Thyroid: Anatomy
General information. The average weight is 15 g. It consists of two lobes located on the lateral sides of the larynx at the level of the middle thyroid cartilage, connected by an isthmus that crosses the trachea. The pyramidal lobe is found in 80% of cases, is located upstream of the isthmus and is a stump of the thyroidopharyngeal embryonic duct. Blood supply: the upper thyroid artery from the external carotid artery, the lower – from the thyrocervical trunk.
The microscopic structure of the thyroid gland. Follicles of irregular spherical shape, an average diameter of 30 microns, are stored in cuboid cells. Calcitonin-secreting interfollicular C cells belong to the APUD system (cells of this system produce biogenic amine precursors and have decarboxylase activity).
Recurrent laryngeal nerves. Their defeat causes paralysis of the vocal cords. Located in the tracheoesophageal cavity: 64% on the right, 77% on the left. On the sides of the trachea: 33% on the right, 22% on the left. Front and sides of the trachea: 3% on the right, 2% on the left. Direct (non refundable): 0.5% on the right. Anterior to the lower thyroid artery: 37% on the right, 24% on the left; in 50% of cases, they are part of the Berry ligament, behind the upper pole, and are sensitive to damage when pulling on the thyroid gland.
Upper laryngeal nerves. Their defeat causes paralysis of the wing-thyroid muscle, which is responsible for the melody of the voice. Adjacent or go to the upper pole of the gland along with the vessels.
Thyroid: Congenital
The lingual thyroid gland, located in the foramen ceeum region on the basis of the tongue, can be significant and cause dysphagia, dyspnea, or apnea. Primary therapy should include suppression of thyroid hormones or removal followed by the use of radioactive iodine. Indications for surgical treatment: bleeding, degeneration and necrosis, the threat of patency of the upper respiratory tract.
Thyroid Gland: Physiology.
The function of the gland is the synthesis and secretion of thyroid hormones. An increase in their number leads to a more intense exchange and vice versa. Calcitonin is produced by C cells. It has no physiological role. It is pharmacologically used in the treatment of hypercalcemia and Paget’s disease (bone pathology), as well as a tumor marker in bone marrow cancer.
Metabolism of iodine. Exogenous iodine enters food products and is rapidly absorbed in the intestine, distributed in the extracellular space as iodine compounds, and then excreted by the thyroid gland and kidneys; 90% of iodine compounds are stored in the thyroid gland. A complete cycle of transformations of exogenous iodine occurs in 48 hours.
Thyroid hormone synthesis
1. Active transport of iodine from plasma to thyroid cells is carried out with a gradient of 20: 1 or more. Thyroid-stimulating hormone (TSH) provides the reverse process with a sufficient amount of iodine. .
2. The rapid transition of iodides to iodine.
3. Tyrosine radicals saturated with iodine pass into 3-monoiodotyrosine and 3-5-diiodotyrosine sensitive to TSH.
4. The hormone-active compound thyroxine (T 4 ) is constructed from two diiodotyrosine molecules, and T 3 from a diiodotyrosine molecule and a monoiodo-tyrosine molecule.
Storage, secretion and metabolism of thyroid hormones. T 4 and T 3 are connected by peptide bonds with thyroglobulin, the main component of the intrafollicular colloid. They are released during hydrolysis (in the presence of TSH) and bind to proteins: plasma. In plasma, the ratio of T 4 : T 3 corresponds to 10-20: 1. T 3 is 3-4 times more active than T 4 , its half-life is 3 days, T 4 – 7-8 days.
Regulation of thyroid activity . The hypothalamus secretes a thyroid-stimulating releasing factor that stimulates the cells of the adenohypophysis, responsible for the secretion of TSH. In turn, TSH activates all the processes leading to the synthesis of thyroid hormones. TSH secretion is controlled on the basis of feedback by the level of thyroid hormones in the blood.
Thyroid: examination of patients
Anamnesis. The question arises of hyperfunction or insufficiency, the pressure of the gland on neighboring structures with the development of dysphagia, dysphonia, dyspnea or feelings of suffocation. The duration of these complaints, the growth rate of the gland, and the appearance of pain are evaluated. Information about the possibility of obtaining low doses of ionizing radiation is very important; the use of drugs that contribute to the development of goiter; hereditary pathology.
