Image source: Thyroid gland
Thyroid disease consists of a multitude of disorders affecting the production or secretion of thyroid hormones resulting in an altered metabolic state. The clinical and biochemical syndromes resulting From too little or too much thyroid hormone production are called hypothyroidism and hyperthyroidism, respectively.
Thyroid hormone regulation:-
»The thyroid gland synthesizes stores and secretes thyroxine (T4) and triiodothyronine (T3) hormones, which are important for growth, development, metabolic rate as well as maintenance. Healthy, mature, central nervous and skeletal system.
»Thyroid hormone secretion and transport are controlled by thyroid-stimulating hormone (thyrotropin; TSH). TSH is released by the anterior pituitary gland that is triggered by thyrotropin-releasing hormone (TRH) emitted from the nerve center.
»Stimulation of the thyroid by TSH causes an increase in thyroid hormone levels (circulating free T4 and free T3), which, in turn, signals the pituitary to stop releasing TSH.
»In contrast, low blood levels of free hormones trigger pituitary release of TSH, which stimulates thyroid secretion to T4 and T3 until free hormone levels return to normal. At this point, the pituitary gland stops releasing TSH.
»This negative feedback mechanism attempts to maintain circulating levels of thyroid hormone within a narrow range.
»The thyroid gland also secretes calcitonin, which plays a role in reducing calcium homeostasis. Blood calcium particle fixation.
Essential for the synthesis of thyroid hormone is dietary iodine, low inorganic iodide, which the thyroid actively extracts from the plasma via iodide trapping (iodide pump). Some of this iodide is stored within the colloid; the lumen of the thyroid ROM has a few different uses.
Iodide is oxidized by thyroid peroxidase, and is bound to the tyrosine residues within the thyroglobulin molecule in the colloid through a process called organ cohesion.
The oxidation of inorganic iodide to iodine and the incorporation of tyrosine residues occur within the thyroglobulin molecules in the colloid, forming moniodotyrosine (MIT).
Diodotyrosine (DIT) results from iodization of MIT.
The combination of two DIT molecules forms tetraiodothyronine (thyroxine, T4), and the combination of MIT with DIT forms triiodothyronine (T3). These reactions are also stimulated by thyroid peroxidase.
Lack of TSH stimulation of the thyroid gland, T4 and T3 are down regulated and released from thyroglobulin Is in vogue When in circulation, thyroid hormone is restricted to several plasma proteins, the process is that:
Helps protect hormones from premature metabolism and excretion, Brings its half-life into circulation
Allows thyroid hormone to reach its site of action, Most thyroid hormone is transported by thyroxine-binding globulin (TBG). Transthyretin (TBPA, thyroxine-binding prealbumin) and albumin also serve as carriers.
T4 and T3 are lipophilic molecules and cross the cell membrane easily, although it contains iodothyronine Transporters that facilitate transportation.
T4 is completely a product of the thyroid gland, while T3 is a product of both thyroid Many other tissues; It is produced by T4’s deodination.
Although the effects of thyroid hormones are known, the basic mechanisms that produce these effects give precise definitions; However, they activate the messenger RNA (mRNA) transcription process, and may promote protein synthesis or (in high amounts) protein metabolism.
Thyroid hormones affect the following:
Growth and development by regulating long bone growth and FT protein synthesis Calorinase by increasing the rate of basal metabolism
Increased metabolic rate increases cardiovascular system, which increases blood flow, cardiac output, and heart rate (may be related in part to increased tissue sensitivity to catecholamine).
Increased or decreased central nervous system (CNS) cerebration
»Sleep by inducing any kind of excitement with hyperthyroidism or hypothyroidism
»Lipid metabolism by stimulating lipid mobilization and degradation
Study of thyroid function:-
Serum thyrotropin (TSH) Aces
»This test is the most sensitive test to detect hypothyroidism because the hypothalamic – pituitary axis compensates very quickly for a slight decrease in the proliferation of free hormones by releasing more TSH. TSH levels can already be increased by clinical testing that lowers circulating levels of serum total T4.
»Current (third generation) serum TSH assay (detection levels ranging from 0.01 to 0.02 mIU / L) using monoclonal antibodies instead of immunoradiometric (IRMA) or immunometric (IMA) approaches have demonstrated greater sensitivity to older RIA techniques. In detecting thyroid disease compared to older tests.
»This assay is commonly used to control hyperbole to diagnose thyroid disease and to monitor replacement therapy for patients. Overtreatment – TSH <0.4 mIU / L- may contribute Excessive bone excretion (decreased bone density), changes in electrocardiogram (ECG), atrial fibrillation, or increased liver function tests.
Test Results In Thyroid Disorders
»IMA technology is very sensitive. Fourth-generation IMAs can detect TSH levels in the range 0.001 to 0.002 mIU / L.
