Examination of a patient with a disease of the endocrine system. VI
- Complaints about fatigue, mood swings, sometimes tearfulness, emotional lability, palpitations that increase with physical activity -1-! these complaints are characteristic of thyrotoxicosis.
- Some patients note a feeling of heat and decreased chilliness (patients sleep under a thin blanket or sheet). It is believed that the pathophysiological basis of this symptom is an increase in metabolism (due to increased activity of the thyroid gland).
- Complaints of drowsiness, chilliness, apathy, lethargy, poor memory, sometimes in combination with constipation, can be manifestations of hypothyroidism.
- Complaints of thirst (polydipsia), polyuria, dry mouth, increased appetite or, conversely, decreased appetite, and periodic itching of the skin are characteristic of diabetes mellitus. In most cases, the listed symptoms are observed during decompensation of the disease.
- Complaints of attacks of unreasonable fear, accompanied by chills, headache, sometimes dizziness, nausea and vomiting, can be observed with pheochromocytoma, a hormonally active tumor of the adrenal glands.
- Complaints about darkening of the skin, pigmentation of certain areas of the body, especially in places of natural pigmentation, combined with complaints of weakness, weight loss, muscle fatigue and muscle pain are characteristic of chronic adrenal insufficiency. Synonyms for this term are: hypocortisolism, bronze disease, Addison's disease.
- Complaints of cramps, often in the flexor muscles of the upper limbs, the appearance of periodic trismus - convulsive clenching of the jaws and other forms of cramps of striated muscles are a sign of hypoparathyroidism.
- Complaints of progressive weakness, severe fatigue, drowsiness, combined with rapid weight gain, make it necessary to exclude the presence of adiposogenital dystrophy in the patient.
- Complaints of severe thirst and corresponding polyuria, when daily diuresis reaches several liters, may be signs of diabetes insipidus.
- Complaints of severe weakness, poor appetite, weight loss, polyuria combined with complaints of bone pain, a tendency to loose teeth and frequent bone fractures that heal poorly may be signs of hyperthyroidism.
The pathological course of menopause occupies a borderline position between therapy (endocrinology) and gynecology. Women's complaints of hot flashes - short-term sensations of heat combined with increased sweating, irritability, and sometimes tearfulness - require a detailed collection of gynecological history and gynecological examination to exclude this disease. Male menopause occurs more smoothly, mainly with the development of symptoms of weakened sexual potency.
The examiner obtains a family and sexual history. The man is asked whether he is sexually active and at what age, and the number of children. The woman is asked if she has periods, their regularity and abundance (in particular, the number of days). In mature and elderly women, the time of menopause and the peculiarities of the menopausal period (presence of hot flashes and their frequency) are clarified. Next, you should find out the number of pregnancies and births; if there was no pregnancy, identify the cause.
Physical research methods
Examination of the patient
In some cases, examination of the patient is the initiating moment that makes one suspect endocrine pathology and direct the examination of the patient along this path.
First of all, the patient’s endocrine status is visually assessed. It is necessary to pay attention to the patient's weight and height. The average height of an adult man in Europe ranges from 170 to 190 cm, women - from 150 to 180 cm. In the second half of the 20th century. the height of the younger generation has increased by an average of 10-20 cm. Accordingly, the weight of a man should be in the range of 70-90 kg, and that of a woman - from 40 to 60 kg.
If these parameters are exceeded, they speak of a pathology that may be associated with the endocrine status. Height above 2.5 m in men and more than 2.1 m in women is called gigantism, below 1 m - dwarfism, which is also associated with pathology of the endocrine system. When growth is very low, it is customary to talk about nanism (nanos - dwarf).
To calculate the ideal ratio of height and weight, it is recommended to use the formula. The simplest method is to use the Broca index:
Ideal body weight = (height in cm - 100) ± 10% correction according to constitutional type.
With a Broca's index in the range of 90-100%, the indicators are considered satisfactory; an index above 110% indicates excess weight.
There are four degrees of obesity:
- I degree: index 110-125%;
- II degree: index 125-150%;
- III degree: index 150-200%;
- IV degree: index above 200%.
If you are overweight or obese, you should pay attention to the distribution of adipose tissue. This is now given great importance, since obesity has become a global problem, and with high weight, mortality increases by 4-6 times.
According to modern concepts, there are two types of obesity:
- android;
- gynoid.
With the android type of obesity, there is a predominant deposition of fat in the upper half of the body and on the abdomen. With the gynoid type of obesity, deposits are more noticeable on the hips and buttocks.
Thus, the characteristic signs of endocrine pathology are the following external manifestations:
- acromegaly (Greek asgop - limb) - disproportionate enlargement of the limbs, face and other parts of the skeleton;
- gigantism - unusually high (more than 2.5 m) height of the patient;
- nanism - dwarfism, when the height of an adult patient is less than 140 cm;
- Itsenko-Cushing syndrome - morbid obesity with the presence of purple scars on the skin (striae, which are often located in the lower abdomen and thighs), often combined with pathological baldness. A sign of chronic elevated serum cortisol concentrations;
- morbid obesity;
- bronze coloration of the skin and mucous membranes due to adrenal insufficiency, Addison's disease;
- the type of hair growth may not correspond to the patient’s gender, which requires genetic analysis. When examining a patient, the presence of severe obesity of the female type with fat deposition on the hips, buttocks, and breasts in combination with hypoplasia of the genital organs requires the exclusion of adiposogenital dystrophy;
Inspection. Examination in the study of endocrine patients is of great importance, and often at the first glance at the patient it is possible to recognize the disease either by the general appearance of the patient, or by individual signs of the disease (Graves' disease, myxedema, acromegaly, gigantism, pituitary dystrophy, Addison's disease).
When examining, you need to pay attention to the following signs.
1) Body growth, as well as the sizes and ratios of its individual parts: significant deviations in growth should direct the doctor’s thoughts to dysfunction of the cerebral appendage, thyroid, reproductive or thymus glands; preservation or violation of proportionality in certain parts of the body and the presence of other characteristic signs make it possible to clarify the pathogenesis of growth disorders; a disproportionate increase in the distal parts of the body (nose, lips, chin, hands, feet) will indicate hyperfunction of the anterior pituitary gland (acromegaly), etc.
2) Fatness of patients and features of fat deposition. Obesity is most often associated with decreased function of the thyroid, pituitary gland or gonads, emaciation with hyperthyroidism, damage to the cerebral appendage (Simmonds disease), and decreased function of the pancreas (diabetes). The distribution of fat in the subcutaneous tissue in typical cases often allows us to get closer to the pathogenetic diagnosis of endocrine obesity: predominant fat deposition in the pelvic girdle (lower abdomen, buttocks, thighs) and on the chest is characteristic of pituitary and sexual obesity, more or less uniform distribution of fat throughout the body will speak for thyroid obesity. Severe weight loss is observed with hyperthyroidism, with Addison's disease and especially with Simmonds' disease (pituitary cachexia).
3) Body hair. Due to the dependence of hair growth on hormonal influences, mainly the gonads, thyroid gland, adrenal cortex and cerebral appendage, the condition and nature of the hairline are important diagnostic signs for disorders of internal secretion, such as: female type of hair growth in eunuchoidism, increased hair growth in hyperthyroidism and acromegaly, hypertrichosis (hirsutism) with tumors of the adrenal cortex, hair loss with myxedema, etc.
4) Condition of the skin - tenderness and brightness in Graves' disease, roughness and pallor in myxedema, dark brown color in Addison's disease, etc.
5) Face, its expression and changes in the eyes.
Of the endocrine glands, only the thyroid gland and testicles are accessible to direct examination: reduction and enlargement of these organs can be easily detected by examination.
Palpation. By palpation, you can examine the same two endocrine glands - the thyroid and the male reproductive glands, determining their size, density, uniformity or unevenness of consistency (nodularity), soreness, etc. Through a special gynecological examination using bimanual palpation, you can also feel the female reproductive glands - ovaries.
Palpation of the skin in Graves' disease and myxedema is of great diagnostic importance: with the first, the skin is thin, soft, smooth, (velvety), moist and hot, with the second - thick, dense, rough, dry and cold.
Percussion. With the help of percussion, it is possible to determine the retrosternally (retrosternally) located struma (goiter), and this is, apparently, the only use of percussion in the study of endocrine glands.
Auscultation. Auscultation in the study of endocrine glands also finds only one application, namely in the study of an enlarged thyroid gland, when one can hear a systolic gurgling noise arising in its dilated arterial vessels.
Anthropometric measurements. Anthropometric measurements can serve to objectively confirm those noted during examination or to identify subtle endocrine-related differences in proportions and body structure. Thus, gender differences are reflected in women, compared to men, by relatively shorter limb lengths, smaller shoulder widths, and larger pelvic sizes. Further, excessive leg length is characteristic of eunuchoidism, and relatively short legs are characteristic of early puberty. Determinations of height and weight also provide useful numerical data for the assessment of endocrine influences and endocrine pathology.
Determination of basal metabolism. Determination of basal metabolism is of great diagnostic importance for a number of diseases of the endocrine glands, especially the thyroid. By basal metabolism we mean the minimum amount of energy, expressed in calories, that the body needs to maintain its basic vital functions, i.e. blood circulation, respiration and constant body temperature. Therefore, the determination of the basal metabolic rate is carried out with complete physical rest on an empty stomach (no earlier than 12 hours after the last meal). The principle of determining the basal metabolic rate is that, using special equipment, the values of pulmonary ventilation are directly determined, i.e., the amount of exhaled air and its composition, over a known period of time (usually 10 minutes). Then, using special tables, the amount of absorbed oxygen and released carbon dioxide and their ratio (respiratory coefficient) are calculated, and then the required number of calories per hour per 1 kg of weight (normally about 1 calorie) or per 1 m2 of body surface (normally about 40 calories ). An increase in basal metabolism by more than 10-15% will indicate an undoubted pathological increase and is most often observed in hyperthyroidism or Graves' disease, in which an increase of 30-50-80-100% is a common occurrence. A decrease in basal metabolism by 15-30-50% against the norm is characteristic of hypothyroidism and myxedema, pituitary dystrophy and Simmonds' disease.
X-ray method. The X-ray method of examination easily makes it possible to determine changes in the bone skeleton and judge endocrine diseases from them. Thus, it is possible to recognize: 1) tumors of the pituitary gland by changes in the size and shape of the sella turcica (its widening and deepening, destruction of the edges); 2) acromegaly - by thickening of the bones and enlargement of the air cavities of the skull, by the large development of exostoses around the joints; 3) eunuchoidism - by insufficient ossification of bone sutures and delayed ossification of the epiphyseal zones; 4) hypergenitalism - by accelerated ossification of the epiphyses.
