Thyroid function is regulated by extra- and intrathyroid mechanisms. The mediator of
extrathyroid regulation is TSH, a glycoprotein secreted by the basophilic cells
(tireotrope) of the adenohypophysis. TSH promotes hypertrophy and hyperplasia of
the thyroid, accelerates most aspects of the intermediate thyroid metabolism,
increases the synthesis of nucleic acids and proteins (including thyroglobulin)
and, finally, stimulates the synthesis and secretion of thyroid hormones. In
turn, TSH is regulated by two opposing mechanisms at the level of the
thyrotropic cell. TRH, a tripeptide of hypothalamic origin, stimulates the
secretion and synthesis of TSH, while the thyroid hormones directly inhibit the
secretion mechanism of TSH and antagonize the action of TRH. Thus, the
homeostatic control of TSH secretion is exerted through a negative feedback
mechanism by the thyroid hormones and the threshold for retroinhibition is
apparently established by TRH. The TRH reaches the pituitary gland through the
pituitary portal system and binds to specific high affinity receptors on the
plasma membrane of the thyrotrope cells.
Thyroid scintigraphy examination
Activation of the adenylyl cyclase system or a simultaneous transfer of extracellular calcium into the cell initiates the secretion of TSH. TRH, in addition to promoting the secretion of stored TSH, stimulates TSH synthesis by activating both the transcription and the translation of the subunit gene. TRH is also important at the post-translational level, as suggested by the fact that patients with hypothalamic hypothyroidism have a TSH characterized by a reduced biological activity. The negative feedback of thyroid hormones seems to take place entirely at the level of the thyrotropic cell. It has been experimentally demonstrated that thyroid hormones inhibit both the TRH mRNA levels and the pro-TRH, and the number of TRH receptors on the thyrotrope cells, thus altering the sensitivity to TRH. The main negative feedback action of the thyroid hormones is at the pituitary level and is induced by the binding of the hormones with the TR located in the nucleus of the thyrotropic cell, with consequent reduction of the expression of the genes of the subunits a and of the TSH. The key element of the action of the thyroid hormones inside the pituitary is T3, both that generated locally by T4 and that deriving from the plasma pool. It is not clear to what extent T4 itself acts within the pituitary gland; however, there are other factors that modify the secretion of TSH and its response to TRH.
It appears that both somatostatin and dopamine are physiological inhibitors of TRH secretion. Estrogens increase sensitivity to TRH, while glucocorticoids inhibit it. The catecholamines, in turn, are able to inhibit (by means of the a1-adrenergic receptors) and to stimulate (by means of alpha 2-adrenergic receptors) the secretion of TSH. Experimentally, tumor necrosis factor (TNF) and interleukin inhibit TSH secretion and may play a role in enteroid malate syndrome.
Furthermore, it is important to regulate intracellular thyroid function. In some ways, changes in glandular iodine content determine reciprocal variations in iodine transport activity in the thyroid and regulate growth, amino acid uptake, glucose metabolism, and nucleic acid synthesis. These mechanisms become evident when TSH stimulation is lacking and can therefore be defined as self-regulators, but their most important role is to modify the response to TSH (iodine inhibition and iodine depletion stimulation), probably influencing the production of cAMP following the stimulation by the TSH. Cytokines can act in vitro both in a stimulatory and an inhibitory sense on the synthesis or secretion of thyroid hormones, but the physiological and physiopathological significance of these substances (such as atrial natriuretic peptide, TNF, transforming growth factor, epidermal growth factor, endothelin, etc.) must still be clarified. Hormones contain iodine, which is therefore an essential component for their production, moreover it "helps" the conversion of carotene in vitamin A, the synthesis of proteins and carbohydrates in the intestine. Iodine comes from the water and we drink from the foods we eat in varying quantities; It is therefore important that it is present in sufficient quantities in our diet. The recommended daily iodine dose is 150 micrograms and 250 micrograms for pregnant women, obviously the doses refer to healthy subjects, those who have problems amounts of iodine! A deficiency of iodine causes a thyroid malfunction and tendency to goiter. On a