Hyperthyroidism Disorders Lesson 5 Of 8
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Posted 06 September 2012 - 11:16 PM
Hyperthyroid Disorders
© Elaine Moore
Lesson 5: Diagnosing Hyperthyroidism
In this lesson students will learn to recognize the laboratory, imaging and biopsy tests used to help diagnose hyperthyroidism and its specific cause.
Topics include:
Disorders that can mimic hyperthyroidism
Thyroid function tests
Obsolete laboratory tests
Thyroid antibody tests
Imaging tests
The radioiodine uptake and scan
Fine needle aspiration biopsy
Topics for Discussion
Introduction
As we learned in the previous lesson, it’s important to determine the exact cause of hyperthyroid disorders. In this lesson course participants are introduced to the various laboratory tests and imaging procedures used to diagnose hyperthyroidism and determine its specific cause. Students are also introduced to other disorders that can mimic hyperthyroidism and confuse diagnosis.
To accurately diagnose hyperthyroidism, the patient’s clinical symptoms and signs must be evaluated along with test results. With this approach physicians are able to form a complete clinical picture and make a proper diagnosis. Laboratory results alone can indicate that disease is likely but when patients are asymptomatic, that is, they have no symptoms of disease, the results should be questioned or repeated at a later time.
While thyroid laboratory tests have an accuracy rate greater than 99 percent, there are other conditions that can cause similar results or affect thyroid function test results. Furthermore, some patients have rare thyroid antibodies or heterophile antibodies that falsely increase or falsely lower their test results.
This lesson includes descriptions of the primary laboratory tests used to screen for and diagnose hyperthyroidism and also the blood tests used to determine if the patient has an autoimmune hyperthyroid disease. Course participants will learn the underlying principle behind specific laboratory tests, they’ll learn what tests are optimal, and they’ll learn about the various sources of error in laboratory medicine.
Imaging tests, including the radioiodine uptake and scan and the thyroid ultrasound, are also described in this section and their limitations are detailed. In addition, students are introduced to the different imaging patterns seen on the scans of patients with different hyperthyroid disorders. The fine needle aspiration biopsy is also described, and its uses and limitations are discussed.
While imaging tests are often used for the purpose of differentiating cold and hot nodules, the results can be erroneous or misleading. There are many gray areas because thyroid tissue that takes up more iodine may be blocked from taking up iodine during the scan. This can make a hot nodule appear cold. While most nodules are benign, nodules that are cold are much more likely to be malignant. A fine needle aspiration biopsy is necessary to determine the type of cells that make up the nodule. This tells if the nodule is malignant or benign.
The importance of tracking laboratory and imaging test results is emphasized in this lesson. Ideally, patients would keep copies of all lab results, indicating what medications they were on and how they felt when their labs were drawn. This can help in determining what thyroid hormone levels are optimal for the individual.
Because all of the treatments for hyperthyroidism have the potential to cause hypothyroidism, and hypothyroidism can lead to a poor treatment outcome, thyroid patients are shown how to make sure they’re receiving optimal treatment and are not being moved into hypothyroidism. When treatments that cause permanent hypothyroidism are used, it’s important to monitor thyroid hormone levels frequently since levels typically fluctuate for the first year, affecting therapy needs.
In autoimmune thyroid disease, it’s important to avoid treatments that cause hypothyroidism. As a homeostatic mechanism, in hypothyroidism thyroid cells increase their activity in an effort to produce more thyroid hormone. This increased activity also causes increased antibody production and a worsening of the original autoimmune disorder.
Lesson 5: Diagnosing Hyperthyroidism
Laboratory Tests
Reference Ranges All laboratory tests have a normal or reference range that is listed below the test results. This range represents levels seen in normal individuals. However, levels that fall within the reference range may not be normal for a given individual. Studies show that thyroid test results vary widely in the normal population. When we’re in good health, our thyroid function test results remain remarkably stable. Normally, the pituitary gland keeps our thyroid hormone levels constant by increasing or decreasing TSH. The current AACE guidelines recommend a reference range of 0.3-2.5 mu/L for TSH. While most people have a TSH level between 0.3-1.0 mu/L, some people optimally function with a TSH level of 2.4 mu/L.
In patients undergoing treatment for hyperthyroidism, having thyroid hormone levels that fall within the reference ranges merely means that the therapy is working. Patients will still have symptoms of hyperthyroidism or hypothyroidism if their thyroid hormone levels are too high or low. Thyroid hormone is extremely potent, and even small variations from one’s optimal levels can have profound effects.
Thyroid Function Tests The FT4, FT3, and TSH tests are the primary tests used to diagnose hyperthyroidism. To screen for hyperthyroidism, a TSH level is run. If it’s abnormal the FT4 and FT3 tests are ordered. In hyperthyroidism, either of the available thyroid hormones, FT4 and/or FT3, may be elevated. It’s important to run both tests because many patients with both GD and toxic multinodular goiter will have elevated FT3 levels and normal FT4 levels.
