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HORMONAL DISORDERS IN WOMEN WHILE TAKING
ANTIEPILEPTIC DRUGS.
Amonova Zakhro Kakhramonovna,
PhD., assistant of the Department of Neurology, Samarkand State Medical
University
Amonova Zilola Kakhramonovna
is a 2nd year student at the Faculty of Dentistry of the EMU
ANNOTATION: The pathogenetic aspects of the hypothalamo-pituitary
syndrome in patients with epilepsy is a very complex and multifaceted problem, which
requires the study of the interaction of the nervous system and the endocrine system
at different levels. This article provides information on the pathogenetic mechanisms
of hypothalamo-pituitary syndrome associated with epilepsy, clinical manifestations,
diagnostic and treatment methods. Epilepsy is a disease that contributes to the
involvement of the patient's brain in the pathological process as a single functional
system. In turn, a violation of the functional state of the patient's brain leads to an
imbalance in the activity of nonspecific systems and manifests itself not only in
electroencephalographic features, but also in characteristic disorders in the
cognitive, mental and vegetative status of the patient.
Key
words:
T3,
T4,
TSH,
TRH,
pathological
process,
electroencephalographic features, pathogenetic mechanisms, epilepsy, patients,
hypothalamic-pituitary syndrome, pituitary gland, hormones, treatment, nervous
activity.
INTRODUCTION
Hypothalamo-pituitary syndrome is a pathological condition caused mainly
by the interaction of the hypothalamus and the pituitary gland. The hypothalamus is
located at the upper level of the nervous system, and it carries out many physiological
processes, including the production of hormones, temperature regulation, and control
of sleep and wakefulness rhythms. The pituitary gland produces its own hormones
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under the influence of hormones produced by the hypothalamus. The development of
hypothalamic-pituitary syndrome in patients with epilepsy is often associated with
pathological changes in the hypothalamus. In this regard, the study of the functional
status of the hypothalamic-pituitary system (HPS) in epilepsy will contribute to the
expansion and in-depth study of pathogenetic mechanisms that will contribute to the
optimization of modern diagnostic methods, which in turn will give a more complete
picture of the clinical manifestation of this disease and optimize treatment methods.
The hypothalamus is an important link in the system of regulation of cerebral
functions and regulates a number of processes outside the pituitary, on the one hand,
and on the other hand, controls the state of the adeno-pituitary gland, constituting a
single hypothalamic-pituitary system, hormones are modulators of epileptic activity,
which is a prerequisite for optimizing the principles of treatment of this disease.
Further study in this direction seems to be relevant and promising, since the low
efficiency of antiepileptic drugs, according to many researchers, is 25%.
Most of the available research concerns the study of hormonal disorders,
which were studied during or immediately after a seizure, when urgent mechanisms
of regulation of hormonal homeostasis are implemented. Whereas between the seizure
period and the formation of a chronic pathological process, which is provided by
slowly acting mechanisms of adaptation, are practically not studied. The mechanism
of chronic pathological adaptation is based on automatically proceeding metabolism,
genetically predetermined with the participation of the regulatory role of the nervous
and endocrine systems. Separate pathogenetic mechanisms of epilepsy,
neurohormonal relationships and their influence on the characteristics of the course
and prognosis of epilepsy have not been studied. Neurological manifestations of
dysfunction of the hypothalamic-pituitary system in patients with epilepsy, as well as
the role of the hypothalamic-pituitary system in the formation of clinical
manifestations of this pathology, have not been sufficiently studied.
Purpose of the study:
to study the peculiarity of clinical manifestations of
imbalance and maladjustment of the hypothalamic-pituitary system in patients with
epilepsy.
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Materials and methods of research:
patients with epilepsy who were
hospitalized in the Department of Neurology and Neurosurgery of the 1-Clinic
Samarkand Medical institute for the period 2020-2021 were subject to examination,
patients who were registered at the endocrinological dispensary in Samarkand,
Tashkent. In accordance with the classification (international classification of
epilepsy and epileptic seizures of the International League Against Epilepsy 2017),
patients were examined with symptomatic epilepsy, cryptogenic epilepsy
(idiopathic).
