Thyroid pathology
The thyroid is a small gland, shaped like a butterfly, located in the lower part of your neck.
The function of a gland is to secrete hormones. The main hormones released by the thyroid are triiodothyronine, abbreviated as T3, and thyroxine, abbreviated as T4. The problems with the thyroid can be:
1. Hypothyroidism
This is an underactive thyroid so produced not sufficient amounts of T3 and T4. Symptoms of hypothyroidism usually go along with a slowdown in metabolism, and can include fatigue, weight gain, and depression, among others. The most common cause of hypothyroidism is an autoimmune disease called Hashimoto disease.
2. Hyperthyroidism
This is a thyroid which become overactive in producing the thyroid hormones. The symptoms are goiter, fatigue, weight changes, heart beat and blood pressure problems. Also here the most common cause is an autoimmune disease called Graves diseases.
3. Thyroid Cancer
4. Thyroiditis
Thyroiditis is an inflammation of the thyroid.
Synthesis and release of the thyroid hormones
Thyroid hormone synthesis and release is controlled by the hypothalamic-pituitary axis involving negative feedback control. Thyrotrophin-releasing hormone (TRH) is released from neurosecretory cells in the hypothalamus and travels via portal capillaries to the anterior pituitary where it stimulates the release of TSH into the general circulation. It is bound by TSH receptors in the thyroid gland which stimulate synthesis of the iodine pump in the follicular cells and the production of thyroglobulin and thyroperoxidase, with the effect of an in an increase in the release of the thyroid hormones. Circulating levels of thyroid hormones exert negative feedback control on the TSH secretion. Conversely, when thyroid hormone levels are low there is stimulation in the secretion of TSH.
Thyroid function tests
These comprise the thyroid hormones (T4 and T3, total or free), thyroid stimulating hormone (TSH) and thyroid autoantibodies: anti-Thyroid peroxidase (TPO) and anti-thyroglobulin (TG). Thyroid function tests can demonstrate the presence or the absence (euthyroid) of thyroid dysfunction but further investigations and clinical assessment are necessary to determine the cause and select appropriate treatment. This is a cancer of the thyroid nodules or tissue.
Interpretation of Thyroid function tests
Hyperthyroidism
TSH will be suppressed to below the reference range and total or free T4 will be elevated. If the TSH is suppressed and the total or free T4 is normal, a total or free T3 should be measured. If this is elevated it is indicative of T3 thyrotoxicosis. If the total or freeT3 is normal, the TSH could be suppressed due to non-thyroidal illness.
Hypothyroidism
TSH will be significantly elevated and total or free T4 below the reference range. Thyroxine replacement is indicated by such results. It is frequently found that there is a moderate elevation of TSH with total or freeT4 in the normal range; the pattern of sub-clinical or compensated hypothyroidism. A positive TPO antibody result indicates that autoimmune disease is present.
Thyroid Markers
Thyroid Stimulating Hormone (TSH)
Thyroid Stimulating Hormone (TSH) is a glycoprotein hormone secreted by the anterior pituitary gland. When feedback suppression of the pituitary is reduced by a reduced production of thyroid hormones (T3 and T4), TSH rises in an attempt to increase thyroid hormone production. In primary hyperthyroidism, such as Grave's disease, TSH secretion is suppressed, whereas, in primary hypothyroidism, TSH secretion is elevated. Particularly in subclinical hyperthyroidism or hypothyroidism, even when the level of thyroid hormones is normal, the level of TSH can be abnormal, and thus TSH serves as a sensitive indicator of thyroid function.
Thyroxine (T4 )
The primary function of the thyroid gland is the secretion of thyroxine (T4) or triiodothyronine (T3). Abnormal secretion of T4 and/or T3 may lead either to hyperthyroidism or hypothyroidism. T4 is largely converted to T3 in peripheral tissues by monodeiodination. In the circulation, 99.97% of T4 is protein bound and 0.03% is free. Measurement of serum thyroxine (T4) concentration is generally regarded as an important in-vitro diagnostic test for assessing thyroid function.
