[Bony orbital decompression in thyroid eye disease]. / Kostnaya dekompressiya orbity pri endokrinnoi oftal'mopatii.

This article summarizes the results of research on the morphological and functional features of different types of orbital bone decompression in thyroid eye disease (TED) and presents an analysis of surgical anatomy of the lateral orbital wall in the context of performing deep lateral bone decompression of the orbit was carried out. The study includes an analysis of the results of orbital bone decompression with resection of the greater wing of the sphenoid bone using ultrasound osteodestructor in comparison with osteodestruction using a high-speed drill, description of transethmoidal orbital decompression with endonasal access both as a single method of surgical treatment of TED and in combination with lateral bone decompression of the orbit, including the advantages and disadvantages of the method, and presents a morphological description of the pathological changes in the medial orbital wall bone fragments obtained during endonasal transethmoidal orbital decompression in patients with TED.

[Clinical and immunological predictors of Graves' orbitopathy after radioiodine therapy of Graves' disease].

BACKGROUND: Data on the effect of 131I on the course of Graves' orbitopathy (GO) are contradictory. A number of studies indicate a deterioration in the course of GO against the background of RAIT, in other studies such a connection has not been established. Cytokines that regulate inflammation could potentially be biomarkers for assessing GO activity and predicting the course of GO after RAIT. AIM: The purpose of this study was to evaluate the dynamics of eye symptoms and analyze immunological parameters: cytokine TGF-ß1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, sIL-6R over time after RAIT, as possible predictors of GO activation. MATERIALS AND METHODS: The study included 59 patients (118 orbits) with GD in the state of euthyroidism and subclinical hyperthyroidism and low active and inactive GO, aimed at conducting RAIT. Concentrations of cytokine TGF-ß1, sTNFα-RI and sTNFα-R2, sIL-2R, sIL-6R, TSH receptor antibodies (rTSH-Ab), free thyroxine (FT4) and free triiodothyronine (FT3), -thyroid-stimulating hormone (TSH) in the blood serum were determined. Ultrasound examination of the thyroid gland, multispiral computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits was performed. The examination was carried out 3, 6, 12 months after the RAIT. RESULTS: The deterioration of the course of the GO (1-2 points according to CAS) was noted after 3 months. (32.5%) and to a lesser degree after 6 and 12 months (13.2% and 8.45%, respectively). Dynamics were not noted, approximately, in the same number of patients (40.5%, 41.5%, 45.8%, respectively). An improvement in the course of the GO was noted after 6 and 12 months (45.3, 45.8, respectively). After 3 and 6 months, the achievement of hypothyroidism and a significant increase in the level of rTSH-Ab were noted. In the analysis of cytokines and their receptors a significant decrease in the level of TGF-ß1 was noted after 3, 6 and 12 months. There was also a significant decrease in sTNF-R1 and sIL-2R at 3 and 6 months. The level of sTNFα-R2 significantly decreased 3 months after RAIT. The level of sIL-6R has not changed significantly. After 3 months in patients with positive dynamics of image intensification, the level of TGF-ß1 did not significantly change compared with the level before RAIT, in patients with worsening of the course of GO or without dynamics, the level of TGF-ß1 significantly decreased. After 6 months, there was the same trend, not reaching statistical significance. The IgG4 level and the IgG4/IgG ratio increased to 6 and 12 months, which corresponded to an increase in diplopia index. CONCLUSION: The main limiting factor in the conduct of RAIT is the activity of the autoimmune process in the orbits. Since patients with inactive (CAS 0-2) or low activity (CAS 3-4) GO were referred for RAIT, there was no pronounced activation of GO after RAIT. There was a slight deterioration in the course of GO by only 1-2 points according to CAS after 3 months. (32.5%) and to a lesser degree after 6 months (13.2%). In the study, it was found that the main predictors of the deterioration of the course of GO after RAIT are uncompensated hypothyroidism, a high level of rTSH-Ab and a decrease in the level of cytokine TGF-ß1.

[An integrated approach to the treatment of pretibial myxedema based on pulse therapy with prednisolone and electrical neuromyostimulation (FREMS-therapy) in a patient with Graves' disease and thyroid eye disease].

Graves' disease (GD) is one of the urgent problems of modern endocrinology, characterized by a high frequency, polysystemic damage to the body, a steadily progressive course, diagnostic difficulties, a high degree of disability and often resistance to therapy. The manifestations of the disease include: thyrotoxicosis syndrome with impaired lipid and carbohydrate metabolism, and activation of multiple organ pathology in the form of thyroid eye disease (TED), pretibial myxedema, cardiovascular insufficiency, acropathy, lesions of the nervous, osteoarticular system, and other lesions. The development of multiple organ pathology can have a different sequence, different time intervals and different degrees of severity. Any developments in the direction of clarifying the etiopathogenetic, clinical diagnostic and treatment-rehabilitation measures are of undoubted significance. We present a clinical case of GD, TED and pretibial myxedema, in which an integrated approach was tested in the tactics of treating pretibial myxedema (a combination of pulse therapy with prednisolone and FREMS-therapy), as a result of which positive results were obtained within a short time.