The total number of examined was 86, including 40 patients with epilepsy
(group 1), 46 patients with epilepsy and signs of hypothalamic-pituitary syndrome
(HHS; group 2).
To determine hormones in blood plasma, a radioimmunological method was
used. All patients were tested for triiodothyronine (T3), thyroxine (T4), thyrotropin
(THG), adrenocorticotropic hormone (ACGH), and cortisol levels (using standard
commercial kits).
Assessment of the functioning of the autonomic nervous system is carried out
according to the method of determining the autonomic index (VI) of Kerdo. In
accordance with the state of the autonomic nervous (VNS) system, 5 tones are
distinguished:
pronounced
parasympathicotonia
-
the
predominance
of
parasympathetic tone, indicator values> (-31); parasympathicotonia - an intermediate
state between the norm and parasympathetic tone, values from (-16 to -30); norm -
balance of sympathetic and parasympathetic influences, values from (-15 to +15);
sympathicotonia - an intermediate state between the norm and sympathetic tone - from
+16 to +30; pronounced sympathicotonia - predominance of sympathetic tone,
indicator values> (+31).
All patients underwent dynamic EEG studies. Basically, the structure of the
brain was studied using magnetic resonance computed tomography (MRI).
Statistical processing was carried out using the Microsoft Excel program
package (version 14.0). During the statistical processing, the methods of parametric
and nonparametric statistics were used.
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Research results.
During the examination of patients, attention is drawn to
the specificity of the external data of patients of group 2, in particular, overweight in
16 patients (χ2 = 10.656; p = 0.453), while in group 1 it is 2 times less. Striae are
clearly visible in the area of the abdominal wall. Young women, 18-28 years old (9),
complained about headache and periodic dizziness (taking into account the main
problem of epileptic seizures).
The duration of the disease in the groups was identical (10.5 ± 2.3 years and
10.9 ± 1.9 years, respectively, in groups), despite these indicators, epileptic seizures
in group 2 were severe, seizures were more prolonged and frequent.
As can be seen from the data presented, patients with epilepsy in most cases
have sympathicotonia, moreover, in patients with HGS burden, sympathicotonia was
observed in 52.1% of cases, while in patients of group 1 - in 36.8% of cases;
parasympathetic was observed in 29.8% of patients with epilepsy in combination with
HGS, while in patients with epilepsy - in 34.7%. The balance of sympathetic and
parasympathetic influences was 2.6 times more often observed in patients of group 1.
Expressed autonomic symptoms, autonomic lability, unstable arterial
hypertension, more often against the background of headaches. The most reliable was
the absence of the menstrual cycle (aminaria), which confirms the hypothalamic-
pituitary syndrome in these patients.
The clinical study contributed to the establishment of the functional state of
HGS in patients with epilepsy, which showed a pronounced polymorphism of
pathological syndromes and symptoms caused by epilepsy, which regulates
vegetative-trophic and endocrinological functions. The severity of symptoms
depended on the presence of a pathological imbalance in the function of the HGS, i.e.
in patients of group 2.
Dysfunctions of the HGS are most often manifested by the presence of
neurotrophic syndrome (χ2 = 2.877; p = 0.233), sleep and wakefulness disorders (χ2
= 2.523; p = 0.219) and the development of emotional and psychological disorders
(χ2 = 6.044; p = 0.333). A comparative analysis of the data obtained allows us to
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conclude that there is a more pronounced pathology in patients with epilepsy and
HGS.
Neurological examination revealed diffuse symptoms in most patients,
however, in patients with epilepsy not aggravated by HGS, disorders were observed
mainly at the cortical-subcortical level, and in patients with HGS with this disease,
the stem level of the vestibular system was involved in the pathological process.
Changes in bioelectric activity in epilepsy, observed by us in the interictal
period, are similar to those described in the literature, however, computer processing
of the electroencephalogram revealed differences between the data of studies in
patients of the 1st and 2nd groups. The day of patients with epilepsy aggravated by
HGS was characterized by a shift in the average effective frequency of the spectrum
towards pathological slow wave activity, as well as the presence of signs of
dysfunction of the mid-depth structures of the brain and a change in correlative
relationships between the main EEG rhythms.