Free Thyroxine (FT4)
Thyroxine (T4) is produced by the thyroid gland and 99.97% of T4 circulates in the blood in a bound form with the plasma proteins including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and albumin. Approximately 0.03 % of the total circulating thyroxine is unbound. Historically measurement of total serum T4 (bound + free) is used to assess the clinical status of the Thyroid gland. But free T4 (FT4) is believed to be the physiologically active portion of the thyroxine which stimulates the metabolism and controls, via the pituitary, the feedback system involving the release of TSH. Therefore measurement of free T4 (FT4) typically co-relates more closely to the patient's actual thyroid status.
Triiodothyronine (TT3)
Triiodothyronine (T3) and thyroxine (T4) regulates a variety of biochemical processes throughout the body. The majority of T3 in circulation is produced enzymatically by monodeiodination of T4 in the peripheral tissues, rather than from direct secretion from the thyroid gland. Approximately one-third of all T4 secreted is deiodinated to yield T3. Serum T3 measurement can be a valuable component of a thyroid-function screening panel in diagnosing certain disorders of thyroid function in addition to conditions caused by iodide deficiency. Assays of T3 are valuable in early detection of hyperthyroidism and for monitoring the efficiency of treatment of thyroid disorders.
Free triiodothyronine (FT3)
Triiodothyronine (T3) is present in human serum in an equilibrium mixture of bound and free forms, with approximately 0.4% of the total T3, circulating as free triiodothyronine (FT3). Any change in the serum concentration of binding proteins will cause a parallel rise in the concentration of total T3 with the FT3 levels remaining relatively unchanged. Direct measurement of free T3 enables precise thyroid function examination even in the presence of abnormal liver function, hormone fluctuation during pregnancy and variations in levels of serum binding proteins.
Human thyroglobulin (Tg)
Human thyroglobulin (Tg) is a large glycoprotein that is stored in the follicular colloid of the thyroid gland. It functions as a prohormone in the intrathyroid synthesis of primary thyroid hormones like Triiodothyronine (T3) and Thyroxine (T4). Tg is elevated in thyroid follicular and papillary carcinoma, thyroid adenoma, subacute thyroiditis, Hashimoto’s thyroiditis and Graves Disease.
TPO Ab (Thyroid Peroxidase (TPO)) and TgAb
Testing for thyroid antibodies is primarily ordered to help diagnose an autoimmune thyroid disease and to distinguish it from other forms of thyroid dysfunction. Thyroid autoantibodies develop when a person's immune system mistakenly targets proteins of the thyroid gland leading to chronic inflammation of the thyroid (thyroiditis), tissue damage, and/or disruption of thyroid function. The following thyroid antibody tests can be performed in order to help the diagnosis of and/or monitor an autoimmune thyroid disorder:
1. Thyroid peroxidase antibody (TPOAb), the most common test for autoimmune thyroid disease; it can be detected in Graves disease and in Hashimoto thyroiditis.
2. Thyroglobulin antibody (TgAb).
3. Thyroid stimulating hormone receptor antibodies (TRAb)
Testing for TgAb in patients with a treatment or follow up for thyroid cancer is monitored with a thyroglobulin tests. In this case a TgAb test is clinical useful to determine if the Tg antibodies present or not as these antibodies will likely interfere with the immunoassay for Tg.
The presence of thyroid antibodies indicate the presence of an autoimmune thyroid disorder and the higher the level, the more likely that is. Levels of autoantibody that rise over time may be more significant than stable levels as they may indicate an increase in autoimmune disease activity.
Antibodies to thyroid peroxidase have been shown to be characteristically present from patients with Hashimotos thyroiditis (95%), idiopathic myeloma (90%) and Graves Disease (80%). In fact, 72% of patients for anti-TPO exhibit some degree of thyroid dysfunction. This had lead to the clinical measurement of Anti-TPO in becoming a valuable tool in the diagnosis of thyroid dysfunction.