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Review Article | DOI: https://doi.org/10.31579/2639-4162/283
Grodno State Medical University, Gorkogo St, Grodno, Republic of Belarus.
*Corresponding Author: I Elizaveta Bon, Candidate of biological science, Assistant professor of pathophysiology department named D. A. Maslakov, Grodno State Medical University; Grodno State Medical University, 80 Gorky St,230009, Grodno, Belarus.
Citation: Bon E.I., Maksimovich N. Ye., Zimatkin S.M., Yusko E.V, (2025), Endocrine System in Embryogenesis, J. General Medicine and Clinical Practice, 8(7); DOI:10.31579/2639-4162/283
Copyright: © 2025, Bon E.I. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 12 June 2025 | Accepted: 11 July 2025 | Published: 21 July 2025
Keywords: embryos; endocrine gland
New experimental methods that made it possible to perform surgical operations on embryos, extirpation of endocrine glands with their subsequent implantation, destruction of endocrine glands by ionizing radiation, blocking of one or another gland by chemical means, introduction of hormones, transplantation of gland rudiments, made it possible to clarify some of the established issues of endocrinology of the antenatal period of development. The results obtained gave grounds to talk about endocrinopathies of intrauterine development. During these periods, the processes of development, formation, differentiation occur with particular intensity, and violation of morphogenesis, maturation of endocrine glands have significant disturbances in the fetus.
New experimental methods that made it possible to perform surgical operations on embryos, extirpation of endocrine glands with their subsequent implantation, destruction of endocrine glands by ionizing radiation, blocking of one or another gland by chemical means, introduction of hormones, transplantation of gland rudiments, made it possible to clarify some of the established issues of endocrinology of the antenatal period of development. The results obtained gave grounds to talk about endocrinopathies of intrauterine development. During these periods, the processes of development, formation, differentiation occur with particular intensity, and violation of morphogenesis, maturation of endocrine glands have significant disturbances in the fetus. [3]
Any disorders of the endocrine system function in a developing organism led to severe changes due to a wide range of physiological effects of hormones. In addition to the specific influence of one or another hormonal principle, all hormones have metabolic, morphogenetic, kinetic and corrective effects. Interacting with enzyme systems, hormones affect metabolic processes, finely regulating the simultaneous course of synthesis and decay processes. In the early stages of ontogenesis, at a certain level of differentiation of cellular structures, hormones act as regulators of this complex process, influencing the activity of the gene apparatus of cells. Therefore, a violation of the formation of the endocrine system in the antenatal period - a delay in the development of any endocrine gland and in subsequent periods can significantly slow down or distort the growth and development of the body The rapid development of endocrinology has significantly changed the understanding of the role of endocrine glands in regulatory processes, helped to more deeply illuminate the pathogenesis of a number of endocrine diseases, but the features of the physiology and pathology of the endocrine glands in children require further study, and in this brief review we are not able to consider all the features of the pathology of the endocrine system of childhood and will focus only on some, in our opinion, more important issues. [1]
Both adults and children may develop endocrine diseases due to a variety of causes: hereditary factors, embryopathies, injuries, including mental ones, infectious diseases, local circulatory disorders, tumors, and poor nutrition. Of particular importance are protein deficiency and lack of microelements such as iodine, zinc, magnesium, copper, etc. Currently, autoimmune processes play a large role in the etiology of endocrinopathies, in particular, derepression of prohibited clones of lymphoid cells, leading to the formation of autoantibodies. There are numerous observations that acute childhood diseases of a viral nature often precede the development of endocrine diseases. It is assumed that the development of an endocrine disease requires a set of factors that can act both in the embryonic and postembryonic periods. Among these factors, an important role is given to genetic disorders of embryogenesis. In the pathogenesis of endocrine diseases, disturbances in the regulatory relationships between the hypothalamus, higher bulbar centers, peripheral parts of the nervous system, and effector organs are important. Pathological impulses to the hypothalamus will lead to a disruption of the neurosecretory function and a change in the activity of pituitary cells. [2]
