The role of interdisciplinary functional diagnostics in the detection of gynecological pathologies of an endocrine nature against the background of anemia

Angelina M. Korchagina, Diana A. Tadevosyan, Daria D. Ivanova, Elizaveta A. Ermakova, Aleksandra D. Kokoreva, Noemi D. Kirkevich, Derenik S. Chragyan, Khava R. Khutieva. The role of interdisciplinary functional diagnostics in the detection of gyne-cological pathologies of an endocrine nature against the background of anemia. Cardiometry; Issue No. 30; February 2024; p. 73-79; DOI: 10.18137/cardiometry.2024.30.7379; Available from:

Pregnant women are more susceptible to iron deficiency, and this can lead to a number of side effects for the mother and fetus. During pregnancy, women’s need for iron increases due to the growth of the fetus and placenta, which makes them more susceptible to deficiency of this element. Iron deficiency can also cause various negative consequences, such as low newborn weight, premature birth, slowing down the fetal development process and increasing the risk of maternal mortality. It is assumed that iron deficiency (hereinafter referred to as ID) and iron deficiency anemia (hereinafter referred to as IDA) will occur during and after pregnancy. Perimenopausal women are at risk of ID/IDA and deserve attention because the symptoms of ID may be misinterpreted or overlooked. In the scientific literature, iron deficiency is considered as a serious health problem for perimenopausal women.

Interdisciplinary functional diagnostics plays an important role in the detection of gynecological pathologies, especially those that are endocrine in nature against the background of anemia. It allows you to establish the relationship between different body systems, assess hormonal balance, organ function, which helps to determine the underlying cause of the disease and prescribe effective treatment. Functional diagnostics may include various methods, such as blood tests for hormone levels, ultrasound examination of pelvic organs, computed tomography or magnetic resonance imaging to identify pathologies and assess the condition of tissues and organs. These methods allow you to get a complete picture of the body’s condition and determine the causes of the problem.

The study of this topic is relevant, since gynecological diseases that have an endocrine nature against the background of anemia are common among women. Interdisciplinary functional diagnostics plays a key role in the careful study of such conditions, allowing us to identify links between hormonal disorders, anemia and gynecological pathologies. This helps to determine the most effective methods of treatment and prevention of possible complications.

The importance of this topic is due to the fact that hormonal disorders in women can greatly affect their health and cause various gynecological problems.

MATERIALS AND METHODS

In the process of writing the study, an analysis of scientific articles and literature was applied within the framework of the topic. This method allowed us to obtain an overview of scientific papers on the role of interdisciplinary functional diagnostics in the detection of gynecological pathologies of an endocrine nature against the background of anemia.

Anemia, as a condition accompanied by a decrease in hemoglobin levels, often occurs in the context of various diseases and can exacerbate the symptoms of gynecological disorders.

Interdisciplinary functional diagnostics allows us to assess the relationship between the endocrine system, blood condition and gynecological pathologies, which helps to improve the accuracy of diagnosis. The importance of this study is highlighted by the possibility of early detection of gynecological diseases associated with endocrine disorders, which contributes to more effective treatment.

The presence of anemia can complicate the course of the disease and complicate the choice of treatment methods, so identifying this problem through interdisciplinary diagnosis is important.

Effective treatment of gynecological diseases, especially with their endocrine nature, requires an integrated approach, which is provided through functional diagnostics. The emphasis on interdisciplinary diagnostics is becoming necessary to more accurately determine the causes and mechanisms of disease development, given their connection with the endocrine system and anemia.

Research in this area is relevant for the development of new therapeutic strategies aimed at correcting endocrine disorders and anemia in combination with gynecological therapy. The development of effective diagnostic and treatment methods will reduce the risk of complications and improve the prognosis for women suffering from gynecological pathologies with anemia.

Modern methods of medical diagnosis are extremely important for a deeper understanding of the interrelationships of endocrine disorders, anemia and gynecological diseases, which helps to optimize treatment and improve the quality of life of patients.

RESULTS

In the course of the research, scientific articles were analyzed within the framework of the topic. This method allowed us to obtain an overview of scientific papers devoted to interdisciplinary diagnostics in the process of detecting gynecological pathologies of an endocrine nature against the background of anemia in women of reproductive age and women in perimenopause.

Anemia is a common clinical disease with disproportionately high prevalence in women. It is estimated that almost 7% of women of reproductive age and up to 20% of women over 85 years of age suffer from anemia worldwide [1]. The number of cases of anemia among perimenopausal women (40-49 years old) has increased from 47.9% to 54.5% over the past five years [2].