Inspection Is there an enlargement of the gland and a deviation of the trachea. Palpation when the doctor is in front and behind the patient with the determination of the size and consistency of the gland and regional lymph nodes. Noises during auscultation.
Thyroid: Functional Assessment
I. Secretion and metabolism of thyroid hormones
A. Hypothalamic-pituitary-thyroid system. The main stimulant of T4 and T3 secretion is TSH. In turn, the secretion of TSH is controlled by two mechanisms:
1. The peptide hormone tyroliberin is formed in the sulfur-tuberous nuclei of the hypothalamus and enters the portal system of the pituitary gland. Tiroliberin stimulates the synthesis and secretion of TSH in the adenohypophysis.
2. Thyroid hormones directly inhibit the secretion of TSH by the principle of negative feedback, affecting the thyroid-stimulating cells of the adenohypophysis. T4 and T3 can also affect the secretion of thyroliberin, but whether their effect is stimulating or inhibitory is not known. Therefore, it is believed that the main target of the negative regulatory effect of T4 and T3 is precisely the adenohypophysis. Regulatory relationships in the hypothalamic-pituitary-thyroid system are presented on.
In addition to thyroliberin and thyroid hormones, many other factors directly or indirectly affect TSH secretion, but their role is not so significant.
B. Free and associated thyroid hormones. T4 and T3 are present in serum in both free (unbound) and bound forms. Only free T4 and T3 possess hormonal activity. The proportion of free hormones is very small. The content of free T4 and free T3 is respectively 0.03 and 0.3% of their total serum content. The predominant amount of T4 and T3 is strongly associated with transport proteins, primarily with thyroxin-binding globulin. Thyroxin-binding globulin accounts for 75% of bound T4 and more than 80% of bound T3. Other binding proteins, transthyretin (thyroxin-binding prealbumin) and albumin, account for approximately 15 and 10% of bound T4, respectively. T3 does not bind to either transthyretin or albumin.
1. Changes in the concentration of thyroid hormone binding proteins lead to changes in the content of T4 and T3 themselves. For example, with an increase in the concentration of thyroxin-binding globulin, the levels of total T4 and total T3 in serum increase, and with a deficiency of thyroxin-binding globulin, they decrease. There is a dynamic equilibrium between the total content of T4 and T3 and the content of free T4 and T3. An increase in the concentration of thyroxin-binding globulin initially leads to a short-term decrease in free T4 and free T3. Then the secretion of T4 and T3 is enhanced and their total serum content increases until the normal levels of free T4 and free T3 are restored. Thus, the levels of free T4 and T3 in serum do not change; therefore, the intensity of the processes regulated by T4 and T3 in target tissues does not change either.
2. Changes in the concentrations of transthyretin or albumin have a lesser effect on the content of T4 and T3, since the affinity of T4 and T3 for these proteins is much lower than for thyroxin-binding globulin. However, familial dysalbuminemic hyperthyroxinemia syndrome has recently been described, in which T4 binding to albumin is enhanced (due to impaired albumin structure). Free T4 in this syndrome is normal, and total T4 is significantly increased. A case of an increase in transthyretin levels was also described, in which the total T4 was increased and the free T4 remained normal. Such violations are rare.
B. Peripheral metabolism of thyroid hormones
1. The only source of T4 is the thyroid gland. 80-90 mcg of T4 is secreted per day. About 30% of T4 is converted to T3 (30 mcg / day). T3 is formed by 5′-monodeiodination of the outer phenolic ring of T4. Approximately 80% of the total amount of T3 is formed as a result of deiodination of T4 in peripheral tissues (mainly in the liver and kidneys), and 20% is secreted by the thyroid gland. The hormonal activity of T3 is 3 times higher than that of T4.
2. An alternative pathway of T4 metabolism is 5-monodeiodination of the internal phenolic ring of T4 to form the positional T3 isomer – reverse T3. The latter does not have hormonal activity and does not inhibit the secretion of TSH. Reversible T3 is formed mainly from T4; total daily production of reversible T3 is approximately 30 mcg. For all violations of the formation of T3 from T4, the content of reverse T3 in serum increases.