X-ray can also identify a retrosternally located enlarged thyroid gland (retrosternal goiter).
Laboratory research. Of the everyday laboratory tests used for diagnostic purposes in recognizing endocrine diseases, we most often have to deal with urine and blood tests.
Urine examination- its daily amount, specific gravity and sugar content in it - is essential in recognizing diabetes mellitus and diabetes insipidus.
Blood test can also play a known role in the recognition of certain endocrine diseases. For example, secondary anemia is often one of the symptoms of insufficiency of the thyroid gland (myxedema) or adrenal glands (Addison's disease). A certain degree of polyglobulia occurs in Graves' disease. A change in the leukocyte formula towards lymphocytosis is characteristic of dysfunction of the thyroid gland in one direction or another - irrespective (Graves' disease, myxedema). In other endocrine disorders, the blood picture also changes, but these changes have not yet been sufficiently studied.
Functional research methods. Functional diagnostics of the endocrine glands has not yet acquired practical significance. Of the various methods used for this purpose (see special manuals on endocrinology), the most complex ones are of greatest importance: 1) determination of basal metabolism to assess the functional state of the thyroid gland; 2) determination of the specific dynamic effect of food - to identify the functional capacity of the pituitary gland and 3) study of glycemic blood curves - to judge the function of the pancreas, adrenal glands and thyroid gland.
Endocrinopathic syndromes
The main endocrinopathic syndromes are based mainly on the phenomena of hyperfunction or hypofunction of one or another endocrine gland.
I. Thyroid syndromes.
1. Hyperthyroid syndrome(hyperthyroidism, hyperthyroidism) is manifested by an increase in the volume of the thyroid gland, goiter (its hyperplasia), increased heart rate - tachycardia and protrusion of the eyeballs - bulging eyes (increased tone of the sympathetic nervous system).
This triad of symptoms is characteristic of severe cases of hyperthyroidism, the so-called Graves' disease. In addition to them, very important symptoms of hyperthyroidism are weight loss, depending on increased metabolism, trembling, diarrhea, sweating, vasomotor phenomena and phenomena of increased neuropsychic excitability associated with overexcitability of the autonomic sympathetic and parasympathetic nervous systems.
2. Hypothyroid syndrome(hypothyroidism, hypothyroidism) is often characterized by a decrease in the volume of the thyroid gland, a slowdown in heart rate and sunken eyeballs, then a tendency towards obesity, constipation, dry skin, a decrease in general nervous and mental excitability and, finally, a peculiar change in the skin and subcutaneous tissue that appears infiltrated, doughy-dense consistency, as if swollen, but when pressure is applied to them, they do not leave pits; This is the so-called mucous edema, hence the name of severe cases of this pathology - myxoedema.
II. Parathyroid syndromes.
1. Hyperparathyroid syndrome(hyperparathyroidism, hyperparathyroidism) is rare, accompanied by pstercalcemia and clinically, due to the loss of significant amounts of calcium salts by the skeleton, is expressed by atrophy and fibrous degeneration of bones with the formation of cavities in them, with their curvatures and fractures and with subsequent deformation of the skeleton "(general osteitis fibrocystis - osteitis or osteodystrophia fibrosa cystica general is ata - Recklinghausen's disease.
2. Typoparathyroid syndrome(hypoparathyroidism, hypoparathyroidism) is observed much more often; Hypocalcemia plays a significant role in its pathogenesis (as well as a shift in the acid-base balance to the alkaline side - alkalosis and a disorder of protein metabolism). The clinical manifestation of this syndrome is increased excitability mainly of the motor apparatus of the nervous system (with a decrease in calcium in the blood to 7 mg% or lower) and a tendency to tetanic convulsions. These cramps most often develop in the upper limbs (the forearms are bent, the fingers are joined together in the “obstetrician’s hand” position), less often the cramps also affect the lower limbs or also spread to the face, gastrointestinal tract or larynx. Seizures last from a few minutes to 1-2 hours and are easily repeated. In the clinic, this syndrome is called Spasmophilia or tetany.
III. Pituitary syndromes.
Disruption of the complex functions of the pituitary gland entails the development of a number of pituitary or pituitary syndromes. We will present here only the more clinically important ones.
A. Hyperfunction of the pituitary gland, more precisely, its anterior lobe (hyperpituitarism) can lead to the development of three pituitary syndromes: the most famous and common acromegalic, the so-called Cushing syndrome, and diabetic.
1. Acromegaly is based on a tumor-like growth (adenoma) of eosinophilic cells of the anterior pituitary gland and overproduction of the growth hormone secreted by them. This syndrome is characterized by large sizes of the hands, feet and skull, brow ridges, cheekbones, nose and chin; At the same time, not only the bones, but also the soft parts, including the lips and tongue, increase.
If this hyperfunction of the pituitary gland appears in childhood, then a sharp increase in overall growth is observed, which ultimately more or less significantly exceeds the physiological norm - gigantism develops. Gigantism, therefore, is like acromegaly of childhood.
The opposite, rare syndrome associated with hypofunction of eosinophilic cells of the anterior pituitary gland is acromicria (micros - Greek - small), expressed in a decrease in the volume of the extremities, mainly the arms.
2. Cushing's syndrome is based on the proliferation (adenoma) of basophilic cells of the anterior lobe and the overproduction of endocrinotropic (stimulating the activity of other endocrine glands) pituitary hormones. The main symptoms of this syndrome are obesity of the face and trunk (but not limbs) with the formation of skin scars and hypertrichosis (stimulation of the adrenal cortex), arterial hypertension and hyperglycemia (stimulation of the adrenal medulla), bone loss - osteoporosis (stimulation of the parathyroid glands).
3. Pituitary diabetes mellitus is associated with overproduction of a hormone that regulates carbohydrate metabolism and has an effect on it that is opposite to the action of insulin. This form of diabetes often accompanies acromegaly.
B. Hypofunction of the pituitary gland(hypopituitarism) underlies the following four syndromes:
1) pituitary obesity;
2) pituitary cachexia;
3) pituitary dwarf growth;
4) diabetes insipidus.
We took the described endocrinopathic syndromes in their isolated form. But, as already mentioned above, individual glands are parts of a single endocrine system. Therefore, in essence, there are no isolated dysfunctions of the gland alone. Inevitably, a number of other glands more closely related to the first are also involved in the process. Consequently, almost every endocrine disease has the character of multiple lesions of the glands - pluriglandular in nature. However, pluriglandular syndromes in the strict sense of the word are also distinguished, and these include those intrasecretory disorders in the pathogenesis of which it is not possible to identify the leading role of damage to one or another gland, such as infantilism, premature aging, endocrine depletion.
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Manifestations of diseases of the endocrine glands are very diverse and can be detected already during a traditional clinical examination of the patient. Only the thyroid gland and testicles are accessible to direct examination (examination, palpation). Laboratory studies currently make it possible to determine the content of most hormonal substances in the blood, however, the nature of metabolic disorders associated with changes in the content of these hormones can also be determined using special methods. For example, in diabetes mellitus, determining blood glucose levels often more accurately reflects metabolic disorders than the level of insulin itself, which controls glucose metabolism.
In the diagnosis of endocrinopathies, it is important to focus primarily on the variety of symptoms from various organs and systems - skin, cardiovascular system, gastrointestinal tract, musculoskeletal and excretory systems, nervous system, eyes, comparing them with data from biochemical and other additional studies . It should be borne in mind that individual clinical manifestations of the disease may be due to differences and uneven distribution in tissues of the receptors with which hormones interact.
History taking
When interviewing the patient, it is possible to identify a number of important data indicating dysfunctions of certain endocrine glands, the time and reasons for their occurrence, and the dynamics of development.
Already at the beginning of the conversation with the patient, certain features can be clearly detected: hasty, confused speech, some fussiness in movements, increased emotionality, characteristic of hyperfunction of the thyroid gland, and, conversely, lethargy, apathy, and some inhibition with its hypofunction.
Complaints. Complaints of patients with endocrine disorders are often of a general nature (poor sleep, fatigue, easy excitability, weight loss), but may also be more characteristic of damage to the corresponding endocrine gland, including they may be associated with involvement in the process (due to metabolic -hormonal disorders) of various organs and systems.
Patients may complain of skin itching (diabetes mellitus, hyperthyroidism), hair loss (thyroiditis), pain in the joints (acromegaly) and bones (hyperparathyroidism), bone fractures (hyperparathyroidism, Itsenko-Cushing syndrome), muscle weakness (Itsenko-Cushing syndrome, hyperaldosteronism), pain in the heart, palpitations with atrial fibrillation (hyperthyroidism, pheochromocytoma). There are often complaints of poor appetite, dyspeptic symptoms (hypothyroidism, adrenal insufficiency), sexual dysfunction - amenorrhea (hyperthyroidism, hypogonadism, Itsenko-Cushing syndrome), menorrhagia (hypothyroidism), impotence (diabetes mellitus, hypogonadism).
Physical methods for studying the endocrine system
Inspection and palpation
As already noted, only the thyroid gland and testicles are accessible to inspection and palpation. However, it is very important both in these cases and in cases of damage to other endocrine glands (which cannot be examined and palpated) to focus on the results of physical examination of various organs and systems (skin, subcutaneous fat, cardiovascular system, etc.).
Already during a general examination, a number of significant signs of pathology of the endocrine system can be identified: changes in growth (dwarf growth while maintaining the proportionality of the body of pituitary origin, giant growth with increased function of the pituitary gland), disproportionate sizes of individual parts of the body (acromegaly), features of the hairline, characteristic of many endocrinopathies , and a large number of other symptoms.
When examining the neck area, they get an approximate idea of the size of the thyroid gland, symmetrical or asymmetrical enlargement of its various parts. When palpating the lobes and isthmus of the thyroid gland, the size, consistency, and nature (diffuse or nodular) of the increase are assessed. The mobility of the gland during swallowing, the presence or absence of pain and pulsation in its area are assessed. To palpate nodes located behind the upper part of the sternum, you need to immerse your fingers behind the sternum and try to determine the pole of the node.
When examining the skin, hirsutism (ovarian pathology, hypercortisolism), hyperhidrosis (hyperthyroidism), hyperpigmentation (hypercortisolism), ecchymosis (hypercortisolism), purplish-cyanotic striae are sometimes revealed - peculiar areas (stripes) of atrophy and stretching, usually on the lateral areas of the abdomen (hypercortisolism).
