Thyroid Function Testing Update
Written by Dr David Deam and Dr Damon Bell.
Altered thyroid function is common in the community, and its prevalence in Australia is estimated to be as high as 10 per cent of the general population. This figure is in line with statistics and rates seen internationally. For example, the American Thyroid Association reports that “more than 12 per cent of the US population will develop a thyroid condition during their lifetime”. Some of the factors influencing this include autoimmune thyroid disease and iodine intake, and many medical interactions may contain thyroid disease as a component. This article will provide a brief summary and update of thyroid function testing.
The thyroid function tests
The main thyroid function tests are Thyroid stimulating hormone (TSH) and Free Thyroxine (FT4).
TSH is a glycoprotein that is synthesised and secreted by the thyrotroph cells in the anterior pituitary gland. It stimulates the thyroid gland to secrete T4 and T3. Although the thyroid gland secretes T3, the majority of T3 is formed in peripheral tissues by the enzymatic conversion of T4 to T3.
Iodine is integral to the formation and structure of thyroid hormones. Because the majority of thyroid hormones are bound to various proteins the measurement of the free hormones, free T4 and free T3, correlate better with the patient’s clinical condition. TSH responds in an inverse log-linear fashion to maintain the thyroid hormones within the correct range.
What to request
The main thyroid function tests are Thyroid stimulating hormone (TSH) and Free Thyroxine (FT4).
TSH is the first-line assessment for detecting thyroid dysfunction, and is the only test funded by Medicare to screen for conditions when there is no history of thyroid problems. In patients with known thyroid disease, FT4 (and sometimes-free T3) are required in addition to TSH to better assess the cause of thyroid dysfunction.
When “thyroid function tests” are requested in our laboratory without a clinical history, we initially perform a TSH measurement and proceed to FT4 measurement if the TSH is abnormal.
Medicare Requirements
Medicare rules regulate that a Medicare eligible request for thyroid function testing (TSH and Free T4) must have a complying clinical indicator written on the pathology request slip by the requesting doctor.
These clinical criteria are:
A) The patient has an abnormal level of TSH;
B) For the purpose is monitoring thyroid disease in the patient; or
C) To investigate the sick euthyroid syndrome if the patient is an admitted patient; or
D) To investigate dementia or psychiatric illness of the patient; or
E) To investigate amenorrhoea or infertility of the patient;
F) The medical practitioner who requested the tests suspects the patients has pituitary dysfunction;
G) The patient is on drugs that interfere with thyroid hormone metabolism or function.
Subclinical conditions
In the early stages of thyroid disease, the first test to become abnormal is usually the TSH level. The finding of normal free T4 levels and an abnormal TSH level may indicate early or developing thyrotoxicosis or hypothyroidism. Although this may not need to be treated, it requires follow up and investigation of the possible cause of the abnormality and to determine if it normalises or progresses to overt thyroid disease in the future.
Medications
A number of drugs may influence thyroid function. The most common is Amiodarone, which has several effects on thyroid function including both hyperthyroidism and hypothyroidism. This is caused by several factors including amiodarone having a significant iodine content and decreasing T4 to T3 conversion in the peripheral tissues. Lithium is also a drug that may influence thyroid function tests and commonly causes hypothyroidism. Other drugs that may influence thyroid function include steroids, anticonvulsants and iodine containing preparations.
Pregnancy
There has recently been greater interest in thyroid function tests during pregnancy. During the first trimester, high levels of hCG can have a TSH-like effect on the thyroid gland. This causes a lower TSH during pregnancy and most laboratories now have specific reference ranges for TSH in pregnancy. Pregnancy requires a 30-50% increase in thyroid hormone secretion, and maternal T4 is important for foetal development for the first 18-20 weeks of gestation. Thyroid dysfunction affects 2–3 % of pregnant women and can lead to adverse pregnancy outcomes. As a result, women should be assessed during pregnancy for any adverse thyroid conditions. It is recommended that specialists are involved in the management of raised TSH levels with four weekly thyroid function monitoring to 20 weeks gestation. After that period, regular monitoring can be decreased. In Grave’s disease, TSH receptor antibodies can cross the placenta and cause foetal issues and post-partum thyroid dysfunction in the baby. This is again better managed by specialists in the area. There is some controversy amongst the various guidelines around universal screening during pregnancy, and the thresholds for treatment of subclinical or mild hypothyroidism. We suggest following the local and/or national guidelines depending on local practices.
Elderly
Research has demonstrated that the frequency of thyroid disorders increases with age - significant when we consider our ageing population. A mild increase in TSH (up to 7 mIU/L) is not uncommon in the elderly and has been shown not to be associated with adverse outcomes. It probably does not require treatment unless there are specific clinical indications.
Testing in Hyperthyroidism and Hypothyroidism
During the treatment of hypothyroidism and hyperthyroidism, changes in TSH usually take four to six weeks to stabilise. Testing before this period makes the results more difficult to interpret. Note that after taking thyroxine medication, the free T4 level may become elevated 4-6 hours after the dose. Therefore, it is better to test the patient at least four hours after their thyroxine dose.
Other tests and investigations
Other useful tests to determine the cause of abnormal thyroid function tests include thyroid antibodies (thyroid peroxidase and thyroglobulin antibodies), which are associated with autoimmune thyroid disease, and TSH receptor stimulating antibodies that are associated with Graves’ disease. Ultrasound and Nuclear Medicine scans are required to determining the size, structure and sometimes function of the thyroid gland and to assess any thyroid nodules.
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