Iodine deficiency disorders and endemic goiter

Iodine deficiency diseases (endemic goiter) is a condition that occurs in certain geographical areas with iodine deficiency in the environment and is characterized by an increase in the thyroid gland (sporadic goiter develops in people living outside the endemic areas of the goiter). This form of goiter is widespread in all countries.

[1], [2], [3]

Epidemiology

According to WHO, there are more than 200 million patients with endemic goiter in the world. The disease is widespread in the mountainous (Alps, Altai, Himalayas, Caucasus, Carpathians, Cordillera, Tien Shan) and lowland areas (Central Africa, South America, Eastern Europe). The first information about endemic goiter in Russia is available in Lezhnev's work "Goiter in Russia" (1904). The author not only cited data on its prevalence in the country, but also suggested that it is a disease of the whole organism. On the territory of the former USSR, endemic goiter is found in the central regions of Russia, in Western Ukraine, Belarus, Transcaucasia, Central Asia, Transbaikalia, in the valleys of large Siberian rivers, in the Urals and the Far East. The terrain is considered endemic if more than 10% of the population have clinical signs of goiter. Women are more often affected by them, but in men with severe endemics too.

The prevalence of the disease is determined by the number of women suffering, the degree of increase in thyroid patients, the frequency of nodular forms of goiter and the ratio of men and women with goiter (the Lenz-Bauer index). Endemia is considered severe, if the incidence of the population is over 60%, the Lenz-Bauer index is 1 / 3-1 / 1, and the nodular goiter frequency is higher than 15%, there are cases of cretinism. An indicator of its severity can serve as an investigation of the content of iodine in the urine. Its results are calculated in μg%. The norm is 10-20 μg%. In areas of pronounced endemia, the iodine level is below 5 μg%. With mild endemia, the incidence of the population is above 10%, the Lenz-Bauer index is 1/6, the nodal forms are found in 5% of cases.

For the evaluation of goiter endemia, the indicator proposed by MG Kolomiytseva is also used. In its basis (the coefficient of intensity of goiter endemia) lies the ratio of the number of initial forms of goiter (I-II degree) to the number of cases of its subsequent forms (grade III-IV), expressed as a percentage. A multiple value is obtained, showing how many times the initial degree of enlargement of the thyroid gland predominates over the subsequent ones. If the Kolomiytsev coefficient is less than 2, the endemy of strong tension, between 2 and 4 is average, more than 4 - weak.

The International Council to Combat Iodine Deficiency Diseases, using data on prevalence and clinical manifestations of iodine deficiency, recommends the allocation of three severity levels of iodine deficiency. With a mild degree of goiter, 5 to 20% occur in the population, the average urinary excretion level of iodine is 5-9.9 mg / kg, the incidence of congenital hypothyroidism is 3 to 20%.

The average degree of severity is characterized by a goiter frequency of 20-29%, the level of iodine excretion is 2-4,9%, the frequency of congenital hypothyroidism is 20-40%. In severe cases, the incidence of goiter is more than 30%, the level of excretion of iodine with urine below 2 μg%, the incidence of congenital hypothyroidism is more than 40%. Cretinism occurs with a frequency of up to 10%.

[4], [5], [6], [7], [8], [9], [10], [11], [12]

Causes of the iodine-deficiency diseases (endemic goiter)

In the middle of the XIX century. Chatin and Prevost put forward a theory that the cause of endemic goiter is iodine deficiency. In subsequent years, thanks to the research of other scientists, the theory of iodine deficiency received further confirmation and is now universally accepted.

In addition to iodine deficiency, the introduction of zobogenic substances (thiocyanates and thio-oxyzolidones, contained in certain types of vegetables), iodine in inaccessible form, genetic disturbances of intra-thyroid iodine metabolism and thyroid hormone biosynthesis, autoimmune mechanisms play an important role in the development of endemic goiter. In the appearance of the disease, the reduced content of trace elements in the biosphere, such as cobalt, copper, zinc, molybdenum, is of great importance, as was shown in detail in the studies of VN Vernadsky and AP Vinogradov, as well as bacterial and helminth contamination of the environment. The family lesion of goiter and high frequency of goiter in monozygotic twins, in comparison with dizygotic ones, presuppose the presence of genetic factors.