A study of subcutaneous fat tissue reveals both excessive development of subcutaneous fat tissue - obesity (diabetes mellitus) and significant weight loss (hyperthyroidism, diabetes mellitus, adrenal insufficiency). With hypercortisolism, excess fat deposition is observed on the face, which gives it a moon-shaped, rounded appearance (Cushing's syndrome). A kind of dense swelling of the legs, the so-called mucous edema, is observed with hypothyroidism (myxedema).
An examination of the eyes may reveal characteristic proptosis (hyperthyroidism), as well as periorbital edema (hypothyroidism). Possible development of diplopia (hyperthyroidism, diabetes mellitus).
Important data can be obtained from studying the cardiovascular system. With the long-term course of some endocrine diseases, heart failure develops with typical signs of edema syndrome (hyperthyroidism). One of the important causes of arterial hypertension is endocrine diseases (pheochromocytoma, Itsenko-Cushing syndrome, hyperaldosteronism, hypothyroidism). Orthostatic hypotension (adrenal insufficiency) is less common. It is important to know that in most endocrine diseases, changes in the electrocardiogram due to myocardial dystrophy are observed, such as rhythm disturbances, repolarization disorders - displacement of the ST segment, T wave. Echocardiography can occasionally reveal pericardial effusion (myxedema).
Sometimes a full complex of symptoms of malabsorption develops with typical diarrhea and corresponding laboratory changes, such as anemia, electrolyte disturbances, etc. (hyperthyroidism, adrenal insufficiency).
Urinary disorders with polyuria characteristic of diabetes mellitus against the background of polydipsia are often missed by both patients and doctors. Urolithiasis with symptoms of renal colic occurs in hyperparathyroidism and Itsenko-Cushing syndrome.
When examining the nervous system, nervousness (thyrotoxicosis) and fatigue (adrenal insufficiency, hypoglycemia) are revealed. Possible disturbances of consciousness up to the development of coma (for example, hyperglycemic and hypoglycemic coma in diabetes mellitus). Tetany with convulsions is characteristic of hypocalcemia.
Additional methods for studying the endocrine system
Visualization of the endocrine glands is achieved by various methods. Conventional x-ray examination is considered less informative. Modern ultrasound examination is more informative. The most accurate picture can be obtained by computed tomography, X-ray or magnetic resonance imaging. The latter study is especially valuable when studying the pituitary gland, thymus, adrenal glands, parathyroid glands, and pancreas. These studies are primarily used to identify tumors of the corresponding endocrine glands.
Radioisotope research of various endocrine glands has become widespread, which primarily applies to the thyroid gland. It allows you to clarify the structural features (size), as well as functional disorders. The most widely used are iodine-131 or pertechnetate labeled with technetium-99. Using a gamma camera, gamma radiation is recorded on photosensitive paper, and thus a scan is performed, which allows you to evaluate the size, shape, and areas of the gland that actively accumulate isotopes (the so-called hot nodes). Radioisotope scanning is used to study the adrenal glands.
There are various methods for determining the levels of hormones in the blood. Among them, radioimmunoassay (RIA-radioimmunoassay) deserves the most attention. Its principle is as follows: antibodies (antiserum) are first prepared for the test substance, which is an antigen, then a standard amount of the resulting antiserum is mixed with a standard amount of the original antigen labeled with radioactive iodine-125 or iodine-131 (up to 80% of the labeled antigen binds to antibodies, forming a radioactive precipitate with a certain radioactivity). Blood serum containing the test substance is added to this mixture: the added antigen competes with the labeled antigen, displacing it from complexes with antibodies. The more analyte (hormone) is contained in the test sample, the more radioactive tracers are displaced from the complex with the antibody. Next, the antigen-antibody complex is separated by precipitation or selective absorption from the free labeled hormone and its radioactivity (i.e., quantity) is measured on a gamma counter. The radioactivity of the precipitate decreases. The more antigen in the test sample, the less radioactivity of the remaining precipitate. Using this method, small amounts of insulin, pituitary tropic hormones, thyroglobulin and other hormones can be detected with great accuracy in the blood and urine. However, it should be borne in mind that an increase in the content of hormones in the blood can occur due to their fraction associated with proteins. In addition, the radioimmune method makes it possible to quantitatively evaluate substances that are chemically very close to hormones, lacking hormonal activity, but having a common antigenic structure with hormones. Determining hormone levels after special stress tests, which allow assessing the reserve function of the gland, is of some importance.
Among biochemical blood tests, the most important is the determination of glucose in the blood and urine, which reflects the course of the pathological process in diabetes mellitus. A decrease or increase in blood cholesterol levels is characteristic of thyroid dysfunction. Changes in calcium metabolism are detected in pathology of the parathyroid glands.
To make this lecture easier to understand, let us recall some brief anatomical and physiological data on the endocrine system. To make this lecture easier to understand, let us recall some brief anatomical and physiological data on the endocrine system. The endocrine system is the system that releases hormones into the blood. “Hormones” are chemical substances secreted into the blood or lymphatic vessels and have various effects on target organs. The endocrine system is the system that releases hormones into the blood. “Hormones” are chemical substances secreted into the blood or lymphatic vessels and have various effects on target organs. Back in the middle of the twentieth century, it mainly included clearly organized morphological formations called glands. Back in the middle of the twentieth century, it mainly included clearly organized morphological formations called glands. By now this concept has become much broader. It turned out that many other organs and tissues have endocrine functions. By now this concept has become much broader. It turned out that many other organs and tissues have endocrine functions.
For example, one of these places turned out to be the hypothalamus. It turned out that the hypothalamus secretes: thyroliberin, luliberin, corticoliberin, prolactoliberin, follikoliberin, somatoliberin, melanocytoliberin, luteostatin, melanocytostatin, which regulate the functioning of the pituitary gland. It turned out that the hypothalamus secretes: thyroliberin, luliberin, corticoliberin, prolactoliberin, folliculol. berine, somatoliberin, melanocytoliberin, luteostatin, melanocytostatin, which regulate the functioning of the pituitary gland
The liver secretes angiotensin. Kidneys – erythropotin and renin. Stomach – gastrin, somatostatin. The liver secretes angiotensin. Kidneys – erythropotin and renin. Stomach – gastrin, somatostatin. Duodenum and small intestine – motilin, secretin, cholecystokinin-pancreozymin, somatostatin. Cardiac atria and brain - atrial and brain natriuric peptides, respectively. Connective tissue and cells of mesenchymal origin are somatomedins. Duodenum and small intestine – motilin, secretin, cholecystokinin-pancreozymin, somatostatin. Cardiac atria and brain - atrial and brain natriuric peptides, respectively. Connective tissue and cells of mesenchymal origin are somatomedins. Adipose tissue – leptin, adiponectin, etc. Adipose tissue – leptin, adiponectin, etc.
In our subject it is not possible to analyze in detail all these hormones and their actions. But this information must be remembered once and for all: the endocrine system is not only the endocrine glands. However, here and today we are forced to talk specifically about the endocrine glands and their functions. In our subject it is not possible to analyze in detail all these hormones and their actions. But this information must be remembered once and for all: the endocrine system is not only the endocrine glands. However, here and today we are forced to talk specifically about the endocrine glands and their functions.
The system of endocrine glands is scattered throughout the body (Fig.) The system of endocrine glands is scattered throughout the body (Fig.) 1. Pituitary gland. 2. Thyroid gland. 3; 4 and 7. Adrenal glands. 5. Sex glands. 6. Pancreas. 8. Thymus (thymus gland) 9. Parathyroid glands. 10. Epiphysis. Let's briefly look at their morphology and functions.
The pineal gland secretes the hormone melatonin, which activates the division of pigment cells in the skin and has an antigonadotropic effect. The pineal gland secretes the hormone melatonin, which activates the division of pigment cells in the skin and has an antigonadotropic effect. The pituitary gland consists of an anterior - adenohypophysis and a posterior - neurohypophysis and intermediate parts (lobes). The pituitary gland consists of an anterior - adenohypophysis and a posterior - neurohypophysis and intermediate parts (lobes). The anterior lobe of the pituitary gland produces somatotropin - growth hormone; gonadotropic hormones that stimulate male and female sex glands; lactogenic hormone that supports the secretion of estrogen and progesterone by the ovaries; lactogenic hormone that supports the secretion of estrogen and progesterone by the ovaries; ACTH, which stimulates the production of adrenal hormones; TSH, which regulates the functioning of the thyroid gland. The posterior lobe of the pituitary gland contains two hormones: oxytocin, which regulates labor and secretion of the mammary glands and oxytocin, which regulates labor and secretion of the mammary glands, and vasopressin or antidiuretic hormone, which mainly regulates the reabsorption of water from the renal tubules, Intermediate part - intermedin hormone, which regulates pigment metabolism in the integumentary tissues.
THE THIROID GLAND produces thyroxine (T4) and triiodothyronine (T3), which regulate general metabolism in the body, influence the formation of the skeleton, accelerate bone growth and ossification of epiphyseal cartilage; calcitonin, which regulates the metabolism of calcium and phosphorus. Its functions are studied by determining these hormones.
The parathyroid glands regulate the metabolism of calcium and phosphorus. Removing the parathyroid glands causes seizures and can lead to death. The parathyroid glands regulate the metabolism of calcium and phosphorus. Removing the parathyroid glands causes seizures and can lead to death. The thymus (thymus gland is the most important organ of the body’s immunological defense. It ensures the differentiation and proliferation of bone marrow stem cells; produces the enzyme thymosin, which ensures the immunological competence of lymphocytes throughout the body. T-lymphocytes formed in the bone marrow enter the thymus and, under the influence of thymosin, become differentiated, immunologically competent and become the main mediators of cellular immunity Thymus (the thymus gland is the most important organ of the body’s immunological defense. It ensures differentiation and proliferation of bone marrow stem cells; produces the enzyme thymosin, which ensures the immunological competence of lymphocytes of the whole organism. T-lymphocytes formed in the bone marrow enter the thymus and under the influence thymosin become differentiated, immunologically competent and become the main mediators of cellular immunity
The adrenal glands consist of two layers - the cortex and the medulla. The adrenal glands consist of two layers - the cortex and the medulla. The medulla produces two hormones - mediators of the sympathetic nervous system - adrenaline and norepinephrine. They increase the contractility and excitability of the heart, constrict the blood vessels of the skin, and increase blood pressure. The medulla produces two hormones - mediators of the sympathetic nervous system - adrenaline and norepinephrine. They increase the contractility and excitability of the heart, constrict the blood vessels of the skin, and increase blood pressure. The cortex is an extremely important formation of the human body. It produces about 30 different hormones that regulate the concentration of sodium, potassium and chlorine in the blood and tissues, carbohydrate, protein and fat metabolism, as well as the production of sex hormones. The cortex is an extremely important formation of the human body. It produces about 30 different hormones that regulate the concentration of sodium, potassium and chlorine in the blood and tissues, carbohydrate, protein and fat metabolism, as well as the production of sex hormones
The pancreas is an organ that has both exocrine and endocrine functions. The exocrine function was discussed in the section on diseases of the digestive system. Endocrine function is provided by special cells collected in small islands (islets of Langerhans), which are embedded in the gland tissue throughout its entire volume. They produce the hormone insulin. Insulin mainly regulates carbohydrate metabolism - the consumption of glucose by various systems of the body, ensuring the transfer of glucose from the blood into the cell.