The anterior pituitary gland. Pituitary diseases in children are rare. In childhood and adolescence, gigantism, acromegaly, pituitary dwarfism, adiposogenital dystrophy, and diabetes insipidus may occur. Pituitary cachexia does not occur in children. The anterior pituitary gland secretes a number of tropic hormones: adrenocorticotropic (ACTH), thyroidstimulating (TSH), somatotropic (STH), lactotropic (LTH), and gonadotropic hormones (GTH), which regulate the activity of other endocrine glands by the feedback principle. The secretion of hormones by the anterior pituitary gland is stimulated by neurosecretion formed in the nuclei of the hypothalamus under the influence of nerve impulses. If the hypothalamus is damaged or its function is changed, the production of neurosecretion is limited or stopped, which disrupts the transmission of impulses to the effector organs both through the hypothalamus and the parahypophyseal pathway. The consequence will be a dysfunction of one or more endocrine glands. [6]
The concentration of somatotropic hormone in the blood of a newborn can be 100 times higher than in the blood of an adult. Eosinophilic adenoma of the anterior pituitary gland causes hypersecretion of STH, and if this occurs before the completion of growth processes, gigantism occurs (a mouth above 190 cm is considered pathological). In the absence of a tumor, gigantism is explained by increased reactivity of the epiphyseal cartilages to a normal amount of STH. Acromegaly in children is very rare. It is assumed that in its pathogenesis, different tissue sensitivity to STH is important. Pituitary dwarfism develops as a result of decreased secretion of STH. It is possible, however, that it may be caused by a genetically determined or antenatal lesion of the central nervous system, namely the pituitary-hypothalamic region. Growth retardation usually begins at 2-3 years of age; bone development is delayed. The growth zones remain open for a long time. Childish body proportions are maintained throughout life; the reproductive system does not develop. Intelligence is not impaired. Cushing's disease occurs when the diencephalon and pituitary gland are affected with secondary hyperplasia of the adrenal cortex. The disease often begins after encephalitis, cranial trauma, or mental trauma. The pathogenesis of the disease is unclear. It is assumed that under the influence of increased secretion of ACTH, the ratio of corticosteroids secreted by the adrenal cortex is disrupted. It is believed that a change in the daily rhythm of ACTH secretion is important in the pathogenesis of the disease. [4]
Under normal conditions, a decrease in the number of corticosteroids in the blood, according to the law of feedback, will cause excitation of basophilic cells of the anterior pituitary gland, resulting in increased secretion of ACTH into the blood. In a stressful situation, other mechanisms for regulating the synthesis and excretion of ACTH into the blood come into effect, and an increase in its content in the blood occurs even with a high level of corticosteroids in the blood.
Studies have shown that in Itsenko-Cushing's disease, the binding capacity of transcortin is very low and therefore there is a large amount of free cortisol in the blood, which can explain the development of the disease. Itsenko-Cushing's disease is characterized by delayed growth and development, obesity, hypertension, decreased total bone mass, trophic skin disorders, and carbohydrate metabolism disorders. Obesity is explained by hypersecretion of glucocorticoids that stimulate neoglucogenesis. One of the possible mechanisms for increased fat deposition in Itsenko-Cushing's disease can be considered the stimulation of the pentose cycle of carbohydrate conversion, as well as the direct formation of fatty acids from glucose.
Hypertension in Itsenko-Cushing's disease has a complex pathogenesis, regarding which there is no consensus. It is explained by an excess of adrenal hormones that regulate electrolyte metabolism, others do not distinguish between essential hypertension and hypertension in Itsenko-Cushing's disease. There may be excessive secretion of aldosterone, leading to sodium retention in the body, and as a consequence to its deposition in the vascular wall, swelling of the endothelium. Under the influence of sodium, actomyosin threads shorten, the sensitivity of the vascular wall to catecholamines increases, and the secretion of ADH increases. In children, insufficiently formed regulation of vascular tone contributes to an increase in arterial pressure.
