Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Increased SOCS1 and SOCS3 expression in papillary thyroid carcinoma and its association with prognosis.

OBJECTIVE: The majority of patients with papillary thyroid carcinoma (PTC) have good outcomes, although the identification of new predictors of a poor prognosis would be beneficial. Chronic thyroiditis is a precancerous condition in which proinflammatory cytokines enhance biologically aggressive features. This study investigated the expression of suppressor of cytokine signaling proteins (SOCS) 1 and 3, which are negative feedback inhibitors, in PTC and benign thyroid nodules (BTN), and analyzed the relations among biomarker expression, pathological prognosis, and clinical features. PATIENTS AND METHODS: The pathological materials and clinical data of 100 patients with PTC and 40 with BTN were retrospectively analyzed. Immunohistochemical SOCS1 and SOCS3 staining were performed. Besides comparing SOCS1 and SOCS3 expression between PTC and BTN, we analyzed the expression according to pathological factors and clinical variables. RESULTS: The expression levels of the proteins were significantly higher in PTC than in BTN (p=0.001). SOCS1 expression was higher in older patients with PTC than in younger patients (p=0.001). Unlike SOCS1, SOCS3 was related to the risk group; these groups were distinguished based on the American Thyroid Association (ATA) risk stratification system (p=0.001). SOCS3 was also significantly related to lymph node involvement (p=0.007), capsule invasion (p=0.005), and extrathyroid extension (p=0.009). CONCLUSIONS: The increased SOCS1 and SOCS3 expression in PTC confirms their roles in thyroid carcinogenesis. Antibodies to both SOCS1 and SOCS3 might aid the diagnosis of PTC through immunohistological staining. SOCS3 provides information on lymph node status and aids risk stratification.

THE EFFECT OF ANTITHYROID DRUGS ON OSTEOPONTIN AND OXIDATIVE STRESS IN GRAVES' DISEASE.

OBJECTIVE: The aim of the present study is to evaluate the effects of methimazole (MTZ) and propylthiouracil (PTU) treatments on osteopontin (OPN) and oxidative stress in Graves' disease (GD). MATERIAL AND METHODS: The study included 60 cases with GD in hyperthyroid state and taking no antithyroid treatment, and 30 healthy volunteers. GD patients were randomly separated into two groups; 30 of them took PTU, and the other 30 took MTZ treatments. Blood samples were taken from the patients with GD before the treatment, and three months after the treatment was begun, when they were in the euthyroid state; blood samples of the healthy control subjects were also taken at these times. RESULTS: TAS and OSI levels before treatment were significantly higher in the GD group, when compared to the control group (p<0.001, for each). GD subjects taking PTU treatment had significantly higher TAS levels (p=0.001), and significantly lower TOS and OSI levels (p=0.008 and p=0.001, respectively). TAS levels significantly decreased in the patients taking MTZ treatment (p=0.029), but TOS and OSI levels did not change significantly (p>0.05). Pretreatment OPN levels were significantly higher in GD patients, when compared to the control group (p=0.014). OPN level significantly decreased in the GD group taking PTU treatment; however OPN levels in the group taking MTZ treatment did not change significantly when compared to the pretreatment value. CONCLUSION: PTU treatment is more effective in decreasing OPN and oxidative stress in GD patients, when compared to the MTZ treatment.

Patients' clinical charecteristics and predictors for diabetic foot amputation.