[Alemtuzumab-induced Graves' disease].

Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves' disease (GD) develops most often, followed by autoimmune thyroiditis.We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.

[Complications of transnasal endoscopic orbital decompression in thyroid eye disease]. / Oslozhneniya transnazal'noi endoskopicheskoi dekompressii orbity pri endokrinnoi oftal'mopatii.

PURPOSE: The study evaluates the frequency of complications after transnasal endoscopic orbital decompression (TEOD). MATERIAL AND METHODS: The study included 40 patients (75 orbits) with thyroid eye disease (TED; also termed Graves' ophthalmopathy, GO; thyroid-associated orbitopathy, TAO), who were divided into three groups depending on the method of surgical treatment. The first group consisted of 12 patients (21 orbits) who were treated with TEOD as the only method of surgical treatment. In the second group, there were 9 patients (18 orbits) who underwent TEOD and lateral orbital decompression (LOD) simultaneously. The third group consisted of 19 patients (36 orbits) who underwent TEOD as the second stage after LOD. Pre- and postoperative observation included assessment of visual acuity, visual field, exophthalmos, heterotropia/heterophoria angle. RESULTS: In group I the new-onset strabismus with binocular double vision was detected in 1 patient (8.3%). In 5 patients (41.7%), there was an increase in the angle of deviation and an increase in diplopia. In group II the new-onset strabismus with diplopia occurred in 2 patients (22.2%). In 8 patients (88.9%), an increase in the angle of deviation and an increase in diplopia were revealed. In group III the new-onset strabismus and diplopia occurred in 4 patients (21.0%). An increase in the deviation angle and an increase in diplopia were noted in 8 patients (42.1%). The number of postoperative otorhinolaryngologic complications in group I was 4 (19.0% of the number of orbits). Two intraoperative complications were recorded in group II - 1 case of cerebrospinal rhinorrhea (5.5% of the number of orbits) and 1 case of retrobulbar hematoma without permanent vision loss (5.5% of the number of orbits). The number of postoperative complications was 3 (16.7% of the number of orbits). In group III the number of postoperative complications was 3 (8.3% of the number of orbits). CONCLUSION: The study showed that the most common ophthalmological complication after TEOD is strabismus with binocular double vision. Otorhinolaryngologic complications included synechiae of the nasal cavity, sinusitis and mucocele of the paranasal sinuses.

[Transnasal endoscopic orbital decompression in the algorithm of surgical treatment of endocrine ophthalmopathy]. / Transnazal'naya endoskopicheskaya dekompressiya orbity v algoritme khirurgicheskogo lecheniya endokrinnoi oftal'mopatii.

OBJECTIVE: To develop an algorithm for the use of transnasal endoscopic orbital decompression (TEOD) in endocrine ophthalmopathy (EOP). MATERIAL AND METHODS: The results of 225 TEODs are analyzed. 139 patients with EOP were under observation, who were divided into two groups. Group 1 included 64 patients with an inactive form of EOP, group 2 included 75 patients with EOP complicated by optical neuropathy. Group 2 patients are divided into three subgroups. In the first subgroup there were 36 patients who underwent only TEDO, in the second subgroup there were 17 patients who underwent simultaneous TEOD and lateral bone orbital decompression (LBOD), in the third subgroup there were 22 patients who underwent TEOD and with an interval of 7-14 days - LBOD. After surgery, visual acuity, visual fields and color perception, regression of exophthalmos, as well as the presence of strabismus and diplopia were evaluated. RESULTS: In patients of group 1 (64 patients, 104 TEODs), the average regression rate of exophthalmos was 5.49±1.22. Diplopia was observed in 23 (36%) patients, strabismus - in 18 (28%) patients. The transient nature of diplopia and strabismus was noted in 11% of cases. Patients of the first subgroup showed an increase in visual acuity from 0.4±0.28 to 0.7±0.2 (p<0.05). Strabismus and diplopia were observed in 54% of cases. In the subgroup with step-by-step performed TEOD and LBOD, the increase in visual acuity was more pronounced and amounted to 74% (from 0.78±0.71 to 0.2±0.3 according to LogMAR, p<0.05), postoperative strabismus and diplopia remained at a high level - 40% of the number of surgical operations performed. The best results of improving visual functions were obtained in patients of the second subgroup with simultaneous TEOD and LBOD (balanced orbital decompression): the increase in visual acuity was 79% (from 0.57±0.47 to 0.12±0.2 according to LogMAR, p<0.05). In patients of this subgroup, strabismus develops less frequently (22% of the number of operated orbits). CONCLUSION: Transnasal endoscopic decompression of the orbit in the inactive form of the disease is indicated for exophthalmos of more than 4-8 mm. In optical neuropathy, transnasal endoscopic orbital decompression is indicated regardless of the initial visual acuity of the patient and should be supplemented with lateral bone orbital decompression with visual acuity below 0.1. The obtained results allowed us to form an algorithm for surgical treatment of patients with endocrine ophthalmopathy and optical neuropathy using transnasal endoscopic orbital decompression as a surgical intervention.

