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UDC 616.366-002.616.441-008.6 DOI: 10.26565/2313-6693-2020-40-13
CHANGES IN THYROID HORMONES IN PATIENTS WITH CHRONIC ACALCULOUS CHOLECYSTITIS IN THE PRACTICE OF A FAMILY DOCTOR
Vovk K. V., Reznichenko O. G., Vlasenko O. O., Gridnieva S. V., Kratenko G. S.
Abstract. Among biliary pathology, chronic acalculous cholecystitis (CAC) occupies one of the central places. The important role of the hormonal system in the regulation of the functioning of the biliary tract has been known for a long time, but the specific mechanisms of these influences remained unclear. Based on the results of a comprehensive clinical, laboratory, biochemical and instrumental examination, all patients with chronic acalculous cholecystitis were divided into three groups depending on the variant of impairment of the motor-kinetic function of the gallbladder. The first group consisted of patients with CAC and hypertensive-hyperkinetic gallbladder dyskinesia (group I) - 17 people; the second - patients with CAC with mixed hypotonic-hyperkinetic gallbladder dyskinesia (group II) - 19 people; the third - patients with CAC and hypotonic-hypokinetic dyskinesia of gallbladder (III group) - 29 people. The level of free FT3, FT4, and thyroid-stimulating hormone (TSH) was determined by the immunofluorescence method using BREAHMS test systems (Henning Berlin GMBH). The disproportion between the thyroid hormones and the quantitative predominance of the inactive form made it possible to identify the relative hypothyroid syndrome in group I patients. The disproportion between the biologically inactive and active forms of thyroid hormones with a quantitative predominance of the inactive form made it possible to judge the presence of a relative hypothyroid syndrome in group II patients. In group III patients, a significantly increased TSH level was revealed, which was a response of the hypothalamic-pituitary system to a decrease in the level of FT3.
KEY WORDS: chronic acalculous cholecystitis, thyroid gland, hormones INFORMATION ABOUT AUTHORS
Kira Vovk, MD, PhD, Associate Professor, Department of General Practice-Family Medicine, School of Medicine, V. N. Karazin Kharkiv National University, 6, Svobody Sq., Kharkiv, Ukraine, 61022, e-mail: vovkkira1970@gmail.com, ORCID ID: https://orcid.org/0000-0003-2971-0842
Oleksandr Reznichenko, MD, PhD, Associate Professor, Department of General Practice-Family Medicine, V. N. Karazin Kharkiv National University, School of Medicine, 6, Svobody Sq., Kharkiv, Ukraine, 61022, e-mail: a.reznichenko@karazin.ua, ORCID ID: https://orcid.org/0000-0001-8189-7048
Olga Vlasenko, MD, PhD, Associate Professor, Department of General Practice-Family Medicine, V. N. Karazin Kharkiv National University, School of Medicine, 6, Svobody Sq., Kharkiv, Ukraine 61022, e-mail: olga.vlasenko@karazin.ua, ORCID ID https://orcid.org/0000-0003-4720-4062
Svitlana Gridnieva, MD, PhD, Associate Professor, Department of General Practice-Family Medicine, V. N. Karazin Kharkiv National University, School of Medicine, 6, Svobody Sq., Kharkiv, Ukraine, 61022, e-mail: s.gridneva@karazin.ua, ORCID ID https://orcid.org/0000-0002-7498-9574
Hanna Kratenko, MD, PhD, Associate Professor, Department of General Practice-Family Medicine, V. N. Karazin Kharkiv National University, School of Medicine, 6, Svobody Sq., Kharkiv, Ukraine, 61022, e-mail: anna-krat@ukr.net, ORCID ID https://orcid.org/0000-0001-7019-5593
INTRODUCTION
In everyday practice, doctors of different specialties have to deal with diseases of the biliary tract: gastroenterologists, therapists, surgeons, emergency and emergency doctors. Among biliary pathology, chronic acalculous cholecystitis (CAC) occupies one of the central places. The most important task of the supervision of patients with chronic acalculous cholecystitis is to prevent the transformation of the process into gallstone disease. Decreased contractility of the gallbladder plays a critical role in the formation of gallstones [1]. Impaired
gallbladder motility potentiates another important factor in cholelithiasis - bile cholesterol oversaturation [2]. Another important event associated with impaired gallbladder motility is the accumulation of lipids in the gallbladder wall [3]. The problem of lipid balance regulation is central to solving the clinical problem of preventing the progression of chronic acalculous cholecystitis.
