HYPOTHYROIDISM, PSYCHO-NEUROLOGICAL STATUS AND MEDIATING AMINO ACIDS

UDC 616.441-008.64

 

HYPOTHYROIDISM, PSYCHO-NEUROLOGICAL STATUS AND MEDIATING AMINO ACIDS

 

L.F. Vudu, PhD in medicine, Associate Professor at the Department of Endocrinology

“Nicolae Testemitanu” State University of Medicine and Pharmacy of the Republic of Moldova

(Moldova, Chisinau, Boulevard Stefan cel Mare si Sfint, 165)

E-mail: Vudu77@mail.com

 

Abstract. The research deals with the character of psycho-neurological disorders and the content of amino acids from the functional group of mediators in patients with hypothyroidism. It has been established that hypothyroidism causes considerable neuropsychological disturbances manifested by the prevalence of clinical and paraclinical syndromes with inhibitory connotation as well as the spectrum and content of inhibitory amino acids, which reveals one of the reasons for the dominance of inhibitory nerve processes in patients with hypothyroidism.

Keywords: hypothyroidism, psycho-neurologic status, mediator amino acids.

 

Introduction. Hypothyroidism is one of the most widespread endocrine diseases in the Republic of Moldova, occupying the second place, after diabetes, among diseases with function disorder. Hypothyroidism is a current problem for practitioners in various areas of activity because of polymorphism of body effects and frequent spread – about 1-5 % of hypothyroidism manifested, and subclinical hypothyroidism – corresponding to 10 % women and 3 % men [1; 2; 3].

Also, we mention that excitatory mediating amino acids (glutamine, asparagine) and inhibitors (glycine, taurine, γ-aminobutyric acid), which play a decisive role in regulating the transmission of nerve signals in the central nervous system, are insufficiently studied. This determined the purpose of the study – the complex investigation of the neuropsychic state and changes in the content of amino acids mediators (AAM) in patients with primary hypothyroidism (PH).

Material and methods. Clinical investigations were performed on a sample, which included 24 patients with PH admitted to the endocrinology clinic of the Republican Clinical Hospital. The control group consisted of 15 healthy people.

The following investigations were carried out:

• Determination of clinical picture and hypothyroid basic syndromes;
• Determination of TSH concentration, free T4, free T3;
• Determination of lipid metabolism;
• Thyroid gland ultrasound;
• Research of vegetative disorders;
• Researching neuropsychological and cognitive status.

The profile and numerical values of AAM (excitators and inhibitors) were studied in 24 patients with PH and 15 subjects without thyroid pathologies and other disorders. The amino acid concentration was studied in part in each patient, the blood samples were collected in the morning after a 10-12 hour fasting. Blood samples were studied by the liquid chromatography method at the AAA339M amino acid analyzer. The results were analyzed statistically and determined their veracity according to the Student criterion.

Results and discussions. Clinical, paraclinical, including neuropsychotic symptoms have been described by
B. Fadeev [2], Petunina N. [1], Garber, J.R. [4], Samuels M.H. [6] etc.

Our own multi-year investigations of the neuropsychic sphere [7] have allowed us to estimate the most common neuropsychiatric and cognitive disorders in patients with hypothyroidism. First of all, we mention the fact that it affects practically all organs and systems in the case of thyroid hormone deficiency, but the most frequent and pronounced it disrupts the nervous system and psyche. It is necessary to indicate that the analysis of neuropsychiatric symptoms studied over several years through the manifestation of intellectual, emotional and behavioral capacities has shown that most neuropsychological and cognitive disorders have inhibitory character. About broad spectrum of dysfunction of the nervous system and psyche confess the following:

• asthenic syndrome – intense and permanent fatigue, physical weakness, decreased working capacity;
• less attention, concentration, interest and initiative;
• decrease in the level of optimism, mood, depressive disorders;
• general intellectual deterioration, slowing associative processes;
• adynamic disorders with mental asthenia and emotional instability;
• apato-abulic syndrome;
• drowsiness;
• reversible neurosensory hypoacusis;
• slowing tendon reflexes.

Concomitantly, the predominance of the body's inhibition status in individuals with hypothyroidism also denotes neuro-vegetative symptoms: diminishing sweating, bradycardia, diminishing body temperature, reducing physical tolerance.

However, the mechanisms that determine the psycho-neurological spheres in hypothyroidism, including cognitive, emotional, behavioral, individual-semantic, neurovegetative with inhibitory connotations, have an unresolved problem.

One of these mechanisms may be to modify the content of the central nervous system mediators, the primary function of which is the fulfillment of some amino acids. It is established that most of the central nervous system neurons use amino acids as mediators [5]. Namely, they transmit about 80 % of sensory and motor nerve signals to the nervous network (excitatory amino acids), and regulate these transmissions.

