4-6 weeks post alteration of thyroxine dose.

On Thyroxine

  • Repeat TFT only if suspected alteration in thyroid function.
  • Perform TFT 4-6 weeks after alteration of dose.
  • Yearly TFT is recommended unless earlier measurement is indicated clinically.
  • Secondary Hypothyroidism
  • Repeat T4 4 weeks after changing the dosage is recommended.

Grave's Disease on Antithyroid Drug Therapy

  • Both T4 and TSH are used to assess thyroid function (occasionally T3).
  • Clinical status of patient should take precedence over TFT in evaluating the adequacy of treatment as TSH may take months to normalise following commencement of therapy.

Repeating TFT measurements

  • Repeat TFT is only indicated in appropriate medical conditions, eg recurrent AF.
  • TFT performed more than 3 times a year is usually inappropriate providing previous TFTs are normal.

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How to request TFTs

Efficient management of patients requires accurate results from investigations. However, in order for the laboratory to correctly interpret TFT results and provide accurate reports, relevant clinical history on the request forms is essential.

The following points serve as a guide as to what should be included with TFT requests:

  • Current diagnosis (in particular, indicate if patient is ill).
  • Purpose for which TFT was requested.
  • Previous TFT findings and when.
  • Current or recent drug therapy (in particular, antiepileptics, NSAIDS, aspirin, amiodarone and lithium).
  • Any known thyroid abnormalities or pathologies.
  • Antithyroid drug therapy (including when commenced or dose altered).
  • Any known thyroid abnormalities or pathologies.
  • Thyroxine therapy (including when commenced or dose altered).Any other forms of treatment related to the thyroid dysfunction.
  • Other endocrinological pathologies.

For patients taking T4 replacement, then requests for TSH alone are adequate unless the patient has pituitary disease.

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Page updated: 12/09/2014 | Updated by: Dr. Julian Barth