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Diagnostics
Disease
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Diagnostic Procedures
TSH The TSH (or Thyroid Stimulating Hormone) assay has been recognized as an exquisitely sensitive indicator of thyroid status. TSH assays have therefore been widely adopted as the first-line thyroid function test. In ambulatory patients with intact hypothalamic and pituitary function, a normal TSH result excludes hypo- or hyperthyroidism; whereas elevated and suppressed TSH results are diagnostic of hypo- and hyperthyroidism, respectively. Abnormal TSH results are generally confirmed with a complementary determination of thyroid hormone levels. T4 The T4 (or Thyroxin) assay complements the TSH assay, and is used to confirm a thyroid disorder when suggested by an abnormal TSH. Furthermore, the T4 assay may become the first-line assay in conditions that are known to possibly compromise the reliability of TSH results. For example, several months may be required for the dynamics of the regulatory mechanism (along the hypothalamic-pituitary-thyroid axis) to fully equilibrate after a treatment regimen is initiated or significantly altered; during this time TSH results may be misleading. Secondary and tertiary hypothyroidism are other conditions in which TSH results may be misleading, and the differential diagnosis is likely to rely on T4 (Free T4) results complemented by the characteristic profile of TSH results obtained during a TRH-stimulation testing procedure. The free form of the hormone (Free T4) is generally considered to provide the more reliable indicator of true thyroid status, because only the free form of the hormone is physiologically active. The total hormone concentration (Total T4) is dependent on the concentration of thyroid transport proteins, specifically thyroid binding globulin (TBG), which is influenced by many common factors. T3 The T3 (or Triiodothyronine) assay is another assay which is used in the diagnosis of thyroid disorders. In developing hyperthyroidism, the Free T3 concentration is a more sensitive indicator of developing disease than is T4 (free T4), and the former is therefore preferred for confirming hyperthyroidism that has already been suggested by a suppressed TSH result. However, the reverse is true for hypothyroidism. In developing hypothyroidism, T4 (free T4) is the more sensitive indicator of developing disease than is T3 (Free T3), and is therefore preferred for confirming hypothyroidism that has already been suggested by an elevated TSH result. The T3 assay is also useful for diagnosing a variant of hyperthyroidism known as T3 thyrotoxicosis, wherein T4 levels remain within the euthyroid range. T3 Resin Uptake The T3 Resin Uptake assay is used in calculating the Free Thyroxin Index (FTI). It is interpreted in conjunction with a Total T4 or Total T3 and corrects for abnormal Thyroid Binding Globulin (TBG) to give an estimate of the amount of unbound (free) T4 available. With the ability to calculate Free T4 (nowadays), the Free T4 assay is now preferred over the Free Thyroxin Index or T3 Resin Uptake. Other Tests Autoantibodies of clinical interest in thyroid disease include thyroid-stimulating antibodies (TSAb), TSH receptor-binding inhibitory immunoglobulins (TBII), antithyroglobulin antibodies (Anti-Tg Ab) and the antithyroid peroxidase antibody (Anti-TPO Ab). Of these, anti-TPO Ab has emerged as the most generally useful marker for the diagnosis and management of autoimmune thyroid disease. Elevated levels of anti-TPO Ab are found in virtually all cases of Hashimoto's thyroiditis and in approximately 85% of Graves' disease cases. Interestingly, approximately 10% of asymptomatic individuals have elevated levels of Anti-TPO Ab, which may suggest a predisposition to thyroid autoimmune disease.
Similar in its use for evaluating a breast mass, ultrasound can be used to assess a thyroid nodule. Its advantage over physical exam alone lies in its ability to distinguish solid from cystic nodules, whether more than one nodule exists, and the exact size and extent of a nodule. In fact, ultrasound can be used to assess the size and shape of the thyroid gland itself. Because of the recent advances in this form of imaging technology, ultrasound has become quite sensitive a modality, particularly when assessing size and numbers of nodules. Ultrasound characteristics which suggest a benign nodule include:
Ultrasound characteristics which suggest malignancy include:
Ultrasound can also be used in conjunction with fine needle aspiration (FNA) in guiding a biopsy. Its only drawbacks are in its inability to distinguish benign from malignant disease or determine the functional status of the thyroid gland. Ultrasound can also be used to assess (in the same manner) the four parathyroid glands that lie within, or next to, the thyroid gland. Normal parathyroid glands are often difficult to see on ultrasound and cannot be felt during physical examination, however, abnormal parathyroid glands may be enlarged and detectable by ultrasound. As ultrasound does not involve the use of radiation, it is a safe imaging technique for use during pregnancy and poses no harm to the developing fetus.
Fine Needle Aspiration (FNA) has become the single-most important step in the evaluation of a thyroid nodule. A number of recent studies have confirmed the high accuracy of FNA, with sensitivities and specificities in the range of greater than 80% and 90%, respectively. The accuracy in diagnosing thyroid abnormalities is dependant both on the expertise of the cytopathologist interpreting the biopsy specimen, as well as the physician performing the biopsy. Provided adequate sample is removed on biopsy, FNA of thyroid nodules can be used to categorize tissue into the following categories: malignant, benign, thyroiditis, follicular neoplasm, suspicious, or non-diagnostic. The technique has decreased unnecessary operative procedures in patients with benign nodules and increased the probability that surgery will be performed on those with malignant disease. The one drawback lies with hypocellular samples and aspirates with high follicular cellularity. Hypocellular aspirates may be encountered in cystic nodules. Aspirates with a high follicular cellularity suggest follicular neoplasm, however, FNA cannot reliably distinguish a benign follicular neoplasm from a malignant one, and thus surgical resection remains the necessary recourse to obtain a definitive diagnosis. Below is an example of a fine needle aspiration from a nodule containing papillary carcinoma. Notice that the cells form papillary structures, the cells have internuclear inclusions (INI), and that the nuclei show grooves.
The thyroid glands' ability to concentrate iodine and certain radioactive isotopes has been exploited in a nuclear imaging technique known as the thyroid scan. Radioactive isotopes are special forms of elements that undergo a process called decay in which they change from higher energy states to lower energy states. As they undergo this change, they release small bursts of energy in the form of radiation that can be detected by special cameras. The tissue that makes up the thyroid gland is unique in that it is able to take up and trap iodine and certain other molecules of similar size. When radioactive isotopes of these substances (tracers) are swallowed or injected into the bloodstream, they are taken up by the thyroid gland. As they decay, a special camera can detect the energy that is released, creating a picture of the thyroid gland. The radioactive isotopes that are most commonly used as tracers to perform thyroid scans are called 123-Iodine, 99m-Technetium pertechnetate and 131-Iodine. Nuclear imaging and the thyroid scan can be used to distinguish a nodule as hot, warm, or cold, based on the relative amount of uptake of radioactive isotope. Hot nodules take up excessive amounts of isotope and indicate autonomously functioning nodules. They appear very dark on thyroid scan (see picture to right) in relation to normal thyroid tissue. Warm nodules appear gray and suggest normal thyroid function. Cold nodules take up minimal amounts of radioactive isotope and therefore indicate hypofunctional or nonfunctional thyroid tissue. Hot nodules are rarely malignant, however, warm or cold nodules are malignant in 5-8% of cases and require further workup (biopsy, removal, etc.). Unfortunately, solitary thyroid nodules are hot in only about 10% of cases and 90% of cold nodules are not malignant. Thus, nuclear imaging (regardless of whether it is used in conjunction with ultrasound or not) is associated with a low yield of cancer diagnoses.
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