Thyroid: Function Assessment Methods
A. Laboratory and instrumental studies :
1. General T4. The simplest and most common way to evaluate thyroid secretion is to determine total serum T4 using RIA. However, the total T4 content does not always accurately reflect the functional state of the thyroid gland and the metabolic status of the body. The level of total T4 is affected by changes in the concentrations of proteins that bind thyroid hormones. These changes are most often observed with estrogen treatment or during pregnancy. Total T4 may increase or decrease in non-thyroid diseases.
2. Free T4 is the most accurate indicator of thyroid secretion and metabolic status. The direct method for determining free T4 (equilibrium dialysis of serum with the addition of 125 I-T4) is complex, time consuming and expensive. Therefore, in most laboratories, until recently, an indirect indicator was used to estimate free T4 – calculated free T4: calculated free T4 (has no dimension) = T4 * thyroid hormone binding index, where T4 is the total T4 content measured by the RIA method (μg%); thyroid hormone binding index = (absorption of 125 I-T3 by resin or other sorbent in the test serum) / (absorption of 125 I-T3 by sorbent in the control serum, determined in each laboratory). This formula takes into account the dependence of the content of free T4 on the concentration of thyroxin-binding globulin. It has been proven that for various thyroid dysfunctions, changes in the calculated free T4 correspond to changes in the true concentration of free T4 in serum.
3. Free T3. Since T3 binds to thyroxin-binding globulin, its content depends on the concentration of this protein in the same way as the content of T4. Therefore, to estimate the free T3, the calculated free T3 is used: the calculated free T3 = T3 * thyroid hormone binding index.
4. Recently, many kits for measuring the content of free T4 and T3 by ELISA have appeared. This method is much simpler, faster, and cheaper than determining the calculated T4 and T3. However, not all kits commercially available provide sufficient sensitivity and specificity of measurements. Therefore, you should use only those kits that have successfully passed external and internal quality control.
5. TTG. To determine the concentration of TSH in serum, RIA, immunoradiometric analysis and ELISA are used. Since the last two methods are based on the use of monoclonal antibodies to TSH, their sensitivity is 2 orders of magnitude higher than the sensitivity of RIA. Modern diagnostic kits make it possible to detect TSH concentrations <0.01 mU / L; therefore, with their help it is possible to detect the slightest changes in TSH levels and to clearly distinguish between thyrotoxicosis and euthyroidism. Such kits are also used to identify individuals with thyroid diseases during mass examinations. However, the determination of TSH alone does not make it possible to establish an accurate diagnosis in patients with clinical signs of thyroid dysfunction; for this it is necessary to determine T4 and T3.
B. Functional tests :
1. The absorption of radioactive iodine by the thyroid gland. The radioactive isotopes of iodine (131I, 123I) or 99mTc-pertechnetate are given orally or given iv. Using a radiometer, the radioactivity of the thyroid gland is measured at any time between 4 and 24 hours after administration of the isotope and absorption is calculated as a percentage of the administered dose. This test provides valuable information in the differential diagnosis of thyrotoxicosis with high and low iodine uptake; it must be carried out to confirm the diagnosis of diffuse toxic goiter in patients with thyrotoxicosis ..
2. A sample with thyroliberin was previously widely used to assess the secretory reserve of TSH and the degree of suppression of TSH secretion. At present, highly sensitive methods for determining TSH have been developed, and therefore, a sample with thyroliberin is rarely used. Methodology: determine the basal concentration of TSH in serum, then 200-500 mcg of protirelin is rapidly injected iv and after 30 minutes TSH concentration is determined again. Normally, the level of TSH after stimulation is 2-10 times higher than the basal TSH level. If secondary hypothyroidism is suspected, TSH levels are also determined 60 and 90 (or 120) minutes after the administration of thyroliberin.
3. Suppressive test with T3. The goal is to verify the autonomy of thyroid function (i.e., the independence of the secretion of thyroid hormones from TSH) in the differential diagnosis of thyrotoxicosis. Methodology: the patient takes a standard dose of lyiotironin daily for 7 days, after which the total T4 is determined and the absorption of radioactive iodine by the thyroid gland is measured. Normally, both indicators are reduced by at least 50%. With thyrotoxicosis, total T4 and absorption of radioactive iodine do not decrease or decrease slightly, since the secretion of thyroid hormones is not dependent on TSH. Recently, this test is rarely used, since sensitive methods have been developed for determining the TSH content and thyroid scintigraphy.
