Interpretation of Thyroid Tests - Common Tests to Examine
If the T4 level is low and TSH is not elevated, the pituitary gland is more likely Measurement of Serum Thyroid Hormones: T3 by RIA . The precise size and activity of nodules in relation to the rest of the gland is also measured. . The purpose of the Patient Guide to Insulin is to educate patients, parents. Secretion of the thyroid hormones T4 (thyroxine) and T3 There is a negative log-linear relationship between serum free T4 and TSH concentrations . status and performance goals for serum thyrotropin (TSH) assays. In describing the T4/TSH relationships we considered T4 and FT4 to be . Though T3, the active thyroid hormone , acting via the TRβ2 receptor, and .. axis—maximum curvature theory for personalized euthyroid targets.
TSH then induces production of thyroxine T4 by the thyroid. In response to the concentration of free T4, which influences the amount of triiodothyronine T3 produced in each site, both the hypothalamus and the pituitary alter production of TrH and TSH, respectively. Elevated free T4 inhibits production, while low free T4 stimulates production.
Not only does the pituitary secrete TSH in a diurnal pattern, but many substances produced in the central nervous system, even in healthy euthyroid individuals, may enhance or suppress TSH production in addition to the feedback effect of thyroid hormone. Furthermore, although TSH levels rise and fall in response to changes in the concentration of free thyroxin T4individuals appear to have their own set-points, and factors such as race and age also contribute to variability in TSH levels.
Alterations of the normal pituitary response are also common in patients with a variety of illnesses. These inter-assay discrepancies are now the focus of an international harmonization effort to improve the reliability of TSH results and their application in clinical guidelines 1.
This article presents an overview of the issues and a discussion of how laboratories can assist clinicians in using TSH results to diagnose and manage thyroid disease. The first TSH tests were competitive immunoassays that used polyclonal antibodies; however, the analytical sensitivity of these assays was not sufficient to differentiate hyperthyroid patients with suppressed TSH from euthyroid individuals.
Non-competitive immunoassays introduced in the s achieved this level of sensitivity, and in the s, manufacturers further improved the assays by using monoclonal antibodies. Today, we refer to the performance of these so-called second- and third-generation TSH assays in terms of functional rather than analytical sensitivity, meaning that imprecision is assessed over a concentration range during an extended period of time.
By convention, second- and third-generation assays detect TSH with this degree of reproducibility down to a level of approximately 0. The majority of currently available TSH immunoassays are capable of third-generation performance. However, daily precision in this low range may not be as robust as it appears when functional sensitivity is initially evaluated 2.
Furthermore, most laboratories probably do not regularly monitor performance in this low range, because it would require the use of in-house pooled sera. In addition, few, if any, proficiency programs regularly challenge laboratories at the limit of third-generation performance.
The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology
The major advantage of using a third-generation TSH assay is that precision at a higher level, 0. In fact, most clinical guidelines recommend 0. Third-generation assays also perform well in the range relevant for monitoring thyroid hormone replacement therapy after thyroid ablation.
The most likely reason for this change was the reduced cross-reactivity afforded by the monoclonal antibodies used in the newer assays. During the past decade, however, there has been considerable debate about the correct upper limit of the reference interval for TSH.
Although there is a consensus that the lower limit of the euthyroid reference interval for TSH should be 0. Inresearchers published an analysis of thyroid function test results from a large survey of individuals representative of the U. The study revealed that within a small standard error the mean TSH level in the general population is approximately 1.
This finding prompted organizations to call for lowering the upper limit of the normal TSH reference range. Many clinicians resisted these new limits, because they worried that a significant number of patients would be unnecessarily labeled as having thyroid dysfunction, especially given the fact that there was no evidence that treatment of these individuals would provide any benefit.
The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology
Inresearchers analyzed the data from the survey a second time to clarify the relationship of TSH and antibodies to thyroid peroxidase TPOa recognized marker of autoimmune thyroid disease 4. TSH levels correlated with anti-TPO positivity, and the investigators asserted that reference interval studies would support the lower upper limit if such individuals, who probably have occult autoimmune hypothyroidism, were excluded.
While some groups also have challenged this position, there is growing consensus that one TSH reference interval does not fit all. Pregnant Women, Newborns Diagnosing thyroid dysfunction in pregnant women has long been problematic.
Pregnancy has a significant effect on thyroid function, which changes over the course of gestation and makes assessment more difficult. The recent guidelines for diagnosing and managing thyroid disease during pregnancy issued by the American Thyroid Association recommend trimester-specific reference intervals for TSH, as well as TSH targets for diagnosing and treating hypothyroidism during pregnancy. Neonatal screening for congenital hypothyroidism is another special problem.
Each screening program sets its own cut-offs, but standardization of TSH immunoassays would benefit from this approach. TSH Glycoforms In addition to inter-assay differences, evidence is now accumulating that there may be significant variability in the structure of the patients' TSH molecules.
TSH is a glycoprotein hormone with a structure similar to other anterior pituitary glycoprotein hormones. This group of hormones consists of non-covalently linked heterodimers: The pituitary actually releases a heterogeneous mixture of TSH glycoforms that consists of molecules with various side chains Figure 2.