INTRODUCTION: Medical and surgical treatment options are available for patients with diabetic foot ulcers. In more severe cases, amputation decisions are determined by patient comorbidities, performance, imaging studies, and clinical examination results. However, an objective indicator that predicts how this amputation process will end has not yet been clarified. This study identifiies clinical characteristics that can be predictors of the need for diabetic foot amputation among patients. METHODS: In this retrospective observational study, a total of 400 patients with type 2 diabetes who were over the age of 18 and possessed diabetic foot ulcers were examined. The clinical, radiological, and scintigraphic profiles of these patients including age, gender, duration of diabetes, smoking history, previous diabetic foot amputation, presence of hypertension (HT), coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease, cardiovascular disease, retinopathy, neuropathy and nephropathy were analyzed. RESULTS: Of the 400 patients with diabetic foot ulcers, 143 (35.75%) underwent foot amputation. Moreover, the frequency of proteinuria in amputees was significantly higher than in non-amputees (p<0,05). Amputees also exhibited significantly longer smoking histories (p<0,001), and the frequency of reamputation was significantly higher in those who possesed histories of previous amputation (p=0.038). After multivariate analysis PAD presence and previous diabetic ulcer history were the significant factors to determine the amputation decision. CONCLUSION: The following patient characteristics were determined as being effective for predicting the need for amputation: male sex, CAD, PAD, HT, proteinuria, ulcers with Wagner Stages 4-5, smoking histories, previous diabetic ulcer histories, and previous amputation histories. The specificity of the model with these variables was determined as 86% in the patients who did not need amputation. Significant determinants were peripheral artery disease presence and diabetic foot ulcer history. Still, further and more extensive research with higher numbers of patients is necessary for determining more precisely the need for amputation.

THE EFFECT OF GLUCOVANCE THERAPY ON BIOMECHANICAL DETERIORATION OF BONE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS.

AIM: Is to evaluate the influence of glucovance therapy on biomechanical properties of bone in streptozotocin - induced diabetes mellitus (DM) in rats. MATERIALS AND METHODS: A total of 28 male Wistar-Albino rats (12-week-old; 210-300 g) were divided into 4 groups including control (C; no treatment; n=7), sham [Sh; distilled water (gavage, for 8 weeks); n=7], diabetes [DM; streptozotocin (45 mg/kg, single i.p injection); n=7] and diabetes+ Glucovance treatment [DM+G; streptozotocin (45 mg/kg, single i.p injection) + Glucovance (Glucovance, 500/5 mg/kg/day/rat, gavage, for 8 weeks); n=7] groups. Body weight, blood glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical properties of bone tissue were evaluated. BGLs in diabetic rats were significantly increased compared to non-diabetic rats, while the body weights were decreased (p<0.05). RESULTS: A significant difference was not detected between groups with regard to cross-sectional area of diaphyseal femur (p>0.05). Maximum load, energy absorption capacity, ultimate stress, ultimate strain, toughness and displacement were shown to decrease and stiffness was shown to increase in DM rats (p<0.05). Ultimate stress and maximum load were significantly increased in DM+G groups compared to DM groups (p<0.05). CONCLUSION: Glucovance treatment seems to be effective in restoration of biomechanical deterioration of bone specific to STZ-induced DM.

DPP-4 INHIBITORS INCREASE THE INCIDENCE OF ARTHRITIS/ARTHRALGIA BUT DO NOT AFFECT AUTOIMMUNITY.

AIMS: In August 2015, FDA published a black box declaring that DPP-4 inhibitors may cause severe joint pains. The impact on autoimmunity marker positivity of these drugs has not been comprehensively evaluated. We compared the incidence of arthritis/arthralgia in patients with T2DM who were using DPP-4 inhibitors and patients who were not using. METHODS: A number of 93 DPP-4 inhibitor users and 107 non-users were included into the study. Arthritis/arthralgia were found in 41 of 93 (44.1%) DPP-4 inhibitor users and in 19 of 107 (17.8%) non-users (p<0.05). RESULTS: No inflammatory rheumatological condition was identified in 27 of 41 (65.9%) patients in DPP-4 inhibitor user group as well as in 13 of 19 (68.4%) patients in non-user group (p>0.05). After adjusting for gender the incidence for arthritis/arthralgia was significantly increased in the DPP-4 inhibitor user group (p value for any DPP-inhibitor <0.05). There was 3.77 times increased risk for arthritis/arthralgia in the DPP-4 inhibitor using group (p value= 0.001) and this risk increases 2.43 times for each year of DPP-4 inhibitor usage. CONCLUSIONS: Arthritis/arthralgia were more common among T2DM patients who were using DPP-4 inhibitors compared to non-users, but the seropositivity did not differ between DPP-4 inhibitor users and non-users.

