Thyroid function test interpretation

Source: Dayan CS, Lancet (2001): 357: 619-24 

The introduction of sensitive thyrotropin (TSH) and free thyroid hormone measurements (free T3 and T4) has made interpretation of thyroid function relatively simple, but there are occasions where the pattern is confusing or misleading. This webpage will divide thyroid function test results into 6 groups and provide an explanation as to what might be the underlying pathology.

The choice of thyroid function test depends on the clinical situation, but often a sensitive TSH measurement alone as a screening test is enough to establish that thyroid function is normal. This has certain limitations however, as it will miss thyrotoxicosis due to pituitary disease, and hypothyroidism occurring within 12 months of treatment for thyrotoxicosis.

Fig. 1: An example of normal thyroid function tests

The addition of a free T4 measurement will overcome these limitations and diagnose the majority of thyroid functional problems. T3 should be added if there is a suggestion of thyrotoxicosis, as it alone may be elevated in some cases of hyperthyroidism. T3 and T4 should not be measured alone as this will miss subclinical hyperthyroidism. My practice is to measure the TSH and T4 as a baseline, adding in T3 if there is any evidence of thyrotoxicosis (Fig. 1).

Low TSH, raised T3 and/or T4

This is caused by primary hyperthyroidism or thyrotoxicosis, with the most common cause being Graves' disease, followed by toxic multinodular goitre and toxic single thyroid nodule (Fig. 2). Generally this can be sorted out by measurement of the anti-TSH receptor antibody (and other thyroid antibodies) and by radioiodine scanning.

Fig. 2: An example of thyrotoxic thyroid function tests, in this case Graves' disease.Other potential causes of this pattern are related to thyroiditis, either Hashimoto's lymphocytic thyroiditis in its early stages, or in postpartum thyroiditis, or after a viral illness (deQuervain's thyroiditis). Measurement of thyroid antibodies will help to establish the cause, but the latter two conditions tend to be self-limiting, while Hashimoto's thyroiditis tends to go on to hypothyroidism in the longer term, with only a transient toxic phase in the first few months. 

Occasionally this thyroid function pattern can emerge during pregnancy, and is usually caused by undiagnosed Graves' disease, but can occur in mild form in the first trimester due to the stimulatory effect of HCG on the TSH receptor.

Other rarer causes include thyroxine ingestion (possibly from over-replacement after surgery, but also factitious), amiodarone therapy and struma ovarii, a rare benign teratoma consisting mostly of thyroid tissue, which results in ectopic thyroxine production from the tumour.

Low TSH, but normal T3 and T4

This usually indicates the condition of subclinical hyperthyroidism, with an underlying cause of a long-standing multinodular goitre, most commonly seen in elderly people (Fig. 3). In this situation, one or two of the thyroid nodules develop autonomy, not responding to pituitary TSH control.

Treatment is not usually required for this subclinical hyperthyroidism unless symptoms develop from the goitre itself, or the TSH is very low, which can result in a higher risk of atrial fibrillation and osteoporosis.

Fig. 3: An example of subclinical hyperthyroidism test results.The other common cause of this result is seen in patients taking thyroxine. It may indicate over-replacement with thyroxine, but not in the case of post thyroid cancer patients, where this is a deliberate policy to achieve TSH suppression.

This TSH suppression has the effect of minimising the risk of thyroid cancer recurrence in the future, as TSH is a growth factor for thyroid tissue (and thyroid cancer tissue). TSH suppression can generally be wound back after 2-5 years, by dropping the thyroxine replacement dose, but should be continued longer if the cancer was high risk.

Low (or normal) TSH, low T4 and T3

This can occur in an unwell patient with a non-thyroidal illness, which typically produces a test result with a normal TSH and low T4 or T3 (Fig. 4).

Fig. 4: An example of thyroid function tests in a non-thyroidal illness.However if all three parameters are low, it may indicate an underlying pituitary disease with secondary hypothyroidism.

The other situation where this functional pattern can occur is after treatment for thyrotoxicosis (Fig. 5). The TSH can remain suppressed for several months after treatment, so that if the thyroid function is measured and all three parameters are found to be low, this actually indicates that the patient is profoundly hypothyroid and needs more thyroxine, not less!

Fig. 5: Thyroid function with pituitary disease, and in post thyrotoxicosis treatment with under-replacement of thyroxine.

This is a situation where all three parameters are equally important, as measurement of only the TSH after thyrotoxicosis treatment can be very misleading. With the example above, only knowing that the TSH was 0.27mU/L would have suggested the patient was thyrotoxic, rather than in reality being hypothyroid.

Raised TSH, low T4 and/or T3 

This combination indicates primary hypothyroidism, which has a number of potential underlying causes (Fig. 6).

Fig. 6: Typical pattern of hypothyroidismThe most common cause of this condition is Hashimoto's thyroiditis, but other forms of transient thyroiditis can go through a hypothyroid phase as well. Generally this is easily diagnosed by measuring thyroid antibody levels.

Patients who have undergone treatment for thyrotoxicosis or thyroid cancer, with either radioiodine ablation or total thyroidectomy may become hypothyroid if not adequately replaced with thyroxine tablets. Hypothyroidism can occur up to 20 years or more after treatment with radioiodine, so regular monitoring is necessary after even apparently successful relief of the thyrotoxicosis.

Other rarer causes of hypothyroidism include iodine deficiency, which is rarely found in Australia, except for Tasmania, but should be considered in recent immigrants from mountainous areas, south Germany and Italy. Certain drugs can also induce hypothyroidism, such as amiodarone, lithium, and cytokine therapy (interferons, interleukin-2). Goitrogens found in the diet, and congenital defects in thyroid function complete the list.

Raised TSH, normal T4 or T3

This is the pattern of subclinical hypothyroidism or mild thyroid failure (Fig. 7). It is typically seen in the early stages of Hashimoto's autoimmune thyroiditis, and may indicate it is time to think about thyroxine supplementation.

Fig. 7: Subclinical hypothyroidism pattern in thyroid functionIt can also follow treatment with radioiodine or thyroid surgery, indicating inadequate capacity of the remaining thyroid to cope with the demand for thyroxine, or inadequate replacement in the case of complete thyroid removal.

Sometimes this pattern can indicate poor compliance with taking the prescribed thyroxine tablets, but if the levels have previously been stable, it could be caused by another new drug interfering with absorption of the thyroxine, like calcium or iron tablets, or with a change in how it is taken (for example, no longer taking it on an empty stomach). More information can be found on the webpage for Thyroxine Treatment.

Normal or raised TSH, raised T3 or T4

This is a rare occurrence in thyroid function tests and is usually artifactual, necessitating a repeat estimation of the thyroid function tests (and thyroid antibodies) to confirm the finding (Fig. 8).

Fig. 8: Thyroid function indicating interfering antibodies or thyroid hormone resistance

If this pattern is confirmed it could be caused by interfering antibodies to the thyroid function assay, and sometimes may be due to thyroid hormone resistance. Amiodarone therapy can also cause this pattern by raising the TSH concentration, as well as preventing the conversion of T4 to T3 in the periphery, although it tends to be in a less dramatic fashion. 

An acute psychiatric illness in its first few weeks can also produce this pattern, and has been reported in more than 16% of cases. Individuals with schizophrenia, affective disorders and amphetamine abuse have all been shown to have raised thyroid hormones, usually with raised TSH, but the mechanism is unclear and it rarely lasts beyond day 14, so no treatment is needed.