The effect of thyroid hormones on lipid metabolism has been a topic of fundamental research for many years. Thyroid hormones help maintain the basal serum cholesterol levels needed to meet the body's normal needs for cell
© Vovk K. V., Reznichenko O. G., Vlasenko O. O., Gridnieva S. V., Kratenko G. S., 2020
synthesis and renewal. Thyroid hormones regulate serum cholesterol levels by stimulating cholesterol biosynthesis, export (primarily in the form of VLDL and LDL), reverse transport from peripheral tissues, liver reuptake through LDL (LDL) receptors and conversion to bile acids in the liver [4]. Thyroid hormones regulate lipid metabolism in the liver in a cell-autonomous manner, induce the expression of genes encoding proteins involved in liver lipogenesis. The possibility of using analogs and mimetics of thyroid hormones as therapeutic agents for the treatment of lipid-associated liver diseases is being studied [5]. The effect of thyroid hormones on the formation of gallstones was studied in vivo using an animal model: hypothyroidism causes the formation of cholesterol stones in the gallbladder, promoting cholesterol biosynthesis [6].
The interest in the role of the thyroid factor in the course of CAC is dictated by the great interest of clinicians in minor variants of hypothyroidism, which are found in the population much more often than clinical hypothyroidism. Subclinical thyroid dysfunction is defined as the change in serum thyroid-stimulating hormone (TSH) level relative to the reference interval at normal free thyroxine (FT4) levels in asymptomatic patients [7]. The phenomenon is especially common in older women [8, 9].
The choice of parameters for monitoring thyroid balance indicators is also dictated by recent trends in thyroid ology. Measurement of TSH levels, although an indirect indicator of thyroid homeostasis, has become central to modern testing of thyroid function [10]. TSH has come to be regarded by the thyroid community as a simple and effective diagnostic parameter. The simplicity of measurement has been converted to simplicity of interpretation, ignoring the fact that TSH is both an indirect measure of thyroid hormone homeostasis and a control element. Thus, this concept of TSH dominance has led to the suppression of the complex relationship of the TSH response with various hormonal processes [11].
While recognizing the strategic benefits of TSH measurement, such as ease of use, suitability for first-line screening, detection of minor functional abnormalities, and association with various health outcomes, including mortality, there are significant risks of
misrepresenting its complex physiological importance.
This is supported by the ongoing discussion around the TSH reference limits, especially its upper limit, which determines subclinical hypothyroidism [12]. TSH values are personalized indicators showing a high degree of individuality. The change in TSH concentration can be either simply adaptive to restore true euthyroidism, or a failed attempt to maintain the euthyroid state [13]. The pulsating nature of TSH secretion increases individual variations in TSH levels, which are significantly higher than the degree of individual fluctuations in FT4 blood concentrations [14]. The same TSH value may be "normal" for one person, but pathological for another. This also applies to patients with subclinical dysfunction, in which the relationship between FT4 and TSH shows both elements of normality and abnormalities [15].
OBJECTIVE
Knowledge of the mechanisms involved in the regulation of thyroid hormone balance has expanded significantly in recent years. The basic system is much more complex than previously thought, which dictates the need to revise old simplified concepts and promotes new multifactorial control concepts with feedback between the thyroid gland and the pituitary gland [16-18]. In the new integrative concept, TSH becomes a context-dependent conditional variable, and is neither an accurate marker of euthyroidism, nor an optimal criterion for fine-tuning thyroid control. A comprehensive interpretation of TSH, FT4 and free triiodothyronite (FT3) and their conditional equilibrium should be the basis for clinical decision-making [19].
The purpose of the work is the study of thyroid hormones in patients with CAC depending on dyskinetic disorders.
MATERIALS AND METHODS
Observation and examination of patients with CAC was carried out in the 26th polyclinic of Kharkov, which was the base of the department of general practice and family medicine of V. N. Karazin Kharkiv National University in the period from 2017 to 2019. A total of 65 patients with CAC were examined. The control group consisted of 12 healthy individuals. The surveyed group included
persons who did not have severe concomitant diseases.
The distribution of patients into clinical groups was carried out in accordance with the working classification of chronic non-calculous cholecystitis by V. A. Galkin (1986) and the classification of biliary dyskinesias by I. I. Degtyareva (1999).