The posterior lobe of the pituitary gland (neurohypophysis) contains a large number of nerve fibers of neurons, the bodies of which are located in the supraoptic and paraventricular nuclei of the posterior region of the hypothalamus. Oxytocin and vasopressin (antidiuretic hormone) are secreted in these nuclei. Through the hypothalamic-pituitary tract, the neurosecretion, which is oxytocin and vasopressin, moves along the axons to the posterior lobe of the pituitary gland, where it is stored. It is possible that some transformation occurs there. The posterior nuclei of the hypothalamus, the hypothalamic-pituitary tract and the neurohypophysis are functionally a single whole. With degeneration, destruction of the supraoptic-pituitary system, diabetes insipidus develops. According to some data, the disease manifests itself clinically when more than 80% of the tissue secreting the neurosecretion is lost. Causes of damage to the hypothalamic-pituitary system may be head trauma, including birth trauma, tumors, meningitis, neurotropic viral infections. The first signs of the disease are thirst, polyuria, weakness. Sick children can drink from 5 to 12 liters of water per day in the absence of sweating. The specific gravity of urine is usually low (1.000-1.005). [5]
Oxytocin is secreted mainly in the paraventricular nuclei of the hypothalamus. This hormone causes contraction of smooth muscles, especially of the pregnant uterus, and inhibits the activity of cholinesterase, increasing the sensitivity of the uterus to acetylcholine. Probably, the violation of oxytocin secretion and the intensity of its breakdown by oxytocinase - an enzyme contained in the blood, myometrium and placenta of pregnant women, are important in the pathogenesis of delayed labor or its premature onset. Hypothalamic-pituitary disorders can lead to a symptom complex called adiposogenital dystrophy, characterized by obesity, delayed sexual development, growth, and sometimes decreased intelligence. The pathogenesis of the disease remains unclear. [6]
Adrenal cortex. The secretion of various corticosteroid metabolites occurs differently in boys and girls, starting from the age of 3-5 years. During puberty, the appearance of secondary sexual characteristics in boys occurs under the influence of androsterone, secreted by the testes, and in girls, the same process is stimulated by androsterone, formed in the reticular zone of the adrenal cortex. In newborns, the total excretion of corticosteroids in the urine usually reflects their content in the blood serum, with the exception of the first day after birth. At this time, the child has very low diuresis and, accordingly, a small number of corticosteroids is excreted, since the kidneys of the newborn are not able to concentrate urine. [17]
It is believed that newborns have instability of the glucocorticoid function of the adrenal cortex, which they associate with the reverse development of the fetal zone of the cortex, which occurs at this time, and the lack of formation of feedback with the pituitary gland. [19]
Hypercorticism in the development of a hormonally active tumor in the adrenal cortex in children is rare and usually leads to supragenital syndrome, manifested in the activation of heterosexual characteristics and the suppression of isosexual ones.
Hypofunction of the adrenal cortex can manifest itself acutely and chronically. Acute adrenal insufficiency is most often a consequence of birth trauma, asphyxia of newborns, intrauterine asphyxia. Difficult births using forceps often result in hemorrhages in the adrenal glands. Severe infectious diseases (typhus, diphtheria, measles, etc.) can also lead to adrenal insufficiency. Acute adrenal insufficiency is characterized by a fulminant course, convulsions, sepsis and ends in collapse.[20]
Birth injury causing minor hemorrhages in the adrenal cortex gives a picture of chronic hypocorticism. Chronic hypocorticism in children is observed with an adenoma of the adrenal cortex originating from the reticular layer. Excessive production of androgens causes depletion of the fascicular and glomerular zones. In these cases, boys experience premature puberty, and girls experience pseudohermaphroditism, combined with insufficiency of glucocorticoid function. [18]
With insufficiency of the glomerular zone of the adrenal cortex, the synthesis of mineralocorticoids is impaired. Deficiency of aldosterone disrupts the balance between sodium and potassium ions. Sodium penetrates and is retained in the cells; potassium is removed in excess. This is due to a disruption of the cell membrane system and membrane potential, which entails the impossibility of maintaining the difference in osmotic pressure in intracellular and extracellular fluids and the transition of a substance against the concentration gradient. The same disorders occur in the membranes of the organelles of the mitochondrial apparatus, ribosomes, lysosomes, which will manifest itself in a disorder of cell function. Deficiency of aldosterone is characterized by hypotension, physical inactivity, impaired absorption of carbohydrates in the intestine, which is impossible without sodium and potassium ions. [21] [22]
Pineal gland. The function of the pineal gland, or epiphysis, is poorly understood and controversial; there is no clarity on the issue of whether the pineal gland is an endocrine gland, what its function is, and what disorders cause disruption of its activity. It has long been noted that with tumors of the pineal gland in boys (under 10 years old), premature puberty (macrogenitosomia) develops. It was assumed that a normally functioning gland inhibits the secretion of gonadotropins and sexual development, delaying the onset of puberty. As the pineal gland involution occurs with age, inhibition is eliminated, and under the influence of secreted gonadotropic hormones, the activity of the sex glands begins. A tumor of the pineal gland, destroying it, prematurely removes the inhibitory effect on the secretion of gonadotropins. According to a number of other authors, the cause of macrogenitosomia is inflammation or destructive changes in the wall of the 3rd ventricle, in the hypothalamus, therefore, along with premature sexual development, water-salt metabolism disorders, polyuria, polydipsia, etc. are often observed. According to the data, macrogenitosomia is not associated with endocrine disorders, but is hereditary, probably its cause is a chromosomal aberration.