In hyperthyroidism, the TSH level is low, usually suppressed to less than .01 mu/L. If TSH is low and thyroid hormone levels are normal, the patient may have subclinical hyperthyroidism. However, TSH can be low or suppressed in other conditions and as a result of various medications. Because TSH test results can be misleading, especially in Graves’ disease and thyroiditis, TSH test results should not be used to monitor anti-thyroid drug therapy. Although a low TSH doesn’t necessarily mean that hyperthyroidism is present, a TSH result higher than 2.5 mud/L suggests hypothyroidism. The TSH level will often rise quickly when patients move into hypothyroidism, either as a result of treatment or spontaneously.
Thyroid Antibody Tests Once hyperthyroidism has been established, it’s important to find out the cause. If characteristic eye symptoms are present, some doctors will diagnose Graves’ disease. However, because eye symptoms related to excess thyroid hormone can appear in any of the hyperthyroid disorders it’s important to run tests for thyroglobulin and TPO antibodies to determine if the hyperthyroidism is autoimmune. If Graves’ disease is suspected, a test for stimulating TSH receptor antibodies should be ordered. These antibodies are also known as thyroid stimulating immunoglobulins or TSI.
Tests No Longer Recommended With the availability of Free T4 and Free T3 tests, several of the older thyroid function tests still in use are no longer recommended. Before sensitive tests for measuring FT4 and FT3 became widely available, older tests, such as T4, T3, T3 uptake and the FT4 index or FTI, were used to approximate, that is, get a rough idea of FT4 and FT3 levels.
Total T4 and Total T3 levels Total T4 and total T3 levels, the T4 and T3 tests, measure levels of free thyroid hormone and also the binding proteins that carry this hormone. In this form, thyroid hormone is linked to protein molecules and inactive. Once the free hormone is cleaved or split from the binding protein, it is available to react with the body’s cells. When binding protein levels are elevated, levels of T4 and T3 are elevated. Binding protein levels are elevated in pregnancy, in patients on estrogens and many other medications. For this reason, FT4 and FT3 levels are the best indicators of thyroid function.
The T3 uptake test and the FT4 index In the T3 uptake procedure, reagent grade T3 is added to the patient’s serum to determine the quantity of binding proteins available to carry T3. From this result and a total T4 result, the approximate amount of free T4 can be calculated. This result is the FT4 index, the FTI, and the FT7. Values of FTI do not correlate well with direct measurements of FT4, and the FT4 assay is considered more reliable.
Test Interferences Many medications interfere with thyroid function tests. These medications are listed in the assigned reading. In addition, a condition of non-thyroidal illness, including recovery from surgery, will lower thyroid hormone levels and TSH. For this reason, thyroid function tests are not recommended in hospitalized patients.
Lesson 5: Diagnosing Hyperthyroidism
Imaging Tests
Several imaging tests are available to help diagnose the specific cause of hyperthyroidism. Imaging tests, which include X-rays and more sophisticated techniques, are the procedures performed in the radiology department.
The RAI-Uptake Test At one time the RAI-Uptake Test and Scan was the only procedure available to help determine the cause of hyperthyroidism. In this test, the patient is given an oral dose of radioiodine usually in the form of I-123. Sometimes technetium or I-131 are used.
At 6 or 24 hours after the dose is administered, the amount of residual radioiodine is measured. The thyroid gland is also scanned at this time to determine the pattern of uptake. Areas that take up less or more radioiodine than the surrounding tissue represent nodules. In Graves’ disease, hereditary hyperthyroidism and thyroiditis, the scan is diffuse or even with all the cells taking up the same amount of radioiodine.
In patients with thyroid nodules and Graves’ disease, the uptake is generally elevated. At 24 hours, patients with mild disease usually have an uptake as high as 60 percent. In patients with thyroiditis, the uptake is low. Excess dietary iodine can falsely decrease the uptake results. Medications with high concentrations of iodine, such as amiodarone, and iodine contrast dyes can falsely decrease the results for several months. The dose of radioiodine used in the uptake is much lower than that used for ablation. Still, radioiodine remains in the blood circulation for several days. Results can suggest Graves’ disease but can’t distinguish between Graves’ disease and hereditary hyperthyroidism. A blood test for TSI can be used to definitively diagnose Graves’ disease.
Ultrasonography
Ultrasonagraphy offers the benefits of a thyroid scan and the advantage that it’s not an invasive procedure. Ultrasound is very sensitive for detecting thyroid lesions and for distinguishing nodules from cysts. Like the thyroid scan, ultrasonography cannot distinguish benign from malignant masses. For this a fine needle aspiration biopsy is needed. Ultrasound can easily determine thyroid volume. A reduction in volume shows a good response to anti-thyroid drug therapy in subsequent ultrasounds.