Based on the results of a comprehensive clinical, laboratory, biochemical and instrumental examination (clinical blood test, C-reactive protein, total, conjugated and unconjugated bilirubin content in blood serum, gammaglutamyl transpeptidase, alkaline phosphatase, cholesterol, triglycerides, dynamic echosonocholecystoscopy, multiphase chroma-tographic duodenal intubation), all patients with chronic CAC were divided into three groups depending on the variant of impairment of the motor-kinetic function of the gallbladder. The first group consisted of patients with CAC and hypertensive-hyperkinetic gallbladder dyskine-sia (group I) - 17 people; the second - patients with CAC with mixed hypotonic-hyperkinetic gallbladder dyskinesia (group II) - 19 people; the third - patients with CAC and hypotonic-hypokinetic dyskinesia of gallbladder (III group) - 29 people.
In the group of surveyed persons, women predominated, the ratio of men and women in the groups approached 1:5. Among the patients of group I, people aged 20 to 30 prevailed. In group II, the distribution of patients by age was almost uniform from 28 to 45 years. Patients in group III were predominantly 45-60 years old.
The hypertensive-hyperkinetic variant of gallbladder dyskinesia prevailed in patients with CAC disease up to 5 years. The mixed variant of gallbladder dyskinesia was equally encountered with the duration of the disease up to 5 years and from 5 to 10 years. The hypotonic-hypokinetic variant of gallbladder dyskinesia was more often detected in patients with the disease duration of more than 10 years.
In group I patients, pain was dominant (sudden colic in the right hypochondrium, intense, radiating to the right shoulder or scapula) and manifestations of neurovegetative dysfunction (emotional lability, sweating). The dominant dyspeptic phenomenon was recurrent moderately severe nausea.
Group II patients had mixed pain syndrome (a combination of background constant aching pains with episodes of colicky painful attacks). In comparison with patients of group I, the
frequency of dyspeptic symptoms increased, among which the most common were bitterness in the mouth and poor appetite.
Patients of group III complained mainly of dull, constant aching pains without clear localization in the right hypochondrium. Dyspeptic symptoms were dominated by persistent bitterness in the mouth, poor appetite, severe flatulence, persistent constipation. Symptoms of asthenia (increased fatigue, decreased motivation and activity) were typical for this group, fever was often observed, with an increase in temperature to sub febrile numbers.
Abdominal pain syndrome was typical for all three studied groups of patients. The frequency of occurrence of dyspeptic syndrome in group II was higher than in group I, and in group III more than in group II. Neurovegetative syndrome was more typical for group I than for groups II and III. Asthenic syndrome was more common in group III than in groups I or II. The presence of exacerbation of CAC in patients at the time of examination was confirmed by the presence of segmental reflex symptoms. Pathological visceral skin reflexes were provoked by pressure with one finger on the corresponding organ-specific points of the skin. Irritative symptoms (Zakharyin, Volsky, Grekov-Ortner, Kera, Murphy, Obraztsov, Gausman) in various combinations were positive in all patients, which is a clinical marker during the period of exacerbation of patients with CAC. Segmental reflex symptoms of Mackenzie (pain when pressing on the Mackenzie pain point, located at the intersection of the outer edge of the right abdomen of the rectus abdominis muscle and the right costal arch); Boas (pain when pressing on Boas's pain point located along the right paravertebral line at the ThX-XI level), Aliev (antidromic irradiation of pain with pressure at the Mackenzie or Boas point) were positive in almost all patients of group III.
Signs of right-sided reactive syndrome were more often observed in group III of patients. Most often, pain was detected in the occipital point of Yonash, the cervical point of Mussi, in the parasolar pain points, in the region of the xiphoid process (Pekarsky's symptom) and below the angle of the right scapula (Karavanov's symptom).
To verify the diagnosis of chronic CAC in the examined patients, a complex of clinical, laboratory, biochemical and instrumental
research methods was used. All patients underwent ultrasound scanning of the thyroid gland and gallbladder. The contractile function of the gallbladder was clarified by performing dynamic echoscopy using an oral stimulator (two raw yolks). If there were sonographic signs of thyroid pathology, patients were excluded from the observation group.
The level of free FT3, FT4, and TSH was determined by the immunofluorescence method using BREAHMS test systems (Henning Berlin GMBH). The level of FT3 and FT4 and TSH in the blood serum of healthy individuals was (4,62 ± 0,28) and (14,45 ± 2,21) pmol/l, (3,31 ± 0,07) nmol/l, respectively.
The content of antibodies to thyroglobulin and antibodies to thyroperoxidase was determined using LUMItest-anti-TPO BREAHMS (Henning Berlin GMBH). In healthy individuals, the level of AT-TG and AT-TPO was (0,92 ± 0,05) and (0,57 ± 0,07) nmol/l, respectively. Determination of the level of AT-TG and AT-TPO was carried out in order to exclude autoimmune thyroiditis and other primary organic thyroid diseases.