B. Serological tests :
1. Markers of autoimmune thyroid damage. These include autoantibodies to thyroglobulin, microsomal antigens, iodide peroxidase, thyroid-stimulating and thyroid-blocking autoantibodies (bind to TSH receptors on thyroid cells), as well as autoantibodies to T4 and T3. The role of thyroid-stimulating autoantibodies and autoantibodies to thyroglobulin and microsomal antigens in the differential diagnosis of hypothyroidism and thyrotoxicosis is described in detail in Ch. 29.
2. Thyroid cancer markers. The diagnostic value of thyroid cancer markers, such as thyroglobulin and calcitonin, is discussed in a separate article on the site.
| Serum T 4 | 49-120 mcg / L |
| Thyroxine free | 28 ± 5 ng / l |
| Serum T 3 | 1.15-1.90 mcg / L |
| Serum TSH | Depending on the laboratory, 0.5-4.0 mcU / ml |
| Serum Free Thyroxine Index | Depending on the laboratory, 6.4-10% |
The thyroid gland: methods for diagnosing dysfunction
A. Hypothyroidism
1. Primary hypothyroidism. Criteria for the laboratory diagnosis of primary hypothyroidism: free T4 (or calculated free T4) is below normal, serum TSH is above normal. An increase in TSH is the most convincing sign of primary hypothyroidism. In mild hypothyroidism, total T4 may remain within normal limits, but TSH levels are elevated. A condition in which the clinical signs of hypothyroidism are mild or absent, total T4 is normal, and the level of TSH is elevated, is called latent hypothyroidism.
2. Secondary hypothyroidism and hypothyroidism associated with non-thyroid diseases. Low total T4 against a background of normal or reduced TSH levels indicates secondary (pituitary or hypothalamic) hypothyroidism. In such situations, a differential diagnostic examination is required, the purpose of which is to identify a disease of the pituitary or hypothalamus. A detailed examination is also carried out in cases where it is necessary to differentiate secondary hypothyroidism from non-thyroid diseases, which may be accompanied by a decrease in the total T4 content against a background of normal or low TSH level.
3. The determination of total T3 is uninformative, since this indicator remains normal in almost a third of patients with hypothyroidism. The examination scheme for suspected hypothyroidism is presented in Fig. 27.2.
B. Thyrotoxicosis
1. To confirm the diagnosis in patients with clinical signs of thyrotoxicosis, it is sufficient to determine the total T4 and free T4. However, an increase in free T4 alone does not say anything about the causes of thyrotoxicosis; thyroid uptake may be required. If thyrotoxicosis is suspected in a patient with normal free T4, TSH levels are determined to confirm the diagnosis.
2. In almost all patients with thyrotoxicosis of any etiology, the total serum T3 is increased (provided that there is no concomitant disease that disrupts the peripheral conversion of T4 to T3). Therefore, in the diagnosis of thyrotoxicosis, total T3, as a rule, is not determined. The definition of T3 is shown in the following cases:
a. With symptoms of thyrotoxicosis without an increase (or with a slight increase) in total T4.
b. With an asymptomatic increase in total T4 (detected by chance or by mass examination). Such patients may indeed have euthyroidism, and an isolated increase in total T4 is due to changes in the concentrations of T4-binding proteins.
at. An increase in total T4 and total T3 without thyrotoxicosis can also be observed with a rare hereditary disease – generalized resistance to thyroid hormones. Despite an increase in total T4, free T4, total T3, and free T3, patients have euthyroidism, and some even have mild hypothyroidism. In recent years, the incidence of individuals with an increase in total T4 without thyrotoxicosis has been steadily increasing.
3. For fuzzy or questionable clinical signs of thyrotoxicosis, it is recommended to determine TSH, since a normal TSH level excludes thyrotoxicosis (except in rare cases of thyrotoxicosis caused by TSH-secreting pituitary adenoma). A reduced TSH level confirms the diagnosis of thyrotoxicosis.