Auditory changes in acromegaly.

OBJECTIVE: The aim of this study is to determine the changes involving auditory system in cases with acromegaly. MATERIALS AND METHODS: Otological examinations of 41 cases with acromegaly (uncontrolled n = 22, controlled n = 19) were compared with those of age and gender-matched 24 healthy subjects. Whereas the cases with acromegaly underwent examination with pure tone audiometry (PTA), speech audiometry for speech discrimination (SD), tympanometry, stapedius reflex evaluation and otoacoustic emission tests, the control group did only have otological examination and PTA. Additionally, previously performed paranasal sinus-computed tomography of all cases with acromegaly and control subjects were obtained to measure the length of internal acoustic canal (IAC). RESULTS: PTA values were higher (p < 0.001 for right ears and p = 0.001 for left ears), and SD scores were (p = 0.002 for right ears and p = 0.002 for left ears) lower in acromegalic patients. IAC width in acromegaly group was narrower compared to that in control group (p = 0.03 for right ears and p = 0.02 for left ears). When only cases with acromegaly were taken into consideration, PTA values in left ears had positive correlation with growth hormone and insulin-like growth factor-1 levels (r = 0.4, p = 0.02 and r = 0.3, p = 0.03). Of all cases with acromegaly 13 (32%) had hearing loss in at least one ear, 7 (54%) had sensorineural type and 6 (46%) had conductive type hearing loss. CONCLUSION: Acromegaly may cause certain changes in the auditory system in cases with acromegaly. The changes in the auditory system may be multifactorial causing both conductive and sensorioneural defects.

Macrophage Infiltration into Subcutaneous Adipose Tissue is Associated with Local Levels of 11BHSD1.

The present study aimed to evaluate the infiltration of macrophages in form of crown-line structures (CLS) in subcutaneous adipose tissue (SAT) of obese individuals, and to investigate the effect of these on both metabolic parameters and adipose tissue 11-beta-hydroxysteroid dehydrogenase type 1 (11BHSD1) enzyme levels. A total of 53 obese (10 men, 43 woman) enrolled in the study. Body mass index (BMI), waist circumference (WC), hip circumfrence, and systolic (SBP) and diastolic blood pressures (DBP) of all subjects were recorded. Insulin resistance was determined using the homeostasis model assessment (HOMA). The concentration of SAT, tumor necrosis factor (TNF)-α, interleukin (IL)-6, 11BHSD1 were performed by enzyme-linked immunosorbent assay (ELISA) method. The infiltration of macrophages in form of CLS in adipose tissue were determined using cell-specific stains against CD68. There was no significant difference between the CLS+group and the CLS- group in terms of age, gender, BMI, WC, waist-to-hip circumference ratio (WHR), SBP and DBP levels. Fasting plasma glucose (FPG), HOMA-IR, insulin and SAT TNF-α levels were higher in the CLS+group compared to the CLS- group. FPG and SAT TNF-α levels were significantly higher in participants with high CLS density compared to participants with low density CLS. SAT 11BHSD1 levels was significant higher in the CLS+group compare to the CLS- group and in the high CLS density group compared to the low density group. In conclusion, the infiltration of macrophages in the form of CLS in SAT is associated with increased 11BHSD1 levels. It may be an important mechanism in the development of metabolic disorders.

High Prolidase Levels may be a Marker of Irreversible Extracellular Matrix Changes in Controlled Acromegaly Patients?

