|
|
|
|
|
|
 |
|
| Issue 10 2000 |  |
| THYROID FUNCTION TESTS - Dead Easy or Impossible? |
|
Dr Errol Wilmshurst Endocrinology, PaLMS tel: +61 2 9926-8388 e-mail: ewilmshurst@doh.health.nsw.gov.au |
Dr.
Sophie Chan Endocrinology, PaLMS tel: +61 2 9926 8388 e-mail: ssychan@doh.health.nsw.gov.au |
 |
| Introduction
Thyroid function tests are frequently used to determine the metabolic status of a patient. Thyroid function may be measured by:
1. Thyroid Hormone Levels Thyroxine (T4) and triiodothyroinine (T3) are extensively protein bound to thyroxine-binding globulin, thyroxine binding prealbumin (TBPA) and albumin. The small unbound fractions are metabolically active and can be measured as free T4 and Free T3. The half life of T4 in the circulation is 6 to 7 days and for T3 is 24 to 36 hours. However, in hyperthyroidism the half-life for both hormones decreases, whereas in hypothyroidism the half-life increases. FT3 and FT4 are measured by competitive immunoassays using a chemiluminescent label. These methods usually yield values comparable with those by dialysis techniques (gold standard) in patients with hypothyroidism or hyperthyroidism. However, erroneous values may occur in other disorders as the labelled tracer does bind to albumin and other proteins. New sensitive TSH assays have come into widespread use. Medicare rebates now cover only TSH as a primary investigation unless this is found to be abnormal. However there are exemptions where the FT4 and TSH should both be performed. These are:
|
| 1.1
Interpretation of TSH and FT4 Although Table 1 lists the probable interpretations of a given TSH and FT4 results, it is vital that interpretation should always be performed in conjunction with the clinical picture since a steady state condition may not yet have been reached. |
| Low FT4 | Normal FT4 | High FT4 | |
| High TSH |
|
|
|
| Normal TSH |
|
|
|
|
Low
TSH
|
|
|
|
|
1.2 Non-thyroidal Illness A variety of systemic illnesses can cause changes in thyroid function tests. The commonest is a low T3 state with normal TSH and T4. Inhibition of 5'deiodinase is responsible. Patients who are severely ill may have a low T4 and low T3. There is an acquired defect in binding of T4 to TBG leading to increase clearance of T4. TSH can decline also with severe illness. Transient high TSH may also be seen in some patients during the recovery phase. 1.3 Drugs and Thyroid Function Tests As shown in Table 2, drugs can have an effect on thyroid function. |
Table
2. Effects of some commmonly used drugs
| Drugs that decrease TSH |
|
| Drugs that cause hypothyroidism |
|
| Drugs that cause hyperthyroidism |
|
| 1.4 Euthyroid Hyperthyroxinaemia This describes conditions where there is an elevated FT4 and normal TSH. Causes include thyroxine administration, transient acute illness, acute psychiatric illness and drug effect. Drugs such as amiodarone inhibit T4 5-deiodinase which converts T4 to T3 peripherally and may cause a low T3, high T4 with a normal TSH. FT4 can increase transiently with heparin which activates lipoprotein lipase and generates free fatty acids inhibiting the protein binding of T4. Thyroid hormone resistance is a rare cause of a high FT4. |
| 2. Thyroid Antibodies |
| 2.1 Thyroid Tissue Antibodies Thyroid tissue autoantibodies are directed against thyroglobulin (TgAb) and thyroid peroxidase (anti TPO). Thyroid microsomal antibodies (TMAB) used to be measured but recent investigations have shown that the main antigen in the thyroid microsomal fraction is the thyroid peroxidase enzyme (TPO). Anti TPO antibodies are a useful biochemical marker for autoimmune thyroid disease, particularly Hashimoto's thyroiditis, but also Grave's disease. In spontaneous hypothyroidism where lymphocytic infiltration of the thyroid gland occur, high titres of Anti-TPO antibodies and also TgAb may be expected. Low titres may be found in normal individuals, especially in the elderly. The normal reference range for Anti-TPO antibody is < 35 mIU/L and for thyroglobulin antibody is < 40 mIU/L. 2.2 TSH Receptor Antibodies There are two classes of antibodies that bind to the TSH receptor. These are found in the serum of patients with Grave's disease. |
|
2.2.1.
