RESUMEN
AIM: To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). SUBJECTS AND METHODS: A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. RESULTS: During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. CONCLUSION: The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.
Asunto(s)
Albuminuria , Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas , Retinopatía Diabética , Hemoglobina Glucada/análisis , Insulina/uso terapéutico , Adulto , Edad de Inicio , Albuminuria/diagnóstico , Albuminuria/etiología , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/terapia , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/etiología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Técnicas de Diagnóstico Oftalmológico/estadística & datos numéricos , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/uso terapéutico , Pruebas de Función Renal/estadística & datos numéricos , Masculino , Estudios Prospectivos , Factores de Riesgo , Federación de Rusia/epidemiologíaRESUMEN
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.
Asunto(s)
Enfermedad de Graves , Oftalmopatía de Graves , Mixedema , Humanos , Enfermedad de Graves/complicaciones , Enfermedad de Graves/tratamiento farmacológico , Oftalmopatía de Graves/complicaciones , Oftalmopatía de Graves/tratamiento farmacológico , Mixedema/complicaciones , Mixedema/tratamiento farmacológico , Pacientes , Prednisolona/uso terapéuticoRESUMEN
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.
Asunto(s)
Enfermedad de Graves , Oftalmopatía de Graves , Hipotiroidismo , Humanos , Oftalmopatía de Graves/radioterapia , Radioisótopos de Yodo/uso terapéutico , Factor de Crecimiento Transformador beta1/uso terapéutico , Enfermedad de Graves/radioterapia , Enfermedad de Graves/tratamiento farmacológico , Hipotiroidismo/tratamiento farmacológico , Inmunoglobulina G/uso terapéuticoRESUMEN
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.
Asunto(s)
Enfermedad de Graves , Oftalmopatía de Graves , Humanos , Oftalmopatía de Graves/terapia , Oftalmopatía de Graves/diagnóstico , Enfermedad de Graves/terapia , Enfermedad de Graves/complicaciones , Inmunosupresores/uso terapéuticoRESUMEN
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.