Cat Scans
Computed tomography can also be used to distinguish nodules and help diagnose Graves’ disease. This procedure is more expensive and not generally used unless the position of the gland in relation to other organs needs to be determined.
MRI
In magnetic resonance imaging, the thyroid can be studied and the amount of fat to muscle can be determined. The vascularity of the thyroid gland can also be studied. This procedure is not routinely used to determine the cause of hyperthyroidism although it can be used to show the degree of gland enlargement and any involvement of adjacent organs.
Lesson 5: Diagnosing Hyperthyroidism
Fine Needle Aspiration Biopsy
Fine needle aspiration or FNA of the thyroid is a biopsy procedure that has been in use since 1930. In this procedure a hollow bore needle is inserted into the thyroid gland and a small amount of tissue is removed. The tissue is then studied to determine its cellular composition.
Today, FNA is the recommended procedure for the investigation of thyroid nodules because of its reliability and cost effectiveness. The routine use of FNA for thyroid nodules has reduced the number of thyroid surgeries and increased the percentages of malignancies that are found surgically. FNA is used to determine if suspicious nodules are malignant or benign.
The Papanicolaou Society of Cytopathology Task Force on Standards of Practice recommends FNA biopsy on solitary nodules and those in a multinodular goiter which are dominant or rapidly growing. In nodules that are small and deep, FNA can be performed with ultrasonography guidance to help locate the suspect nodule.
A pathologist, radiologist, endocrinologist or surgeon with proper training and experience can perform the aspiration. Criteria for an adequate sample vary. Some experts recommend six to eight groups of follicular cells and others recommend a minimum of ten clusters. Experts agree that the nature of the lesion affects adequacy and fewer cells may be adequate when there is abundant colloid or cystic material.
Cytologists study the aspirated tissue microscopically to determine the type of cells present in the biopsy specimen. Normal thyroid tissue is composed of spherical follicles or follicular cells filled with colloid protein and surrounded by a rich bed of capillaries. The three major diagnostic categories are benign non-neoplastic lesions, indeterminant cellular follicular lesions and malignant lesions. Benign lesions include goiters which may be nodular, cystic or colloid or inflammatory in nature. Indeterminant lesions generally consist of many follicular or Hurthle cells without diagnostic malignant features.
Tumors of the thyroid are divided into differentiated neoplasms, which arise from follicular cells and constitute 95 percent of cases, and non-differentiated, most of which are medullary carcinomas arising from interfollicular C cells. Papillary cancer is the most common thyroid malignancy. It constitutes 50 to 90 percent of differentiated carcinomas worldwide. The cells of a benign follicular adenoma cannot be distinguished from those of a well-differentiated follicular carcinoma with FNA. Surgery is required to determine if the thyroid capsule has been invaded.
Inflammatory thyroid diseases of the thyroid cause distinct cellular changes when studied microscopically. The most common inflammatory thyroid disease biopsied is Hashimoto’s thyroiditis. This condition is characterized by Hurthle cell changes in follicular cells and scant colloid.
Lesson 5: Diagnosing Hyperthyroidism
Bibliography
Andersen,Stig, Niels Bruun, et. al., Biologic Variation is Important for Interpretation of Thyroid Function Tests, Thyroid, Volume 13(11), 2003.
Arem, Ridha, The Thyroid Solution, Ballantine, New York, 1999.
Braverman, Lewis E. and Robert D. Utiger, Werner & Ingbar’s The Thyroid, A Fundamental and Clinical Text, Eighth Edition, Lippincott Williams & Wilkins, Philadelphia, 2000.
DeGroot, Leslie, Graves' disease and the Manifestations of Thyrotoxicosis, Thyroid Manager, Dec 10, 2003, www.thyroidmanager.org/Chapter10/10-text.htm
Foweler, Michael, Pannone, Aaron, et.al., Pitfalls to Avoid While Interpreting Thyroid Function Tests: Five Illustrative Cases, medscape, www.medscape.com/viewarticle/433853
Laboratory Medicine Practice Guidelines for the Diagnosis and Monitoring of Thyroid Disease, www.nacb.org/lmpg/thyroid_LMPG_PDF.stm
Moore, Elaine A. Graves’ Disease, A Practical Guide, McFarland and Company, Jefferson, NC, 2001.
Moore, Elaine A. Autoimmune Diseases and Their Environmental Triggers, McFarland and Company, Jefferson, NC, 2002
Stowell, Susan, Thyroid Aspiration: What We Can and Cannot Do, Laboratory Medicine, Nov 1, 2004, 16-19.
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