Blood sampling to determine indicators of hormonal status was performed in the morning at 6-7 hours, after a night's sleep for 810 hours, on an empty stomach.
Statistical processing of the research results was carried out using the developed patient card, adapted for processing the results using the Microsoft Excel program. In the tables reflecting the results of our own research, for each indicator, the average value (M) and its error (m) are given. The results obtained were processed by the Student-Fisher statistical method using the standard package of functions «MS Excel» and «StatgraphWin».
Along with this, the thyroid status of patients with CAC was also studied. The results of the study confirming the presence of autoimmune thyroiditis or other thyroid diseases were negative (table 1). The level of antibodies to thyroglobulin and antibodies to thyroperoxidase did not exceed physiological concentrations. Ultrasound scanning of the thyroid gland revealed no abnormalities in the size and structure of the gland.
Table 1
Indicators of anti-thyroid autoantibodies (M ± m) in patients with CAC
Index Control group (n = 12) Groups of patients with CAC
I (n = 17) II (n = 19) III (n = 29)
AT-TG, nmol/l 0,92 ± 0,05 0,87 + 0,06 0,74 + 0,09 0,85 + 0,07
AT-TPO, nmol/l 0,57 ± 0,07 0,60 + 0,08 0,52 + 0,11 0,64 + 0,10
For a more in-depth study of the nature of hormonal relationships, some relative indicators were analyzed, representing the ratio of integer values of the studied hormones.
To investigate the violation of the relationship between the main thyroid hormones, the FT4 / FT3 index was used.
RESULTS
Changes in hormonal levels in patients of group I were characterized by a tendency towards a decrease in the level of FT3 against the background of a trend towards an increase in the concentration of FT4. The serum TSH level did not change. Along with this, the FT4/FT3 index significantly increased, which indicated a change in the ratio between the biologically active form of FT3 and its inactive precursor FT4 (table 2).
Table 2
Indicators of hormonal balance (M ± m) in patients of group I
Index Control group (n = 12) Patients I group (n = 17) P
FT3, pmol/l 4,62 ± 0,28 4,33 ± 0,11 p = 0,96
FT4, pmol/l 14,45 ± 2,21 17,46 ± 0,29 p = 0,18
FT4/FT3 3,21 ± 0,07 4,07 ± 0,09 < 0,01
TSH, nmol/l 3,31 ± 0,44 3,75 ± 0,39
The nature of the relationship between FT4 and FT3 changed. If healthy donors showed a weak direct correlation between FT4 and FT3: (r = +0,18 ± 0,04; p < 0,05), then in group I patients the type of relationship between FT4 and FT3 changed - a weak negative relationship appeared (r = -0,22 ± 0,03; p < 0,05).
Group II patients showed a tendency to decrease in the level of FT3. The concentration
Indicators of hormonal balance
of FT4 in the blood serum tended to increase (table 3). The serum TSH content remained unchanged. However, the FT4 / FT3 index was significantly increased, which was a manifestation of an imbalance in the thyroid hormone system.
In group II patients, there was a weak negative relationship (r = -0,31 ± 0.03; p < 0,05) between FT4 and FT3.
Table 3
(M ± m) in patients of group II
Index Control group (n = 12) Patients with CAC, group II (n = 19) P
FT3, pmol/l 4,62 ± 0,28 4,25 ± 0,18 P = 0,66
FT4, pmol/l 14,45 ± 2,21 17,94 ± 0,32 P = 0,12
FT4/FT3 3,21 ± 0,07 4,21 ± 0,13 < 0,01
TSH, nmol/l 3,31 ± 0,44 4,23 ± 0,41
Patients in group III showed a significant decrease in the level of FT3, while in patients in groups I and II, only a tendency towards a decrease in this indicator was observed. The concentration of FT4 in the blood serum tended to increase (tab. 4). There were no significant differences between the content of FT4 in the
blood serum of patients with CAC with various variants of gallbladder dyskinesias. An increase in the FT4 / FT3 index was significant in group III patients. The value of the index FT4 / FT3 in them was significantly higher than in patients of group I (respectively 5,27 ± 0,11 h 4,07 ± 0,09, p < 0,05).
Table 4
Indicators of hormonal balance (M ± m) in patients of group III
Index Control group (n = 12) Patients with CAC, group III (n = 29) P
FT3, pmol/l 4,62 ± 0,28 3,65 ± 0,12 < 0,05
FT4, pmol/l 14,45 ± 2,21 18,89 ± 0,61 p = 0,06
FT4/FT3 3,21 ± 0,07 5,27 ± 0,11 < 0,05
TSH, nmol/l 3,31 ± 0,44 5,48 ± 0,31 < 0,05
DISCUSSION
Since the main marker of thyroid hormone-forming activity is the level of FT4, it can be considered that the cause of thyroid imbalance in patients of group I was not thyroid lesion, but a violation of the peripheral metabolism of FT4 - a slowdown in the conversion of FT4 to FT3.