[Treatment of Graves' disease in patients with thyroid eye disease]. / Lechenie bolezni Greivsa pri soputstvuyushchei endokrinnoi oftal'mopatii.

Graves' disease (GD) is an autoimmune disease that is often complicated by thyroid eye disease (TED). Clinical presentations of TED can develop simultaneously with the manifestation of GD, after the manifestation of GD amid treatment, and before the development of thyrotoxicosis. Treatment of such patients is a difficult task, because on the one hand, it is necessary to take into account the clinical picture of thyrotoxicosis, and on the other - the symptoms of eye damage. The combination of the two pathologies determines the need for simultaneous treatment of GD and TED, and the choice of a treatment method for GD will depend on the manifestations of TED. This article presents current views on the treatment of GD with concomitant TED. The choice of GD treatment method will be largely determined by the clinical manifestations of TED and will be conducted jointly by endocrinologists and ophthalmologists.

[Potential of bony regrowth after deep lateral orbital decompression]. / O vozmozhnosti kostnogo rosta posle glubokoi dekompressii lateral'noi stenki orbity.

The article describes a very rare case of bony regrowth after deep lateral orbital decompression for thyroid eye disease. Bony regrowth was observed in the area of the resected «trigone¼ of the greater wing of the sphenoid bone and in the area of the exposed dura mater. This case demonstrates that bony regrowth can be a possible cause of exophthalmos (proptosis) recurrence after orbital decompression in thyroid eye disease without clinical or laboratory evidence of reactivation of the disease.

[Autoantibodies, immunoglobulins and cytokine profile in patients with graves' disease and Graves' orbitopathy].

BACKGROUND: Graves' Orbitopathy (GO) - also known as Thyroid Eye Disease (TED) - is an autoimmune condition in the modern sense. It is closely associated with autoimmune thyroid diseases. Cytokine-mediated mechanisms play a critical part in immunopathogenesis of autoimmune thyroid diseases including GO. Investigating cytokine profiles as well as antibodies to tissue-specific antigens is essential for explaining GO pathogenesis and developing future therapeutic strategies. AIMS: The study examines serum levels of cytokines, autoantibodies and immunoglobulins IgG and IgG4 as mediators of autoimmune inflammation in patients with GO and Graves' Disease (GD). MATERIALS AND METHODS: The study included 52 patients (104 orbits) aged 25-70 years (mean age 48,8±12,3) in the active phase of GO and GD verified with the international diagnostic standards. These patients did not get any treatment for GO before. The control group consisted of 14 individuals (28 orbits) aged 30-68 years without known autoimmune disease.Serum levels of IgG, IgG4,TNFα, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-13, sIL-6R, sTNFα- RI и TNFα- R2 IL-2R, TGFß1, TGF ß3, antibodies to TSH-receptor, free T4, free T3 and TSH were measured. A diagnostic ultrasound exam of thyroid gland, multislice computed tomography (MSCT) / magnetic resonance imaging (MRI) of orbits were performed. RESULTS: Mean duration of GO prior to being admitted to the centre was 8,8±1,5 months (range: 1 - 48 months). According to the degree of thyrotoxicosis compensation: 24 patients were clinically euthyroid, TSH 3,3±0,7 mU/L, free T4 11,9±0,59 pmol/L, free T3 3,97±0,1 pmol/L; 28 patients were considered to have subclinical thyrotoxicosis: TSH 0,03±0,01 mU/L, free T4 14,2±1,0 pmol/L, free T3 5,77±0,49 pmol/L. Serum levels of sTNFα-R2 (p=0,041, p≤0,05), sIL-2R (p=0,020, p≤0,05), TGFß1 (p=0,000, p≤0,001) were significantly higher in patients with GO compared to the control group. Serum levels of sTNFRα2 (p=0,038, p<0,05) and TGFß1 (P=0,011, p≤0,05) were positively correlated with the duration of GO. The positive correlations between the serum level of sIL-6R (p=0,034, p≤0,05) and the severity of GO as well as between the serum level of sTNFα- R 1 (P=0,012, p≤0,05) and activity of GO were observed. 54% of patients had elevated concentration level of IgG4 in IgG ( >5%). CONCLUSION: High levels of soluble cytokine receptors sTNFα-R2 and sIL-2R and cytokine TGFß1 in patients with long-standing untreated GO and GD being euthyroid or having subclinical thyrotoxicosis indicate activation of regulatory T cells aimed at suppressing autoimmune processes. High concentration level of IgG4 in IgG and cytokine TGFß1 can determine the development of fibrotic changes in the orbital tissues. A decrease in the concentration of cytokine TGFß1 can indicate an unfavorable course of the disease GO.

