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 (swelling of the thyroid gland). Most patients who develop a lump or nodule in the thyroid will have a normal thyroid function as well. A minority of patients with thyroid nodules will have a hyperfunctioning one and present with hyperthyroidism (overactive thyroid).
The most important uses of laboratory tests are:
- to confirm the clinical diagnosis of thyroid disease;
- to monitor patients with thyroid disease who have been treated;
- 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 suppressed by drugs (such as corticosteroids) or by severe psychiatric or non-thyroidal illness. However, such circumstances are extremely rare in the out-patient setting.
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. Since using the TSH assay as a primary test, doctors have identified patients who have an isolated low or high TSH in association with normal T4 and T3 levels. 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 we believe to be active at the tissue level. However, free levels represent less than 1% of the total thyroid hormone levels. In certain circumstances, such as pregnancy or the birth control pill, the elevated estrogen or female sex hormone, associated with these conditions, raises the level of thyroid hormone binding protein. In these individuals the total T4 and T3 are higher because the body will compensate by increasing the production of T4 and T3 so that the free level remains normal. In these individuals, even though there are higher total T4 and T3 the free level remains normal and TSH does not change. Current laboratory procedures usually measure free T4 and/or free T3 . The availability of the TSH screening has largely eliminated any confusion caused by changes in thyroid binding proteins as the TSH will remain normal in these circumstances.
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 permanent causes of hyperthyroidism such as Graves’ disease and temporary causes such as thyroiditis; in Graves’ disease the iodine uptake is elevated while in thyroiditis it is low. Alternatively, the gland can be photographed or “imaged” and the distribution within the gland of a radio labelled tracer, (usually technetium) recorded. This is called a thyroid scan. The scan is usually used together with the uptake to give a complete idea of the shape and size of the thyroid gland as well as its function. These tests can also be used to determine whether a thyroid nodule is functioning and can lead to excess amount of hormones.
This can be performed by ultrasound, which is very sensitive, and provides precise information about the size and shape of the thyroid gland and nodules, CAT scans and MRIs can also give information about the presence of nodules but are not the first choice. Certain characteristics of a nodule on thyroid ultrasound can provide additional information about its risk of being cancerous.
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 is presently in common use and is considered to be the first line of investigation for patients with thyroid nodules. In this procedure, a small needle on the end of a syringe is inserted into the abnormal part of the thyroid gland. The plunger of the syringe is drawn out and 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 and the pathologist can examine the smears for evidence of thyroid disease. This procedure is simple, quick, and painless and is equivalent to having blood taken. In patients with a thyroid nodule due to a thyroid cyst, the fluid can be evacuated 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 usually not necessary even with children.
Thyroid biopsy can be carried out with or without ultrasound guidance. It is very sensitive for detecting certain types of thyroid cancer and is a procedure to be considered for most nodules that are larger than 1 cm. 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 experience of the individual performing the biopsy and the pathologist reading the smears.
Updated in May 2010 by Hortensia Mircescu, MDFRCPC, Endocrinology Division, Centre Hospitalier de l’Université de Montréal, Assistant Clinical Professor, Faculty of Medicine, Université de Montréal from the original text written by: IrvingB.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.