ART OF MEDICINE 2017

 

NEUROENDOCRINE ASPECTS OF THYMUS HORMONE ANA-LOGUES APPLICATION

 

I.O. Yakubovska

          State Educational Establishment “Ivano-Frankivsk National Medical University”, Ivano-Frankivsk, This email address is being protected from spambots. You need JavaScript enabled to view it.

  

Abstract

Abstract. Immune system cells express receptors to neuropeptides and hormones (GH, PRL, PG, CRH, ACTH, TRH, TSH, β-endorphin, VIP, Met5-Enkephal). The cells of the immune system also produce hormones (ACTH, GH, PRL, TRH, CGGT, FSH and LG). They are isolated by activated lymphocytes and act as messengers between the endocrine and immune system, and have both auto and paracrine functions.

The objective of the study is to detect the neuroendocrine effects of the synthetic analogue of the modified fragment of the biologically active part of the thymus hormone molecule thymopoietin (Immunophane). Clinical model was selected from the patients with CHF.The research was conducted on the basis of Ivano-Frankivsk Regional Clinical Hospital in 2009. We examined 45 patients with CHF FCIII-FKIV: the main group included 25 people, the control one - 20 people. The patients’average age is 53 ± 6.6 years old. The patients in both groups were randomized by age, sex, and the duration of the disease.

Methods. Clinical Examination: A 6-Minute NFP Test (NYHA), a CHO Rating Scale, a Biomass Index, an ECG, an EchoCS, an NT-proBNP. Laboratory Tests: lipidogram, ALT, AST, homocysteine. Neurohormonal status was evaluated in terms of:ACTH, cortisol, β-endorphin, prolactin, STH, TTH,  free thyroxin, TPOAb (IFA - tests performed in the Certified Diamed Laboratory). The synthetic analogue of thymopoietin was administered to the main group of patientswith doses 1.0-0.005% intramuscularly (1 ampoule daily within 10 days), then 5 ampoules with doses 1.0- 0.005% intramuscularly every second day, 1ampoule at a time (15 ampoules totally for the course of treatment).

Results. In both groups of patients, 45% of them revealed balanced correlation of ACTH/cortisol and they did not exceed the norm after treatment. At the same time, 42.2% of patients revealed the reduced level of ACTH (<19p / ml). 11.1% of them, low levels of ACTH (<19p / ml) were combined with a correspondingly elevated cortisol level (greater than 100ng / ml), indicating to the stress of adaptive processes. However, 31% of patients showed very low levels of ACTH (<19p / ml) which were combined with a very low level of cortisol (below 10 ng / ml); one patient had cortisol level equal to 0 ng / ml - a "low hormones syndrome". Clinically, they were patients CHF FIIІ-FC IV with a complicated disease course.

During the immunotropic treatment, the part of patients (10 people) of the main group with a syndrome of "inappropriate hormones secretion" revealed that the correlation of ACTH / cortisol became more equable, but in 5 of them the threatening tendency persisted. Patients’ condition with the syndrome of "inappropriate hormones secretion" in the control group did not improve. Perhaps this moment is the starting point of the fatal event onset. This study showed that the combination of basic therapy with a synthetic analogue of thymopoietin in some patients with CHF contributes to the restoration of ACTH / cortisol regulation without the risk of excessive sympathetic adrenal system activation.

The correlation of ACTH / cortisol within the range of 0.5-0.7 was characteristic to patients with satisfactory and prognostically favourable course of CHF (45% of the surveyed). Higher and lower correlations of ACTH / cortisol showed incomplete adaptation and complicated course of the disease (55%). The signs of subclinical hypothyroidism were identified in 73.3% of the examined patients before treatment for the first time.

After immunotropic treatment, 24% of patients had their T3 levels higher and their TTH/T3 correlation improved while only 5% of patients in the control group felt some imrovements. In the 20% of the newly diagnosed autoimmune thyroiditis (AIT) examined before treatment. After treatment 2 patients of the main group revealed the increased level of TPOAb, and 2 patients had their levels decreased. In the control group, 2 patients revealed the increased level of TPOAb and 3 patients- a decreased one (the difference is not reliable). The use of this drug for the patients with concomitant autoimmune thyroiditis is undesirable and should be avoided. It has a potentially metabolic effect on the patients with CHF, CVD. The examined patients did not reveal the increased STH. In some patients (46%) it was 0 ng / ml (within the range of 1-5ng / ml). After treatment in the main group, the average values of the level of STH increased significantly, but they did not exceed the norm, in the control group they remained unchanged. Hyperprolactinemia was not detected in the examined patients. 28% of the examined patients had a decreased prolactin level before treatment. In the main group, against the background of treatment with a synthetic analogue of thymopoietin, patients’ level of prolactin significantly increased, but it did not exceed the norm, however, it decreased in the patients of the control group. An increase of the prolactin level and of STH on the background of immunotherapy therapy can be explained by the fact that they were produced by the activated T lymphocytes. The role of prolactin in this case is potentiation of analgesia. All patients had twice lower level of β-endorphinin than the reference value. The main group patients’ average β-endorphin level before treatment was significantly lower than in the control group ones. After the treatment, the main group patients’ average β-endorphin level increased significantly, while in the control group ones, it remained practically unchanged. Analyzing individual patients’ parameters, it was found out that increase of β-endorphin on the background of immunotropic therapy was observed in 80% of patients, while in the control group this indicator increased slightly only in 30% of patients. The synthetic analogue of the modified fragment of the biologically active part of the thymuspoetin molecule has proved to have not only immunocorrective but also neuroendocrine controlling activity.

Conclusion. The conducted pilot investigation initiated an extensive mechanism study of the synthetic analogue of the modified fragment of the thymuspoetin molecule (immunophan), biologically active part, on the neurodendocrine system of the body. It has been established that this medication, together with immunocorrective action, has an effect on the level of ACTH, cortisol, prolactin, STH, TTH, free thyroxin and β-endorphin production, balancing their correlation. It is not advisable to use this drug in case of autoimmune thyroiditis.

 

Key words: immune system, neuroendocrine regulation, thymus hormones.

 

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