Thyroid Stimulating Immunoglobulin (TSI) These bind to the TSH receptor and cause stimulation of the gland to release thyroid hormones. Indications for test:
Less than 10 U/ml = negative 10 — 50 U/ml = weakly positive 50 — 100 U/ml = moderate activity Greater than 100 U/ml = strongly active. 2.2.2 Thyrotrophin Binding Inhibitor Immunoglobulin (TBII) These are antibodies that bind the TSH receptor but do not stimulate it. By binding to the TSH receptor they inhibit the binding of TSH. Clinically, they may be associated with hypothyroidism. The indications are the same as those for TSI. This binding assay parallels TSI in most patients with Grave's disease. However, it may also give positive results for some patients who are TSI negative such as in euthyroid exophthalmos of long term treated patients who were previously hyperthyroid, but subsequently develop hypothyroidism. The assay may be performed during pregnancy where blocking antibodies may predict neonatal hypothyroidism. TBII is measured as an index of binding inhibition. Values of: 80 — 100 negative 60 — 80 weakly positive 40 — 60 moderately positive < 40 strongly positive |
Specimen Information
|
| 3. Less commonly used tests |
|
3.1 Thyroglobulin Thyroglobulin (Tg) is a high molecular weight storage protein found in the thyroid gland. A small amount is detectable in normal circulation arising from thyroid sources only. Elevated levels are found in many abnormal thyroid states, including goitre (both toxic and non-toxic), thyroid tumours and following thyroid trauma. Tg should be undetectable following successful thyroidectomy and ablation of residual tissue with radioactive iodine. Therefore, the most common indication for this test is in the followup of treated thyroid cancer patients. All samples for thyroglobulin measurement are screened for the presence of thyroglobulin autoantibody (TgAb) which can interfere with the assay. 3.2 Calcitonin This hormone is secreted from the parafollicular C cells of the thyroid. Measurement of the serum calcitonin is performed to help diagnose medullary cell carcinoma of the thyroid. It is also used for monitoring recurrence of this cancer after surgery. 3.3 TSH Alpha-subunit Most patient with TSH — secreting pituitary tumours have raised serum alpha—subunit levels, but the values may also be elevated in post menopausal women and hypogonadal men because both the thyrotrophs and gonadotrophs secrete this subunit. 3.4 Thyrotrophin Releasing Hormone (trH test) The development of high sensitivity TSH assays have deceased the need for trH testing. It can still be useful in the following circumstances:
|
| In summary; Interpreting thyroid function tests needs to be done with the patient’s clinical state in mind and recognising that a steady state may not have been reached. If test results appear to be confusing or inconsistent with the patient’s clinical condition, discussion with or referral to an endocrinologist is recommended. |
| News from PaLMS |
|
The Synovial Fluid article in the last issue of InfoLink certainly generated a lot of interest. In response to demand PaLMS now offers Synovial Fluid Collection Kits. These kits include tubes, labels and instructions for collection and transport of the specimens. Supplies are available at any of our Collection Centres or by contacting the PaLMS Service Centre on 9926 6066. PaLMS are actively involved in numerous educational activities. Over the coming months we will be participating in seminars suitable for GPs and specialists covering topics including:
If you would like additional information or have a suggestion on how we can improve our service to you, please contact me. 
PaLMS Customer Relations Manager tel 02 9926 8086 or 02 9926 8574 (direct line) e-mail mhardy@doh.health.nsw.gov.au |