»Third-generation IMA assays can also detect subclinical thyroid disease (TSH = 0.1 to 0.45 mIU / L). Treatment of sub-propyl hypothyroidism is controversial because there is insufficient evidence to indicate benefit.
»Psychiatry can also affect TSH levels. Some studies of hospitalized patients have reported abnormally high or low TSH levels otherwise thyroid patients. Current findings in HIV-positive patients are inconclusive; however, autoimmune thyroid disease is more prevalent in these patients.
Peripheral conversion of T4 to T3 is for pituitary gland, liver and kidney. About 80% of the T3 generation.
Oxidation accounts for the degradation of most thyroid hormones.
Toxic hormones are excreted in feces and urine.
Minor nondeiodination pathways of metabolism include conjugation with sulfate and glucuronide, Deafness and fragmentation.
»There is some controversy as to the appropriate upper limit of normal for serum TSH. Most laboratories use values of about 4.5 to 5.0 mIU / L.
Serum Total Thyroxine (TT4):-
This test provides the most direct reflection of thyroid function by indicating the availability of hormones to the tissues. This determines the total (free and bound) T4 by the RIA, which is sensitive and rapid.
»Virtually all (99.97%) serum T4 is bound to TBG, TBPA or albumin.
»Changes in thyroid globulin concentration, particularly TBG, which increases during pregnancy, alter the total concentration of T4, and can produce a misleading high or low test result.
»However, these changes in TBG do not affect the concentration of free T4. Therefore, to clarify thyroid function, either protein-binding (T3 fast test) or free T4 must be measured.
»An elevated TT4 level indicates hyperthyroidism; A low TT4 level, hypothyroidism. However, the level of TT4 in a thyroid patient may be altered by other factors such as pregnancy or febrile diseases (which increase TT4), nephrotic syndrome or cirrhosis (which reduces TT4) and various medications.
»Common boundaries vary between laboratories; A typical range is 4.6 to 11.2 mcg / dl
Serum total triiodothyronine (TT3):-
»This sensitive and highly specialized test measures total (independent and bound) T3 through RIA.
»T3 is less tightly bound to TBG and TBPA, but more tightly bound to albumin than T4.
»Serum T4 and T3 usually rise and fall together; However, hyperthyroidism usually causes an asymmetric increase in T3, and TT3 may arise before the TT4 level. Therefore, TT3 is useful for detecting or controlling hyperthyroidism early. Many symptoms associated with hyperthyroidism are the result of elevated TT3.
»This test may not be clinically significant for hypothyroidism in which TT3 levels may fall but remain within the normal range. TT3 can occur in only 50% of patients with hypothyroidism.
»If there is an abnormality in the binding protein, this test may give misleading results similar to TT4 readings. Other factors that may affect test results include pregnancy (in which TT3 levels rise), malnutrition or liver or kidney disease (in which TT3 levels are low), or various medications.
»Common boundaries vary between laboratories; A typical range is 75 to 195 mg / dL.
Resin triiodothyronine uptake (RT3U):-
»This test clarifies whether abnormal T4 levels are the result of thyroid disorders or abnormalities in binding proteins as it evaluates the binding capacity of TBG.
»If an abnormal amount (high or low) of thyroid hormone is present in the blood, then RT3U The results change in the same direction as altered levels – increase in hyperthyroidism, decrease in hypothyroidism.
»However, if there is an inherent abnormality in the binding protein then abnormal levels of TTT4, TT3 or both, RT3U result in the opposite direction – TBG decreases as TBG increases.
Free Thyroxine Index (FTI)
»The free hormone represents only 0.03% serum total T4.
»FTI has the advantage that the physician is given a total T4 and thyroid hormone ligation ratio or index (THBI), which makes it clear that the patient is deficient in abnormal proteins.
THBI = RT3U / mean serum RT3U
Strategies and cost considerations for testing:–
Image source: Thyroid test Blood sample
»ATA recommends a free thyroxine (FT4) and a sensitive TSH assay as the primary laboratory test for the diagnosis of thyroid disease.
»Thyroid disease screening for otherwise otherwise healthy populations has not been shown to be cost effective based on the rate of detection and cost associated with mass screening. However, with improvements in usage and technology, costs declined.
»Screening of asymptomatic individuals is controversial, and recommendations from major medical groups have been conflicting. The most appropriate target population for screening includes:
»Women over 60 years of age and at greater risk for other thyroid dysfunction (history of autoimmune disease or type 1 diabetes)
»Family history of B thyroid disease
»Patients with clinical signs of hypothyroidism / hyperthyroidism
»Pregnant Women or Expecting to Get Pregnant
»The sensitive TSH assay is useful in detecting patients at risk of receiving an overdose of thyroxine as a replacement therapy.
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