Based on comparative anatomical studies, it was established that the pineal gland belongs to the organs that undergo reverse development in phylogenesis. He suggested that the pineal gland is a remnant of the proximal part of the parietal eye, a highly differentiated receptive organ of ancient amphibians. Through this eye, animals received signals about the brightness of lighting. The pineal gland is closely connected with the diencephalon, therefore, in case of pathological processes affecting the pineal gland, it is very difficult to decide whether the observed disorders are a consequence of the pineal gland lesion or the result of the spread of the pathological process to neighboring areas of the brain. [7] [8]
Thyroid gland. This gland occupies an important place in the child's endocrine gland system. Its hormones affect morphogenetic processes, growth, tissue differentiation, and metabolism. In a newborn child, the thyroigland has signs of incomplete development; this is indicated by the insufficiency of the follicular structure of the gland, the almost complete absence of colloid in them, and the low iodine content. In early postnatal ontogenesis, there is a rapid accumulation of iodine in the thyroid gland tissue, and in a child of 4-5 years, the iodine content in the gland reaches the same values as in an adult, 300 times exceeding its amount in the blood plasma. High activity of metabolic processes - oxidative, plastic, at an early age requires large amounts of thyroid hormone, which is ensured by its intensive secretion. This explains the faster replacement of iodine in the gland. In an adult, iodine is replaced after 1 - 1.5 months, in a child almost twice as fast. [10]
Dysfunction of the thyroid gland in a child is a common phenomenon, and at an early age, hypothyroidism occurs somewhat more often than hyperthyroidism. Complete functional insufficiency of the thyroid gland in newborns is called cretinism and most often it is based on aplasia of the gland caused by an embryonic developmental defect. The causes of thyroid aplasia can be poor nutrition of a woman during pregnancy, inadequate nutrition of plant proteins that do not contain the necessary amino acids, in particular tyrosine, needed for the synthesis of thyroid hormones, or iodine deficiency; severe infectious diseases, the effect of various toxic substances. It is believed that iodine deficiency during pregnancy, which is aggravated by the above factors, plays an important role in the mechanism of athyroidism development in a child. Hypothyroidism can be hereditary; low hormonal activity of the gland is transmitted by an autosomal recessive type of inheritance. Congenital hypothyroidism occurs as a result of damaging factors during the sensitive period of formation of the fetal thyroid gland, and this form of gland deficiency is detected after breastfeeding, i.e. after the thyroid hormones stop entering the child's body with mother's milk.
In a young child with hypothyroidism, as a result of insufficient oxidative processes, heat production (chemical thermoregulation) decreases. Taking into account the immaturity of physical thermoregulation, characteristic of this age period, the manifestations of poikilothermia in a child become understandable. With hypothyroidism, the basal metabolic rate drops by 25-35%, hypercholesterolemia develops, and the content of iodine-bound protein in the blood decreases. As a rule, bradycardia develops, pulse pressure drops, peripheral vessels narrow, limiting heat transfer, and, accordingly, the volume of circulating blood decreases due to a decrease in the volume of the vascular system; hypovolemia develops, caused by both hypoplasmy and a decrease in globular volume. Hypothyroidism is always accompanied by hypoplastic normochromic anemia.
