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College of Health Sciences Department of Medical Laboratories Third Year – Second Term Hormones Practice NO (1) Determination of Thyroid Hormones Hyper- and hypofunction Imbalance in production of thyroid hormones arises from disfunction of the thyroid gland itself, the pituitary gland, which produces thyroidstimulating hormone (TSH), or the hypothalamus, which regulates the pituitary gland via thyrotropin-releasing hormone (TRH). Concentrations of TSH increase with age, requiring age-corrected tests Hypothyroidism affects between three and ten percent of adults, with incidence higher in women and the elderly. Hypothyroidism (underactivity) o o o o o o o o o Hashimoto's thyroiditis / thyroiditis Ord's thyroiditis Postoperative hypothyroidism Postpartum thyroiditis Silent thyroiditis Acute thyroiditis Iatrogenic hypothyroidism Thyroid hormone resistance Euthyroid sick syndrome Hyperthyroidism (overactivity) o Thyroid storm Prepared By Dr. Abdelrahman Elreshid 1 o o o o o o Graves' disease Toxic thyroid nodule Toxic nodular struma (Plummer's disease) Hashitoxicosis Iatrogenic hyperthyroidism De Quervain's thyroiditis (inflammation starting as hyperthyroidism, can end as hypothyroidism) Anatomical problems Goitre o Endemic goitre o Diffuse goitre o Multinodular goitre Lingual thyroid Thyroglossal duct cyst Tumors Thyroid adenoma Thyroid cancer o Papillary o Follicular o Medullary o Anaplastic Lymphomas and metastasis from elsewhere (rare) Deficiencies Cretinism Medication linked to thyroid disease includes amiodarone, lithium salts, some types of interferon and IL-2. Diagnosis Prepared By Dr. Abdelrahman Elreshid 2 Blood tests The measurement of thyroid-stimulating hormone (TSH) levels is often used by doctors as a screening test. Elevated TSH levels can signify an inadequate thyroid hormone production, while suppressed levels can point at excessive unregulated production of hormone. If TSH is abnormal, decreased levels of thyroid hormones T4 and T3 may be present; T4 and T3 levels may be determined with blood tests to confirm that their levels are decreased. Autoantibodies may be detected in various disease states (antiTG, anti-TPO, TSH receptor stimulating antibodies). There are two cancer markers for thyroid derived cancers. Thyroglobulin (TG) for well differentiated papillary or follicular adenocarcinoma, and the rare medullary thyroid cancer has calcitonin as the marker. Very infrequently, TBG and transthyretin levels may be abnormal; these are not routinely tested. To differentiate between different types of hypothyroidism, a specific test may be used. Thyroid-releasing hormone (TRH) is injected into the body through a vein. This hormone is naturally secreted by the hypothalamus and stimulates the pituitary gland. The pituitary responds by releasing thyroid -stimulating hormone (TSH). Large amounts of externally administered TRH can suppress the subsequent release of TSH. This amount of releasesuppression is exaggerated in primary hypothyroidism, major depression, cocaine dependence, amphetamine dependence and chronic phencyclidine abuse. There is a failure to suppress in the manic phase of bipolar disorder. Radioiodine scanning and uptake Thyroid scintigraphy, imaging of the thyroid with the aid of radioactive iodine, usually iodine-123, is performed in the nuclear medicine department of a hospital or clinic. Radioiodine collects in the thyroid Prepared By Dr. Abdelrahman Elreshid 3 gland before being excreted in the urine. While in the thyroid the radioactive emissions can be detected by a camera, producing a rough image of the shape (a radiodine scan) and tissue activity (a radioiodine uptake) of the thyroid gland. A normal radioiodine scan shows even uptake and activity throughout the gland. Irregularity can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive, different from the rest. For example, a nodule that is overactive ("hot") to the point of suppressing the activity of the rest of the gland is usually a thyrotoxic adenoma, a surgically curable form of hyperthyroidism that is hardly ever malignant. In contrast, finding that a substantial section of the thyroid is inactive ("cold") may indicate an area of non-functioning tissue such as thyroid cancer. The amount of radioactivity can be counted as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8 to 35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland as may occur with hypothyroidism or hyperthyroidism is usually reflected in decreased or increased radioiodine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism. How is a thyroid panel used? A thyroid panel is used to screen for or help diagnose hypo- and hyperthyroidism due to various thyroid disorders. The preferred test to screen for thyroid disorders is a TSH test. If your TSH level is abnormal, it will usually be followed up with a test for total T4 or free T4. Sometimes a total T3 or free T3 will also be performed. Often, the laboratory will do this follow-up testing automatically, and this is known as reflex testing. This saves your doctor time from having to wait for the results of the initial test and then requesting the additional testing to confirm or clarify a diagnosis. Follow-up tests are often performed on the original Prepared By Dr. Abdelrahman Elreshid 4 sample that was submitted when the initial test was requested. A thyroid panel may be requested by your doctor to have all three tests performed at the same time to get a more complete picture. When is it ordered? A thyroid panel may be ordered as part of a health checkup or when symptoms suggest hypo- or hyperthyroidism due to a condition affecting the thyroid. Signs and symptoms of hypothyroidism may include weight gain, dry skin, constipation, cold intolerance, puffy skin, hair loss, fatigue, and menstrual irregularity in women. Signs and symptoms of hyperthyroidism may include increased heart rate, anxiety, weight loss, difficulty sleeping, tremors in the hands, weakness, and sometimes diarrhea. There may be puffiness around the eyes, dryness, irritation, and, in some cases, bulging of the eyes. What do the test results mean? If the feedback system involving the thyroid gland is not functioning properly due to one of a variety of disorders, then increased or decreased amounts of thyroid hormones may result. When TSH concentrations are increased, the thyroid will make and release inappropriate amounts of T4 and T3, and the patient may experience symptoms associated with hyperthyroidism. If there is decreased production of thyroid hormones, the patient may experience symptoms of hypothyroidism. The following table summarizes test results and their potential meaning. Prepared By Dr. Abdelrahman Elreshid 5 TSH T4 T3 INTERPETATION High Normal Normal Mild (subclinical) hypothyroidism High Low Low or normal Hypthyroidism Low Normal Normal Mild (subclinical) hyperthyroidism Low High or normal High or normal Hyperthyroidism Low Low or normal Low or normal Nonthyroidal illness; rare pituitary (secondary) hypothyroidism Is there anything else I should know? In the past, panels of tests were more common. More recently, however, the practice is to order, where possible, one initial or screening test and then follow up with additional testing, if needed, to reduce the number of unnecessary tests. With thyroid testing, one strategy is to screen with a TSH test and, if the results are abnormal, then order additional tests. Many laboratories still perform thyroid panels, but this will become less common in the future as better screening strategies are developed. 1. What conditions are associated with hypo- and hyperthyroidism? The most common causes of thyroid dysfunction are autoimmune-related. Graves’ disease causes hyperthyroidism, and Hashimoto’s thyroiditis causes hypothyroidism. Both hyperPrepared By Dr. Abdelrahman Elreshid 6 and hypothyroidism can also be caused by thyroiditis, thyroid cancer, and excessive or deficient production of TSH. 2. What other tests may be ordered in addition to a thyroid panel? Tests that may be performed in addition to a thyroid panel may include: Thyroid antibodies - to help differentiate different types of thyroiditis and identify autoimmune thyroid conditions Calcitonin - to help detect the presence of excessive calcitonin production Thyroglobulin - to monitor treatment of thyroid cancer Thyroxine-binding globulin (TBG) - to evaluate patients with abnormal T4 and T3 levels Prepared By Dr. Abdelrahman Elreshid 7