RU2658465C1 - Method for predicting the individual risk of developing endemic goiter in humans for different life periods - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and ecology. In human biomass, the content of iodine, zinc, nickel, manganese, chromium and lead is determined. Define diagnostic laboratory indicators: thyroxine free (T₄ free); thyroid-stimulating hormone (TSH); antibodies to thyroglobulin (antibodies to TG); antibodies to thyroid peroxidase (antibodies to TPO). Define the marker indicators of ultrasound of the thyroid: volume of the thyroid, its structure and blood flow, and compare these values with the physiological norm. Find the function of violation of F_i according to the claimed mathematical formula. Using the appropriate weighting factor ϕ_i, an initial probability value p(t₀) the emergence of endemic goiter at the current age of a person according to the corresponding formula. Using an iterative procedure, individual risk R is predicted for the development of endemic goiter with a time step of 1 day. For this use the prognostic indicators of TSH, antibodies to TG, antibodies to TPO, malonic dialdehyde (MDA), antioxidant activity (AOA) and glutathione peroxidase (GLPO) and compare their level with the physiological norm. Determine the increase in the probability of deviation from the physiological norm of these indicators by mathematical formulas. Establish for each indicator the total probability p⁺ _i (t) exceeding it over the norm according to the claimed formulas. Calculate the overall probability of endemic goiter p(t+K) according to the claimed formula. Individual risk R of the development of endemic goiter for different lengths of life is determined by the appropriate formula. At R less than 0.05, the risk is predicted to be negligible. At a value of 0.05–0.35 – as a moderate. At a value of 0.35–0.6 – as high. At a value of more than 0.6 – as very high.

EFFECT: method allows to demonstratively and informatively predict the individual risk of endemic goiter in a person for different life spans by assessing the complex of the most significant indicators.

1 cl, 2 dwg, 8 tbl, 1 ex

Description

The invention relates to the field of medicine and ecology and can be used to predict a person at an individual level, living in various conditions of the influence of the environment, the risk of an endemic goiter disease. The invention can be used to prevent the development of endemic goiter in the population.

It should be clarified that endemic goiter is a chronic thyroid disease characterized by an increase in its size (goiter), as well as a violation of its function due to iodine deficiency. Endemic goiter can occur, on the one hand, due to a naturally caused iodine deficiency, and on the other hand, due to an increased blood content of manganese, chromium, lead, nickel, zinc. These metals with an increased content in the blood interfere with the synthesis of thyroid hormones and interferes with the normal absorption of iodine by thyrocytes. Such disorders of the thyroid gland are characteristic of the population living in conditions of technogenic pollution of habitat objects (atmospheric air, drinking water, soil) with metals. Given that every year a person lives in such unfavorable conditions, from the point of view of the quality of the environment, the risk of thyroid disease (hereinafter referred to as the thyroid gland), and, consequently, the development of endemic goiter, increases. In this regard, the task of predicting the risk of endemic goiter is relevant.

A number of technical solutions are known from the prior art aimed at predicting thyroid disease, some of which are even aimed at predicting a short (5-6 year) period of a person’s life.

From the RF patent No. 2421127, a Method for predicting the risk of thyroid disease in perimenopausal women is known, according to which, based on data on the cause of menopause, the use of estrogen preparations, body mass index, thyroid volume, concentration of antibodies to thyroid peroxidase and thyroid stimulating hormone, a prognostic index is calculated F according to the formula F = -0.372⋅P1 + 0.288⋅P2 + 1.879⋅P3 + 0.397⋅P4 + 0.084⋅P5 + 0.382⋅P6-6.918,

where P1 is the cause of menopause, if premenopause or natural menopause, then P1 = 0; if surgical menopause (panhisterectomy), then P1 = 1,

P2 - thyroid volume in ml,

P3 is the concentration of antibodies to thyroid peroxidase (AT-TPO) in the blood (IU / ml), if AT-TPO> normal, then P3 = 1, if AT-TPO≤norm, then P3 = 0,

P4 is the concentration of thyroid-stimulating hormone (TSH) in the blood (mIU / L),

P5 - body mass index (BMI), BMI = weight in kg / height in m ² ,

P6 - taking drugs containing estrogen, if it takes, then P6 = 1, if not, then P6 = 0,

Const = -6.918;

and with a value of F greater than zero, an increased risk of developing thyroid diseases in the next five years is predicted, and with a value of F less than zero, a conclusion is made about the absence of this risk in the patient.

The disadvantage of this method is that the method is intended only for a limited contingent of the population (women of perimenopausal age); short forecasting period (for 5 years); the influence of naturally determined and anthropogenic environmental factors is not taken into account.

From the practice of medicine, methods are known for predicting the number of cases of thyroid cancer on the basis of registration data for all new cases of the disease detected among people who applied for medical care and medical examinations that significantly increase the possibility of timely diagnosis (Z. Afanasyeva. Organization of timely and early diagnosis of thyroid cancer / Sat .: Modern aspects of surgical endocrinology, Smolensk, 2002. S. 30-31).

There is also a method for predicting the expected number of patients with thyroid cancer based on an analysis of the average incidence rate (EP Demidchik, AF Tsyb, EF Lushnikov. Thyroid cancer in children (consequences of the Chernobyl accident). M. : Medicine, 1996.S. 52-53).

However, these known methods for predicting the incidence of thyroid cancer have the following disadvantages:

- Organized contingents are most often involved in research, subject to various long-term external influences that modify the development of malignant tumors, and standardization of these influences is practically impossible, i.e. there is no way to determine individual risk to humans;

- getting close to real values of the number of new cases of the disease is very difficult, more often you have to use the prevalence rate of thyroid cancer;

- the prevalence of thyroid cancer includes both new cases and those recorded at different times, which significantly changes the idea of the timing of the onset of the disease;

- `` obligate '' forms of `` precancer '' were not identified, in connection with which patients with various nodal diseases can be considered in the group of patients with thyroid cancer, significantly changing the results of the study and statistics.

From RF patent No. 2264168, a Method for predicting the number of cases of thyroid cancer is known, including an analysis of the incidence of thyroid cancer and calculating the predicted number of cases of thyroid cancer, while the analysis also includes all indicators of thyroid nodular diseases, the forecast is carried out for a 5-6 year period based on the determination of the maximum and minimum harmonics of the periodic function of the annual incidence using the regression equation, taking for the period of the periodic function of the incidence the period of the third harmonic of this function, equal to 11 years, and the calculation of the predicted number X of cases of cancer is carried out in the interval Xsr <X <Xmax or Xmin <X <Xcp,

while calculating from Xmax use the formula

X = Xmax- × t,

and when calculating from Xmin use the formula

X = Xmin + × t,

where X is the estimated value of the number of cases of cancer;

Xmax - the maximum value of the periodic function for the previous 11-year period;

Xmin - the minimum value of the periodic function for the previous 11-year period;

Hsr - the average value of the periodic function for the previous 11-year period;

A is the amplitude of fluctuations in the values of the periodic function revealed over the previous 11-year period;

t is the period for which the forecast is carried out (5-6 years).