The child's growth and development are delayed, which is especially pronounced in congenital hypothyroidism. In this case, all signs of the disease appear in the first 6 months of life, as breastfeeding is limited. The development of cartilaginous tissue of the epiphysis, ossification is impaired, and teething slows down. Very characteristic of hypothyroidism is the development of ossification from irregular foci scattered throughout the area of the altered cartilage. The large fontanelle and cranial sutures do not close for a long time. Early hypothyroidism delays brain development, but hypothyroidism that occurs at a later age inevitably entails a delay in the development of both mental and motor activity. Skin changes (dryness, peeling), so characteristic of hypothyroidism in adults, are not always expressed in childhood. Thyroid insufficiency in childhood and adolescence is referred to as childhood or adolescent hypothyroidism, and in cases of severe insufficiency - as childhood or adolescent myxedema. [11] Removal of the thyroid gland in young animals produces a picture similar to cretinism in children. Growth retardation is explained by a violation of the correlation between the pituitary gland and the thyroid gland, since the introduction of growth hormone (STH) to such animals has no effect.
It is known that most of those suffering from endemic goiter are children. Endemic goiter occurs in certain geographical areas, the so-called biogeochemical provinces, poor in iodine. In coastal areas, if they are not separated from the sea by high mountains, endemic goiter does not occur, since the iodine in sea water evaporates and enters the atmosphere. In addition to the iodine content, the concentration of some trace elements is important. Thus, copper and zinc weaken the manifestations of iodine deficiency, lead and fluorine - increase it. Hard water with a high content of calcium ions contributes to the development of hypothyroidism due to the fact that calcium hinders the absorption of iodine in the gastrointestinal tract.
Deficiency of thyroid hormone synthesis causes increased secretion of thyroid stimulating hormone (TSH), which leads to the formation of goiter without hyperthyroidism. Although such goiter is considered euthyroid, it is accompanied by a number of painful phenomena - hypochromic anemia, leukopenia, dystrophic changes in the myocardium. Hyperthyroid endemic goiter is rare and usually occurs without an increase in basal metabolism. In the pathogenesis of thyroid hypofunction, the main role is played by the insufficiency of the synthesis of thyroid hormones: triiodothyronine and thyroxine. Hyposecretion is based on a violation of enzymatic reactions involving iodine oxidase and peroxidase. The following mechanisms of disorders are possible: insufficient accumulation of iodine by the gland and its conversion into an organic form, the inclusion of iodine in tyrosine, the conversion of monoiodotyrosine into diiodotyrosine may be disrupted.
Hypothyroidism reduces oxidative processes in cell mitochondria, thereby undermining the energy supply of cells; the synthesis of DNA, messenger RNA, protein - cell-specific antigens - decreases, which leads to insufficient differentiation of cellular formations. Thyroid hormones activate respiratory enzymes, and with hypofunction of the gland, oxidative processes decrease, in particular, fat oxidation is disrupted.
Diffuse toxic goiter (Graves' disease, hyperthyroidism, thyrotoxicosis) occurs in childhood. The disease can be caused by various reasons (mental and physical trauma, infectious diseases). According to the data, toxic goiter occurs mainly in girls in the prepubertal and pubertal period, and the main significance is the disruption of the interaction of the endocrine glands at the time when the sex glands begin to function. A congenital form of diffuse toxic goiter is known. In these cases, as a rule, the mother has a similar disease. In the pathogenesis of the disease, the penetration of the maternal thyroid hormone through the placenta or stimulation of the thyroid gland of the fetus by excess TSH of the mother's body, also penetrating through the placenta, are important. In hyperthyroidism, thyroid hormones have a high catabolic effect, increasing the basal metabolic rate by 100 - 150% and increasing oxygen consumption by 2 times or more, which makes the child's body highly sensitive to oxygen deficiency. The experiment established that the rate of oxygen consumption by the myocardium, kidneys, liver, and skeletal muscles increases sharply with hyperthyroidism. Thyroid enlargement in children develops earlier than in adults and is also accompanied by cardiovascular changes, which primarily include tachycardia (from 90 to 200 heartbeats per minute, an increase in the heart border to the left, caused by dilation of the left ventricle). Dilation is based on an increase in the volume of circulating blood and the cardiac output. Vascular peripheral resistance is usually reduced. In hyperthyroidism, a regular increase in the volume of circulating blood is established, which is explained by an increase in the capacity of the vascular system - the expansion of cutaneous vessels, providing heat transfer with increased heat production. As indicated, excess thyroid hormones increase the myocardium's need for oxygen and cause oxygen debt and hypoxia. Therefore, myocardial hypertrophy does not develop, but only dilation is observed, initially tonogenic, and later often myogenic. [13]