Anemia due to endocrine diseases usually occurs from mild to moderate degrees, however, a decrease in plasma volume in some of these diseases may mask the severity of a decrease in red blood cell mass. The pathophysiological basis of anemia observed in endocrine diseases is often multifactorial.

Let’s look at the background of which endocrine diseases anemia can develop.

Thyroid dysfunction. Anemia in hypothyroidism can be normocytic, macrocytic, or microcytic; the co-existing deficiency of iron, vitamin B12, and folic acid may partially explain this heterogeneity. Iron deficiency often occurs in hypothyroidism as a result of an increased predisposition to menorrhagia associated with achlorhydria or because a deficiency of thyroid hormones can reduce iron absorption. In patients with concomitant iron deficiency anemia and subclin-ical hypothyroidism, anemia often does not respond adequately to oral iron therapy. The mechanism underlying the association of hypothyroidism and pernicious anemia is unknown [3].

The average volume of red blood cells cannot be used to differentiate hypothyroid patients with low vitamin B12 levels from patients with uncomplicated hypothyroidism.

Anemia is also a direct consequence of thyroid hormone deficiency, thyroid hormones enhance the effect of erythropoietin on the formation of erythroid colonies.

Diseases of the adrenal glands. The mass of red blood cells decreases with primary adrenal insufficiency (Addison’s disease), but this may not affect hematocrit or hemoglobin due to the concomitant decrease in plasma volume. The pathophysiological basis of anemia and any effect of adrenal cortex hormones on erythropoiesis are not clearly defined. Some patients with Addison’s disease develop a temporary decrease in hematocrit and hemoglobin concentration after initiation of hormone replacement therapy (presumably secondary to an increase in plasma volume) [3].

Pernicious anemia occurs in patients with autoimmune adrenal insufficiency, but is observed mainly in patients with polyglandular autoimmune syndrome type I, other manifestations of which include candidiasis of the skin and mucous membranes and hypoparathyroidism.

Anemia affects about 42% of pregnant women worldwide, which is caused by iron deficiency. Iron is an important micronutrient involved in vital processes such as erythropoiesis, immune responses and, importantly during pregnancy, in the development of the placenta and fetus.

Anemia occurs when the number of healthy red blood cells is insufficient to meet the physiological needs of the body in delivering oxygen to the brain, heart, muscles and other vital tissues. Hemoglobin is the main molecule that carries oxygen in red blood cells, so anemia is most often measured by the hemoglobin content in the blood, rather than by the volume of red blood cells [4]. Anemia can reduce cognitive and physical abilities, and is associated with a decrease in economic productivity [5] and an increase in morbidity and mortality from all causes.

Anemia is a complex disease with multiple causes, including nutritional disorders, infections, inflammation, gynecological and obstetric diseases and hereditary disorders of red blood cells, requiring a multisectoral approach based on existing interventions to make progress towards the global goal.

In addition, anemia in women may be associated with a decrease in cognitive functions, concentration and attention (in women in childhood) [6], a decrease in the body weight of newborns at birth, a possible increase in the risk of premature birth and a violation of postpartum interaction between mother and child, which potentially leads to developmental disorders in childhood.

Anemia-related quality of life disorders include loss of vitality, fatigue, depression, decreased physical function and decreased performance. Iron deficiency anemia can lead to a decrease in physical performance and intolerance to cold. Standardized tools for assessing the quality of life show that the indicators in women with anemia are comparable to those in patients with serious chronic diseases of the main organ systems. These indicators are directly proportional to the severity of anemia [7].

The period between 40 and 55 years, which covers premenopause (45-50 years), perimenopause (40-49 years), and in some women, postmenopause, has a great impact on women’s health and quality of life. This natural stage of life lasts from 4 to 11 years and is associated with hormonal fluctuations, menstrual irregularities with an increased risk of profuse bleeding.

While estrogen levels decrease due to the cessation of ovarian function, iron levels increase as a result of shortening menstrual cycles. This is often associated with a restrictive diet and lack of exercise, as well as subsequent changes in physical and mental well-being.

Thus, it can be said that iron deficiency (ID) is, today, a problem for women of the age group during perimenopause, since the symptoms of ID / IDA are non-specific in nature and can be misinterpreted in many differential diagnoses in the clinical picture.

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DISCUSSIONS

Today, specialists in practice apply methods of interdisciplinary diagnostics in the detection of gynecological pathologies of an endocrine nature against the background of anemia in pregnant women.