The disadvantage of this method is that the prediction of thyroid cancer is carried out at the population level, and not at the individual level; the forecast is carried out for a short time period (5-6 years), the influence of natural and anthropogenic environmental factors is not taken into account.

The prior art still knows a method of hygienic diagnosis and assessment of the tension of iodine deficiency states (IDS) in the territory with the combined impact of environmental factors (RF Patent No. 2206272). It is based on the diagnosis of iodine deficiency in the population under conditions of chemical pollution of the territory according to clinical and biochemical parameters. Based on the allocation of priority chemical pollutants in the known method, mapping of IDS tension in a given territory is carried out, and priority indicators of IDS are selected. Based on the data obtained, a territorial monitoring, prevention and correction program for IDS in the study area is being formed. The analysis of the given examples shows the influence of chemical ecotoxicants of the environment (OS) on the occurrence and spread of IDS in the population of the study area.

However, the approaches used in the aforementioned known method to the sanitary-hygienic assessment of the danger of chemical pollution of OS facilities, the determination of the real and permissible human load of chemicals and the development of environmental assessment criteria mainly provide for a qualitative assessment of the load hazard of adverse factors in the occurrence of IDS in the population. This circumstance limits the possibilities for the applied use of the known method and system of such an assessment for managing the health of the population of the study area, the development and implementation of specific systems for the integrated assessment of multiple combinations of various adverse environmental factors in the development of IDS among the population, taking into account the totality of the factors of the integral impact in the “environment” system - public health ”in the administrative territory. As a basis for the territorial program of monitoring, correction and prevention of IDS in the study area, the known method proposes a scheme for assessing the harmful load on the environment and predicting the development of IDS in the population, as well as the real load of adverse OS factors on the health of the population, taking into account the total clinical and biochemical parameters. However, the proposed methodological approaches do not provide for the establishment of a relationship between the identified real chemical load and changes in the health of the population, in particular, the functional state of the thyroid system.

The Known Method for predicting the risk of developing iodine deficiency in the population of the administrative territory under the conditions of anthropogenic chemical environmental pollution (RF Patent No. 2316260), according to which the indicator of environmental pollution is determined for each chemical element that is dangerous for each of the health group (P _x ), for each region of the study territory, the incidence of thyroid gland associated with the iodine deficiency state (IDS) is determined, and the incidence is determined by For different age groups, and on the basis of the incidence detected, the probability of developing IDS (D _x ) is determined, based on the obtained thyroid incidence associated with IDS, nosological forms of diseases are determined, the risk R _{x of the} development of various nosological forms of thyroid diseases associated with IDS is determined by formula: R _x = P _x D _x ,

where x is any chemical ecotoxicant;

put the resulting risks on a district map reflecting the incidence in the region, on the basis of which a risk forecast for the development of an iodine deficiency condition is carried out.

However, this known method is not intended to predict the individual risk of developing endemic goiter in humans for different periods of life, which is the main disadvantage of this method.

Moreover, the known methods for predicting the individual risk of developing endemic goiter in humans for the upcoming period of life have not been identified from the prior art, therefore, it is not possible to choose the closest analogue to the claimed object.

The technical result achieved by the present invention is to create an informative and evidence-based method for predicting the individual risk of developing endemic goiter in a person living in a environment contaminated by metals (manganese, lead, chromium, nickel, zinc), which are dangerous for the state of the thyroid gland, so how are these metals strumogens?

The technical result achieved is achieved by the proposed Method for predicting the individual risk of developing endemic goiter in humans for different periods of life, namely, in the human biological environment, the content of chemical elements that are dangerous for the state of the thyroid gland (thyroid gland) and antioxidant system of the body is determined: iodine, zinc, nickel, manganese, chromium and lead; calculate the initial probability value p (t _o ) of the occurrence of endemic goiter in humans at the current age of the person t _o at the time of examination, for this the following diagnostic laboratory parameters are determined: thyroxine free (T _{4 free} ); thyroid-stimulating hormone (TSH); antibodies to thyroglobulin (antibodies to TG); antibodies to thyroid peroxidase (antibodies to TPO); marker indicators of ultrasound examination (ultrasound) of the thyroid gland: thyroid volume, its structure and blood flow; compare these indicators with the physiological norm; further for each quantitative person [Onishchenko, Zaitseva, May, Andreeva, 2016; Onishchenko, 2015]. The leading role among regulatory systems that ensure the adaptation of the human body to environmental conditions is played by the endocrine system, and in particular, the thyroid gland, while it is most susceptible to the negative effects of various factors, for example, chemical [Luzhetsky, Ustinova, Palagina, 2013; Luzhetsky et al. 2010].

At the same time, a person is more likely to have an endemic goiter, and this can happen either in the near future or in the future. That is why it is very important to predict the risk of this disease both in the short and medium term, using a strictly defined set of diagnostic and prognostic indicators, followed by their mathematical processing. This approach is very relevant and can effectively prevent the occurrence of endemic goiter due to the timely implementation of preventive measures.

Due to the fact that when implementing the proposed method, along with laboratory diagnostic indicators, the diagnostic indicators obtained by ultrasound (ultrasound) are also used to expand the information base to predict the individual risk of developing endemic goiter for the upcoming period of life, up to 30 years. As a result, the reliability of the obtained value of individual risk is increased, which means that the conclusions obtained during the studies will meet the condition of reliability and accuracy.