As a response to long-term and severe iodine deficiency the goiter develops a number of mechanisms of adaptation, the main of which are an increase in the thyroid clearance of inorganic iodine,  hyperplasia of the thyroid gland, a decrease in the synthesis of thyroglobulin, the modification of iodine-containing amino acids in iron, an increase in thyroid synthesis of triiodothyronine, increase the conversion of T ₄  to T ₃  in peripheral tissues and the production of thyroid hormone.

Increased metabolism of iodine in the body reflects the stimulation of the thyroid gland by thyroid-stimulating hormone. However, in general, the mechanisms of regulation of the synthesis of thyroid hormones depend on the intracythroid concentration of iodine. In pituitary-ectomized rats, which are kept on a diet with insufficient iodine, there was an increase in thyroid absorption  ¹³¹ 1.

In newborns and children in endemic areas, epithelial hyperplasia of the thyroid gland without cell hypertrophy and relative decrease in follicles is noted. In the regions of moderate iodine deficiency in adults, there are parenchymal crabs with the formation of nodes on a hyperplastic basis. A progressive decrease in the iodine content is detected, correspondingly an increase in the ratio of monoiodotyrosine to diiodotyrosine (MIT / DIT) and reduction of iodothyronines. Another important result of reduction in the iodine concentration is to increase synthesis of T ₃  and maintaining its level in the serum, despite the reduction in the level of T ₄. In this case, the level of TSH can also be increased, sometimes very significantly.

G. Stockigt believes that there is a direct correlation between the size of goitre and the content of TSH.

[13], [14], [15], [16], [17], [18], [19]

Pathogenesis

With endemic goiter, the following morphological variants of goiter are encountered.

Diffuse parenchymal goiter occurs in children. The enlargement of the gland is expressed in varying degrees, but more often its mass is 1.5-2 times greater than the mass of the thyroid tissue of a healthy child of the corresponding age. The gland substance is a gland of a homogeneous structure, soft-elastic consistency. The gland is formed by small closely located follicles lined with cubic or flat epithelium; The colloid, as a rule, does not accumulate in the cavity of the follicle. Interlocalic islands are found in separate lobules. The gland is profusely vascularized.

Diffuse colloid goiter - iron weighing 30-150 grams and more with a smooth surface. On the cut, the substance is of amber-yellow color, shiny. Easily distinguishable are large, diameters from a few millimeters to 1-1.5 cm, colloid inclusions surrounded by fine fibrous strands. Microscopically, large elongated follicles lined with flat epithelium are found. Their cavities are filled with a small or non-resorbable oxyphilic colloid. In the areas of resorption, the epithelium is mostly cubic. Among the large follicles are foci of small functionally active follicles lined with a cubic, sometimes proliferating epithelium. Iodination of thyroglobulin in the largest follicles.

Nodal colloid struma - can be solitary, multi-node and conglomerate, when the nodes are intimate, unlike the multinodal nodes, are welded together. Such craw can reach 500 g or more. The surface of the gland is uneven, covered with a dense fibrous capsule. The diameter of the nodes varies from a few millimeters to several centimeters. Their number varies, sometimes they replace the entire gland. Nodules are usually located in the altered thyroid tissue. They are formed by different-caliber follicles lined with epithelium of various heights. Large nodes cause compression of the surrounding thyroid tissue and vascular network with the development of ischemic necrosis, interstitial fibrosis, etc. In the necrosis foci and outside it, part of the follicular cells is loaded with hemosiderin. In the areas of lime deposition, ossification can be observed. In the follicles are often found fresh and old hemorrhages, atheromas. Local damage induces, in turn, hyperplasia of the follicles. Thus, the basis of the pathological process in nodular colloid goiter is the processes of degeneration and regeneration. In recent years, lymphoid infiltration of the stroma of the nodes and especially of the surrounding thyroid tissue with the changes observed in autoimmune thyroiditis has become a frequent phenomenon.

Against the background of nodular goitre in the nodes and / or in their surrounding tissue, formation of adenocarcinomas, more often microfragments of highly differentiated cancers, occurs in approximately 17-22% of cases. Thus, the main complications of nodular goiter are acute hemorrhages, sometimes with a sudden increase in the gland, lymphoid infiltration with autoimmune struma phenomena, more often focal, and the development of cancers.