preventive level, it is possible to supplement the diet with the use of iodized salt. The iodine deficiency in soil and consequently in food is a predisposing factor for thyroid disease. The iodine taken from the food is absorbed, and is captured by the thyroid that stores it. The function of the gland is controlled by the pituitary gland by a hormone called TSH; if the thyroid hormone is lowered, the TSH commands its release from the thyroid; if instead thyroid hormone circulates too much, the hypophysis puts the thyroid gland at rest. The first tests to undergo, to exclude or highlight thyroid problems, are the blood tests with various hormone and antibodies. (TSH, T3, T4, TPO Antibodies, Anti-Tireoglobulin ANTI-TG Antibodies, Calcemia). Anti Peroxidase Antibodies (TPO) are produced to the most important enzyme involved in the synthesis of thyroid hormones. They expose a cellular damage by activating the complementary system. These IgG class antibodies are present in almost all thyroid autoimmune diseases such as Hashimoto's disease, mixedema, Graves-Basedow disease. Anti-thyroglobulin antibodies is essential in the differential diagnosis if the anti-peroxidase (ATPO) antibodies are greater than pathogenetic importance, as they correlate with the active phase of the pathology. Anti-Thyroglobulin Antibodies can be detected in 40% -70% of patients with chronic thyroiditis, in 70% of patients with hypothyroidism, in 40% of patients with graves-based disease, and in a small proportion of patients affected by other autoimmune diseases , in particular pernicious anemia. The alterations of T3 and / or T4 levels, and the corresponding alterations of TSH, indicate if there is a normal thyroid function, or if the gland works too little or too much. Moderately high TSH in the presence of other normal indices indicating a hypofunction condition, which is in most cases treated with appropriate therapy (sub-clinical hypothyroidism). The TSH is also particularly useful for defining the correct application of thyroid hormone therapy. If the TSH is reduced, then instead, if the TSH is high, the thyroid is working little (hypothyroidism). The gland may undergo inflammation (thyroiditis) or enlarge (goiter), or produces one or more swellings (nodules); some of these nodules may be sites of tumors.
Laboratory tests for the evaluation of thyroid function can be divided into five
main categories:
1) direct testing of thyroid function evaluation
2) assessment test of the concentration and binding of thyroid hormones in the
blood,
3) metabolic indices,
4) evaluation test of homeostatic control of thyroid function,
5) other tests.
Tests involving in vivo administration of radioactive iodine evaluate intrinsic thyroid function. The measure of uptake by the thyroid radioactive iodine uptake (RAIU) is the most common of these tests. For this purpose, 131I was often used, but 123I is preferable because it allows the use of lower radiation doses. The radioiodio administered spreads uniformly with the endogenous iodide in the extracellular fluids and, under conditions of equilibrium, can be used to determine, in the time unit, the percentage of iodide which, when entering and exiting the extracellular space, is accumulated by the thyroid. Thyroid uptake of radioactive iodine is usually measured 24 hours after administration of the isotope since, after this period, it usually reaches a stable value; however, in severe thyroid hyperfunction states, its levels may rise early. The extent of the uptake is inversely proportional to the plasma concentration of iodide and directly proportional to the functional state of the thyroid. At the usual levels of iodic intake in the United States (up to 1 mg / day) the normal value of radioactive iodine uptake after 24 hours varies approximately between 10 and 30% of the administered dose. Consequently, this test is not very discriminating as regards the distinction between normal and hypothyroid state. However, values above grandmother usually indicate a thyroid hyperfunction and are useful for diagnosing hyperthyroidism. Radioactive iodine uptake is also used as part of the thyroid suppression test. The finding of low levels of radioactive iodine uptake during thyrotoxicosis is very important for the differential diagnosis. This eventuality occurs in the case of iodine-induced hyperthyroidism, fictitious thyrotoxicosis, involuntary ingestion of meat containing thyroid fragments ("hamburger toxicosis") and spontaneous resolution thyrotoxicosis associated with painless chronic thyroiditis, postpartum thyroid or subacute thyroiditis.