It should be noted that an assessment of the current state of an individual is a prerequisite for building a forecast of the likelihood of an endemic goiter disease using mathematical modeling tools. But the use of indicators separately as estimates is not correct, because the accuracy of the evaluation of the diagnostic indicator decreases, in addition to the qualitative indicator - the structure and blood flow of the thyroid gland, find the function of its violation F _i according to the formula:

where 5 is the number of diagnostic indicators: T _{4 free} ; TTG; antibodies to TG; antibodies to TPO; thyroid volume;

x _i is the concentration of the diagnostic indicator;

- минимальное нормативное значение диагностического показателя;

- the minimum normative value of the diagnostic indicator;

- максимальное нормативное значение диагностического показателя;

- the maximum normative value of the diagnostic indicator;

- среднее значение нормативного интервала для выбранного диагностического показателя;

- the average value of the normative interval for the selected diagnostic indicator;

in this case, for a qualitative diagnostic indicator - the structure and blood flow of the thyroid gland, take Ф _i = 1 in case of a violation of the structure and blood flow of the thyroid gland, and Ф _i = 0 - in the absence of a violation; further, each specified diagnostic indicator is given the following weight coefficient ϕ _i , in accordance with its contribution to the formation of the probability of development of endemic goiter:

and taking into account the previously established violation functions Ф _{i of the} indicated diagnostic indicators and their weight coefficients ϕ _{i, the} initial probability p (t ₀ ) of the occurrence of endemic goiter for the current age of a person is calculated by the formula:

where p (t _o ) - the initial value of the probability of occurrence of endemic goiter in humans at the current age at the time of examination;

6 - the number of diagnostic indicators: T _{4 free} ; TTG; antibodies to TG; antibodies to TPO; thyroid volume; thyroid structure and blood flow, characterizing the occurrence of endemic goiter;

ϕ _i is the weight coefficient of the diagnostic indicator;

F _i - the value of the deviation of the diagnostic parameter from the norm;

then, using an iterative procedure that takes into account the peculiarities of changes in prognostic indicators over time t, the individual risk of developing endemic goiter in a person with a time step of 1 day is forecasted, for this, the increase in the probability of deviation from the physiological norm of prognostic indicators from the influence of previously established harmful chemical elements of the environment is first determined human habitation: iodine, zinc, nickel, manganese, chromium and lead; at the same time, the blood levels of the following indicators are determined as prognostic indicators for the person’s current age: thyrotropic hormone (TSH), antibodies to TG, antibodies to TPO, malondialdehyde (MDA), antioxidant activity (AOA) and glutathione peroxidase (GLPO) ;

его относительно нормы, а для ГлПО - вероятность снижения

его относительно нормы: где t₀ - текущий возраст на момент обследования, год p_i - вероятность отклонения от нормы i-ого прогностического показателя; причем, если значение i-го прогностического показателя соответствует норме, то указанная вероятность равна нулю, а если значение выше или ниже нормы, то указанная вероятность равна единице; затем, принимая во внимание следующую систему взаимосвязей между отклонением от физиологической нормы указанных прогностических показателей и экспозицией химических элементов в биосредах человека: вероятность превышения нормы уровня ТТГ возникает под воздействием йода, никеля, марганца; вероятность превышения нормы уровня антитела к ТГ - под воздействием хрома, йода, никеля, марганца; вероятность превышения нормы уровня антитела к ТПО - под воздействием никеля и свинца; вероятность превышения нормы уровня МДА - под воздействием цинка, никеля, марганца, хрома; вероятность превышения нормы уровня АОА - под воздействием марганца; а также принимая во внимание систему зависимостей между следующими прогностическими показателями из вышеуказанного перечня: зависимость антител к ТГ от ТТГ; зависимость антител к ТПО от антител к ТГ; зависимость МДА от антител к ТПО; зависимость АОА от МДА; определяют прирост вероятности отклонения от физиологической нормы указанных показателей по следующим математическим формулам:compare their level with the physiological norm; in addition, for TSH, antibodies to TG, antibodies to TPO, MDA, AOA, in addition to its numerical value measured for the current age of a person at the time of the examination, the probability of exceeding

its relative to the norm, and for GLPO - the probability of a decrease

its relative to the norm: where t ₀ is the current age at the time of the survey, year p _i is the probability of deviation from the norm of the i-th prognostic indicator; moreover, if the value of the i-th prognostic indicator corresponds to the norm, then the indicated probability is zero, and if the value is above or below the norm, then the indicated probability is equal to one; then, taking into account the following system of relationships between the deviation of the specified prognostic indicators from the physiological norm and the exposure of chemical elements in human biological media: the probability of exceeding the level of TSH levels occurs under the influence of iodine, nickel, manganese; the probability of exceeding the norm of the level of antibodies to TG - under the influence of chromium, iodine, nickel, manganese; the probability of exceeding the norm level of antibodies to TPO - under the influence of nickel and lead; the probability of exceeding the norm of the MDA level - under the influence of zinc, nickel, manganese, chromium; the probability of exceeding the standard level of AOA - under the influence of manganese; and also taking into account the system of dependencies between the following prognostic indicators from the above list: dependence of antibodies to TG on TSH; the dependence of antibodies to TPO from antibodies to TG; MDA dependence on antibodies to TPO; AOA dependence on MDA; determine the increase in the probability of deviations from the physiological norm of these indicators according to the following mathematical formulas:

- the increase in the probability of exceeding the norm of the level of TSH in blood serum on a person’s age t is expressed by the following functions from the influence of chemical elements:

where Δp ⁺ ₁ (F (t)) is the function of the increase in the probability of exceeding the standard level of TSH associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ;

F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ;

F ₆ (t) is the concentration of iodine in the urine, mcg / (100⋅cm ³ );

- the increase in the probability of exceeding the norm of concentration of antibodies to TG in blood serum at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₂ (F (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TG associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₄ (t) is the concentration of chromium in the blood, μg / cm ³ ;

Δp ⁺ ₂ (p ⁺ ₁ (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TG, associated with the probability of exceeding the norm of the level of TSH;

- the increase in the probability of exceeding the norm of concentration of antibodies to TPO in blood serum at the age of a person associated with the influence of t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₃ (F (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TPO associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ;

F ₅ (t) is the concentration of lead in the blood, μg / cm ³ ;

Δp ⁺ ₃ (p ⁺ ₂ (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TPO, associated with the probability of exceeding the norm of the level of antibodies to TG;

- the increase in the probability of exceeding the norm of MDA concentration in blood plasma at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₄ (F (t)) is the function of the increase in the probability of exceeding the norm of the MDA level associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₁ (t) is the concentration of zinc in the blood, μg / cm ³ ;

F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ;

F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ;

F ₄ (t) is the concentration of chromium in the blood, μg / cm ³ ;

Δp ⁺ ₄ (p ⁺ ₃ (t)) is the function of the increase in the probability of exceeding the norm of the MDA level, associated with the probability of exceeding the norm of the level of antibodies to TPO;

- the increase in the probability of exceeding the norm of AOA concentration in blood plasma at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₅ (F (t)) is the function of the increase in the probability of exceeding the norm of AOA level in blood plasma associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ;