Let us now consider the issues of the norm of hormones secreted by these glands. Here, unfortunately, we must immediately make a reservation that in various sources in Russia you can find significantly different normal values of these hormones, which depends on the lack of standardization of research methods and on the chaos that exists today place in this country. Even if there were uniform standards in Russia, no one is going to adhere to them - everyone uses the method that is easier for them to fulfill or that they like best. However, we must outline approximate standards for you, and you should know them. As mentioned above, the anterior lobe of the pituitary gland secretes a significant amount of a wide variety of hormones. As mentioned above, the anterior lobe of the pituitary gland secretes a significant amount of a wide variety of hormones.
The fasting GH level is 8 ng/ml. As you know, overproduction of this hormone can be observed with gigantism or acromegaly, and underproduction can be observed with pituitary dwarfism, which we discussed in the lecture “Questioning, examining...for endocrine diseases.” The level of fasting growth hormone is 8 ng/ml. As is known, overproduction of this hormone can be observed with gigantism or acromegaly, and underproduction can be observed with pituitary dwarfism, which we discussed in the lecture “Questioning, examining...for endocrine diseases” TSH is 0.45 - 6.2 µIU/ml. Thyroid-stimulating hormone regulates the function of the thyroid gland, and its overproduction can lead to hyperthyroidism, and decreased production can lead to myxedema. TSH is 0.45 - 6.2 µIU/ml. Thyroid-stimulating hormone regulates the function of the thyroid gland, and its overproduction can lead to hyperthyroidism, and decreased production can lead to myxedema
ACTH – (on an empty stomach, at 8 o’clock in the morning, in the supine position) - 
The delusion gets me everywhere - the nonsense of newspapers, television, radio. The shelling is nonsense: it's a short flight, but it always hits and wounds. It is impossible to interrupt this nonsense, It is impossible to interrupt this nonsense, You can’t protect yourself from it with earplugs... You can’t protect yourself from it with earplugs... Some people create troubles from victories, Some people create troubles from victories, And sells lost souls And sells lost souls And others, to block the op , And others, in order to block the shouting, So that they are finally heard, Show hysterical agility Even in church in prayers to the Almighty.
The PL level in men is 2–12 ng/ml, in women 2–20 ng/ml. The PL level in men is 2–12 ng/ml, in women 2–20 ng/ml. The level of ADH in the blood is 29 ng/ml. The level of ADH in the blood is 29 ng/ml. Targeted radiography of the sella turcica and especially nuclear magnetic resonance (NMR) studies and computed tomography are of great help in diagnosing diseases of the pituitary gland. Targeted radiography of the sella turcica and especially nuclear magnetic resonance (NMR) studies and computed tomography are of great help in diagnosing diseases of the pituitary gland. These methods make it possible to detect pituitary tumors up to 0.2 cm in diameter (microadenomas) with 97% confidence. These methods make it possible to detect pituitary tumors up to 0.2 cm in diameter (microadenomas) with 97% confidence.
Pancreas The main methods for studying the endocrine function of the pancreas are the direct determination of the level of insulin and glucagon in the blood. The main methods for studying the endocrine function of the pancreas are the direct determination of the levels of insulin and glucagon in the blood. However, these methods have not yet entered into widespread practice. The most widely used methods for indirectly studying the insulin-producing function of the pancreas are the determination of glucose in the blood and urine and the glucose tolerance test.
Blood glucose is determined on an empty stomach. The normal level is fluctuating from 3.33 to 5.5 (according to some methods up to 6.105) mmol/l. Blood glucose is determined on an empty stomach. The normal level is fluctuating from 3.33 to 5.5 (according to some methods up to 6.105) mmol/l. An increase in blood glucose levels is called hyperglycemia. An increase in blood glucose levels is called hyperglycemia. This indicator is an almost reliable sign of the presence of diabetes mellitus in a person (it should be remembered that hyperglycemia can also have other origins). This indicator is an almost reliable sign of the presence of diabetes mellitus in a person (it should be remembered that hyperglycemia can also have other origins). A decrease in blood glucose levels, which is called hypoglycemia, may also occur. This condition can occur both with diabetes mellitus and with a number of diseases, which may be based on tumors or damage to the endocrine glands of another order. A decrease in blood glucose levels, which is called hypoglycemia, may also occur. This condition can occur both with diabetes mellitus and with a number of diseases, which may be based on tumors or damage to the endocrine glands of another order.
Determination of glucose (sugar) in urine is usually carried out in a daily volume of urine. Normally, there is no glucose in the urine. Its appearance is called glycosuria and is a serious sign of diabetes mellitus, although sometimes it can occur after heavy consumption of sweet foods and a rare disease - renal diabetes. Determination of glucose (sugar) in urine is usually carried out in a daily volume of urine. Normally, there is no glucose in the urine. Its appearance is called glycosuria and is a serious sign of diabetes mellitus, although sometimes it can occur after heavy consumption of sweet foods and a rare disease - renal diabetes. Glucose tolerance test. In many people, diabetes occurs hidden, latently (the so-called impaired glucose tolerance). These people may have minor stigmata of diabetes that are not confirmed by routine urine and blood tests. To clarify the diagnosis in these cases, this test was developed. Glucose tolerance test. In many people, diabetes occurs hidden, latently (the so-called impaired glucose tolerance). These people may have minor stigmata of diabetes that are not confirmed by routine urine and blood tests. To clarify the diagnosis in these cases, this test was developed.
Typically, the test is performed as follows: the subject is taken for glucose on an empty stomach, then given 75 g (or, more precisely, 50 g per m2 of body area) of glucose dissolved in ml of water to drink, and the blood is tested for glucose every 30 minutes for the next 3 h. Usually the test is performed as follows: the subject is taken to test blood for glucose on an empty stomach, then given 75 g (or, more precisely, 50 g per m2 of body area) of glucose dissolved in ml of water to drink, and the blood is tested for glucose every 30 minutes for the next 3 hours. Interpretation of the results: in a healthy person, the rise in glucose level after 1 hour does not exceed 80% of the initial level, by 2 hours it drops to normal and by 2.5 hours it may fall below normal. Interpretation of the results: in a healthy person, the rise in glucose level after 1 hour does not exceed 80% of the initial level, by 2 hours it drops to normal and by 2.5 hours it may fall below normal. In patients, the maximum rise is observed after 1 hour, reaching figures above 80% of the initial value, and normalization is delayed for 3 hours or more. In patients, the maximum rise is observed after 1 hour, reaching figures above 80% of the initial value, and normalization is delayed for 3 hours or more.
Thyroid gland Thyroid gland Methods for studying the functions and clinical morphology of the thyroid gland include determination of protein-bound iodine, the level of thyroid hormones, the shape and size of the gland. Methods for studying the functions and clinical morphology of the thyroid gland include determining protein-bound iodine, the level of thyroid hormones, and the shape and size of the gland. Determination of protein-bound iodine (PBI) is one of the most important and accurate methods for studying gland function. 90-95% of SBI consists of thyroxine, a thyroid hormone. Determination of protein-bound iodine (PBI) is one of the most important and accurate methods for studying gland function. 90-95% of SBI consists of thyroxine, a thyroid hormone. Normally, the SBI is 315.37 nmol/l. Normally, the SBI is 315.37 nmol/l. With thyrotoxicosis, its level is higher than 630.37 nmol/l, with hypothyroidism - less than 315.18 nmol/l. With thyrotoxicosis, its level is higher than 630.37 nmol/l, with hypothyroidism - less than 315.18 nmol/l.
Thyroxine (T4) and triiodothyronine (T3) are determined from the thyroid hormones. Approximate norms: T nmol / l, and T3 - 1.2 - 2.8 nmol / l. Thyroxine (T4) and triiodothyronine (T3) are determined from the thyroid hormones. Approximate norms: T nmol / l, and T3 - 1.2 - 2.8 nmol / l. At the same time, as a rule, the TSH level is determined, which, according to the same methods, is normally 0.17 - 4.05 nmol/l. At the same time, as a rule, the TSH level is determined, which, according to the same methods, is normally 0.17 - 4.05 nmol/l. One of the objective methods of studying the morphology and function of the thyroid gland is scanning using radioactive isotopes. The scanograms can outline the size of the thyroid gland, areas of hypo- and hyperfunction. One of the objective methods of studying the morphology and function of the thyroid gland is scanning using radioactive isotopes. The scanograms can outline the size of the thyroid gland, areas of hypo- and hyperfunction.
In recent years, ultrasound examination (ultrasound) has been widely used to examine the thyroid gland. Ultrasound is currently the method of choice in determining the size of the thyroid gland and the presence of changes in its structure. In recent years, ultrasound examination (ultrasound) has been widely used to examine the thyroid gland. Ultrasound is currently the method of choice in determining the size of the thyroid gland and the presence of changes in its structure. A highly effective research method is CT, which allows you to study the size and structure, identify tumors or other changes in it. A highly effective research method is CT, which allows you to study the size and structure, identify tumors or other changes in it.