Such minimal changes in the balance of thyroid hormones are described in the literature as T3-low-syndrome. This phenomenon in patients with CAC is of a non-thyrogenic nature, since there were no objective and subjective signs of thyroid lesion. The relative deficit of FT3, revealed only when analyzing the
indicator FT4/FT3, was most likely a manifestation of the adaptive response of the neuroimmunohormonal system of patients with CAC, aimed at reducing the severity of catabolic processes in conditions of exacerbation of the inflammatory process.
Thyroid status in mixed variant of gallbladder dyskinesia was characterized by the presence of minimal changes - a relative decrease in the level of FT3 against the background of a relative increase in the level of FT4. The imbalance of thyroid hormones with a relative predominance of the biologically inactive form of FT4 can be regarded as a variant of T3-low-syndrome. The cause of the
thyroid imbalance in group II patients, most likely, was not thyroid gland damage, but a violation of the peripheral metabolism of FT4 -a slowdown in the conversion of FT4 to FT3.
Consequently, in patients of group III, more significant changes in the balance of thyroid hormones were observed. The deficiency of the biologically active form of FT3 acquires the features of not a relative, but an absolute phenomenon in patients of group III. The change in the balance of hormones of the pituitary-thyroid system in group III patients consisted in the overproduction of TSH, a relative deficit of FT3 against the background of a relative excess of FT4.
The analysis of the role of the age factor caused certain difficulties. Loss of the contractile function of the gallbladder occurs as a result of prolonged progression of the pathological process in the gallbladder with a combination of several unfavorable factors, which include aging (the age of representatives of group III is significantly greater than in other groups). The groups could not be randomized according to age - in the real clinical practice of this institution, it was simply not possible to identify patients with this type of motor-evacuation disorders of gallbladder of a different age.
The problem of the reliability of the classical TSH indicator as a criterion for diagnosing thyroid insufficiency in the aging population is being discussed quite actively, there are many reports of an increase in the level of circulating TSH in older people [20]. The impressive Baltimore Long-Term Aging Study (BLSA), a long-term study of 1,483 participants who underwent thyroid function tests between 2003 and 2015.
The mean TSH value progressively increased with age from 2,4 mIU / L in persons under 60 years of age to 2,6 mIU/L in persons aged 60-69 years, 2,7 mIU/L in persons aged 70-79 years and 3,2 mIU/L in persons > 79 years old. The increase in the mean TSH value is not linear, but mainly refers to the oldest age group in persons over 79 years old [21]. Patient group III was much younger, up to
60 years old, so the factor of age-related increase in TSH level cannot be considered decisive. Non-thyroid factors are often considered as possible causes of increased TSH levels. TSH is proposed to be considered as an early predictor of stress, more sensitive than levels of cortisol, glucose or norepinephrine [22].
CONCLUSIONS
1. The disproportion between the thyroid hormones and the quantitative predominance of the inactive form made it possible to identify the relative hypothyroid syndrome in group I patients.
At the same time, the quantitative relationships between hormones change, which can be used as additional diagnostic criteria.
2. The disproportion between the biologically inactive and active forms of thyroid hormones with a quantitative predominance of the inactive form made it possible to judge the presence of a relative hypothyroid syndrome in group II patients. Thus, the general anabolic-catabolic potential of the organism is somewhat leveled.
3. Patients of group III showed a significantly increased level of TSH, which was a response of the hypothalamic-pituitary system to a decrease in the level of FT3. Thus, the hypothalamic-pituitary system reacts to thyroid imbalance as hypothyroid syndrome.
The results of the studies carried out in patients with CAC have revealed the peculiarities of changes in the hormonal status. Various changes in the hormonal status of patients were observed depending on the type of dyskinetic disorders in the gallbladder. There was a syndrome of hormonal dysfunction, which characterized the tension of the body' s adaptive systems.
PROSPECTS FOR FUTURE STUDIES. AUTHOR CONTRIBUTIONS
Further study of hormonal characteristics in this category of patients and the development of rational treatment regimens are promising.
REFERENCES
1. Venneman NG, van Erpecum KJ. Pathogenesis of gallstones. Gastroenterol Clin North Am. 2010 Jun; 39 (2): 171-83, vii. DOI: 10.1016/j.gtc.2010.02.010. PMID: 20478481.