Δp ⁺ ₅ (p ⁺ ₄ (t) is the growth function of the probability of exceeding the norm of the AOA level, associated with the probability of exceeding the norm of the MDA level;

and, based on the obtained values of the probability increase, set for each of these prognostic indicators: TSH, antibodies to TG, antibodies to TPO, MDA, AOA, the total probability of p ⁺ _i (t) exceeding it above the norm in a person’s age t according to the following formulas :

- for TTG:

- for antibodies to TG:

- for antibodies to TPO:

- for MDA:

- for AOA:

; если значение в норме, то

; затем производят расчет общей вероятности развития у человека эндемического зоба; учитывая, что при расчете используют итерационную процедуру, расчет указанной общей вероятности развития эндемического зоба проводят последовательно на каждом временном шаге, основываясь на результатах расчета предыдущего временного шага; расчет выполняется до достижения возраста обследуемого, соответствующего периоду, для которого выполняется прогнозирование риска, по следующей формуле:and taking into account that the prognostic indicator of HLP in blood serum has no internal connections with other prognostic indicators, then the value of the probability of deviation from the norm for it is constant and takes on the value: if the value of HLP is lower than normal, then

; if the value is normal, then

; then calculate the overall likelihood of a person developing endemic goiter; Considering that the iterative procedure is used in the calculation, the calculation of the indicated total probability of development of endemic goiter is carried out sequentially at each time step, based on the results of the calculation of the previous time step; the calculation is performed until the age of the subject corresponding to the period for which the risk prediction is performed, according to the following formula:

where p (t + K) is the total probability of development of endemic goiter in humans at the age corresponding to the time step t + K (years);

K is the value of the time step, and the time step adequate to the task of predicting the risk of developing endemic goiter is 1 day, which corresponds to the value K = 1/365 years, and at the first time step, the calculation is performed based on data from the time step corresponding to the initial age the subject, i.e. t in the first step will be equal to t ₀ ;

p (t) is the total probability of developing an endemic goiter in a person at an age corresponding to a time step;

k ₁ (t), k ₂ (t), k ₃ (t), k ₄ (t) - calculated variables;

however, these calculated variables are determined by the following formulas:

and the individual risk R of the development of endemic goiter in humans for different periods of life is determined by the formula: R (t + K) = g (t + K) ⋅ P (t + K),

where R (t + K) is the individual risk of endemic goiter at time t + K;

g (t + K) - the severity of the disease "endemic goiter" at time t + K;

p (t + K) - probability of endemic goiter disease at time t + K;

t + K is the person’s age at the point in time predicting the risk of developing endemic goiter;

moreover, the severity of the disease “endemic goiter” is determined by the formula: g (t + K) = 2.84⋅10 ^-5 ⋅е ^0.0933t ; and with an individual risk of less than 0.05, the risk of developing endemic goiter in humans is predicted to be negligible; with a value of from 0.05 to 0.35 as moderate; at a value of 0.35-0.6 as high; with a value of more than 0.6 as very high.

The specified technical result is ensured by:

- the use of a certain set of diagnostic indicators in the initial period of time of the examination of a person and a certain set of prognostic indicators in subsequent calculations of the probability of risk;

- application in the implementation of the proposed method of an extended system of interconnections of prognostic indicators among themselves and their relationship with chemical elements that are dangerous for the state of the thyroid gland and the antioxidant system of the body: iodine, zinc, nickel, manganese, chromium and lead;

use of an iterative calculation procedure that provides calculation under conditions of variable deviations from the physiological norm of the levels of prognostic indicators in time at specified time steps.

When implementing the new method, using the totality of the proposed operations, their sequence and estimating the obtained probability values of the deviation from the norm of prognostic indicators characterizing thyroid disease and antioxidant system impairment, allows with sufficient reliability to assess the individual risk of developing endemic goiter in humans for different periods of life, up to 30 years.

To understand the essence of the issue, the following should be clarified. Much attention is currently focused on the study of the characteristics of the negative impact of environmental factors on health.

Therefore, in the proposed method, the need was built to build integral parameters.

Using in the implementation of the proposed method, tools of mathematical modeling through finding according to the mathematical formula of the violation function Ф _i for each declared diagnostic indicator by the formula:

where 5 is the number of diagnostic indicators;

x _i is the concentration of the diagnostic indicator;

- минимальное нормативное значение диагностического показателя;

- the minimum normative value of the diagnostic indicator;

- максимальное нормативное значение диагностического показателя;

- the maximum normative value of the diagnostic indicator;

- середина нормативного интервала для выбранного диагностического показателя;

- the middle of the normative interval for the selected diagnostic indicator;

provides an objective nature of the results.

In addition, in the inventive method, it was proposed to classify all deviations of the diagnostic indicators of thyroid conditions on a conditional interval scale from 0 to 1 by the corresponding numerical value of the weight coefficient ϕ _i . It was found that the use of this coefficient allows you to most accurately determine in the future the initial value of the probability of occurrence of endemic goiter at the current age of a person, according to the formula:

which makes the proposed method informative and accurate.

The numerical values of ϕ _i were established empirically, based on the objectives of the present invention.

Due to the fact that a certain set of prognostic indicators was used at the forecast stage, and also their interrelations with each other and between the probability of their deviation from the norm under the influence of a naturally occurring iodine deficiency and high blood levels of zinc, nickel, manganese, chromium and lead are taken into account, accuracy is ensured the proposed method, because in subsequent calculations, all these factors were taken into account.

Based on mathematical formulas and the values of the initial level of indicators at the time of the survey, successive calculations were carried out according to probability at the following time steps: p ₁ , p ₂ , p ₃ , p ₄ , etc. It uses the iterative procedure for calculating the probability of time from the person’s age t at the time of the survey to the forecast time period in order to calculate the probability, for example, for the 16th forecast year, you need to know this probability for the 15th forecast year, which, in turn, is determined through the probability for the 14th forecast year, etc. (considering this explanation of course, one should not take into account the annual time step, but the time step claimed in the proposed method for 1 day. This is clearly illustrated in Fig. 2, which shows a schematic diagram for predicting the probability of an endemic goiter disease by the proposed method). Naturally, such a calculation procedure begins with some “initial” probability value at age at the time of the survey. It is convenient and understandable to use as the initial level the value when the person’s age t corresponds to the person’s age at the time of the examination t ₀ (i.e. t = t ₀ ).

The choice of time step when performing calculations using mathematical formulas depends on the detail of the exposure task. But in an advantageous embodiment, in the proposed method, it is set 1 day.