Family goiter is one of the variants of endemic goiter with autosomal recessive inheritance. This form of the disease is verified histologically. It is characterized by the same type, more often of medium caliber follicles, lined with cubic epithelium, expressed hygroscopic vacuolization of the cytoplasm, nuclear polymorphism; often noted increased follicle formation. Colloid liquid with a lot of parietal vacuoles. Cases with signs of cancer are frequent: areas of glandular tissue from anaplastic cells, phenomena of angioinvasia and penetration of the glandular capsule, psammom bodies.

Especially pronounced these changes with congenital goiter with a violation of the organization of iodine. This gland has a small-lobed structure. Lobules are formed by strands and accumulations of large atypical epithelial cells with polymorphic, often ugly nuclei, embryonic and less often fetal or follicular structure. Follicular cells with pronounced hygroscopic vacuolization of the cytoplasm, and nuclei - polymorphic, often hyperchromic. These goiter can recur (with partial thyroidectomy).

[20], [21], [22], [23], [24], [25], [26]

Symptoms of the iodine-deficiency diseases (endemic goiter)

Symptoms of endemic goiter are determined by the form, size of goiter, the functional state of the thyroid gland. Patients are concerned about general weakness, fatigue, headaches, discomfort in the heart. With large sizes of goiter, there are symptoms of pressure on nearby organs. With compression of the trachea, there may be attacks of suffocation, dry cough. Sometimes there are difficulties in swallowing due to compression of the esophagus.

Distinguish between diffuse, nodular and mixed forms of goiter. By consistency, it can be soft, dense, elastic, cystic. In areas of severe endemia, nodes appear early and are found in 20-30% of children. Often, especially in women, the thyroid gland is represented by multiple sites and there is a marked decrease in the synthesis of thyroid hormones with the appearance of clinical signs of hypothyroidism.

With endemic goiter, there is an increase in absorption by the thyroid gland  ¹³¹ 1. When a sample with triiodothyronine is tested, suppression of I absorption is detected, which indicates the autonomy of thyroid nodules. In the regions of moderate endemia in diffuse goiter, the absence of a response of a thyrotropic hormone to the administration of tyroliberin was detected. Sometimes in areas of iodine deficiency, patients with unimproved thyroid gland, elevated thyroid clearance  ¹³¹ 1 and further growth after TSH administration are found. The mechanism of development of thyroid atrophy is still unknown.

In the regions of expressed endemia, the most typical manifestation of endemic goiter is hypothyroidism. Appearance of patients (puffy pale face, pronounced dry skin, hair loss), lethargy, bradycardia, deafness of cardiac tones, hypotension, amenorrhea, delayed speech - all testify to the decrease in thyroid function.

One manifestation of hypothyroidism in endemic goiter, especially in severe cases, is cretinism, whose frequency varies from 0.3 to 10%. The close relationship between endemic goiter, deaf-mute and cretinism in one locality suggests that the main cause of the latter is iodine deficiency. Conducting iodine prophylaxis in endemic areas leads to a clear decrease in its frequency. Cretinism is associated with a deep pathology that begins in the intrauterine period from the earliest childhood.

Its characteristic features: marked mental and physical backwardness, small growth with disproportionate development of individual parts of the trunk, severe mental inferiority. Cretins are sluggish, inactive, with a coordination of movements, they are difficult to come into contact. McKarrison identified two forms of cretinism: "Myxedematous" cretinism with a pronounced picture of hypothyroidism and growth defect and a less common "nervous" cretinism with central nervous system pathology. Characteristic signs of both types are mental insufficiency and deaf-mute. In the endemic areas of Central Africa, there are more frequent "myxedematous" and atheregenic cretinism, while in the mountainous regions of America and the Himalayas the form of "nervous" cretinism is more common.

In "myxedematous" cretins, the clinical picture is characterized by severe signs of  hypothyroidism, mental retardation, growth defects and delayed maturation of bones. The thyroid gland is usually not palpable, while scanning - its residual tissue in the usual location. There is a low content of plasma T3, T4, significantly increased the level of TSH.

Clinical manifestations of "nervous" cretinism are described in detail by R. Norna-brook. There is an initial slowing of neuromuscular maturation, a delay in the development of ossification nuclei, hearing and speech disorders, strabismus, intellectual backwardness. The majority have goiter, the functional state of the thyroid gland is euthyroid. Patients with normal body weight.