2. Lavoie B, Nausch B, Zane EA, Leonard MR, Balemba OB, Bartoo AC, Wilcox R, Nelson MT, Carey MC, Mawe GM. (2012). Disruption of gallbladder smooth muscle function is an early feature in the
development of cholesterol gallstone disease. Neurogastroenterol Motil. 2012; 24 (7): e313-e324. DOI: 10.1111 / j.1365-2982.2012.01935
3. Smelt AH. Triglycerides and gallstone formation. Clin Chim Acta. 2009; 411: 1625-1631. DOI: 10.1016/j.cca.2010.08.003
4. Bonde Y, Plosch T, Kuipers F, et al. Stimulation of murine biliary cholesterol secretion by thyroid hormone is dependent on a functional ABCG5/G8 complex. Hepatology. 2012; 56 (5): 1828-1837. DOI: 10.1002/hep.25861
5. Sinha RA, Singh BK, Yen PM. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol. 2018; 14 (5): 259-269. DOI: 10.1038/nrendo.2018.10
6. Wang Y, Yu X, Zhao QZ, et al. Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms. J Zhejiang Univ Sci B. 2016; 17 (7): 515-525. DOI: 10.1631/jzus.B1500210
7. Floriani C, et al. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Eur Heart J. 2018; 39: 503-507. DOI: 10.1093/eurheartj/ehx050
8. Gencer B, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012; 126: 1040-1049. DOI: 10.1161/circulationaha. 112.096024
9. Taylor PN, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018; 14: 301-316. DOI: 10.1038/nrendo.2018.18
10. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014; 24: 1670-751. DOI: 10.1089/thy.2014.0028
11. Pearce EN, Hennessey JV, McDermott MT. New American Thyroid Association and American Association of Clinical Endocrinologists guidelines for thyrotoxicosis and other forms of hyperthyroidism: significant progress for the clinician and a guide to future research. Thyroid. 2011; 21: 573-597. DOI: 6.10.1089/thy.2011.0104
12. Laurberg P, Andersen S, Carle A, Karmisholt J, Knudsen N, Pedersen IB. The TSH upper reference limit: where are we at? Nat Rev Endocrinol. 2011; 7: 232-241. DOI: 9.10.1038/nrendo.2011.13
13. Larisch R, Giacobino A, Eckl W, Wahl HG, Midgley JE, Hoermann R. Reference range for thyrotropin. Post hoc assessment. Nuklearmedizin. 2015; 54 (3): 112-7. DOI: 10.3413/Nukmed-0671-14-06. Epub 2015 Jan 8. PMID: 25567792.
14. Ehrenkranz J, Bach PR, Snow GL, Schneider A, Lee JL, Ilstrup S, Bennett ST, Benvenga S. Circadian and Circannual Rhythms in Thyroid Hormones: Determining the TSH and Free T4 Reference Intervals Based Upon Time of Day, Age, and Sex. Thyroid. 2015 Aug; 25 (8): 954-61. DOI: 10.1089/thy.2014.0589. PMID: 26061389.
15. Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. Journal of Thyroid Research. 2012 ; 2012: 351864. DOI: 10.1155/2012/351864.
16. Hadlow NC, Rothacker KM, Wardrop R, Brown SJ, Lim EM, Walsh JP. The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex. J Clin Endocrinol Metab. 2013 Jul; 98 (7): 2936-43. DOI: 10.1210/jc.2012-4223. Epub 2013 May 13. PMID: 23671314.
17. Midgley JE, Hoermann R, Larisch R, Dietrich JW. Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. J Clin Pathol. 2013 Apr; 66 (4): 335-42. DOI: 10.1136/jclinpath-2012-201213. Epub 2013 Feb 19. PMID: 23423518.
18. Hoermann R, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW, Larisch R. Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clin Endocrinol (Oxf). 2014 Dec; 81 (6): 907-15. DOI: 10.1111/cen.12527. Epub 2014 Jul 7. PMID: 24953754.
19. Hoermann R, Midgley JE, Larisch R, Dietrich JW. Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. Front Endocrinol (Lausanne). 2015 Nov 20; 6: 177. DOI: 10.3389/fendo.2015.00177. PMID: 26635726; PMCID: PMC4653296.
20. Vadiveloo T, Donnan PT, Murphy MJ, Leese GP. Age- and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS). J Clin Endocrinol Metab. 2013 Mar; 98 (3): 1147-53. DOI: 10.1210/jc.2012-3191. Epub 2013 Jan 23. PMID: 23345094.