Due to the fact that the calculation of the proposed mathematical formulas for the total individual risk of a person also takes into account the increase in the probability of deviation from the physiological norm of each prognostic indicator depending on the influence of other indicators and the influence of chemical elements, an almost complete account of all degrees and risk factors is provided when predicting development endemic goiter in humans, which provides sufficient accuracy. A general view of the system of relations between the development indicators of endemic goiter, which were taken into account in the proposed method, is shown in Fig. one.

The calculation according to the proposed method of individual risk R of the development of endemic goiter in humans for different periods of life is carried out according to the formula:

R (t + K) = g (t + K) ⋅ P (t + K),

where R (t + K) is the individual risk of endemic goiter at time t + K;

g (t + K) - the severity of the disease "endemic goiter" at time t + K;

p (t + K) - probability of endemic goiter disease at time t + K;

t + K is the person’s age at the point in time predicting the risk of developing endemic goiter.

It can be seen that in this case, the severity of the disease is taken into account as a characteristic of damage to health. Moreover, the severity of the disease "endemic goiter" is determined by a certain formula:

g (t + K) = 2.84⋅10 ^-5 ⋅е ^0.0933t .

In addition, the proposed method introduced a quantitative value of individual risk, namely: when the value of individual risk is less than 0.05, the risk of developing endemic goiter in humans is predicted to be negligible; with a value of from 0.05 to 0.35 as moderate; at a value of 0.35-0.6 as high; with a value of more than 0.6 as very high. This scale is known and used to assess non-carcinogenic risk [MP 2.1.10.0062-12 Quantitative assessment of non-carcinogenic risk when exposed to chemicals based on the construction of evolutionary models].

Based on the foregoing, we can conclude that the technical result is achieved due to the totality of all operations of the proposed method, their sequence and modes of implementation.

The proposed method is illustrated by drawings, where in Fig. 1 shows a general view of the system of relationships between chemical compounds and prognostic indicators, as well as between the prognostic indicators themselves; in Fig. 2 is a schematic diagram for predicting the proposed method for the likelihood of an endemic goiter.

When implementing the proposed method carry out the following operations in the following sequence. Moreover, to illustrate immediately after the name of the operation is an example of a specific implementation.

1. In the biological media of a person for whom an individual risk of developing endemic goiter is to be predicted, a venous blood sample and a urine sample are taken. The blood sample determines the content of zinc, nickel, manganese, chromium and lead. The determination is carried out using an inductively coupled plasma mass spectrometer with an Agilent 7500 cx octopole cell. Inductively coupled plasma mass spectrometry is used. Measurements are carried out in accordance with MUK 4.1.3230-14, MUK 4.1.3161-14. In the urine sample, the content of cerium iodine is determined by the arsenite method using a PE 5300 spectrophotometer.

For example, measurements of the content of chemicals in biological media in an individual - men aged 30 years are shown in table 1.

2. The following diagnostic laboratory parameters are determined in a blood sample: thyroxine free (T _{4 free} ); thyroid-stimulating hormone (TSH); antibodies to thyroglobulin (antibodies to TG); antibodies to thyroid peroxidase (antibodies to TPO), and marker diagnostic parameters of ultrasound examination (ultrasound) of the thyroid gland: thyroid volume, its structure and blood flow. Methods for determining these indicators are described in the source of information: "Clinical Laboratory Analytics", Volume II. Private analytical technologies in a clinical laboratory / Edited by V.V. Menshikov; M .: Labinform-RAMLD, - 1999. - 352 p. (pp. 198-220, 239).

These indicators are compared with the physiological norm. The data obtained are shown in table 2.

In the claimed method, as criteria for assessing deviations of diagnostic indicators, standard generally accepted age-related physiological levels are used [Clinical Laboratory Analytics. Volume II Private Analytical Technologies in the Clinical Laboratory / Edited by V.V. Menshikov. M .: Labinform-RAMLD, 1999. - 352 p.].

3. For each quantitative diagnostic indicator, in addition to a qualitative indicator - the structure and blood flow of the thyroid gland, find the function of its violation Ф _i according to the formula:

where 5 is the number of diagnostic indicators: T _{4 free} ; TTG; antibodies to TG; antibodies to TPO; thyroid volume;

x _i is the concentration of the diagnostic indicator;

- минимальное нормативное значение диагностического показателя;

- the minimum normative value of the diagnostic indicator;

- максимальное нормативное значение диагностического показателя;

- the maximum normative value of the diagnostic indicator;

- среднее значение нормативного интервала для выбранного диагностического показателя;

- the average value of the normative interval for the selected diagnostic indicator;

Moreover, for a qualitative diagnostic indicator:

structure and blood flow of the thyroid gland, take Ф _i = 1 in case of violation of the structure and blood flow of the thyroid gland, and Ф _i = 0 - in the absence of violation.

Taking into account the data of table 2, the calculation of the function of violation Ф _i for each diagnostic indicator was performed as follows:

Ф _{T4 sv} = (17-17.5) ² / (25-17.5) ² = 0.00444;

Ф _TTG = (2.3-2.15) ² / (4-2.15) ² = 0.00657;

F _{ant.k TG} = (52 -50) ² / (100-50) ² = 0.0016;

F _{ant.k TPO} = (16-15) ² / (30-15) ² = 0.00444;

F = _{about thyroid} ^{(12-11,2) 2 / (18-11,2)} 2 = 0.0138 ;

F _{p and shelter thyroid} = 0

4. Next, each specified diagnostic indicator is given the following weight coefficient ϕ _i , in accordance with its contribution to the formation of the probability of development of endemic goiter:

and taking into account the previously established violation functions Ф _{i of the} indicated diagnostic indicators and their weight coefficients ϕ _{i, the} initial probability p (t ₀ ) of the occurrence of endemic goiter for the current age of a person is calculated by the formula:

where p (t _o ) - the initial value of the probability of occurrence of endemic goiter in humans at the current age at the time of examination;

6 - the number of diagnostic indicators: T _{4 free} ; TTG; antibodies to TG; antibodies to TPO; thyroid volume; thyroid structure and blood flow, characterizing the occurrence of endemic goiter;

ϕ _i is the weight coefficient of the diagnostic indicator;

F _i - the value of the deviation of the diagnostic parameter from the norm.

Data for a particular individual about ϕ _i , Ф _i , p (t _o ) are shown in table 3.

The initial value of the probability of occurrence of endemic goiter in the examined person at the current age (30 years) at the time of the examination is p (t _o ) = 0.0223.

It should be clarified that the norm of the thyroid gland volume depends on the surface area of the body. In males, the thyroid volume is calculated by the formulas: x _{5 min} = 0.9S ² + 2S-0.07; x _{5 max} = 2.5437S ² + 1.6744S + 0.2392,

where x _{5 min} , x _{5 max} - the minimum and maximum value of the norm of the volume of the thyroid gland, cm ³ .

