Thyroid lesion as a manifestation of comorbidity in patients with diabetic polyneyropathy

The study of clinical and anamnestic and paraclinical characteristics, highlighting their dominant features in patients with DP and existing thyroid diseases occupies an important place in modern neuroendocrinology and requires more focused attention of clinicians. The objective: to determine the leading clinical and laboratory-instrumental parameters in patients with DP and thyroid pathology, to analyze the mutual influence of neuroendocrine pathology on the patient’s somatoneurological condition. Materials and methods. Was done a clinical examination of 64 patients with DP , in 27 (42%) of them was diagnosed the comorbid thyroid pathology, in 37 (58%) it was absent. All patients were divided into two groups: with DP in the background of type I, II DM and thyroid pathology (A) and with DP in the background of type I, II DM without thyroid pathology (B). During the examination of patients were used clinical-anamnestic, clinical-neurological, laboratory-instrumental, neurophysiological methods of examination. Pain characteristics were assessed using the McGill Pain Questionnaire (MPQ). Statistic calculation was done in MS Excel 2003 and using the package for statistical analysis STATISTICA 10. Results. In patients of both groups comorbidly were dominated diseases of the cardiovascular system, in group A, increasingly was revealed gastrointestinal pathology. Polyneuritic disorders of sensitivity and autonomic-trophic disorders are more common in persons of group B, they have a higher frequency of comorbid pathology and longer duration of DM. In group A lack of Achilles and knee reflexes was recorded more often than in comparison group. In 18 (65%) of the examined persons of group A was detected a fatty liver dystrophy by ultrasound scanning of the abdominal organs, which exceeds the number in group B – 13 (35%). There is an inverse average dependence between the level of TSH and BMI (correlation coefficient = -0,65). The general index of pain rating (Pain Rating Index – PRI) in group A is higher (30,62±2,64 scores). Conclusions. Among the thyroid diseases in the examined patients of group A hypothyroidism was most often detected, so 30% of patients had a pronounced violation of lipid metabolism in the form of obesity, besides, in this group the number of people with type II DM was prevailed. The influence of thyroid pathology on the manifestations of DP is reflected in the intensification of neuropathic pain syndrome. There is also a significant effect on the metabolism of fats and carbohydrates, which aggravate and sometimes deepen the somatic condition of the patient.

T he nervous and endocrine systems are closely interconnected and play the most important role in maintaining homeostasis of the organism [5].
As Since type 1 DM occurs as a result of autoimmune disorders, the detection of thyroid diseases (thyroid), such as autoimmune thyroiditis (AIT) in such individuals, is not uncommon. In addition, patients with type 2 DM often have nodular goiter, which is diagnosed more often in the hypothyroidism phase. Some thyroid dysfunction is closely related to carbohydrate metabolism, therefore, can increase the fluctuations of glycemia, both in the direction of hyper-and hypoglycemia, and disrupt the general well-being of the patient, exacerbate the manifestations of polyneuropathy.
The prevalence of AIT and/or antibodies to the thyroid in patients´ relatives with type 1 DM can reach 48% compared with 3-10% in the general population. In addition, one person has a combination of type 1 DM and autoimmune thyroid disease, the so-called polyglandular syndrome of type 3, one of the variants of autoimmune polyendocrine syndromes [8,9].
The frequency of subclinical hypothyroidism is in ranges from 4% to 20% of the adult population depending on gender (higher among women), age (over 60 years), body mass index (BMI), race, smoking, iodine intake and other factors (Razvi S. et al., 2018; Livingston E., 2019).
In patients with DM there was a decrease in nocturnal peak secretion of thyroid-stimulating hormone (TSH) and impaired response of TSH to stimulation by thyroliberin. In patients with insufficient glycemic control (HbAlc >10%) there is an inhibition of deiodinase type 1 activity and as a resultdecrease of conversion T4 to T3, decrease serum T3 and increase concentration rT3 (reversible), which can be interpreted as a protective mechanism of the organism in response to increase of tissue catabolism and decrease of tissue oxygen consumption [3].
The deterioration of metabolic control of DM in hyperthyroidism is associated with increased concentration and activity of contrainsular hormones -glucagon and catecholamines [4].
In the general population the prevalence of thyrotoxicosis is much lower than hypothyroidism [7], but the gravity of its clinical manifestations does not give the posibility to suggest a decrease in the relevance of the study of thyroid dysfunctions, especially in connection with dysfunctions of other organs and systems [2].
In hypothyroidism reduces blood circulation in adipose tissue and muscles, which can be considered as one of the pathogenetic mechanisms of insulin resistance [6].
The study of clinical and anamnestic and paraclinical characteristics, highlighting their dominant features in patients with DP and existing thyroid diseases occupies an important place in modern neuroendocrinology and requires more focused attention of clinicians.
The objective: to determine the leading clinical and laboratory-instrumental parameters in patients with DP and thyroid pathology, to analyze the mutual influence of neuroendocrine pathology on the patient's somatoneurological condition.
All patients were divided into two groups: with DP in the background of type I, II DM and thyroid pathology (A) and with DP in the background of type I, II DM without thyroid pathology (B).
During the examination of patients were used clinicalanamnestic, clinical-neurological, laboratory-instrumental, neurophysiological methods of examination. Pain characteristics were assessed using the McGill Pain Questionnaire (MPQ). Statistic calculation was done in MS Excel 2003 and using the package for statistical analysis STATISTICA 10.