[27], [28], [29]

Diagnostics of the iodine-deficiency diseases (endemic goiter)

The diagnosis of endemic goiter is based on a clinical examination of individuals with an increase in the thyroid gland, information about the mass character of the disease and the place of residence. To determine the volume of the thyroid gland, its structure is performed by ultrasound. Functional state of the thyroid gland is assessed according to ¹³¹ 1-diagnostic data  , TSH and thyroid hormone content.

Differential diagnosis should be carried out with autoimmune thyroiditis, thyroid cancer. In diagnostics with autoimmune thyroiditis, an increased thyroid density, an increase in the titer of antithyroid antibodies, a "mottled" picture on a scan, and a puncture biopsy may help.

Rapid and uneven development of the tumor, uneven contour of the node, tuberosity, restriction of mobility, weight loss may be suspicious for thyroid cancer. In far-reaching cases, there is an increase in regional lymph nodes. For the correct and timely diagnosis, the results of puncture biopsy, scanning of the gland, ultrasound echography are important.

[30], [31], [32], [33], [34], [35]

Treatment of the iodine-deficiency diseases (endemic goiter)

For the treatment of euthyroid goiter, iodine preparations are used in children and adolescents at physiological doses, 100-200 μg per day. Against the background of treatment with iodine, there is a decrease and normalization of the size of the thyroid gland. In adults, there is a method of treatment 3: I-thyroxine monotherapy at a dose of 75-150 micrograms per day, monotherapy with iodine (potassium iodide at a dose of 200 micrograms per day) and combined treatment with iodine levothyroxine (yodtiroks contains 100 mg of T ₄  and 100 mcg of iodine, 1 tablets per day, thyreocom - 70 mcg T ₄  and 150 mcg iodine). Reducing the size of the thyroid gland, usually occurs 6-9 months from the start of treatment. Duration of treatment should be from 6 months to 2 years. In the future for the prevention of recurrence prescribe the reception of preventive doses of preparations of iodine 100-200 mkg. Control examinations are carried out at intervals of 3-6 months (measurement of the neck circumference, goitre palpation for node detection, ultrasound examination).

Patients with signs of a decrease in thyroid function are treated with thyroid hormones in doses adequate to compensate for the condition. Patients who have an elevated TSH level, a decrease in T3, T4, an increase in the titer of antibodies to thyroglobulin, that is, subclinical forms of hypothyroidism and autoimmune thyroiditis are also treated.

With nodular goiter, its large size and symptoms of compression of surrounding organs, patients are shown surgical intervention.

Prevention

Since the 30-ies in our country, a network of anti-TB dispensaries has been established, whose activities are aimed at organizing activities for the prevention and treatment of endemic goiter. The most convenient method of mass iodine prophylaxis is the use of iodized salt. The scientific basis for iodine prophylaxis was first proposed in 1921 by D. Marine and S. Kimball. In the USSR, a great contribution to the solution of the problem of endemic goiter was made by OV Nikolaev, IA Aslanishvili BV Aleshin, IK Akhunbaev, Ya. X. Turakulov and many others.

In 1998, Russia adopted a new standard for iodized salt, which involves the introduction of 40 ± 15 mg iodine per 1 kg of salt in the form of a stable salt - potassium iodate. Control of the content of potassium iodide in iodized salt is carried out by sanitary-epidemiological stations. The obligatory supply of iodized salt of the population in affected areas has been organized.

In recent years, due to insufficient attention to iodine prophylaxis, there has been a tendency in our country to increase the incidence rate. So, according to VV Talantov, the frequency of endemic goiter of I-II degree is 20-40%, III-IV degree - 3-4%.

In addition to mass prophylaxis, group and individual iodine prophylaxis is conducted in endemic areas. The first - an anti-ultramine (1 tablet contains 0,001 g of potassium iodide) or potassium iodide 200, 1 table. Daily - is held in organized children's groups, pregnant and lactating women, taking into account the increased need of a growing organism in thyroid hormones under the control of the determination of iodine excretion in the urine, which reliably reflects the amount of iodine entering the body. Individual iodine prophylaxis is administered to persons who underwent surgery for endemic goiter; patients who, for any indication, can not be treated; Persons temporarily residing in areas of goitre endemia.

In the tropical countries of the world, prevention of iodine deficiency disorders using iodized oil is widely used. Apply lipidol - a preparation of iodized oil in capsules for reception per os or ampoules for intramuscular injection.

In 1 ml of iodized oil (1 capsule) contains 0.3 g of iodine, which ensures the body's need for a year.

[36], [37], [38], [39], [40], [41]