Amino acid from the functional group of mediators are characterized by an identical synaptic effect: some of these amino acids (glutamine, asparagine) exhibit excitatory, other (γ-aminobutyric, glycine, taurine) – inhibiting capabilities.

On that basis we have conducted research to determine the content of AAM in patients with hypothyroidism. The amino acid concentration was studied in part in each patient, then according to the specificity of similar numerical changes of all amino acids, the patients were divided into 3 groups: the I group consisting of patients in which the majority of the amino acids were spores, the II group was made up of people whose concentration – change vector of most of the amino acids had a downward character, and the III group was composed of patients whose amino acid content was of individual character.

AAM were studied in part in each patient, being assigned to one or other of the above-mentioned groups and categorized according to the dominant vector of altered free amino acid concentration in the blood.

The content of AAM in patients with hypothyroidism is presented in the following table.

 

Table

Content of mediator amino acids in blood plasma in patients with primary hypothyroidism

amino acids		Control lot	Patients with hypothyroidism with the amino acid pool vector
			upward, lot I	downward, lot II	individual, lot III
Inhibitors	γ-amino-butyric	0,28 ± 0,05	0,55 ± 0,16*	0,58 ± 0,24*	0,29 ± 0,11
	glycine	17,48 ± 2,58	32,06 ± 10,70*	23,58 ± 2,18*	25,42 ± 2,17*
	taurine	5,98 ± 1,03	10,27 ± 1,98*	3,31 ± 0,84*	5,13 ± 1,14
	∑	23,75 ± 4,37	42,89 ± 9,93*	27,48 ± 5,46	30,85 ± 2,91*
Excitators	glutamine	39,12 ± 5,59	49,55 ± 4,45*	18,51 ± 2,86*	17,14 ± 4,93*
	asparagine	7,96 ± 1,57	6,19 ± 1,69	6,84 ± 1,08	9,46 ± 2,49
	∑	26,80 ± 5,20	37,43 ± 5,76*	19,67 ± 9,01	11,99 ± 1,30*
Inhibitors/excitators		0,89 ± 0,11	1,15 ± 0,18*	1,55 ± 0,44*	2,60 ± 0,36*

 

Note: the veracity of the differences vs. control – * p˂0.05.

 

The study of the individual inhibitor amino acid content, as shown in the table, testifies that the vector of taurine and GABA and glutamine change in all hypothyroid patients is of individual character, whereas glycine increases in all three groups of patients with hypothyroidism. The increase in glycine content can be considered as a specific test of hypothyroidism and is probably caused by both its intensification of synthesis and the reduction of glyoxal acid deamination, although other causes cannot be excluded because it participates in the organization of tertiary and quaternary structures of proteins, to the biosynthesis of porphyrins, purines, multiple amino acids and biologically active substances, to stimulate the synthesis of the somatotropic hormone. Glycine is also the donor of the amino group in the synthesis of hemoglobin, glutathione, creatine, betanine, etc.

Exploration of the excitatory amino acid content has shown that asparagine in hypothyroid patients does not undergo true changes, while glutamine in patients in group I increases, and in groups II and III – diminished.

The pool of amino acids that constitute the functional group of amino acid inhibitors increases in both group I and patients in group III where most of the amino acids undergo individual changes, whereas in lot II where the numerical value of most amino acids decreases – the sum of amino acids does not support true changes.

The total amount of excitatory amino acids is amplified in patients in group I, to which most other amino acid functional groups also increase, in group II for which the reduction of majority of amino acids is characteristic, the excitatory amino acid pool is maintained at the level of the control group, and in group III, which is characterized by individual changes in the content of most amino acids – decreases.

Estimation of the inhibitory / excitatory amino acid ratio index demonstrated its increase in patients in group I with increased pool of both inhibitory and excitatory amino acids up to 1.15 ± 0.18 (p = 0.05); in group II, which included patients whose majority of amino acids decreased, – up to 1.55 ± 0.44 (p ˂ 0.05), and those in group III who presented patients with hypothyroidism where most of the amino acids support individual changes – up to 2.60 ± 0.36 (p ˂ 0.05). In the control group, this index is 0.89 ± 0.11.