One of the cross-sectional studies pursuing the above-mentioned goal was conducted with the participation of a group of women who were in the early stages of pregnancy. The selection of patients took place according to certain criteria, for which a systematic selection was carried out. Initial assessments were based on hospital records. According to hospital records, 400 pregnant women visited the antenatal clinic in the early stages of pregnancy in the four months preceding the study. The sampling interval (≈ 3) was achieved by dividing the expected number of pregnant women (400) during the study period by the required sample size, which was 127 women (400/127 ≈ 3). Pregnant women were then interviewed at three intervals until the required sample size was reached (127) [8].

All the participants in the study had their blood samples taken for analysis. To measure the blood composition (hemogram) of the mother, an automatic hematology analyzer Sysmex KX-21 from Japan was used, according to the manufacturer’s recommendations. Five milliliters of venous blood were taken from each pregnant woman, which were subsequently placed in special vials with ordinary serum. The samples were coagulated, then centrifuged to separate the serum, which was then stored at -20 °C until analysis. The analysis was performed to determine the level of serum ferritin and the serum profile of the thyroid gland, including TSH (thyroid stimulating hormone), T4 (free thyroxine – the active form of the hormone) and T3 (free triiodothyronine – the active form of the hormone). These data were important for assessing the health status of pregnant women and the potential impact on fetal development.

To measure the level of ferritin in the mother’s blood serum, a gamma counter of radioimmunolog-ical analysis (Riostad, Germany) was used using kits provided by Beijing Isotope Nuclear Electronic Co., Beijing, China. Iron deficiency was defined as serum ferritin levels <15 mcg/l.

The levels of thyroid hormones (T3, T4 and TSH) in the mother’s blood serum were measured using the AIA 360 immunoassay analyzer from Tosoh Bioscience. These measurements were carried out in accor- dance with the instructions provided by the analyzer manufacturer. Two samples were taken from each participant, and the average value of the measurements was calculated and used as the final indicator of hormone levels. This method provided more accurate data for assessing the state of thyroid hormones in pregnant women, allowing them to more accurately determine their health and impact on fetal development.

All statistical analyses were performed using Statistical Product and Service Solutions (SPSS) software version 22.0 for Windows, developed by IBM. Continuous data, such as hormone levels T3, T4 and TSH, were tested using the Shapiro–Wilk test, which allows us to test the hypothesis that the set of indicators has a normal distribution. It allows you to evaluate how well the data corresponds to the normal distribution by comparing the observed data with the expected results from the normal distribution.

Clinical and biochemical data for the independent variable “iron deficiency status” and its two groups (women who had iron deficiency and women without it) were compared using either an independent sample t-test for normally distributed data or the Mann– Whitney U-test for data that did not obey the normal distribution. The proportions between the two groups were compared using the Chi-squared criterion (a statistical test used to determine whether there is a statistically significant relationship between categorical variables).

A Spearman correlation analysis was also performed between continuous variables, and the values of p < 0.05 were considered statistically significant, indicating the presence of a correlation between these variables [8].

In total, 127 pregnant women with an average age (IQR) of 27.0 (23.0-31.2) years participated in the described study. The median (IQR) of parity, gestational age and BMI was 1 (1-3), 10.0 (8.0-13.0) weeks and 26.6 (24.0-29.7) kg/ m2, respectively. Median (IQR) TSH, FT3 and T4 were 1,600 (1,162 2,092) IU/ml, 2,020 (1,772-2,240) pmol/l and 1,070 (0.960 – 1,190) pmol/L, respectively.

Forty-seven (37.0%) of these 127 women had ID. Age, ratio, gestation period, BMI (body mass index), TSH and T3 did not differ in women with ID and women without ID. The mean value (SD) of T4 was significantly lower in women with ID compared with women without ID [1.0 (0.17) vs. 1.11 (0.19) pmol, P

= 0.007)]. Serum ferritin was inversely correlated with T3 (r = – 0.225, P = 0.011). No correlation was found between S-ferritin, TSH and T4.

The values of T3 and T4 were within the normal range in pregnant women who underwent the study [9]. However, 31 (24.4%) women had higher TSH levels. Compared with women who did not have ID, a significantly smaller number of patients with ID had high TSH levels (6/47 [12.8%) versus 25/80 [31.3], P = 0.015).

It was also studied in pregnant women in the first trimester of pregnancy. The prevalence of ID among pregnant women in this study was 37.0%, which is common, given that a recent study examining the prevalence of ID among pregnant women in Sri Lanka reported 41.9% [10].

The main results of this study demonstrated that T4 levels were significantly lower in women (in early pregnancy) with ID and that serum ferritin was inversely correlated with T3 levels. As mentioned above, various studies of thyroid function and function have shown different results; for example, it was reported that in women in the second trimester, serum ferritin levels were negatively correlated with serum TSH levels and positively correlated with T4 levels [11].