B. Pseudodysfunction of the thyroid gland. In many non-thyroid diseases, serum total T4, total T3 and TSH levels change, but there are no clinical signs of thyroid dysfunction, i.e., the patient has euthyroidism. Changes in laboratory indicators of thyroid function in non-thyroid diseases are called thyroid pseudodysfunction. Thus, it is necessary to distinguish between pseudodysfunction of the thyroid gland from changes in the content of thyroid hormones due to diseases of the thyroid gland. Changes in total T4, total T3, and TSH in non-thyroid diseases can be due to impaired transport and peripheral metabolism of T4 and T3, impaired TSH secretion, or (in rare cases) thyroid dysfunction. The heavier the underlying disease, the more pronounced the listed violations. Two variants of thyroid pseudodysfunction are distinguished: 1. Thyroid pseudodysfunction with low T4 a. T4 and T3. The most frequent and early violation is a decrease in total T3 and free T3 due to inhibition of the conversion of T4 to T3. Since total T3 is rarely determined during an initial examination of a patient with a non-thyroid disease, isolated thyroid pseudodysfunction with a low T3 is usually not detected. As disease severity increases, total T4 and free T4 decrease. There is a correlation between the level of total T4 and the prognosis of the underlying disease: the lower the total T4, the worse the prognosis. The main reason for the decrease in T4 in non-thyroid diseases is a violation of the binding of T4 to thyroxin-binding globulin. Binding inhibitors appear to be cytokines (e.g., tumor necrosis factor beta or interleukin-2). b. TTG. An increase in TSH is characteristic of hypothyroidism, but TSH can be increased in older people with non-thyroid diseases. The concentration of TSH in such cases, as a rule, does not reach 20 mU / L, and the total T4 and free T4 are normal or slightly below normal. On the other hand, a low level of TSH can be observed not only in severe non-thyroid diseases, but also in thyrotoxicosis. Thus, the results of the determination of TSH in non-thyroid diseases are interpreted with caution. At the same time, the normal TSH content makes it possible to exclude thyroid dysfunction. at. Free T4 is usually normal, which corresponds to euthyroidism. Sometimes free T4 slightly decreases or rises, but the deviations of free T4 from the norm with non-thyroid diseases are always less than with hypothyroidism or thyrotoxicosis. d. Thyroid hormone binding index. In hypothyroidism, this index is lowered due to an increase in the number of unoccupied binding sites on thyroxin-binding globulin. In non-thyroid diseases, the index is increased, which determines the value of this indicator for the differential diagnosis of hypothyroidism and pseudodysfunction of the thyroid gland with low T4. We found that an increase in the thyroid hormone binding index in patients with low free T4 indicates a non-thyroid disease, not hypothyroidism. The exception is patients with a deficiency of thyroxin-binding globulin. 2. High T4 pseudodysfunction of the thyroid gland. A temporary increase in total T4 is observed in almost 20% of patients admitted to psychiatric clinics. Total T4 rises in other non-thyroid diseases, especially in relatively mild. Typically, after a few days, total T4 normalizes without treatment. In many patients, metabolism is increased, therefore, thyrotoxicosis and pseudodysfunction of the thyroid gland with high T4 should be differentiated. For this, the following indicators are determined : a. T3 In non-thyroid diseases with increased total T4, total T3 is reduced. Normal total T3 is suspicious, and increased total T3 convincingly confirms thyrotoxicosis. b. TTG. A normal TSH level is excluded, and a TSH level <0.2 mU / L confirms the diagnosis of thyrotoxicosis. at. Test with thyroliberin. If the level of TSH is reduced, a test with thyroliberin is recommended to exclude thyrotoxicosis. In non-thyroid diseases, the concentration of TSH after stimulation with tyroliberin increases by at least 2 times.
Thyroid: effects of drugs.
Many drugs used to treat non-thyroid diseases significantly alter thyroid function. Medicines can affect the secretion of TSH, the synthesis or secretion of T4 and T3, the content of proteins that bind T4 and T3, and their affinity for hormones, disrupt the peripheral metabolism of T4 and T3 or their absorption by target cells, as well as the absorption of exogenous thyroid hormones in the digestive tract .
A. Drugs acting on the secretion of TSH
1. Dopamine, used to treat arterial hypotension, suppresses the secretion of TSH; therefore, a low TSH level in patients receiving dopamine has no diagnostic value. It is also shown that dopamine can lower the TSH level to normal in patients with hypothyroidism.
2. Glucocorticoids suppress TSH secretion. Therefore, in patients receiving glucocorticoids, TSH levels are often reduced.