One of the important manifestations of diffuse toxic goiter in children is increased nervous excitability, emotional and motor instability. Thyroid hormones exert their effect at the cellular level, being included in the phospholipids of cell membranes and mitochondrial membranes, they change the permeability of the latter. Excessive amounts of thyroid hormones damage highly dynamic structures such as mitochondria, they swell, increase in size, the number of cristae decreases, which reduces the overall surface area of mitochondrial membranes, the electron density of the matrix changes, which leads to disruption of the energy-producing and genetic functions of the mitochondria of somatic cells. All electron carriers of the coupled respiration and phosphorylation chain are located on the mitochondrial membranes - pyridine nucleotides, flavoproteins, cytochromes, enzymes of the Krebs cycle. This is the central place in the system of enzymes of amino acid deamination, beta-oxidation of fatty acids. Excessive amounts of thyroid hormones disrupt the complex system of the respiratory chain. When the coupling of oxidative phosphorylation is dissociated, the accumulation of energy-rich phosphorus compounds in the cell (ATP, creatine phosphate) decreases, and the function of the mitochondria is directed not at providing energy for complex functional functions and plastic processes of a growing, developing organism, but at excess heat generation. Iodine, contained in thyroxine and triiodothyronine, imparts mobility to metabolic processes by activating sulfhydryl groups in the protein molecule, enhances protein breakdown, as evidenced by the increased content of amino acids in the blood, increased excretion of nitrogen, potassium, and phosphorus in the urine. This state of protein metabolism leads to a decrease in immunogenesis and disrupts immunological reactions. The catabolic effect of thyroid hormones extends to carbohydrate, fat, and lipid metabolism. The process of glycogenolysis is increased, as a result of which the amount of glycogen in the liver, kidneys, striated muscles, and myocardium is reduced. [12]
Children have hyperglycemia due to active glycogenolysis, increased absorption of carbohydrates in the intestine and high tone of the sympathoadrenal system. This condition leads to tension and overstrain of the cells of the insular apparatus of the pancreas, which can result in its failure and diabetes mellitus. With hyperfunction of the thyroid gland, diabetes mellitus occurs 2-3 times more often. Under the influence of excess thyroid hormones, there is an increased mobilization of fatty acids, cholesterol from their depots, which is accompanied by emaciation and growth retardation. Such pronounced catabolic processes, the formation of a large number of metabolic products causes the loss of intracellular water, which is a serious damaging factor for the cell. Hypoalbuminemia enhances the phenomena of hyperthyroidism, since the hormone in the blood binds to albumin, and with a deficiency of the latter, the bond is fragile and the flow of the hormone into the tissues accelerates. [14]
In hypothyroidism and hyperthyroidism, the adaptive role of the hormones of this gland is disrupted. As adaptive hormones, they participate in the regulation of metabolism, and depending on the conditions, either anabolic or catabolic effect prevails. The anabolic effect of thyroid hormones is expressed during the period of growth of the body, even if the child is on a low-protein diet, during the recovery period after an illness. Under the influence of thyroid hormones, wound healing is accelerated, as they stimulate cell division, accelerate the synthesis of mRNA, thereby promoting the formation of protein in the body. Under these conditions, catabolic processes are reduced and anabolic ones prevail. Thyroid hormones affect the adrenal glands. An experiment on dogs showed a decrease in the activity of the adrenal cortex with hypothyroidism. With unilateral adrenalectomy, the thyroid gland affects the process of vicarious hyperplasia of the remaining adrenal gland. Patients with hyperthyroidism often have signs of adrenal cortex insufficiency in the form of general weakness, hypotension, lymphocytosis, skin pigmentation and other manifestations. [9] [11]
Parathyroid glands. The main function is to regulate the level of calcium and phosphorus in the blood, and their action in this regard is so closely related to vitamin D that it is impossible to consider the effect of parathyroid hormone and vitamin D on the body in isolation. [24]