Adrenal glands (cortical layer) To study the function of the adrenal cortex, aldosterone is determined in the urine, 17-hydroxycorticosteroids (17-OX) in the blood and urine, and neutral 17-ketosteroids (17-KS) in the urine. To study the function of the adrenal cortex, aldosterone is determined in the urine, 17-hydroxycorticosteroids (17-OX) in the blood and urine, and neutral 17-ketosteroids (17-KS) in the urine. Determination of aldosterone. It is believed that there is a directly proportional relationship between the amount of aldosterone in the urine and the mineralocorticoid activity of the adrenal cortex. Determination of aldosterone. It is believed that there is a directly proportional relationship between the amount of aldosterone in the urine and the mineralocorticoid activity of the adrenal cortex. In healthy people, 8.34 to 41.7 nmol/day is excreted. aldosterone. In healthy people, 8.34 to 41.7 nmol/day is excreted. aldosterone. An increase in urinary aldosterone excretion can be observed with so-called primary and secondary hyperaldosteronism (adenoma or tumor or hyperfunction of the cortical layer). An increase in urinary aldosterone excretion can be observed with so-called primary and secondary hyperaldosteronism (adenoma or tumor or hyperfunction of the cortical layer).
The definition of 17-OX reflects the level of glucocorticosteroids in the blood. The definition of 17-OX reflects the level of glucocorticosteroids in the blood. Normally, 17-OX in the blood contains from 0.14 to 0.55 µmol/l. Normally, 17-OX in the blood contains from 0.14 to 0.55 µmol/l. A persistent increase in 17-ox levels is observed in adrenal tumors and in Itsenko-Cushing syndrome. A persistent increase in 17-ox levels is observed in adrenal tumors and in Itsenko-Cushing syndrome. A decrease in 17-OX is found with hypofunction of the adrenal cortex or insufficiency of the anterior pituitary gland. A decrease in 17-OX is found with hypofunction of the adrenal cortex or insufficiency of the anterior pituitary gland. Excretion of 17-OX in urine normally parallels changes in the blood. Excretion of 17-OX in urine normally parallels changes in the blood. Determination of cortisol in urine is considered even more specific for studying glucocorticosteroid function of the adrenal glands. Determination of cortisol in urine is considered even more specific for studying glucocorticosteroid function of the adrenal glands. Norm nmol/day. Norm nmol/day.
Definition 17-KS. Most of the 17-CS comes from androgens, so their determination allows us to make a judgment about the androgenic function of the adrenal cortex. Definition 17-KS. Most of the 17-CS comes from androgens, so their determination allows us to make a judgment about the androgenic function of the adrenal cortex. Normally, 27.7 - 79.7 µmol/day is excreted in men and 17.4 - 55.4 in women. Normally, 27.7 - 79.7 µmol/day is excreted in men and 17.4 - 55.4 in women. A decrease in the release of 17-KS is characteristic of adrenal insufficiency, an increase is characteristic of tumors. A decrease in the release of 17-KS is characteristic of adrenal insufficiency, an increase is characteristic of tumors. There are also methods for indirectly determining the functions of the adrenal cortex. These include the determination of sodium and potassium in blood and urine. There are also methods for indirectly determining the functions of the adrenal cortex. These include the determination of sodium and potassium in blood and urine.
It is known that in the regulation of electrolyte levels (especially sodium and potassium), the main role belongs to mineralocorticoids, in particular aldosterone, and to a lesser extent glucocorticoids. It is known that in the regulation of electrolyte levels (especially sodium and potassium), the main role belongs to mineralocorticoids, in particular aldosterone, and to a lesser extent glucocorticoids. In this regard, the level of sodium and potassium in the blood and their excretion in the urine will indirectly indicate the state of production of these hormones by the adrenal glands. In this regard, the level of sodium and potassium in the blood and their excretion in the urine will indirectly indicate the state of production of these hormones by the adrenal glands. Normally, sodium in the blood plasma contains mmol/l, and potassium - 3.8 - 4.6 mmol/l. Normally, sodium in the blood plasma contains mmol/l, and potassium - 3.8 - 4.6 mmol/l. Normally, mmol/day is excreted in urine. sodium and mmol/day. potassium Normally, mmol/day is excreted in urine. sodium and mmol/day. potassium In practice, determination in urine is carried out. In practice, determination in urine is rarely performed. rarely.
Adrenal glands (medulla) Studying the function of the adrenal medulla is most often resorted to when a tumor is suspected. To study the function of the adrenal medulla is most often resorted to when a tumor is suspected. 3 hormones are studied - adrenaline, norepinephrine, dopamine in the blood or plasma. 3 hormones are studied - adrenaline, norepinephrine, dopamine in the blood or plasma. Their level in plasma is equal to - adrenaline 
Federal Agency for Education of the Russian Federation
State Educational Institution of Higher Professional Education Bashkir State University
Department of Biology
Department of Biochemistry
Course work
Methods for studying the endocrine system in normal and pathological conditions
Completed:
5th year OSE student
Group A
Usachev S. A.
Ufa 2010
Content
Introduction………………………………………………………………4
1. Review of methods for studying the endocrine system
normal and pathological………………………………………………………………6
1.1. Brief historical sketch……………………………………………………...6
1.2. Review of modern methods for studying the endocrine system..12
1.3. Modern methods of studying the endocrine system
example of a study of the thyroid gland……………………………28
2. Problems and prospects of endocrine research methods
systems…………………………………………………………… …………45
Conclusion……………………………………………………………..58
List of used literature……………………………………………………59
List of abbreviations adopted in the work
AOK – antibody-forming cells
AG – antigen
ACTH – adrenocorticotropic hormone
HPLC – high speed liquid chromatography
HI – compensatory hyperinsulinemia
DNA – deoxyribonucleic acid
LC – liquid chromatography
ELISA – enzyme immunoassay
IR – insulin resistance
CT – computed tomography
LH – luteinizing hormone
MS – metabolic syndrome
MRI – magnetic resonance imaging
PCR – polymerase chain reaction
RIA – radioimmunoassay
DHT – delayed-type hypersensitivity reaction
DM 2 – type 2 diabetes mellitus
TSH – thyroid stimulating hormone
T4 – thyroxine
T3 – triiodothyronine
TBG – thyroxine binding globulin test
Ultrasound – ultrasound examination
FIA – fluorescence immunoassay
Color Doppler mapping
CNS - central nervous system
thyroid gland - thyroid gland
Introduction
Over the past few years, as a result of the development of more subtle, sensitive and specific methods for determining hormones and other methods for studying the endocrine system in health and disease, clinical endocrinology and biochemistry has largely transformed from a kind of art into a branch of applied chemistry, physiology, physics and genetics. This progress was made possible thanks to the introduction into practice of a large number of new and high-tech methods for studying the endocrine system, the isolation and subsequent biological and biochemical characterization of various highly purified polypeptide hormones, steroids, vitamins, derivatives of small polypeptides and amino acids, which are classified as hormones, as well as the production of radioactively labeled atoms of hormones with high specific activity.
Relevance of the topic:
Currently, on the threshold of understanding the most hidden and mysterious phenomena of a living organism, the most important task is to find the most reliable, accessible and high-tech research methods. The new era of nanotechnology and highly specialized discoveries is beginning to make its contribution to biological chemistry, which has long been using methods not only of chemical analysis, but the most modern technologies in all branches of physics, computer science, mathematics and other sciences. Time dictates its conditions to humanity - to know more deeply, to know thoroughly, to find the cause of the processes occurring in a living organism in normal and pathological conditions. The search for new research methods does not stop, and the scientist simply does not have time to generalize, systematize this area of cognition, or highlight what he needs at the moment. In addition, when I studied the problem of research on the endocrine system, I did not find a sufficiently complete, generalizing manual on this topic. Many researchers, in particular biochemists, are faced with the problem of searching and systematizing modern methods for studying the endocrine system in health and disease. This is due, first of all, to the fact that new sources of literature and new research methods appear every day, but there is not a single guide on research methods that would systematize data on methods. It is for these reasons that the relevance of the topic I have chosen is very high.
Goal of the work:
Systematize data on the state of methods for studying the endocrine system in normal and pathological conditions in the modern world.
Tasks:
- Make a historical overview of the topic.
Reflect current knowledge about methods for studying the endocrine system, without a detailed description of research methods and techniques.
Describe research methods using the example of one endocrine gland.
Highlight the problems and prospects of modern methods for studying the endocrine system in health and disease.
1. Review of methods for studying the endocrine system in normal and pathological conditions
1.1. Brief historical sketch
The study of the endocrine system and endocrinology itself are relatively new phenomena in the history of science. The endocrine system was an inaccessible part of the human body until the beginning of the 20th century. Before this, researchers could not unravel the secrets of endocrine formations due to the fact that they could not isolate and study the fluids they secrete (“juices” or “secrets”). Scientists have not discovered any “juices” or special excretory ducts through which the produced fluid usually flows out. Therefore, the only method for studying the functions of the endocrine gland was the method of excision of part or the whole organ.
Scientists and historians argued that the organs of the endocrine system in the East were known in ancient times and respectfully called them “glands of fate.” According to Eastern healers, these glands were receivers and transformers of cosmic energy flowing into invisible channels (chakras) and supporting human vitality. It was believed that the coordinated work of the “glands of fate” could be disrupted by disasters occurring at the behest of evil fate.
A mention of a disease, most likely diabetes, is contained in Egyptian papyri from 1500 BC. e.. Goiter and the effects of castration in animals and humans belong to the first clinical descriptions of diseases, the endocrine nature of which was subsequently proven. Old clinical descriptions of endocrine diseases were made not only in the West, but also in ancient China and India.
If we arrange significant discoveries in many areas of endocrinology in time, the resulting picture reflects in miniature the history of all biology and medicine. After fragmentary clinical observations made in antiquity and the Middle Ages, these sciences progressed extremely slowly. The second half of the 19th century saw rapid advances in many areas of medicine, both in the quality of clinical research and in the understanding of disease mechanisms. This process was due to the complexity of the interconnection of historical reasons.
First, the industrial revolution led to the accumulation of capital, which was used to develop many sciences, mainly chemistry and biology.
Another revolution that took place in the second half of the 19th century and was of fundamental importance for the development of not only endocrinology, but also medicine and biology, was the advent of experimental animal modeling. Claude Bernard and Oscar Minkowski demonstrated the possibility of conducting controlled and reproducible experiments in laboratory conditions. In other words, the opportunity to “cross-examine” nature was created. Without the work of these pioneers, we would be deprived of much of our current knowledge in the field of endocrinology. The study of all those substances called hormones began with experiments on whole animals (and often preceded by observations on sick people). These substances were called substance "X" or factor "?". Koch's postulates for endocrinology provided for the following work order:
1. Removal of the suspected gland. After the removal of an endocrine gland, a complex of disorders occurs due to the loss of the regulatory effects of those hormones that are produced in this gland. Due to the traumatic nature of surgery, instead of surgical removal of the endocrine gland, the introduction of chemicals that disrupt their hormonal function can be used. For example, administration of alloxan to animals disrupts the function of β-cells of the pancreas, which leads to the development of diabetes mellitus, the manifestations of which are almost identical to the disorders observed after extirpation of the pancreas. 1
2. Description of the biological effects of the operation. For example, the assumption about the presence of endocrine functions in the pancreas was confirmed in the experiments of I. Mering and O. Minkowski (1889), who showed that its removal in dogs leads to severe hyperglycemia and glycosuria; the animals died within 2-3 weeks. after surgery against the background of severe diabetes mellitus. It was subsequently found that these changes occur due to a lack of insulin, a hormone produced in the islet apparatus of the pancreas.