In women, the thyroid gland volume is calculated by the formulas: x _{5 min} = 0.68S ² + 3.34S-1.02; x _{5 max} = 0.777S ² + 6.52S + 2.269.

The surface area of the body, depending on the height and weight of the individual, is calculated by the formula: S = 0.00714W ^0.425 N ^0.725 .

where S is the surface area of the body of the individual, m ² ,

W is the mass of the individual, kg;

H is the growth of the individual, see

5. Then, using an iterative procedure that takes into account the peculiarities of changes in prognostic indicators over time t, individual risk of developing an endemic goiter in a person is predicted with a time step of 1 day:

- To do this, first determine the increase in the probability of deviations from the physiological norm of prognostic indicators from the influence of previously established harmful chemical elements of the human environment: iodine, zinc, nickel, manganese, chromium and lead;

- at the same time, the blood levels of the following indicators are determined as prognostic indicators for the person’s current age: thyrotropic hormone (TSH), antibodies to TG, antibodies to TPO, malondialdehyde (MDA), antioxidant activity (AOA) and glutathione peroxidase (GlPO) ),

- compare their level with the physiological norm;

его относительно нормы, а для ГлПО - вероятность снижения

его относительно нормы: где t₀ - текущий возраст на момент обследования, год; p_i - вероятность отклонения от нормы i-ого прогностического показателя,- for TSH, antibodies to TG, antibodies to TPO, MDA, AOA, in addition to its numerical value measured for the current age of a person at the time of the examination, the probability of exceeding

its relative to the norm, and for GLPO - the probability of a decrease

its relative to the norm: where t ₀ is the current age at the time of the survey, year; p _i - the probability of deviation from the norm of the i-th prognostic indicator,

- moreover, if the value of the i-th prognostic indicator corresponds to the norm, then the indicated probability is zero, and if the value is above or below the norm, then the indicated probability is equal to one;

The individual at the current age (t ₀ ) at the time of the survey, i.e. at the age of 30 years, the content of six prognostic indicators was determined in the blood: TSH, antibodies to TG, antibodies to TPO, MDA, AOA and Glpo.

The data obtained are shown in table 4.

6. Then, taking into account the following system of relationships between the deviation from the physiological norm of the indicated prognostic indicators and the exposure of chemical elements in human biological media:

- the probability of exceeding the standard level of TSH occurs under the influence of iodine, nickel, manganese;

- the probability of exceeding the norm of the level of antibodies to TG - under the influence of chromium, iodine, nickel, manganese;

- the probability of exceeding the norm level of antibodies to TPO - under the influence of nickel and lead;

- the probability of exceeding the norm of the MDA level - under the influence of zinc, nickel, manganese, chromium;

- the probability of exceeding the standard level of AOA - under the influence of manganese;

and also taking into account the system of dependencies between the following prognostic indicators from the above list:

- dependence of antibodies to TG from TSH;

- dependence of antibodies to TPO from antibodies to TG;

- dependence of MDA on antibodies to TPO;

- dependence of AOA on MDA;

determine the increase in the probability of deviations from the physiological norm of these prognostic indicators according to the following mathematical formulas:

- the increase in the probability of exceeding the norm of the level of TSH in blood serum on a person’s age t is expressed by the following functions from the influence of chemical elements:

where Δp ⁺ ₁ (F (t)) is the function of the increase in the probability of exceeding the standard level of TSH associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ;

F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ;

F ₆ (t) is the concentration of iodine in the urine, mcg / (100⋅cm ³ );

- the increase in the probability of exceeding the norm of concentration of antibodies to TG in blood serum at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₂ (F (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TG associated with the influence of the chemical element F of the living environment in a person’s age

F ₄ (t) is the concentration of chromium in the blood, μg / cm ³ ;

Δp ⁺ ₂ (p ⁺ ₁ (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TG, associated with the probability of exceeding the norm of the level of TSH;

- the increase in the probability of exceeding the norm of concentration of antibodies to TPO in blood serum at the age of a person associated with the influence of t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₃ (F (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TPO associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ;

F ₅ (t) is the concentration of lead in the blood, μg / cm ³ ;

Δp ⁺ ₃ (p ⁺ ₂ (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TPO, associated with the probability of exceeding the norm of the level of antibodies to TG;

- the increase in the probability of exceeding the norm of MDA concentration in blood plasma at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₄ (F (t)) is the function of the increase in the probability of exceeding the norm of the MDA level associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₁ (t) is the concentration of zinc in the blood, μg / cm ³ ;

F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ;

F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ;

F ₄ (t) is the concentration of chromium in the blood, μg / cm ³ ;

Δp ⁺ ₄ (p ⁺ ₃ (t)) is the function of the increase in the probability of exceeding the norm of the MDA level, associated with the probability of exceeding the norm of the level of antibodies to TPO;

- the increase in the probability of exceeding the norm of AOA concentration in blood plasma at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₅ (F (t)) is the function of the increase in the probability of exceeding the norm of AOA level in blood plasma associated with the influence of the chemical element F of the living environment at the age of a person t;

F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ;

Δp ⁺ ₅ (p ⁺ ₄ (t)) is the function of the increase in the probability of exceeding the norm of the AOA level, associated with the probability of exceeding the norm of the MDA level.

For the subject being examined, the above calculations were performed using the results shown in tables 1 and 4.

As a specific example, mathematical calculations of the increase in the probability of exceeding the normal level of TSH in the blood serum by a person's age of 30 years from the influence of nickel (Ni), manganese (Mn), iodine (J) are given:

Calculations of the increase in the probability of exceeding the normal levels of other prognostic indicators, depending on the chemical elements, were carried out in a similar way, using the mathematical formulas indicated above for each indicator. The data obtained for an individual aged 30 years are shown in table 5.

Table 6 shows the results of calculating the increase in the probability of exceeding the normal level of prognostic indicators in an individual aged 40 years (i.e., with a forecast period of 10 years).

7. Based on the obtained values of the probability increase, for each prognostic indicator, the total probability p ⁺ _i (t) of exceeding it over the norm at the person’s age t is established using the following formulas:

- for TTG:

- for antibodies to TG:

- for antibodies to TPO:

- for MDA:

- for AOA:

; если значение в норме, то

.- and taking into account that the prognostic indicator of HLP in blood serum has no internal connections with other prognostic indicators, then the value of the probability of deviation from the norm for it is constant and takes on the value: if the value of HLP is lower than normal, then

; if the value is normal, then

.

