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To Confirm the Clinical Diagnosis

Laboratory Investigation of Thyroid Disease

For many patients with thyroid disease, the gland produces excessive amounts of thyroid hormone (hyperthyroidism) or insufficient amounts of thyroid hormone (hypothyroidism). Some patients will also have an associated goitre (enlargement of the thyroid gland). Most patients who develop a lump or nodule in the thyroid will have normal thyroid function but a small minority of thyroid nodules can produce excessive thyroid hormone and cause hyperthyroidism.

The most important uses of laboratory tests are:

  1. to confirm the clinical diagnosis of thyroid disease;
  2. to monitor patients with thyroid disease who have been treated;
  3. to select, for removal by the surgeon, those single nodules which may be malignant.

Measurement of TSH

The pituitary hormone TSH stimulates the thyroid gland to make and release the thyroid hormones (T4 and T3). When thyroid hormone levels decrease, the TSH rises and vice versa. Measurement of TSH using a sensitive assay is presently the recommended initial screening test when thyroid disease is suspected. The TSH assay is able to separate hypothyroid and hyperthyroid patients from normal individuals. Basically, a normal TSH excludes primary thyroid disease. When the TSH is elevated, this suggests hypothyroidism and, when suppressed, suggests hyperthyroidism. Rarely the TSH level may be affected by drugs or supplements (such as biotin).

Measurement of Blood Thyroxine (T4) or Triiodothyronine (T3)

In some cases of abnormal TSH values, measurement of T4 or T3 is performed to determine the extent of the thyroid abnormality. An elevated T4 or T3, in association with a low or suppressed TSH, establishes hyperthyroidism. An elevated TSH in conjunction with a low T4, is encountered in hypothyroidism. Some patients have an isolated low or high TSH with normal T4 and T3 levels. This is called subclinical disease. Although some of these patients will eventually develop overt thyroid disease, their assessment and management needs to be individualized.

Thyroid Hormone Binding Proteins

Thyroid hormones circulate in association with proteins which bind thyroid hormones. It is only the free or unbound portion which is active. Therefore, current laboratory procedures usually measure free T4 and/or free T3.s.

Radioactive Iodine Uptake and Thyroid Scan

The thyroid gland takes up iodine and uses this to make thyroid hormone. Radioactive iodine is taken up and metabolized by the thyroid in exactly the same way. Approximately 20-25% of a dose of radioactive iodine, given orally, is taken up by the thyroid gland within 24 hours after the dose is given. This is measured by counting the radioactivity over the thyroid gland after a 24h period. The test is safe since the radiation dose is very small, although it is usually not carried out in pregnant women. The test distinguishes between overproduction of thyroid hormone with a high uptake and temporary causes such as thyroiditis where the uptake is low and the hyperthyroidism is because of temporary inflammation causing leakage of preformed thyroid hormone into the bloodstream. Usually at the same time a thyroid scan is performed with a special camera that can detect what parts of the thyroid have taken up the iodine. If the iodine uptake is high the scan can determine if the reason is that the whole gland is producing too much thyroid hormone (Graves’) or if specific area(s) (nodule(s)) are the problem.

Thyroid Ultrasound

Thyroid ultrasound is the best modality for imaging the thyroid.  It is very sensitive, and provides precise information about the size and shape of the thyroid gland and nodules. Certain characteristics of a nodule on thyroid ultrasound can provide additional information about its risk of being cancerous.  Thyroid ultrasound should be performed in any patient known or suspected to have a thyroid nodule, and is the major factor in determining what thyroid nodules should go on to have further testing, be monitored by ultrasound over time, or require no further investigation or follow up.

Thyroid Antibodies

The majority of diseases causing thyroid dysfunction are caused by autoimmune diseases. Thyroid antibodies are blood proteins which react against certain of the patient’s own proteins (called antigens) within the thyroid gland. In patients with Hashimoto’s thyroiditis, the major cause of hypothyroidism, high levels of antibodies are usually found and are therefore markers of the autoimmune process. Low levels of antibodies are sometimes found in older, normal women and do not necessarily indicate clinical disease. Patients with Graves’ hyperthyroidism have circulating thyroid stimulating antibodies which act like TSH and cause the thyroid cells to over-function.

Thyroid Biopsy

When thyroid ultrasound suggests a thyroid nodule is both large enough and suspicious enough for thyroid cancer the best next test is fine needle biopsy of the nodule. In this procedure, a small needle on the end of a syringe is inserted into the abnormal part of the thyroid gland usually under ultrasound guidance. A small number of thyroid cells are drawn up into the base of the needle. These cells are then smeared onto glass slides or placed in a special liquid, often 2-5 samples are taken to ensure an adequate sample, and the pathologist can examine the cells under a microscope for evidence of thyroid cancer.  This procedure is simple and quick; the needles are similar to those used for blood samples. In patients with a thyroid nodule due to a thyroid cyst, the fluid can be drained using the biopsy technique. Some patients may experience mild pain at the site and, rarely, swelling and bruising. It is almost unheard of that the needle would damage structures outside the thyroid gland. There have been no reports of spread of thyroid cancer after thyroid biopsy. Local anaesthetic is optional.

Approximately 10% of biopsies can be non-informative because the number of cells obtained for pathology examination is insufficient. Among the factors determining the success of the thyroid biopsy is the composition of the nodule, the experience of the individual performing the biopsy and the pathologist reading the smears.

Updated in August 2018 by Deric Morrison, MD, FRCPC, Div. of Endocrinology, Dept. of Medicine, University of Western Ontario. Original text written by Irving B. Rosen, MD, FRCS(C), FACS, Professor of Surgery, University of Toronto, Department of Surgery, Mount Sinai Hospital; Consultant in Surgery, Princess Margaret Hospital, Ontario Cancer Institute and Paul G. Walfish CM, MD, FRCP(C), FACP, FRSM, Professor of Medicine, Pediatrics and Otolaryngology, University of Toronto; Senior Consultant, Endocrinology and Metabolism and Head and Neck Oncology Program, Mount Sinai Hospital.

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