3. Introduction of gland extract.
4. Evidence that the administration of the extract eliminates the symptoms of absence of the gland.
5. Isolation, purification and identification of the active principle.
During the Second World War, a large amount of data was accumulated in the field of endocrinology, many of which were of fundamental importance for the subsequent development of science. After the war, due to the emergence of many new techniques, there was a generally unprecedented acceleration in the pace of research. And now, as a result of a sharp influx of technical and creative forces, the number of publications, both on endocrinology and on all other aspects of biomedical knowledge, is growing at an impressive rate. This means a constant supply of new data, which requires periodic revision of old ideas in their light. 2
The 20th century was marked by the birth of the science of hormones, or endocrinology. The word “hormone” itself was introduced in 1905 by the British physiologist, Professor Ernst Starling, at a lecture at the Royal College of Physicians in London. It was formed by two Cambridge University professors from the Greek word hormao, which means “to quickly set in motion,” “to raise,” or “to excite.” Starling used it to describe the "chemical carriers" released into the blood by the endocrine glands (endon - internal + krino - produce), such as the testes, adrenal glands and thyroid gland, as well as from the external, exocrine (exo - external) glands. glands such as salivary and lacrimal glands. This new science developed very quickly, exciting the minds of not only doctors, but also society.
As a rule, the history of studying any hormone goes through four stages.
First, the effect produced on the body by the secretion secreted by the gland is observed.
Secondly, methods are being developed to determine internal secretions and the degree of its influence on the body. This is first done through biological tests to determine the effect of the hormone on an organism that is deficient in it. Later, chemical methods for such measurements were established.
Thirdly, the hormone is isolated from the gland and isolated.
And finally, fourthly, its structure is determined by chemists, and it is synthesized. 3
Nowadays, researchers who start with observations at the whole organism level have more and more questions as their work progresses until they try to solve the original problem at the molecular level. Here, endocrinological research is taken into its own hands by biological chemistry and its section – molecular biology (endocrinology).
As soon as new morphological, chemical, electrophysiological, immunological and other techniques appear, they find very rapid application in endocrinology. For example, in the 30s and 40s, very complex methods were used to study steroids. This has led to great advances in understanding the structure and biosynthesis of steroid hormones. The possibility of using radioactive isotopes, which appeared in the late 40s - 50s, expanded our knowledge about many aspects of the iodine cycle, intermediate metabolism, ion transport, etc. To study the functional activity of the endocrine gland, its ability to capture from the blood and accumulate certain compound. It is known, for example, that the thyroid gland actively absorbs iodine, which is then used for the synthesis of thyroxine and triiodothyronine. With hyperfunction of the thyroid gland, iodine accumulation increases; with hypofunction, the opposite effect is observed. The intensity of iodine accumulation can be determined by introducing the radioactive isotope 131I into the body, followed by assessing the radioactivity of the thyroid gland. Compounds that are used for the synthesis of endogenous hormones and are included in their structure can also be introduced as a radioactive label. Subsequently, it is possible to determine the radioactivity of various organs and tissues and thus assess the distribution of the hormone in the body, as well as find its target organs.
Later, a combination of polycrylamide gel electrophoresis and autoradiography was used creatively to study many proteins, including hormone receptors. Simultaneously with these impressive advances in chemistry, the use of histochemical, immunohistochemical and electron microscopic methods turned out to be even more fruitful.
All variants of chromatography—column, thin-layer, paper, multidimensional, gas-liquid (with or without mass spectrometry), high-performance liquid—were used by endocrinologists immediately after their introduction. They made it possible to obtain important information not only about the amino acid sequence of peptides and proteins, but also about lipids (especially prostaglandins and related substances), carbohydrates and amines.
As molecular biological research techniques are developed, endocrinologists are rapidly using them to study the mechanisms of hormone action. Currently, the recombinant DNA method is used not only for this purpose, but also for the production of protein hormones. Indeed, it is difficult to name a biochemical or physiological method that would not be adopted by endocrinologists. 4
1.2. Review of modern methods for studying the endocrine system
When examining patients with suspected endocrine pathology, in addition to collecting an anamnesis of the disease, examination and complaints of the patient, the following diagnostic methods are used: general laboratory methods (clinical and biochemical), hormonal studies, instrumental methods, molecular genetic methods.
In most cases hormonal study has not a key, but a verifying value for making a diagnosis. Hormonal testing is not used at all to diagnose a number of endocrine diseases (diabetes insipidus and diabetes mellitus); in some cases, hormonal testing has diagnostic value only in combination with biochemical indicators (calcium level in hyperthyroidism).
A hormonal study may reveal a decrease in the production of a particular hormone, an increase and its normal level (Table 1). The most commonly used methods for determining hormones in clinical practice are various modifications radioimmune method
. These methods are based on the fact that the radiolabeled hormone and the hormone contained in the test material compete with each other for binding to specific antibodies: the more a given hormone is contained in the biological material, the fewer labeled hormone molecules will bind, since the number of hormone-binding sites in sample constantly. More than 20 years ago, Berson and Yalow proposed a radioimmunoassay method for the determination of insulin.
This method was based on their observation that in the peripheral blood of diabetic patients treated with insulin there was a protein (later shown to be a globulin) that binds insulin labeled with 131I. The significance of these data and the subsequent development of a radioimmunoassay for the determination of insulin is emphasized by the awarding of the Nobel Prize to Yalow and Berson.
Soon after the initial reports by these researchers, corresponding methods for the determination of other hormones were developed and described by other laboratories. These methods use either antibodies or serum proteins that bind a specific hormone or ligand and carry a radiolabeled hormone that competes with the standard hormone or hormone present in the biological sample.
Principle radioreceptor method
essentially no different from radioimmunoassay, only the hormone, instead of binding to antibodies, binds to a specific hormonal receptor on the plasma membrane or cytosol. Specific receptors for most polypeptide hormones are located on the outer surface of the plasma membrane of cells, while receptors for biologically active steroids, as well as thyroxine and triiodothyronine, are located in the cytosol and nuclei. The sensitivity of radioreceptor analysis is lower than that of radioimmunoassay and most biological methods in in vitro systems. In order to interact with its receptor, the hormone must have the appropriate conformation, i.e., be biologically active. It is possible that a hormone loses its ability to bind to its receptor but continues to interact with antibodies in the radioimmunoassay system. This discrepancy reflects the fact that antibodies and receptors “recognize” different parts of the hormone molecule.
A number of radioreceptor methods for hormonal analysis have been proposed. Typically, tissue from organs specific to a given hormone is obtained and receptors are isolated from it using standard techniques. Isolated plasma membrane receptors in sediment are relatively stable when stored at temperatures below -20°C. However, solubilized receptors of polypeptide and steroid hormones, isolated from plasma membranes or from the cytosol and not associated with ligands, turn out to be unstable, which is manifested by a decrease in their ability to bind specific hormones, even if they were stored frozen for a relatively short time.
Recently, non-radioactive methods have become most widespread. As a standard method for the determination of various compounds in clinical chemistry, immunoassay
, characterized by good sensitivity, specificity and a wide range of applications. In particular, immunoassay is used to determine hormones. Such methods include:
- 1) enzyme-linked immunosorbent assay (ELISA), solid-phase ELISA type ELISA or homogeneous ELISA type EMIT.
- 2) fluorescence immunoassay (FIA), based on the measurement of fluorescence enhancement, quenching or polarization or on the study of fluorescence with time resolution.
- 3) bio- or chemiluminescent immunoassay.
1) be applicable both for two-site immunometric analysis of proteins and for direct competitive assays of haptens based on the binding principle.
2) have appropriate sensitivity, accuracy and working range of determined concentrations with minimal scatter of results over the entire range.
3) easy to improve to further increase sensitivity and simplify analysis.
Potentially, the technique should have the possibility of its improvement and application to the analyzes of other substances, out-of-laboratory and separation-free analyzes and to the simultaneous determination of several substances (the so-called multiple immunoassay). The ideal methods of immunoassay are most closely matched by luminescent or photoemission methods, in which the label is detected by recording light emission.
Luminescence is the emission of light by a substance in an electronically excited state. There are several types of luminescence, differing only in the energy sources that transfer electrons to an excited state, i.e. to a higher energy level, namely:
1) Radioluminescence, in which the excitation of the corresponding fluorophore is achieved by absorbing the energy released during the process of irreversible radioactive decay. The excited fluorophore emits light, returning to the ground state.
2) Chemiluminescence, in which excitation is achieved as a result of a chemical reaction (usually an irreversible oxidation reaction). If a chemical reaction is carried out in biological systems under the action of enzymes, then in this case the term bioluminescence is usually used. If a chemical reaction is initiated by an increase in the temperature of the reagents, then this type of luminescence is called thermochemiluminescence, but if the reaction is initiated by an electric potential, then the corresponding phenomenon is called electrochemiluminescence.
3) Photoluminescence, in which excitation is caused by photons of infrared, visible or ultraviolet light. Photoluminescence can be further subdivided into fluorescence, where the excited molecule quickly returns to its original state through a singlet state, and phosphorescence, where the excited molecule returns to its original state through a triplet state. Phosphorescence emission decays much more slowly. The emitted light quanta have a long wavelength. Photoluminescence differs from radio- and chemiluminescence in that it is usually reversible, and therefore can be repeatedly induced in a given system (since the formation of an excited intermediate and its subsequent inactivation by light emission does not lead to chemical transformations).