21. Mammen JS, McGready J, Oxman R, Chia CW, Ladenson PW, Simonsick EM. Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging. Thyroid. 2015 Sep; 25 (9): 979-86. DOI: 10.1089/thy.2015.0180. Epub 2015 Aug 13. PMID: 26177259; PMCID: PMC4560848.
22. Harbeck B, Suefke S, Haas CS, Lehnert H, Kropp P, Moenig H. No stress after 24-hour on-call shifts? J
Occup Health. 2015; 57 (5): 438-47. DOI: 10.1539/joh.14-0276-OA. Epub 2015 Jun 25. PMID:
26119209; PMCID: PMC6706192.
ЗМ1НИ ГОРМОН1В ЩИТОПОДIБНОÏ ЗАЛОЗИ У ХВОРИХ НА ХРОН1ЧНИЙ НЕКАЛЬКУЛЬОЗНИЙ ХОЛЕЦИСТИТ В ПРАКТИЦ1 С1МЕЙНОГО Л1КАРЯ
Вовк К. В., Резтченко О. Г., Власенко О. О., rpidHeea С. В., Кратенко Г. С.
Резюме. Серед патологи жовчовиввдних шляхiв одне з центральних мюць займае хронiчний некалькульозний холецистит (ХНХ). Важлива роль гормонально1' системи в регуляцiï функцiонування жовчовивщних шляхiв вiдома давно, але конкретш механiзми цих впливiв залишалися неясними. За результатами комплексного клшчного, лабораторного, бiохiмiчного та iнструментального обстеження вс пацiенти з хронiчним некалькульозним холециститом були роздшеш на три групи в залежностi вiд варiанту порушення моторно-кiнетичноï функцiï жовчного мiхура. До першо1 групи увiйшли пацiенти з ХНХ та гшертошчно-гшеркшетичною дискiнезiею жовчного мiхура (I група) - 17 оаб; друга -пацiенти з ХНХ зi змiшаною гiпотонiчно-гiперкинетичною дискiнезiею жовчного мiхура (II група) -19 оаб; третя - пащенти з ХНХ та гiпотонiчно-гiпокiнетичною дискiнезiею жовчного мiхура (III група) - 29 оаб. Рiвень вiльного T3, T4 i тиреотропного гормону (ТТГ) визначали iмунофлуоресцентний методом з використанням тест-систем BREAHMS (Henning Berlin GMBH). Диспропорщя гормонiв щитовидно1 залози i шльшсне переважання неактивноï форми дозволили виявити вiдносний гiпотиреоïдних синдром у пащенпв I групи. Диспропорщя мiж бiологiчно неактивними i активними формами тиреовдних гормонiв з кiлькiсним переважанням неактивно!' форми дозволила судити про наявшсть вiдносного гiпотиреоïдного синдрому у пащенпв II групи. У пащенпв III групи виявлено достовiрне шдвищення рiвня ТТГ, що е ввдповвддю гiпоталамо-гiпофiзарноï системи на зниження рiвня FT3.
КЛЮЧОВ1 СЛОВА: хронiчний некалькульозний холецистит, щитоподiбна залоза, гормони ИНФОРМАЦ1Я ПРО АВТОР1В
Вовк Юра ВпалИвна, к.мед.н., доцент, кафедра загально1 практики-амейно1 медицини, медичний факультет, Харювський нацюнальний унiверситет iменi В. Н. Каразша, майдан Свободи, 6, Харюв, Украша, 61022, e-mail: vovkkira1970@gmail.com, ORCID ID: https://orcid.org/0000-0003-2971-0842
Резшченко Олександр Геоpгiйович, к.мед.н., доцент, кафедра загально1 практики-сiмейноï медицини, Харювський нацiональний унiверситет iменi В. Н. Каразша, майдан Свободи, 6, Харюв 61022, Украша, e-mail: a.reznichenko@karazin.ua, ORCID ID: https://orcid.org/0000-0001-8189-7048
Власенко Ольга Олексaндpiвнa, к.мед.н., доцент, кафедра загально1 практики-имейно1 медицини, медичний факультет, Харювський нацюнальний ушверситет iменi В. Н. Каразша, майдан Свободи, 6, Харюв, Украша, 61022, e-mail: olga.vlasenko@karazin.ua, ORCID ID: https://orcid.org/0000-0003-4720-4062
Гриднева Свплана Вiктоpiвнa, к.мед.н., доцент, кафедра загально1 практики-амейно1 медицини, медичний факультет, Харкiвський нацюнальний ушверситет iменi В. Н. Каразша, майдан Свободи, 6, Харюв, Украша, 61022, e-mail: s.gridneva@karazin.ua, ORCID ID: https://orcid.org/0000-0002-7498-9574
Кратенко Ганна Степашвна, к.мед.н., доцент, кафедра загально1 практики-амейно1 медицини, медичний факультет, Харювський нацюнальний ушверситет iменi В. Н. Каразша, майдан Свободи, 6, Харюв, Украша, 61022, e-mail: anna-krat@ukr.net, ORCID ID: https://orcid.org/0000-0001-7019-5593
ИЗМЕНЕНИЕ ГОРОМОНОВ ЩИТОВИДНОЙ ЖЕЛЕЗЫ У БОЛЬНЫХ ХРОНИЧЕСКИМ НЕКАЛЬКУЛЕЗНЫМ ХОЛЕЦИСТИТОМ В ПРАКТИКЕ СЕМЕЙНОГО ВРАЧА
Вовк К. В., Резниченко А. Г., Власенко О. А., Гриднева С. В., Кратенко А. С.