For a specific individual, the total probability p ⁺ _i (t) of exceeding the norm at the age of an individual of 30 years is calculated using the results of Tables 3 and 5. Data on the overall probability obtained as a result of calculations by the above formulas are given in Table 7. In this case , you can see that the prognostic indicators calculated by the formulas coincide with the initial values of the levels of indicators of an individual at the age of 30 years.

Table 8 shows the results of calculating the probability of an excess of the indicator over the norm for a person aged 40 years.

9. Then calculate the total likelihood of developing an endemic goiter in a person:

- taking into account that the iterative procedure is used in the calculation, the calculation of the indicated total probability of development of endemic goiter is carried out sequentially at each time step, based on the results of the calculation of the previous time step;

- the calculation is performed until the age of the subject corresponding to the period for which the risk prediction is performed:

where p (t + K) is the total probability of development of endemic goiter in humans at the age corresponding to the time step t + K (years);

K is the value of the time step. The time step adequate to the task of predicting the risk of developing endemic goiter is 1 day, which corresponds to the value K = 1/365 years, and at the first time step, the calculation is performed based on data from the time step corresponding to the initial age of the subject, i.e. t in the first step will be equal to t ₀ ;

p (t) is the total probability of developing an endemic goiter in a person at an age corresponding to a time step;

k ₁ (t), k ₂ (t), k ₃ (t), k ₄ (t) - calculated variables;

- while the specified design variables are determined by the following formulas:

- and the individual risk of developing endemic goiter in humans for different periods of life is determined by the formula: R (t + K) = g (t + K) ⋅ P (t + K),

where R (t + K) is the individual risk of endemic goiter at time t + K;

g (t + K) - the severity of the disease "endemic goiter" at time t + K;

p (t + K) - probability of endemic goiter disease at time t + K;

t + K is the person’s age at the point in time predicting the risk of developing endemic goiter;

- and the severity of the disease "endemic goiter" is determined by the formula:

g (t + K) = 2.84 · 10 ^-5 ⋅e ^0.0933t ;

- and with an individual risk of less than 0.05, the risk of developing endemic goiter in humans is predicted to be negligible; with a value of from 0.05 to 0.35 as moderate; at a value of 0.35-0.6 as high; with a value of more than 0.6 as very high.

были приняты следующие параметры:When calculating the overall likelihood of an examined individual developing endemic goiter, the formula

The following parameters were adopted:

the forecast period of 10 years;

the forecast begins with t = 30 years;

K - time step 1 day;

k ₁ (t), k ₂ (t), k ₃ (t), k ₄ (t) are the calculated variables.

As a result of applying the formulas 3650 times (the forecast at the step of 1 day for 10 years), the total probability of the development of an endemic goiter in an examined person at the age of 40 was determined as a value of 0.0253.

And when calculating the individual risk of developing endemic goiter in a person aged 40 years, according to the formula: R (40) = g (40) ⋅Р (40), the risk was determined to be 3.01⋅10 ^-5 . The severity of disease g (40) of 0.00119 was taken into account.

Using the risk scale further, it was found that at the established individual risk in the examined person, after 10 years, the risk of developing endemic goiter is predicted to be negligible.

To prove the reliability of the results obtained by the proposed method, 50 individuals (20 men, 20 women, 10 children) from different territories were examined. The forecast period ranged from 1 year to 3 years inclusive. Through this period, a comparison of predicted and actual indicators was carried out. It was found that in 95% of cases the difference between the data obtained by the proposed method and the real indicators did not exceed 5%, which confirms the reliability of the proposed method.

The new method can be used in predicting the individual risk of developing endemic goiter in humans for different periods of life.

Note: t ₀ - current age at the time of the survey, year;

p _i - probability of deviation from the norm of the i-th prognostic indicator

Claims (85)

A method for predicting the individual risk of developing endemic goiter in humans for different periods of life, namely, that the biological elements of a person determine the content of chemical elements that are dangerous for the state of the thyroid gland (thyroid gland) and the antioxidant system of the body: iodine, zinc, nickel, manganese chrome and lead; calculate the initial probability value p (t _o ) of the occurrence of endemic goiter in humans at the current age of the person t _o at the time of examination, for this the following diagnostic laboratory parameters are determined: thyroxine free (T _{4 free} ); thyroid-stimulating hormone (TSH); antibodies to thyroglobulin (antibodies to TG); antibodies to thyroid peroxidase (antibodies to TPO); marker indicators of ultrasound examination (ultrasound) of the thyroid gland: thyroid volume, its structure and blood flow; compare these indicators with the physiological norm; further for each quantitative diagnostic indicator, in addition to a qualitative indicator - the structure and blood flow of the thyroid gland, find the function of its violation Ф _i according to the formula:

where 5 is the number of diagnostic indicators: T _{4 free} ; TTG; antibodies to TG; antibodies to TPO; thyroid volume; x _i is the concentration of the diagnostic indicator;

- the minimum normative value of the diagnostic indicator;

- the maximum normative value of the diagnostic indicator;

- the average value of the normative interval for the selected diagnostic indicator; in this case, for a qualitative diagnostic indicator - the structure and blood flow of the thyroid gland, take Ф _i = 1 in case of a violation of the structure and blood flow of the thyroid gland, and Ф _i = 0 - in the absence of a violation; further, each specified diagnostic indicator is given the following weight coefficient ϕ _i in accordance with its contribution to the formation of the probability of development of endemic goiter:

and taking into account the previously established violation functions Ф _{i of the} indicated diagnostic indicators and their weight coefficients ϕ _{i, the} initial probability p (t ₀ ) of the occurrence of endemic goiter for the current age of a person is calculated by the formula:

where p (t _o ) - the initial value of the probability of occurrence of endemic goiter in humans at the current age at the time of examination; 6 - the number of diagnostic indicators: T _{4 free} ; TTG; antibodies to TG; antibodies to TPO; thyroid volume; thyroid structure and blood flow, characterizing the occurrence of endemic goiter; ϕ _i is the weight coefficient of the diagnostic indicator; F _i - the value of the deviation of the diagnostic parameter from the norm; then, using an iterative procedure that takes into account the peculiarities of changes in prognostic indicators over time t, the individual risk of developing endemic goiter in a person with a time step of 1 day is forecasted, for this, the increase in the probability of deviation from the physiological norm of prognostic indicators from the influence of previously established harmful chemical elements of the environment is first determined human habitation: iodine, zinc, nickel, manganese, chromium and lead; at the same time, the blood levels of the following indicators are determined as prognostic indicators for the person’s current age: thyroid-stimulating hormone (TSH), antibodies to TG, antibodies to TPO, malondialdehyde (MDA), antioxidant activity (AOA) and glutathione peroxidase (GLPO) ; compare their level with the physiological norm; in addition, for TSH, antibodies to TG, antibodies to TPO, MDA, AOA, in addition to its numerical value measured for the current age of a person at the time of the examination, the probability of exceeding