In the study of the hormonal status in patients with epilepsy, data were
obtained indicating the presence of significant changes in the hormonal function of
the hypothalamic-pituitary system, which is manifested by an imbalance of the
hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axis. When
examining the content of ACTH in patients with epilepsy during the interictal period,
no significant changes in its concentration were found. An increase in the level of
ACTH according to the literature, during seizures and its normal content in the inter-
paroxysmal period, suggests that ACTH is a factor in the adaptation of the div to
stress.
A significant increase in the level of cortisol varied depending on the duration
of the disease and was maximal in patients who were ill over 5 years (mean values
7.4 ± 0.09 years).
Since glucocorticoids increase the synthesis of serotonin, reduce the level of
GABA in the brain, increase the permeability of neuronal membranes for Na + and
Ca +, and decrease protein synthesis in the brain, an increase in cortisol levels can
cause a decrease in the seizure threshold and a characteristic sign of an epileptic
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seizure. An increase in cortisol levels with normal ACTH values is a manifestation of
dysregulation in the hypothalamus-pituitary-adrenal system. A decrease in the content
of T3 in the blood plasma of patients with epilepsy and a significant variability in the
level of T4 and TSH in all examined patients were found. Moreover, the severity of
changes in thyroid status correlates with the severity of epilepsy, clinical signs of
hypothalamic pathology, as well as the duration of the disease, the frequency and type
of seizures.
Under stress (of any nature), a synergistic increase in the activity of the
suprarenal and thyroid complexes at the hypothalamic, pituitary and peripheral levels
occurs only in the initial phase. But in the future, activation of the adrenal complex
inhibits the function of the thyroid gland at the hypothalamic-pituitary and peripheral
levels. These mechanisms explain the presence of subclinical hypothyroidism in the
examined patients during the interparoxysmal period.
Thus, the hypothyroid state disrupts bioelectrical processes in organs with a
high level of metabolism, including the brain, where the activity of glycolytic and
oxidative enzymes decreases. In addition to energy metabolism, the exchange of
mucopolysaccharides in the vascular wall is disrupted, the tone of the cerebral vessels
decreases.
It is known that repeated epileptic seizures of various origins are accompanied
by persistent disorders of energy metabolism, in particular, a decrease in the rate and
coefficient of phosphorylation. Along with this, anticonvulsants lead to a decrease in
the respiratory activity of the brain tissues, dissociation of respiration by
sforphorylation, and this aggravates the disturbances in the bioenergetics of patients
with epilepsy caused by the epileptic process.
T3 deficiency leads not only to a distortion of the hormonal status of the div,
but also due to the variety of the influence of thyroid hormones to the development
of a pathological energy and metabolic state, which aggravates the course of the
disease and creates a pathological basis for its progression.
Thus, functional restructuring of the state of the brain in patients with epilepsy
significantly alters the activity of the hypothalamic-pituitary system. This is
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confirmed by the identified autonomic disorders, changes in the bioelectrical activity
of the brain, disorders in the hypothalamus-pituitary-thyroid gland and hypothalamus-
pituitary-adrenal glands, and disruption of the integrated connections between these
systems.
Conclusions:
1.
The clinical and neurological picture of maladjustment of the
hypothalamic-pituitary system is characterized by disorders of the autonomic nervous
system with a predominance of sympathetic orientation.
2.
The hypothalamic-pituitary system, affects the functional restructuring of
the brain in patients with epilepsy and is manifested by polymorphic symptoms on
the one hand, dysfunction of the HGS enhances arousal through biologically active
substances, on the other hand, reduces the level of arousal through the synthesis of
some neurotransmitters and disorders of the autonomic nervous system.
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Epilepsy on the background of hypothalamic-pituitary system dysfunction from the
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Neuro-Endocrinological Aspects In Patients With Epilepsy. Z.K. Amonova, A.T.
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HARMFUL ASPECTS OF EPILEPSY. Amonova Z.K. Amonova Z.K.
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