[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.

[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

[Phasing and continuity of the treatment of thyroid eye disease in patients with Graves' disease].

 According to modern concepts, thyroid eye disease (TED) is an independent progressive autoimmune disease of the organ of vision, closely associated with the autoimmune pathology of the thyroid gland (TG), (ICD code - H06.2, proptosis in case of impaired thyroid function E05.0). TED treatment is a long step-by-step process, including immunosuppressive therapy, radiation therapy of the orbits and surgical treatment.TED is a multidisciplinary problem. A patient with thyrotoxicosis clinic and TED symptoms will be taken to an endocrinological clinic for normalization of thyroid hormones and treatment of thyrotoxicosis complications. At the same time, under the supervision of an ophthalmologist, TED diagnostics and treatment will be carried out. Teamwork is of utmost importance because the effectiveness of TED treatment will depend on the speed of achieving a stable euthyroid state, the accuracy of determining the TED activity and severity, and the presence of complications requiring surgical treatment.There are two main phases in the TED development. In the first phase of active inflammation, an increase in the symptoms of TED occurs, then a plateau phase follows, when the symptoms of activity persist but do not progress, then the symptoms regress and the process becomes inactive, while visual disturbances and cosmetic defects may persist. Determining the TED activity is very important from a clinical point of view, because the choice of treatment and tactics of patient management depend on the inflammation activity.We describe a clinical case of phasing treatment of TED complicated by optic neuropathy and movement disorders in a patient with Graves' disease, resistant to immunosuppressive therapy with glucocorticoids and requiring deep lateral bony orbital decompression.

[Clinical and radiological diagnosis of hypophysitis: a review of literature and own data].

This article presents a literature review of the various forms of hypophysitis, its varieties, as well as the problem of radiation diagnosis and treatment of this pathology. Hypophysitis is a poorly understood and multifactorial disease which the difficulty of diagnosing is not only to a variety of nonspecific clinical manifestations and hormonal research data, but also the ambiguous results of MRI studies, the lack of clear MR patterns. The article reflects the main histological types of hypophysitis, the peculiarities of diagnosis in connection with general clinical symptoms, outlines the features of each type of hypophysitis with their own clinical observations. This review is devoted to modern ideas about the clinical course of hypophysitis, presented a set of characteristic diagnostic signs of the disease according to MRI and the treatment algorithms recommended today are also highlighted. The article summarizes data from foreign literature and our own clinical observations in order to develop an optimal protocol for MRI studies in patients with suspected hypophysitis, to develop recommendations for radiologists and endocrinologists for the correct results interpretation. The uniqueness of this review is the lack of data on the clinic, diagnosis and treatment of hypophysitis in the Russian literature today.