The comparative analysis of clinical-vegetative, neuropsychic, cognitive disorders and of inhibitory / excitatory amino acids ratio index denotes the predominance in hypothyroid patients of both inhibitory neuropsychiatric, cognitive changes and of inhibitors amino acid levels. Taking into account the role of amino acids from the functional group of mediators in regulating the body's reflective activity, hypothalamic-pituitary interrelations, cardiovascular and respiratory systems, sleep and wake, behaviors, etc. it can be concluded that the disturbances of the profile and content of this amino acids largely determine the occurrence of various neuropsychological, cognitive and neurovegetative symptoms of inhibitory nature (asthenic, apato-abulic syndrome, adynamics, tendinous reflex reduction, worsening of cognitive activity, intellectual impairment, mood swings, depression , somnolence, bradycardia, diminishing perspiration, etc.).

Conclusions:

1. In patients with primary hypothyroidism, psycho-neurologic symptoms that reflect disorders of intellectual, emotional, behavioral and neurovegetatory activity predominantly have inhibitory connotations.
2. For hypothyroidism, the predominance of the inhibitory effect of mediating amino acids in the transmission and regulation of sensory, motor and other signals in the nerve networks is characteristic.
3. The increased level of the glycine inhibitor mediated amino acid and the mediating amino acid inhibitory function may serve as specific nozological indicators of hypothyroidism.

 

REFERENCES

1. Петунина, Н.А. Гипотиреоз / Н.А. Петунина // Consilium medicum. – 2008. – № 9 (10). – С. 83-88.
2. Фадеев, В.В. Гипотиреоз: руководство для врачей / В.В. Фадеев, Г.А. Мельниченко. – М.: РКИ Северо пресс, 2004. – 216 c.
3. Anestiadi, Z., Vudu, L. Incidența maladiilor endocrine și problema diminuării ei. // Sănătate Publică, Economie și Management în Medicină. – 2011. – No. 2 (2). – Pp. 61-62.
4. Garber, J., Cobin, R., Gharib, H. et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. // Endocrine Practice. – 2012. – No. 6. – Pp. 988-1028.
5. Kurbat, M.N., Lelevich, V.V. Metabolism of amino acids in the brain. Neurochem. J. – 2009. – 3: Pp. 23-28.
6. Samuels, M.H. Psychiatric and cognitive manifestations of hypothyroidism. // Curr Opin Endocrinol Diabetes Obes. – 2014. – No. 21 (5). – Pp. 377-383.
7. Vudu, L. Hipotiroidia primară (aspecte clinico-patogenice, diagnostice și terapeutice). – Chișinău: Balacron, 2017. – 192 p.

 

REFERENCES

1.   Petunina N.A. Gipotireoz [Hypothyroidism]. N.A. Petunina. Consilium medicum. 2008. № 9 (10). pp. 83-88. (In Riss.).

2.   Fadeev V.V. Gipotireoz: rukovodstvo dlya vrachej [Hypothyroidism: A guide for doctors]. V.V. Fadeev, G.A. Mel'nichenko. Moscow. RKI Severo press, 2004. 216 p.

3.   Anestiadi Z., Vudu L. Incidența maladiilor endocrine și problema diminuării ei. // Sănătate Publică, Economie și Management în Medicină. 2011. No. 2 (2). Pp. 61-62.

4.   Garber J., Cobin R., Gharib H. et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine Practice. 2012. No. 6. Pp. 988-1028.

5.   Kurbat M.N., Lelevich V.V. Metabolism of amino acids in the brain. Neurochem. J. 2009. 3: Pp. 23-28.

6.   Samuels M.H. Psychiatric and cognitive manifestations of hypothyroidism. Curr Opin Endocrinol Diabetes Obes. 2014. No. 21 (5). Pp. 377-383.

7.   Vudu L. Hipotiroidia primară (aspecte clinico-patogenice, diagnostice și terapeutice). Chișinău: Balacron, 2017. 192 p.

 

Материал поступил в редакцию 01.11.25.

 

 

ГИПОТИРЕОЗ, ПСИХОНЕВРОЛОГИЧЕСКИЙ

СТАТУС И МЕДИАТОРНЫЕ АМИНОКИСЛОТЫ

 

Л.Ф. Вуду, кандидат медицинских наук, доцент кафедры эндокринологии

Государственный медицинский и фармацевтический университет имени Николая Тестемицану

(Молдова, Кишинёв, бульвар Штефан чел Маре ши Сфынт, 165)

E-mail: Vudu77@mail.com

 

Аннотация. Исследование касается характера психоневрологических расстройств и содержания аминокислот из функциональной группы медиаторов у пациентов с гипотиреозом. Установлено, что гипотиреоз вызывает значительные нейропсихические нарушения, проявляющиеся различными клиническими и параклиническими синдромами с ингибирующей коннотацией, а также изменением содержания ингибирующих аминокислот, что может быть одной из причин доминирования ингибиторных нервных процессов у пациентов с гипотиреозом.

Ключевые слова: гипотиреоз, психоневрологический статус, медиаторные аминокислоты.