In addition to these methods, chemical methods for the determination of a number of substances (usually metabolites of hormones and their precursors) have not completely lost their importance. They are often used to purify protein fractions and study hormones. chromatography . Liquid chromatography is widely used as a rapid and selective analytical method for the separation and identification of various substances. Liquid chromatography (LC) in its classic version (at atmospheric pressure) and high-speed or HPLC at elevated pressure is the optimal method for analyzing chemically and thermally unstable molecules, high molecular weight substances with reduced volatility, which is explained by the special role of the mobile phase: in contrast to the gaseous eluent in liquid chemistry it performs not only a transport function. The nature and structure of the components of the mobile phase control the chromatographic behavior of the separated substances. Among the most typical objects of liquid chromatography are proteins, nucleic acids, amino acids, dyes, polysaccharides, explosives, drugs, plant and animal metabolites. Liquid chromatography, in turn, is divided into liquid-adsorption (separation of compounds occurs due to their different ability to be adsorbed and desorbed from the surface of the adsorbent), liquid-liquid, or distribution (separation is carried out due to different solubility in the mobile phase - eluent and stationary phase , physically sorbed or chemically grafted onto the surface of a solid adsorbent), ion exchange chromatography, where separation is achieved through the reversible interaction of the analyzed ionizing substances with the ionic groups of the sorbent - ion exchanger. A special place in the use of liquid chromatography methods in medicine is occupied by size exclusion or gel chromatography and affinity or biospecific chromatography. This version of LC is based on the principle of separating a mixture of substances according to their molecular weights. In exclusion chromatography (from the English exclusion - exception; outdated name - sieve) chromatography, molecules of substances are separated by size due to their different ability to penetrate the pores of the sorbent. The mobile phase is a liquid, and the stationary phase is the same liquid that has filled the pores of the sorbent (gel). If these pores are inaccessible to the molecules of the analyte, then the corresponding compound will leave the column earlier than the one with smaller molecular sizes. Molecules or ions whose sizes are between the maximum and minimum pore diameters of the gel are divided into separate zones. Size exclusion chromatography has received particularly intensive development in the last two decades, which was facilitated by the introduction into chemical and biochemical practice of Sephadex - dextran gels cross-linked with epichlorohydrin. On various types of Sephadex, chemicals with different molecular weights can be fractionated, so they are widely used for the isolation and purification of biopolymers, peptides, oligo- and polysaccharides, nucleic acids and even cells (lymphocytes, erythrocytes), in the industrial production of various protein preparations, in particular enzymes and hormones. 5 Affinity chromatography is characterized by the extremely high selectivity inherent in biological interactions. Often, one chromatographic procedure can purify the desired protein thousands of times. This justifies the effort required to prepare an affinity sorbent, which is not always an easy task due to the risk of biological molecules losing the ability to interact specifically during their covalent attachment to the matrix. 6
When studying the functional state of the endocrine glands, the following methodological approaches are used:
1. Determination of the initial level of a particular hormone.
2. Determination of the hormone level over time, taking into account the circadian rhythm of secretion.
3. Determination of the hormone level under the conditions of a functional test.
4. Determination of the level of hormone metabolite.
Table 1. Pathogenesis of endocrine diseases 7
Most often in clinical practice, determination of the basal level of a particular hormone is used. Blood is usually taken on an empty stomach in the morning, although food intake does not affect the production of many hormones. To assess the activity of many endocrine glands (thyroid, parathyroid), assessing the basal level of hormones is quite sufficient. When determining the basal level of a hormone, certain difficulties may arise due to the circulation in the blood of several molecular forms of the same hormone. First of all, this concerns parathyroid hormone.
Most hormones circulate in the blood bound to carrier proteins. As a rule, the level of free, biologically active hormone in the blood is tens or hundreds of times lower than the total level of the hormone.
The levels of most hormones have a characteristic daily dynamics (circadian rhythm of secretion), and very often this dynamics acquires clinical significance. The most important and illustrative in this regard is the dynamics of cortisol production (Fig. 1.1). 8
Other examples in this regard are prolactin and growth hormone, the secretion rhythm of which is also determined by the sleep-wake cycle. The pathogenesis of a number of endocrine diseases is based on a disruption of the circadian rhythm of hormone production.
In addition to the circadian rhythm, most biological parameters can be reflected in the level of the hormone in the blood. For many hormones, reference values largely depend on age (Fig. 1.2) 9, gender, and phase of the menstrual cycle.
The level of a number of hormones can be influenced not only by concomitant somatic diseases and medications taken for them, but also by factors such as stress (cortisol, adrenaline), environmental features (thyroxine levels in regions with different iodine consumption), and the composition of food taken the day before ( C-peptide) and many others.
The fundamental principle for assessing the activity of pituitary-dependent glands (thyroid gland, adrenal cortex, gonads) and a number of other endocrine glands is the determination of so-called diagnostic pairs of hormones. In most cases, hormone production is regulated by a negative feedback mechanism. Feedback can occur between hormones belonging to the same system (cortisol and ACTH), or between hormones and its biological effector (parathyroid hormone and calcium). In addition, there does not have to be a direct interaction between the hormones that make up the pair. Sometimes it is mediated by other humoral factors, electrolytes and physiological parameters (renal blood flow volume, potassium level and angiotensin for the renin-aldosterone pair). An isolated assessment of the indicators that make up a pair can lead to an erroneous conclusion.
Despite the improvement of hormonal analysis methods, functional tests still have great diagnostic value in the diagnosis of endocrinopathies. Functional tests are divided into stimulation and suppressive (suppressive). The general principle of testing is that stimulation tests are prescribed for suspected insufficiency of the endocrine gland, and suppressive tests are prescribed for suspected hyperfunction.
Along with assessing the level of hormones in the blood, in some cases the determination of their excretion in the urine may have a certain diagnostic value. The diagnostic value of these studies, for example, determining the excretion of free cortisol, is significantly less than that of modern functional tests. Similarly, the use of determining the excretion of hormone metabolites has now almost completely ceased, the only exception being the determination of the level of catecholamine metabolites for the diagnosis of pheochromocytoma.
In recent years, fully automated methods of hormonal research have become widespread, which reduces the number of errors such as incorrect blood collection, storage, delivery and other “human factors”.
From instrumental methods The studies most commonly use ultrasound (US), radiography, computed tomography (CT), and magnetic resonance imaging (MRI). In addition, special methods are used in endocrinology: angiography with selective sampling of blood flowing from the endocrine gland, radioisotope study (thyroid scintigraphy), bone densitometry. The main instrumental methods used to study the endocrine glands are presented in Table 2.
Molecular genetic research methods.
The rapid development of science over the past few decades and research in the field of molecular biology, medical genetics, biochemistry, biophysics, closely intertwined with microbiology, immunology, oncology, epidemiology, etc., have led to the creation and active implementation of molecular biological diagnostic laboratories methods for researching the genome of humans, animals, plants, bacteria and viruses. These methods are most often called DNA research.
DNA research methods allow for early and more complete diagnosis of various diseases, timely differential diagnosis and monitoring of the effectiveness of therapy. The active development of DNA diagnostic methods and their introduction into practice suggests that the moment is not far off when these methods will significantly narrow the scope of tasks of more traditional diagnostic studies, such as cytogenetics methods, and perhaps will displace them from practical medicine into the scientific sphere.
Table 2. Basic instrumental methods
research of endocrine glands 10
Currently, there are two areas of DNA diagnostics: hybridization analysis of nucleic acids and diagnostics using polymerase chain reaction.
PCR was immediately introduced into practice, which made it possible to raise medical diagnostics to a qualitatively new level. The method has become so popular that today it is difficult to imagine working in the field of molecular biology without its use. The PCR method has received particularly rapid development thanks to the international Human Genome program. Modern sequencing technologies (deciphering DNA nucleotide sequences) have been created. If in the recent past it took a week to decipher DNA of 250 nucleotide pairs (bp), modern automatic sequencers can determine up to 5000 bp. per day. This, in turn, contributes to the significant growth of databases containing information about nucleotide sequences in DNA. Currently, various modifications of PCR have been proposed, dozens of different applications of the method have been described, including “long-PCR”, which allows copying ultra-long DNA sequences. For the discovery of PCR, K. W. Mullis was awarded the Nobel Prize in Chemistry in 1993.
All approaches to gene diagnostics can be divided into several main groups:
1. Methods for identifying specific DNA sections.
2. Methods for determining the primary sequence of nucleotides in DNA.
3. Methods for determining DNA content and cell cycle analysis. eleven
PCR allows you to find in the material under study a small section of genetic information contained in a specific sequence of DNA nucleotides of any organism among a huge number of other DNA sections and multiply it many times. PCR is an “in vitro” analogue of the biochemical reaction of DNA synthesis in a cell.
PCR is a cyclic process, in each cycle of which thermal denaturation of the double strand of target DNA occurs, subsequent addition of short oligonucleotide primers and their extension using DNA polymerase by adding nucleotides. As a result, a large number of copies of the original target DNA accumulate, which are easily detected.
The discovery of PCR resulted in immediate practical use of the method. In 1985, an article was published that described a PCR-based test system for diagnosing sickle cell anemia. Since 1986. To date, more than 10,000 scientific publications have been devoted to PCR. The prospects for using PCR seem more than impressive. 12
Cytochemical research methods.
These methods are variants of the described in vitro biological studies. They usually have greater sensitivity than radioimmunoassay methods, but are much more cumbersome and expensive per determination. The results of cytochemical biological studies are quantitatively assessed on histological sections using a special device - a microdensitometer.
Histological sections are prepared from hormone-specific tissues or target cells that have previously been exposed to different concentrations of the standard and test hormone. Using a densitometer, an area with a diameter of 250 - 300 nm is scanned to quantify the color reaction caused by a change in the redox state of the object under the influence of hormonal stimulation. For quantitative analysis, histological dyes that are sensitive to these changes are used.
The first cytochemical biological assay system was developed for ACTH, and the target tissue in this system was the adrenal cortex. Other methods for the biological determination of ACTH are either too insensitive or require large volumes of plasma. Thus, cytochemical determination of the redox state of tissue is a valuable means of analyzing the normal and altered function of the hypothalamic-pituitary-adrenal system based on ACTH levels.
A cytochemical method for determining LH has been developed, but significant difficulties have been encountered associated with significant fluctuations in the results of different determinations and the variable sensitivity of the object, which may reflect known biological differences in different animals. Sensitive specific cytochemical methods have been proposed for the determination of parathyroid hormone, ADH and thyrotropin.
With further sophistication of equipment, which will increase the number of studies in one determination, this method may find wider application. It is especially attractive because it does not require the use of radioactive compounds. Cytochemical methods are not widely used in the clinic and are used mainly as a sensitive method in scientific research. 13
1.3. Modern methods of studying the endocrine system using the example of studying the thyroid gland
In my work, limited in scope, I will consider modern methods of studying the endocrine system in normal and pathological conditions using the example of studying the endocrine gland, which is relevant due to the high prevalence of thyroid diseases in the Republic of Bashkortostan.