its relative to the norm, and for GLPO - the probability of a decrease

its relative to the norm: where t ₀ is the current age at the time of the survey, year; p _i - probability of deviation from the norm of the i-th prognostic indicator; moreover, if the value of the i-th prognostic indicator corresponds to the norm, then the indicated probability is zero, and if the value is above or below the norm, then the indicated probability is equal to one; then, taking into account the following system of relationships between the deviation from the physiological norm of the indicated prognostic indicators and the exposure of chemical elements in human biological media: the probability of exceeding the norm of TSH level occurs under the influence of iodine, nickel, manganese; the probability of exceeding the norm of the level of antibodies to TG - under the influence of chromium, iodine, nickel, manganese; the probability of exceeding the norm level of antibodies to TPO - under the influence of nickel and lead; the probability of exceeding the norm of the MDA level - under the influence of zinc, nickel, manganese, chromium; the probability of exceeding the standard level of AOA - under the influence of manganese; and also taking into account the system of dependencies between the following prognostic indicators from the above list: dependence of antibodies to TG on TSH; the dependence of antibodies to TPO from antibodies to TG; MDA dependence on antibodies to TPO; AOA dependence on MDA; determine the increase in the probability of deviations from the physiological norm of these indicators according to the following mathematical formulas: - the increase in the probability of exceeding the norm of the level of TSH in blood serum on a person’s age t is expressed by the following functions from the influence of chemical elements:

where Δp ⁺ ₁ (F (t)) is the function of the increase in the probability of exceeding the standard level of TSH associated with the influence of the chemical element F of the living environment at the age of a person t; F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ; F ₃ (f) is the concentration of manganese in the blood, μg / cm ³ ; F ₆ (t) is the concentration of iodine in the urine, mcg / (100⋅cm ³ ); - the increase in the probability of exceeding the norm of concentration of antibodies to TG in blood serum at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₂ (F (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TG associated with the influence of the chemical element F of the living environment at the age of a person t; F ₄ (t) is the concentration of chromium in the blood, μg / cm ³ ; Δp ⁺ ₂ (p ⁺ ₁ (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TG, associated with the probability of exceeding the norm of the level of TSH; - the increase in the probability of exceeding the norm of concentration of antibodies to TPO in blood serum at the age of a person associated with the influence of t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₃ (F (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TPO associated with the influence of the chemical element F of the living environment at the age of a person t; F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ; F ₅ (t) is the concentration of lead in the blood, μg / cm ³ ; Δp ⁺ ₃ (p ⁺ ₂ (t)) is the function of the increase in the probability of exceeding the norm of the level of antibodies to TPO, associated with the probability of exceeding the norm of the level of antibodies to TG; - the increase in the probability of exceeding the norm of MDA concentration in blood plasma at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₄ (F (t)) is the function of the increase in the probability of exceeding the norm of the MDA level associated with the influence of the chemical element F of the living environment at the age of a person t; F ₁ (t) is the concentration of zinc in the blood, μg / cm ³ ; F ₂ (t) is the concentration of nickel in the blood, μg / cm ³ ; F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ; F ₄ (t) is the concentration of chromium in the blood, μg / cm ³ ; Δp ⁺ ₄ (p ⁺ ₃ (t)) is the function of the increase in the probability of exceeding the norm of the MDA level, associated with the probability of exceeding the norm of the level of antibodies to TPO; - the increase in the probability of exceeding the norm of AOA concentration in blood plasma at the age of a person t is expressed by the following functions of the influence of chemical elements:

where Δp ⁺ ₅ (F (t)) is the function of the increase in the probability of exceeding the norm of AOA level in blood plasma associated with the influence of the chemical element F of the living environment at the age of a person t; F ₃ (t) is the concentration of manganese in the blood, μg / cm ³ ; Δp ⁺ ₅ (p ⁺ ₄ (t)) is the growth function of the probability of exceeding the norm of the AOA level, associated with the probability of exceeding the norm of the MDA level; and, based on the obtained values of the probability increase, set for each of these prognostic indicators: TSH, antibodies to TG, antibodies to TPO, MDA, AOA, the total probability of p ⁺ _i (t) exceeding it above the norm in a person’s age t according to the following formulas : - for TTG:

- for antibodies to TG:

- for antibodies to TPO:

- for MDA:

- for AOA:

and taking into account that the prognostic indicator of HLP in blood serum has no internal connections with other prognostic indicators, then the value of the probability of deviation from the norm for it is constant and takes on the value: if the value of HLP is lower than normal, then

; if the value is normal, then

; then calculate the overall likelihood of a person developing endemic goiter; Considering that the iterative procedure is used in the calculation, the calculation of the indicated total probability of development of endemic goiter is carried out sequentially at each time step, based on the results of the calculation of the previous time step; the calculation is performed until the age of the subject corresponding to the period for which the risk prediction is performed, according to the following formula:

where p (t + K) is the total probability of development of endemic goiter in humans at the age corresponding to the time step t + K (years); K is the value of the time step, and the time step adequate to the task of predicting the risk of developing endemic goiter is 1 day, which corresponds to the value K = 1/365 years, and at the first time step, the calculation is performed based on data from the time step corresponding to the initial age the subject, i.e. t in the first step will be equal to t ₀ ; p (t) is the total probability of developing an endemic goiter in a person at an age corresponding to a time step; k ₁ (t), k ₂ (t), k ₃ (t), k ₄ (t) - calculated variables; however, these calculated variables are determined by the following formulas:

and the individual risk R of the development of endemic goiter in humans for different periods of life is determined by the formula: R (t + K) = g (t + K) ⋅ P (t + K), where R (t + K) is the individual risk of endemic goiter at time t + K; g (t + K) - the severity of the disease "endemic goiter" at time t + K; p (t + K) - probability of endemic goiter disease at time t + K; t + K is the person’s age at the time point for predicting the risk of developing endemic goiter; moreover, the severity of the disease “endemic goiter” is determined by the formula: g (t + K) = 2.84⋅10 ^-5 ⋅е ^0.0933t ; and with an individual risk of less than 0.05, the risk of developing endemic goiter in humans is predicted to be negligible; with a value of from 0.05 to 0.35 as moderate; at a value of 0.35-0.6 as high; with a value of more than 0.6 as very high.

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