The majority have carbohydrate side chains terminating with sulfated N-acetylgalactosamine or galactose, and some have internal fucosylation as well arrows. The liver recognizes all of these moieties and removes TSH bearing them from circulation. By contrast, TSH glycoforms produced by hypothyroid patients have side chains lacking fucose and terminating with sialic acid residues.
These are not removed by the liver and they have a longer half-life. Adapted from reference 5; used with permission. TSH isolated from normal pituitaries contains primarily branched glycans with sulfated acetylgalactosamine GalNAc residues; however, the sera of patients with hypothyroidism contain TSH with branched glycans composed of sialic acid attached to galactose residues.
The liver recognizes glycoproteins with the GalNAc sulfate signal and removes them; therefore, sialylated TSH has a longer half-life. As a result, patients with hypothyroidism not only produce more TSH, but also TSH glycoforms that circulate longer in blood 5. Data from the U. National External Quality Assessment Service proficiency testing program revealed poor correlation between observed method bias and the reference intervals recommended in the package inserts from various manufacturers, which are essentially equivalent.
These observations suggest that standardization of TSH assays would be helpful for improving patient care, particularly given the current discussions about lowering the upper decision limit for TSH in clinical practice guidelines. Overview HyperthyroidismHyperthyroidism - overactive thyroid is a disease in which the thyroid is hyperactive and makes too much thyroid hormone. Like most conditions of the thyroid gland, it is more common in women.
It is important to distinguish between these two causes, in order to choose the appropriate treatment. A thyroid uptake scanThyroid uptake scan - radioactive iodine scan to detect hyperfunctioning thyroid nodules also known as a radioactive iodine scan can help tell the difference between these two causes.
Problems causing thyroid hormone overproduction have increased uptake on thyroid scanning i. Overproduction of thyroid hormone is the most common cause of hyperthyroidism and can be caused by Graves' diseaseGraves' disease - autoimmune overproduction of thyroid hormone resulting in hyperthyroidismtoxic multinodular goiterGoiter - enlarged thyroidand toxic adenomaToxic adenoma - single nodule in an otherwise normal thyroid gland that makes too much thyroid hormone and leads to hyperthyroidism.
Symptoms Symptoms that may be associated with hyperthyroidismHyperthyroidism - overactive thyroid include anxiety, insomnia inability to sleep through the nighttremors, palpitations, weight loss, muscle weakness, heat intolerance, excessive sweating, and menstrual changes.
The number, degree, and severity of these symptoms can provide some clue as to the severity of hyperthyroidism. Diagnosis Diagnosing hyperthyroidismHyperthyroidism - overactive thyroid is based on history and physical exam findings along with appropriate laboratory testing.
On physical exam, the physician may find that the patient has a rapid heart rate tachycardiairregular heart beats arrhythmias, including atrial fibrillationeye symptoms such as dryness, burning, bulging, double visionor hand tremors.
In addition, the thyroid gland may be larger than normal. Laboratory testing to confirm the diagnosis of hyperthyroidism will include thyroid function tests. Thyroid uptake scanning is used to determine if the thyroid is making too much thyroid hormone, leading to a high, or "hot" uptake scan versus if the thyroid is being destroyed as in thyroiditisin which case the scan will be a low, or "cold" uptake scan.
Common causes Graves' disease Graves' diseaseGraves' disease - autoimmune overproduction of thyroid hormone resulting in hyperthyroidism is an autoimmune problem where the body's immune system overstimulates the thyroid. It is the most common cause of hyperthyroidismHyperthyroidism - overactive thyroid.
The hormone that causes the thyroid to make and release thyroid hormone receptor, causes the overproduction of thyroid hormone. The thyroid uptake scanThyroid uptake scan - radioactive iodine scan to detect hyperfunctioning thyroid nodules will be high, or "hot".
On physical exam, patients with Graves' disease may have bulging eyes and violet plaque-like lesions, on the front of their lower legs, which are possibly associated with itchiness.
Thyroid Gland Function Tests
Toxic multinodular goiter Hyperthyroidism due to toxic multinodular goiterGoiter - enlarged thyroid occurs when one or more nodules growths in the thyroid begin to make too much thyroid hormone.
In general, the hyperthyroidism tends to be less severe than that seen in Graves' disease. Laboratory diagnosis is the same as in other cases of hyperthyroidism with low TSH and high T4 and T3 levels. Thyroid uptake scans may note several separate "hot" spots corresponding to the hyperactive nodules, while the rest of the gland has decreased activity. Toxic adenoma If a single nodule, or a solitary toxic adenomaToxic adenoma - single nodule in an otherwise normal thyroid gland that makes too much thyroid hormone and leads to hyperthyroidismin an otherwise normal thyroid gland makes too much thyroid hormone, it can lead to hyperthyroidism.
How Your Thyroid Works - Controlling hormones essential to your metabolism
This is a less common cause of hyperthyroidism than either Graves' disease or toxic multinodular goiterToxic multinodular goiter - multinodular goiter that produced excess thyroid hormone and causes hyperthyroidism.
The diagnosis can be made in the same fashion as above. Treatment The three main treatments for hyperthyroidismHyperthyroidism - overactive thyroid are: The best treatment depends on a number of factors and the treatment plan should be made with the help of experts in thyroid disease including endocrinologists and surgeons.
In general, the first treatment that is usually tried once a diagnosis is made is usually antithyroid medications.
If medical therapy does not work, then a more definitive therapy such as surgery or RAI ablation is considered.