1. Ultrasound examination.
Ultrasound allows you to verify rather subjective palpation data. Sensors with a frequency of 7.5 MHz and 10 MHz are optimal for research. Currently, color Doppler mapping is used, which allows visualization of small vessels in the thyroid gland and provides information about the direction and average speed of flow. The capabilities of the method depend on the experience and qualifications of the specialist conducting the research. The principle of the method is that ultrasound, sent in frequent pulses, penetrates human organs, is reflected at the interface between media with different ultrasonic resistance, is perceived by the device and reproduced on the screen and ultraviolet paper. The method is harmless and has no contraindications (Fig. 1.3).
Fig.1.3. Ultrasound of the thyroid gland.
Complex ultrasound examinations using color Doppler mapping (CDC), (Fig. 1.4). 14
Rice. 1.4. AIT with thyroid nodule formation in the CD mode.
2. Fine-needle puncture biopsy of the thyroid gland.
Fine-needle biopsy of the thyroid gland is the only preoperative method for directly assessing structural changes and establishing the cytological parameters of formations in the thyroid gland. The efficiency of obtaining adequate cytological material during fine-needle puncture biopsy increases significantly if this diagnostic procedure is carried out under ultrasound control, which makes it possible to identify the most altered areas of the thyroid gland, as well as select the optimal direction and depth of the puncture. 15
3. Cytological examination.
Cytological diagnosis of formations in the thyroid gland is based on a set of certain characteristics, such as the amount of material obtained, its cellular composition, morphological characteristics of cells and their structural groups, quality of the smear, etc.
4. Radioisotope study (scanning), scintigraphy.
Radioisotope scanning (scanning) is a method of obtaining a two-dimensional image reflecting the distribution of a radiopharmaceutical in various organs using a scanner.
Fig.1.6. Result of radioisotope scanning
thyroid gland
Scanning allows you to determine the size of the thyroid gland, the intensity of accumulation of radioactive iodine in it and in its individual areas, which allows you to assess the functional state of both the entire gland and focal formations (Fig. 1.6).
Scintigraphy- a method of functional imaging, which consists of introducing into the bodyradioactive isotopesand obtaining an image by determining the emitted radiation . The patient is given radio indicator - a drug consisting of a vector molecule and a radioactive marker. The vector molecule is absorbed by a certain structure of the body (organ, liquid). The radioactive tag serves as a “transmitter”: it emits gamma rays, which are recorded by a gamma camera. The amount of radiopharmaceutical administered is such that the radiation it emits is easily captured, but it does not have a toxic effect on the body.
For thyroid scintigraphy, the most commonly used technetium isotope is 99m Tc-pertechnetate. The use of 131 iodine is limited to identifying functioning metastases of thyroid cancer. To diagnose substernal and aberrant goiter, as well as in some cases with congenital hypothyroidism (atherosis, dystopia, organification defect), 123 iodine is used. 16
5. Determination of TSH and thyroid hormone levels.
A study of the level of TSH and thyroid hormones (free thyroxine and triiodothyronine) is indicated for everyone with suspected thyroid pathology. At present, it is more expedient to study the free fractions of thyroid hormones in combination with determining the TSH level.
6. Determination of the level of thyroglobulin in the blood.
An increased content of thyroglobulin in the blood is characteristic of many thyroid diseases; it is detected within 2-3 weeks after a puncture biopsy, as well as within 1-2 months after surgery on the thyroid gland.
7. Determination of the level of calcitonin in the blood.
In patients with a family history of medullary thyroid cancer (multiple endocrine neoplasia syndrome types 2 and 3), the level of calcitonin in the blood should be determined. In all other cases, calcitonin determination is not indicated.
The normal level of calcitonin in the blood does not exceed 10 pg/ml. The level of this marker, more than 200 pg/ml, is the most important diagnostic criterion for medullary thyroid cancer.
8. Thyroid function test.
Thyroid function tests are blood tests used to assess how effectively the thyroid gland is working. These tests include the thyroid stimulating hormone (TSH) test, thyroxine (T4), triiodothyronine (T3) test, thyroxine binding globulin (TBG) test, triiodothyronine tar test (T3RU), and long-term thyroid stimulant test (LATS). ).
Thyroid function tests are used to:
- help in diagnosing an underactive thyroid gland (hypothyroidism) and an overactive thyroid gland (hyperthyroidism)
assessment of thyroid activity
monitoring response to thyroid therapy
TSH tells the thyroid gland to release the hormones thyroxine (T4) and triiodothyronine (T3). Before using TSH tests, standard blood tests measuring T4 and T3 levels were used to determine whether the thyroid gland was working properly. The triiodothyronine (T3) test measures the amount of this hormone in the blood. T3 is usually present in very small quantities but has a significant effect on metabolism. It is an active component of thyroid hormones.
Thyroxine-binding globulin (TBG) test tests blood levels of this substance, which is produced in the liver. GTD binds to T3 and T4, preventing hormones from being flushed out of the blood by the kidneys, and releasing them when and where they are needed to regulate body functions.
Triiodothyronine Tar Uptake Test (T3RU) measures T4 levels in the blood. Laboratory analysis of this test takes several days and is used less frequently than tests whose results are available more quickly.
Long Acting Thyroid Stimulator Test (LATS) indicates whether the blood contains a long-acting thyroid stimulant. If present in the blood abnormally, LATS causes the thyroid to produce and release abnormally large amounts of hormones.
9. Computer, magnetic resonance imaging, transmission optical tomography.
CT and MRI are highly informative non-invasive methods that visualize the thyroid gland. However, these studies are currently performed quite rarely due to the high cost and low availability of appropriate equipment. Along with assessing the localization of the thyroid gland, its contours, shape, size, structure, relationship with adjacent tissues, size and structure of regional lymph nodes, CT allows one to determine the densitometric density of formations in the thyroid gland. Both CT and MRI are the methods of choice in diagnosing substernal goiter. Computed tomography (CT) is an X-ray examination method based on the unequal absorption of X-ray radiation by various tissues of the body, mainly used in the diagnosis of pathology of the thyroid gland, abdominal region (liver, gallbladder, pancreas, kidneys, adrenal glands, etc.)
Computed tomography allows you to obtain information about the configuration, size, location and extent of any formation, since this method differentiates hard and soft tissues by density.
Magnetic resonance imaging (MRI) is an instrumental diagnostic method used in endocrinology to assess the condition of the hypothalamic-pituitary-adrenal system, skeleton, abdominal and pelvic organs.
MRI allows you to obtain information about the configuration of bones, size, location and extent of any formation, since this method differentiates hard and soft tissues by density.
MRI, in recent years, has become increasingly important in diagnosing pathology of the hypothalamic-pituitary region and is becoming the method of choice when examining patients with suspected lesions in this particular area (Fig. 1.7).
Fig.1.7. Preparing for an MRI.
During magnetic resonance imaging, a movable table with the patient moves through a “tunnel” that generates an electromagnetic field, which in turn creates radiation that allows a three-dimensional image of the internal structure of the body to be obtained.
Diseases diagnosed using MRI:
- ? pituitary tumors (egprolactinoma
, Itsenko-Cushing's disease)
- ? adrenal masses (eg, Cushing's syndrome, aldosteroma, pheochromocytoma)
- ? osteoporosis
- ? and etc.
- ? allows you to obtain sections 2-3 mm thick in any plane
- ? the ability to judge by the nature of the signal not only the presence of a formation, but also its internal structure (hemorrhages, cysts, etc.)
- ? absence of exposure to ionizing radiation on the patient and almost complete harmlessness, which is important when examining children, as well as, if necessary, repeated repeated examinations.
Rice. 1.8. The CTLM system is one of the world's first serial optical tomographs.
10. Immunohistochemical study of thyroid tumor tissue.
They are carried out in the tissue of thyroid tumors obtained as a result of surgery. The main purpose of this study is prognostic. In the thyroid tissue, the presence of substances such as p53 (tumor growth suppressor gene), CD44, Met (proteoglycans responsible for metastasis), PTC, ras-oncogenes (oncogenes regulating tumor progression) and others is determined. The most important thing in clinical practice is the detection of immunoreactivity p53, Met and PTC in thyroid cancer tissue. The presence of these markers in the tumor tissue is a sign of rapid (within 2-5 months) development of metastatic disease in the operated patient. The study is expensive and requires special laboratory equipment. Currently, the determination of tumor markers is mainly carried out in specialized oncology clinics for certain indications, namely, if the patient has other prognostic signs of tumor recurrence or the development of metastatic disease (poorly differentiated thyroid cancer, patient age over 55 years, invasion of surrounding tissues by the tumor and etc.). 18
11. Immunological methods.
Immunological methods primarily include enzyme-linked immunosorbent assay (ELISA). ELISA is a method for detecting antigens or antibodies, based on the determination of the antigen-antibody complex due to:
- preliminary fixation of the antigen or antibody on the substrate;
adding the test sample and binding the fixed antigen or antibody to the target antigen or target antibody;
subsequent addition of an antigen or antibody labeled with an enzymatic label with its detection using an appropriate substrate that changes its color under the action of the enzyme. A change in the color of the reaction mixture indicates the presence of a target molecule in the sample. The determination of the products of enzymatic reactions when studying test samples is carried out in comparison with control samples.
Study of antithyroid antibody levels – immunochemiluminescent method. The prevalence of antibodies to thyroid tissue antigens: thyroglobulin, thyroid peroxidase and TSH receptor in patients with diffuse toxic goiter and endocrine ophthalmopathy was studied. When examined, such patients have a high level of antibodies to the TSH receptor, which decreases with thyreostatic therapy. 20 It has been shown that the determination of antibodies to the TSH receptor and thyroglobulin should serve as an additional diagnostic criterion during the examination. 21
Methods for determining antibodies to the TSH receptor:
1. Definition of TBII
1.1. Radioreceptor method
1.1.1. Using porcine rTSH (TRAK)
1.1.2. Using human rTSH expressed by CHO cells (CHO-R)
1.1.3. Using leukemic cell-expressed rTSH (K562)
1.2. FACS
1.3. Immunoprecipitation
2. Biological methods for determining stimulating (TSAb) and blocking (TBAb) antibodies
2.1. Assessment of cAMP production (determined by RIA)
2.1.1. in FRTL-5 cells
etc.................