B. Drugs acting on the synthesis and secretion of thyroid hormones
1. Suppressing secretion
a. Iodine-containing drugs normally inhibit the secretion of thyroid hormones, inhibiting the attachment of inorganic iodine to thyroglobulin and the formation of T3 and T4 from mono- and diiodotyrosine (iodine-induced hypothyroidism, or the Wolf-Tchaikov phenomenon). In healthy people, the effect of iodine-containing drugs disappears after 1-2 weeks. In people with thyroid disease, such as chronic lymphocytic thyroiditis or treated with diffuse toxic goiter, iodine-containing drugs can cause hypothyroidism. According to data obtained in the USA, approximately 10% of patients taking amiodarone (an antiarrhythmic drug containing a large amount of iodine) have primary hypothyroidism. It was found that most patients with hypothyroidism caused by amiodarone had autoimmune thyroid diseases.
b. Lithium carbonate, used in the treatment of MDP, inhibits the secretion of T3 and T4. As a result, serum T3 and T4 levels decrease, and TSH levels increase. Prescribing lithium carbonate in conjunction with iodine-containing drugs can cause severe hypothyroidism. Like iodine-containing drugs, lithium has a stronger effect on T3 and T4 levels in people with existing or previous thyroid diseases.
2. Enhancing secretion
a. Iodine-containing drugs can not only reduce, but also enhance the production of T3 and T4. For example, in patients with treated multinodular toxic goiter, iodine can significantly increase T4 and T3 levels up to thyrotoxicosis (thyrotoxicosis caused by iodine, or the iodine-Bazedov phenomenon). The fact is that in such patients autonomously functioning follicles are preserved in the thyroid gland. Thyrotoxicosis caused by iodine is most often observed in people who have moved from places with a lack of iodine in water and food to places with its sufficient consumption. Thyrotoxicosis caused by iodine can also occur when iodine is prescribed to patients with sporadic non-toxic goiter in places with sufficient iodine intake.
b. Thyrotoxicosis caused by iodine can occur in patients who are constantly receiving amiodarone, especially in places with a relative lack of iodine in water and food.
B. Drugs acting on thyroxin-binding globulin
1. Changing the concentration of thyroxin-binding globulin
a. An increase in the concentration of thyroxin-binding globulin is most often due to the intake of estrogen and estrogen-containing drugs.
b. A decrease in the concentration of thyroxin-binding globulin is caused by androgens (for example, danazol), as well as the antitumor drug asparaginase.
at. With an increase in the concentration of thyroxin-binding globulin, the levels of total T4 and total T3 increase, and with a decrease, they decrease; the levels of free T3 and free T4 do not change.
2. Changing the affinity of thyroxin-binding globulin to T3 and T4. Some drugs block the binding of T3 and T4 to thyroxin-binding globulin. Phenytoin has a very strong effect. This drug lowers total T4, but does not affect TSH. Therefore, patients receiving phenytoin have euthyroidism.
D. Drugs acting on the peripheral metabolism of thyroid hormones
1. Peripheral deiodination T4. A number of drugs inhibit T4 deiodination, resulting in a decrease in T3 levels. Propranolol, propylthiouracil and glucocorticoids suppress deiodination mainly in the liver and kidneys. The sodium salt of iopodic acid, iopanoic acid, and amiodarone seem to inhibit the conversion of T4 to T3 not only in these organs, but also in the pituitary gland. Due to the decrease in the concentration of T3 in the pituitary gland, the secretion of TSH is slightly increased, and as a result, the levels of total T4 and free T4 in serum slightly increase. An increase in total T4 is also observed in patients receiving high doses of propranolol.
2. Absorption of thyroid hormones by target cells. Phenytoin and phenobarbital enhance T4 uptake by cells of different tissues and accelerate T4 metabolism. Therefore, patients with hypothyroidism receiving phenytoin or phenobarbital need larger than usual doses of thyroid hormones.
D. Drugs acting on the absorption of thyroid hormones in the digestive tract. Hypolipidemic agents cholestyramine and colestipol, as well as soy flour, inhibit the absorption of exogenous thyroid hormones by binding them in the intestine. Therefore, for the treatment of hypothyroidism patients taking lipid-lowering drugs, larger than usual doses of levothyroxine may be required.