[Comparative electron microscopy study of the bone surfaces relief after ultrasonic and mechanical high-speed bone removal in orbital decompression]. / Sravnitel'noe élektronno-mikroskopicheskoe issledovanie rel'efa kostnykh poverkhnostei posle ul'trazvukovoi i vysokoskorostnoi mekhanicheskoi osteodestruktsii pri dekompressii orbity.

PURPOSE: To compare the results of scanning electron microscopy studies of the surface of bone fragments of orbital lateral wall formed by mechanical and ultrasonic bone removal devices. MATERIAL AND METHODS: The surfaces of 7 bone fragments have been investigated after bony orbital decompression in patients with thyroid eye disease (TED). Electron microscopy of the bone relief was performed after exposure to an ultrasonic surgical system or a high-speed drill. RESULTS: Electron microscopy revealed that relief of the bony surface within a compact substance after application of an ultrasonic aspirator had parallel grooves of the same type up to 100 µm in depth and 80-100 µm wide, with relatively smooth edges. In the area of impact on spongy substance the bone surface became more amorphous, rougher due to the exposure of cellular structures at different depths. High-speed drill used in the area of compact substance left monotonous, almost flat relief with individual compact conglomerates of bone 'dust'. Removal of thinned fragments of the compact substance of the specimen led to appearance of the cellular structure typical for a spongy substance. CONCLUSION: Data on features of the relief of the edges of bone 'window' obtained for the first time, as well as specifics of working in conditions of limited surgical access allowed the conclusion that modern ultrasonic bone aspiration is promising for deep lateral wall decompression and some other orbital interventions.

[Surgical rehabilitation of patients with thyroid eye disease: systematic approach]. / , Khirurgicheskaya reabilitatsiya patsientov s endokrinnoi oftal'mopatiei: sistematizirovannyi podkhod.

AIM: to analyze the results of surgical treatment of patients with thyroid eye disease (TED), including the type of surgery, indications, and outcomes. MATERIAL AND METHODS: Hundred thirty-nine patients with TED (112 females, 27 males) aged 45.8±13.6 years. RESULTS: Bony orbital decompression was performed in 91 patients (128 orbits). After the surgery, visual acuity increased from 0.84±0.47 up to 0.94±0.32 (р<0.05), exophthalmos got reduced by the average of 3.4 mm. Strabismus surgery was performed in 15 patients. The absence of diplopia in the primary position of gaze was achieved in 12 cases and the degree of residual heterophoria averaged 3.33 PD (2-6 PD). Ocular motility improved from 10.7° up to 34.58°. Eyelid surgery was performed in 81 patients. CONCLUSIONS: 1. Surgical treatment for thyroid eye disease is indicated in patients with visual impairment and/or significant decrease in the quality of life, if pathogenetic treatment fails. 2. The choice of surgical strategy depends on several factors, such as TED activity and severity, thyroid function, pathologic changes in the orbital tissues, and surgeon's experience and preference. 3. Current surgical techniques for thyroid eye disease enable correction of disease consequences, such as exophthalmos, optic neuropathy, impairment of ocular movement, and exposure keratopathy. 4. Adherence to the systematic approach that includes bony orbital decompression, strabismus surgery, and correction of lagophthalmos and eyelid retraction, ensures high-level functional and cosmetic rehabilitation in patients with TED.

[Graves' disease and pregnancy].

Thyvrotoxicosis is a clinical syndrome related to the negative influence of excess thyroid hormones. Its main cause in young and mid-aged patients is Graves' disease. Therapy with thyrostatic medications are most frequently used in this country as the primary method for the treatment of this disease. The experience of both Russian and foreign authors indicate that 70% of Graves' disease cases require radical treatment. Special caution is needed in the choice of therapies for young women planning pregnancy. Graves'disease developing prior to pregnancy is a contraindication for it because of high risk of its interruption and complications. Such women should be recommended careful contraception. A 27-year-old patient with Graves' disease is described who planned pregnancy and received conservative therapy for an unnecessary, long time. Therapy of thyrotoxicosis during pregnancy and after it is described.