The Common Vein Copyright 2010
Given the fact that thryoid hormones intervine in the majority of organs and systems, this makes thyroid function testing almost a daily necessity. Not only endocrinologists are related to this reality, actually in maybe all other specialties thyroid usually becomes a part of the workup for narrowing differential diagnosis or as screening test to consider. Some examples to ilustrate this could be a cardiologyst evaluating a patient with new onset Atrial Fibrilation, also a pediatrician screening neonates for congenital hypothyroidism, a primary care doctor screening for subclinical thryoid disfuction or a surgeon extending workup for a thyroid nodule.
In this sense is important to differentiate the level of suspicious when it comes to ordering serum levels to evaluate thyroid fuction.
Screening has being performed for neonatals as a national program to prevent congenital hypothyroidism, because in most of the newborns the clinical manifestations become apparent very late when there is not much to do to prevent mental retardation. For this purpose either T4 or TSH are measured in heel-stick blood samples from newborns to detect any abnormality as soon as posible.
Regarding the level of suspicion when the clinician has very low suspicion in a particular patient, the best test to performed is TSH because is highly sensitive (which means few false negative cases), also is wide available and is low cost. Thyroid disfunction usually is due to a primary disorder where the thyroid gland is affected and TSH would reflect well if the problem is due to excess or decrease function of the thyroid gland.
If the thyroid gland is hyperfunctioning then the thyroid hormones raise in the bloodstream and by negative feeback supress the TSH secretion in the pituitary gland, in this situation the TSH levels will be low. The opposite happens if the thyroid function is decrease than the thyroid hormone levels in the blood are low and TSH is secreted actively to maintain thyroid function, in this case TSH levels will be high when measured in a blood sample.
If the suspicion is moderate to high either because the clinical manifestations points towards a thyroid disorder or because other laboratory tests raise the question for it, than TSH plus free T4 can be measured, this makes easier to distinguish between a primary disorder where the thryoid is directly affected or a central problem where the pituitary gland or the hypothalamic nuclei are affected.
T4 has high afinity for proteins and therefor can be find in two ways in the blood, either bound to proteins, in this case does not shift to target tissue only gets transported in the blood, and the other way is as a free hormone, this allows the hormone to penetrate the target organs, be converted into T3 and exert its effect. This is the reason why free T4 is a better marker to assess the thyroid function.
If the thyroid gland is hypofunctioning than free T4 levels will be low but TSH will be high in the blood trying to stimulate the thyroid gland more and more. When the pituitary gland is afftected and unable to produce TSH, a low TSH would be reflected in the blood, and since TSH is not stimulating the thyroid gland to produce thyroid hormones than a low free T4 will result too correlating with secondary hypothyroidism. In the other hand if the disorder is primary leading to an overproduction of thyroid hormones than a free T4 is going to be high in the blood and since T4 has a negative feebback in the hypotalamic-pituitary axis than TSH will be supresed leading to low blood levels of TSH.
When the situation is that the diagnosis is obvious by history and physical exam or the initial screening with TSH or other lab values like free T4 suggests a thyroid disorder then the clinician can complete the work up adding total T3, thyroid-stimulating immunoglobulin titer or even extended with some studies like radionuclide thyroid uptake to be able to identify the exact thyroid pathology and plan the appropiate therapy for each thyroid condition.
T3 levels will be high in hyperthyroid states and help to determine the severity of the disease, but in hypothyroid states is the last hormone to become abnormal and therefor does not help much for this type of diagnosis.
When measuring particular antibodies this helps to determine the exact cause of the thyroid problems. Like in other autoimmune diseases, sometimes the body starts to produce antibodies but this case against the thyroid gland leading either to a destruction of the gland or hyperstimulating the gland. Antuantibodies develops against specific proteins or molecules within the thyroid; between the most common targets for these antibodies there are two well study: thyroid peroxidase (an enzime that helps processing the thyroid hormones) and thyroglobulin (protein also called colloid, substrate for thyroid hormone production).
Radioactive iodine uptake is a useful test and the rational behind this test is that T4 contains much iodine therefore the thyroid gland is specialized in absorb large amounts of iodine from the blood streem in order to process the thyroid hormones. If an individual ingest small amounts of iodine previously tagged with radioactive material, it is possible to track where the iodine molecules are absorbed in the body and by measuring the radioactivity in the thyroid gland it is possible to assess the overall functionally of the gland as well as recognize wheter there are other tissues taking up iodine, ectopic thyroid tissue for example can be seen in any point between the floor of the oral cavity and the thyroid gland in the neck because of the pathway the thyroid takes when forming in the embriologic face. The measure of iodine in the thyroid gland is called RAIU (radioactive iodine uptake).
High RAIU can be seen in hyperthyroidism because the thyroid gland is overworking and producing large amounts of thyroid hormones, in the other hand in hypothyroid states the production fo thyroid hormones decrease and therefore the RAIU is low.