Removal of the parathyroid glands leads to the death of the animal within 1-3 days due to convulsions. In this case, blood calcium drops and phosphorus increases. The level of calcium in the blood determines the excitability of the neuromuscular apparatus and is regulated very precisely, but the regulatory mechanism remains not fully understood. It is only known that the following take part in the regulation: parathyroid hormone - parathyroid hormone, vitamin D and thyroid hormone - thyrocalcitonin. Their points of application are the intestines, bones and kidneys. With a deficiency of parathyroid hormone, calcium absorption in the intestine decreases, phosphorus reabsorption in the renal tubules increases and calcium and phosphorus are not mobilized from the bones. In bone cells, calcium is combined with phosphorus in the form of oxyapatite. Under the influence of parathyroid hormone, glucose metabolism in bones switches to the formation of citric acid and, due to the shift to the acidic side, osteoclasts are activated, the activity of osteoblasts is inhibited - apatite dissolves. Apparently, under the influence of parathyroid hormone, which inhibits metabolism in cells, some osteoblasts are converted into osteoclasts. The released calcium combines with citric acid, and in the kidneys this compound is oxidized, is destroyed, and calcium returns to the blood. Thyrocalcitonin stops the formation of citric acid, thereby stopping the mobilization of calcium from the bones and, conversely, promoting its fixation in the bones. In this regard, the effect of thyrocalcitonin is opposite to the effect of parathyroid hormone. Thyrocalcitonin is apparently formed in the parafollicular cells of the thyroid gland, arising from the so-called ultimobranchial bodies. With a lack of vitamin D, the absorption of calcium and phosphorus from the intestines decreases, since a poorly soluble calcium-phosphorus compound is formed there. A decrease in the level of calcium in the blood stimulates the secretion of the parathyroid glands, and blood calcium is restored by mobilizing it from the bones. [25]
The most common form of phosphorus-calcium metabolism disorder in childhood is rickets. It is caused by a lack of vitamin D, the need for which is especially great during the period of intensive growth in the first 2 years of life. Hypovitaminosis D can be a consequence of low vitamin B content in breast and cow's milk, with insufficient ultraviolet insolation in the winter months, due to which the conversion of provitamin 7-dehydrocholesterol into vitamin B3 does not occur. The insufficiency of ultraviolet insolation is especially great in cities, where air pollution contributes to the absorption of ultraviolet rays by smoke particles. [15]
Rickets is characterized by insufficient calcium deposition in the bones, as a result of which the cartilaginous substances between the epiphysis and diaphysis expand, since the cartilaginous cells do not degenerate and do not calcify. The formation of bone tissue slows down. The load caused by crawling, lying, sitting, walking leads to the deformation of wide rickety metaphyses, and disturbances in the formation of the spine, ribs, and pelvic extremities occur. Already calcified bones are poor in calcium, which leads to further disturbances in their shape. [22]
In addition to bone changes, a child with rickets is characterized by a lag in physical and often mental development, impaired emotional tone, slow formation and instability of conditioned reflexes, rapid onset of inhibition, and hypotension. These changes indicate that although the main factor in the pathogenesis of rickets is a lack of vitamin D, metabolic processes can also be affected by a disturbance in the activity of the subcortical centers In the first weeks of life, newborns sometimes experience tetany caused by hypofunction of the parathyroid glands, the cause of which is hyperparathyroidism in the mother. If this condition is combined with hyperventilation, i.e. with sharply increased breathing, then a significant drop in the concentration of ionized calcium in the blood can pose a threat to the child's life. In latent tetany, an attack of convulsions can be caused by any, even moderate irritation, including hyperventilation. [16]
Excessive dosage of vitamin D, especially in combination with irradiation of food products, can lead to chronic hypercalcemia, when the calcium level exceeds 15 mg. Calcium absorption in the intestine increases, the phosphorus content in the blood decreases, the acidbase balance is disturbed, and the excretion of ammonium salts by the kidneys increases. Calcium is deposited in the walls of the stomach, in the lungs, in the kidneys, in the walls of blood vessels. Osteoblast activity decreases. High calcium levels suppress the secretion of the parathyroid glands. A picture of calciphylaxis is created. The clinical picture is characterized by anorexia, vomiting, thirst with polydipsia. In severe cases, intelligence is impaired.[15]
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This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
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As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