RESULTS AND DISCUSSION
The average age in group A is 50,62±2,24 years, B -45,21±2,57 years. In group A, females predominated (Fig. 1), in group B -males, which confirms data in the literature about more frequent thyroid lesion in women.
Thus, in patients of both groups comorbidly were dominated diseases of the cardiovascular system, in group A, increasingly was revealed gastrointestinal pathology.
Among the complaints in both groups the dominants were numbness in the lower extremities, headache and fatigue (table 1). Complaints of dry mouth, fluctuations of blood pressure (BP), numbness in the upper extremities, ringing in the ears and diarrhea were more often in group A.
Vegetative-trophic disorders (Fig. 2) in group B are presented with greater frequency, in particular, hyperkeratosis, hypotrichosis, hypohidrosis of the distal legs, foot fissure. In В П О М О Щ Ь П Р А К Т И К У Ю Щ Е М У В Р А Ч У group A trophic changes on the part of the nail plate are presented in a slightly larger number of individuals than in the comparison group. The predominance of trophic disorders in persons of group B is due to their longer duration of DM.
In group B, checking the neurological status (Fig. 3) hyporeflexia was found in a larger number of patients, in particular it concerns most often knee and Achilles reflexes. In group A lack of Achilles and knee reflexes was recorded more often than in comparison group.
Polyneuritic sensitivity disorders with hyperesthesia of the distal extremities were recorded in 6 patients of group A and in 9 of group B, with hypesthesia -16 in group A and 26 in group B.
The main laboratory parameters (table 2) in group A and B are within normal values, except the level of gammaglutamattransferase, the level of which is significantly increased in group A. There is a close interconnection between autoimmune thyroid pathology and functional state of the liver, that»s why can consider a violation of the balance of thyroid hormones (hyper -or hypothyroidism) as a starting point for the development of insulin resistance, on the one hand, and liver pathology, on the other hand [1].
The level of glycated hemoglobin is elevated, mostly in group A, which indicates the unsatisfactory glycemic control. There is an inverse average connection (Fig. 4) (correlation coefficient= -0,35) between the level of TSH and glycated hemoglobin. Given that TSH acts by a feedback mechanism: its decrease causes an increase in T3 and T4, and an increase -a decrease in T3 and T4, depending on whether hypo-or hyperthyroidism respectively will decrease or increase blood glucose level.
In 18 (65%) of the examined persons of group A was detected a fatty liver dystrophy by ultrasound scanning of the abdominal organs, which exceeds the number in group B -13 (35%). Hypothyroidism is often accompanied by fatty liver disease (Liangpunsakul S., Chalasani N., 2003).
According to the electrocardiography (ECG) in group A, in 1 of the examined was found the prolongation of the Q-T interval, in 4 -blockade of the legs of the His bundle, while in group B conduction disturbances in the His bundles -in 6 patients.
During the ultrasound scanning of the thyroid gland by the BRUNN method in group A, were revealed the following deviations : the total volume of the thyroid gland is 19,07±2,11 cm3 (norm is to 14,0 cm3), volume of the right share is 10,11±1,10 cm3, left -11,54±1,66 cm 3 (norm is to 7,0 cm 3 ), the presence of additional formations is in 15 (55%) patients. In group B the total volume of the thyroid gland is 13,52±1,00 cm3, the volume of the right share is 7,03±0,42 cm3, and that of the left share is 6,26±0,34 cm3, in 9 (24%) were found additional formations. BMI in group A -29,5±1,01%, in group B -25,4±0,71%, reflecting the presence of excess body weight -«obesity» in both groups. In group A I degree obesity is in 4 (15%) examined, II degree is in 3 (11%), III degree is in 1 (4%). Wasn"t detected obesity in group B. There is an inverse average dependence between the level of TSH and BMI (correlation coefficient = -0,65) (Fig. 5), which, in our opinion, depends on the thyroid (hypo-, hyper-) status of the patient, which affects metabolism.
The general index of pain rating (

CONCLUSIONS
1. Among the thyroid diseases in the examined patients of group A hypothyroidism was most often detected, so 30% of patients had a pronounced violation of lipid metabolism in the form of obesity, besides , in this group the number of people with type II DM was prevailed.
2. Rating of the evidence of pain syndrome on the McGill scale showed in both groups the presence of deviations, in particular, higher average scores were recorded in group A, showing a more pronounced DP degree of pain in these individuals, also due to poorer glycemic control, according to glycated hemoglobin.
3. Polyneuritic disorders of sensitivity and autonomic-trophic disorders are more common in persons of group B, they have a higher frequency of comorbid pathology and longer duration of DM. Changes in the reflex area of the lower extremities, namely areflesia are more common in group A.
4. The influence of thyroid pathology on the manifestations of DP is reflected in the intensification of neuropathic pain syndrome.
5. There is a significant effect on the metabolism of fats and carbohydrates, which aggravate and sometimes deepen the somatic condition of the patient. An important additional factor of high glycemia in such individuals is a liver damage, which is unable to deposit glycogen quickly enough, resulting in its rapid release.