Experts reported a positive correlation between T3 and T4 and serum ferritin in 74 pregnant women in early pregnancy [12].

Moreover, it was reported that the T4 level was significantly lower and the TSH value was significantly higher in women with ID (39.06% of them had ID, with serum ferritin < 15 mcg/l) in the first trimester [13].

Similarly, in a large inpatient study (168 cases with ID and 1,831 women without ID), T3 and T4 levels were significantly lower, and TSH levels were significantly higher in pregnant women. In the latest study, the authors reported that serum ferritin was positively correlated with T3 and T4 and inversely correlated with TSH [14].

In a recent study conducted on women in the first trimester of pregnancy, serum ferritin was a significant predictor of T4 and T4I [15].

The difference in the prevalence of ID between this study and others may explain the difference in these results. The results showed that 37.0% of women had ID, while in Heetal. The study reported that only 11.4% of women had ID. In addition, while this study used a serum ferritin level of less than 15 mcg/L as a threshold value for ID, in another study, the authors used a serum ferritin level of less than 12 mcg/L as a threshold value for ID [16].

The reasons for this may be different in different conditions. For example, one study reported a parasitic infection such as malaria as the main cause of anemia during pregnancy. It should be noted that in a recent meta-analysis (2021), pregnant women with ID had significantly increased serum TSH levels, decreased T4 levels, and increased hypothyroidism [17].

Interestingly, in a large study that was conducted in India (491 women in early pregnancy), Savitha et al. There was no reported association between hypothyroidism and ID [18].

Iron plays an important role in the functioning of the thyroid gland. For example, thyroid peroxidase (TPO), a hemo-dependent protein, facilitates the entry of iodine into the thyroid gland [19].

Iron deficiency anemia is associated with hypothyroidism. Many studies have shown that ID can reduce or worsen the synthesis and metabolism of thyroid hormones, possibly due to impaired activity of the enzyme hemo-dependent thyroid peroxidase (TPO) [20].

ID can reduce the activity of TPO and thereby disrupt the metabolism of iodine in the thyroid gland. Thyroid peroxidase catalyzes the first two stages of thyroid hormone synthesis, the iodination of thyroglobulin and the binding of iodine-tyrosine residues. In addition, IDA can lead to a decrease in peripheral conversion or even deiodination of T4 to T3, as well as alter the central nervous system’s control of thyroid metabolism and nuclear binding of T3.

Thyroid diseases can affect metabolism, which can worsen anemia and oxygen transport. Iron deficiency and abnormalities in the thyroid gland may have common causes, such as chronic inflammation or insufficient and adequate nutrition. These factors can also affect the functions of the central nervous system, which, in turn, can disrupt the functioning of the thyroid gland and its hormone levels. Homeostasis of the necessary iron levels in the body, necessary for a variety of biological processes, including protein and DNA synthesis, plays an important role in the functioning of the thyroid gland.

However, this study has its limitations. Firstly, the causes of iron deficiency caused by inflammatory markers have not been studied in this study. Secondly, due to limited resources, a study of antibodies to the thyroid gland has not been conducted. These factors

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can have a significant impact on understanding the mechanisms of iron’s effect on thyroid function.

Thus, iron deficiency was common during the first trimester of pregnancy and was associated with thyroid dysfunction. Therefore, it is necessary to evaluate ID in order to avoid thyroid dysfunction.

Conclusions. The study conducted at the Saad Abuelela Maternity Hospital is a significant step in the application of interdisciplinary diagnostics to identify gynecological pathologies in pregnant women. The method of systematic random sampling, based on the analysis of hospital records, allowed 127 women to be selected for further research. Laboratory tests for serum ferritin and thyroid levels of the participants revealed iron deficiency and determined the levels of T3, T4 and TSH. Data analysis using statistical methods such as the t-test and the Chi-square test showed significant differences between groups of women with different indicators. These results highlight the importance of an interdisciplinary approach in the diagnosis and management of the health of pregnant women with anemia and endocrine disorders.

The results of the study showed that 37% of pregnant women had iron deficiency anemia. The level of thyroid hormone T4 was significantly lower in women with ID compared with those who did not have this disorder. An inverse correlation was also found between serum ferritin and T3 levels. Some of the results did not coincide with previous studies, which revealed differences in the levels of thyroid hormones and serum ferritin. The differences may be due to the characteristics of the sample and the thresholds for the diagnosis of ID. It is also important to note that the causes of iron deficiency anemia in this study were not fully elucidated, including the possible effects of inflammatory markers and antibodies to the thyroid gland. The overall results highlight the complex relationship between ID and thyroid function in the context of pregnancy, where iron homeostasis plays an important role in the functioning of this gland.