Резюме. Среди патологии желчевыводящих путей одно из центральных мест занимает хронический некалькулезный холецистит (ХНХ). Важная роль гормональной системы в регуляции функционирования желчевыводящих путей известна давно, но конкретные механизмы этих влияний оставались неясными. По результатам комплексного клинического, лабораторного, биохимического и инструментального обследования все пациенты с хроническим некалькулезным холециститом были разделены на три группы в зависимости от варианта нарушения моторно-кинетической функции желчного пузыря. В первую группу вошли пациенты с ХНХ и гипертонически-гиперкинетической дискинезией желчного пузыря (I группа) - 17 человек; вторая - пациенты с ХНХ со смешанной
гипотонико-гиперкинетической дискинезией желчного пузыря (II группа) - 19 человек; третья -пациенты с ХНХ и гипотоно-гипокинетической дискинезией желчного пузыря (III группа) - 29 человек. Уровень свободного T3, T4 и тиреотропного гормона (ТТГ) определяли иммунофлуоресцентным методом с использованием тест-систем BREAHMS (Henning Berlin GMBH). Диспропорция гормонов щитовидной железы и количественное преобладание неактивной формы позволили выявить относительный гипотиреоидный синдром у пациентов I группы. Диспропорция между биологически неактивными и активными формами тиреоидных гормонов с количественным преобладанием неактивной формы позволила судить о наличии относительного гипотиреоидного синдрома у пациентов II группы. У пациентов III группы выявлено достоверное повышение уровня ТТГ, что является ответом гипоталамо-гипофизарной системы на снижение уровня FT3.
КЛЮЧЕВЫЕ СЛОВА: хронический некалькулезный холецистит, щитовидная железа, гормоны ИНФОРМАЦИЯ ОБ АВТОРАХ
Вовк Кира Витальевна, к.мед.н., доцент кафедры общей практики-семейной медицины, медицинский факультет, Харьковский национальный университет имени В. Н. Каразина, площадь Свободы, 6, Харьков, Украина, 61022, e-mail: vovkkira1970@gmail.com, ORCID ID: https://orcid.org/0000-0003-2971-0842 Резниченко Александр Георгиевич, к.мед.н., доцент кафедры общей практики-семейной медицины, медицинский факультет, Харьковский национальный университет имени В. Н. Каразина, площадь Свободы, 6, Харьков, Украина, 61022, e-mail: a.reznichenko@karazin.ua, ORCID ID: https://orcid.org/0000-0001-8189-7048 Власенко Ольга Александровна, к.мед.н., доцент кафедры общей практики-семейной медицины, медицинский факультет, Харьковский национальный университет имени В. Н. Каразина, площадь Свободы, 6, Харьков, Украина, 61022, e-mail: olga.vlasenko@karazin.ua, ORCID ID: https://orcid.org/0000-0003-4720-4062 Гриднева Светлана Викторовна, к.мед.н., доцент кафедры общей практики-семейной медицины, медицинский факультет, Харьковский национальный университет имени В. Н. Каразина, площадь Свободы, 6, Харьков, Украина, 61022, e-mail: s.gridneva@karazin.ua, ORCID ID: https://orcid.org/0000-0002-7498-9574 Кратенко Анна Степановна, к.мед.н., доцент кафедры общей практики-семейной медицины, медицинский факультет, Харьковский национальный университет имени В. Н. Каразина, площадь Свободы, 6, Харьков, Украина, 61022, e-mail: anna-krat@ukr.net, ORCID ID: https://orcid.org/0000-0001-7019-5593