The present study aimed to evaluate the activity of prolidase in controlled acromegaly patients and its association with oxidative stress. 25 acromegalic patients in remission who were followed in our outpatient clinic and 31 healthy controls were enrolled in the study. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), total antioxidative status (TAS), total oxidative stress (TOS), total free sulfhydryl (-SH), paraoxonase (PON), arylesterase (ARE), lipid hydroperoxide (LOOH) and prolidase activity levels were measured. Percent ratio of TOS to TAS level was accepted as oxidative stress index (OSI). Serum prolidase activity, TOS, OSI, and LOOH levels were significantly higher in acromegaly patients compared to the healthy control group (p<0.001, p=0.001, p<0.001, and p<0.001, respectively). SH levels were significantly lower in the acromegaly patients compared to the healthy control group (p=0.002). Prolidase activity were positively correlated with TOS, OSI, LOOH and negatively correlated with -SH in patients with acromegaly (r=0.471, p<0.001; r=0.527, p<0.001; r=0.717, p<0.001; r=- 0.516, p<0.001, respectively). These associations were confirmed in the multiple regression analysis (R(2)=0.502, p<0.001). In conclusion, serum prolidase activity and oxidative stress levels were high in controlled acromegaly patients. These results suggest that extracellular matrix changes continue eventhough the disease is controlled, and elevated oxidative stress is involved in the increased prolidase activity in acromegaly patients.

Subcutaneous Adipose Tissue Type II Deiodinase Gene Expression Reduced in Obese Individuals with Metabolic Syndrome.

The present study aimed to evaluate the role of subcutaneous adipose tissue (SAT) type II deiodinase enzyme gene (DIO2) expression in developing metabolic syndrome (MetS). A total of 51 obese patients with MetS and without MetS and 13 healthy subjects enrolled in the study. Body mass index (BMI), waist circumference (WC), waist-to-hip circumference ratio (WHR), hip circumference, and systolic (SBP) and diastolic blood pressures (DBP) of all subjects were recorded. Fasting plasma glucose (FPG), fasting plasma insulin, high density lipoprotein- cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) and triglyceride (TG) of all subjects were analyzed. Expression of the DIO2 gene in adipose tissue was determined by reverse transcription polymerase chain reaction (qRT-PCR). BMI, WC and WHR were not significantly difference between obese with and without MetS. SBP, DBP, FPG and TG were significantly higher in obese with MetS group than obese without MetS group. While the free triiodothyronine (T3) level was in the normal range in all group, it was significantly lower in the obese with MetS than both obese without MetS and control group. DIO2 expression was significantly lower in the obese with MetS group compared to the control. In correlation analysis, DIO2 expression was negatively correlated with DBP, TG and homeostasis model assessment of insulin resistance (HOMA-IR) levels and positively correlated with free T3. In conclusion, the reduction of SAT DIO2 expression is negatively correlated with DBP and TG levels that are associated with the MetS. This might have an effect on developing MetS. We believe that DIO2 gene may be an important molecular target for future studies in developing targeted treatment options for obese people with MetS.

Serum prolidase levels in Graves' disease without ophthalmopathy and its association with oxidative status.

OBJECTIVE: The aim of this study was to evaluate serum prolidase levels and its association with oxidative stress in autoimmune thyroid disease (AITD). MATERIALS AND METHODS: 25 with Hashimoto thyroiditis (HT) and 25 patients Graves' disease (GD), and 27 healthy controls were enrolled in the study. The patients with signs of Graves' ophthalmopathy were excluded from the study. Serum samples were obtained in euthyroid period at the third month of treatment. Serum prolidase, total antioxidant status (TAS), total oxidative stress (TOS), and total free sulfhydryl (-SH) levels were measured. RESULTS: Serum prolidase levels were significantly higher in the patients with GD compared to the HT and the healthy control group. Oxidative stress index (OSI) and TOS levels of the patients with both GD and HT were significantly higher compared to those of the control group (p < 0.001, for each), while -SH levels were significantly lower (p < 0.001, for each). There was no significant difference between the patients with HT and healthy control group in terms of prolidase levels (p = 0.580). Prolidase levels were positively correlated with TOS and OSI and negatively correlated with -SH (r = 0.565, p = 0.003; r = 0.604, p = 0.001; r = -0.532, p = 0.006). CONCLUSION: Serum prolidase activity is increased in GD patients without signs of ophthalmopathy, and showed a positive correlation with oxidative stress parameters.

Serum calprotectin: a new potential biomarker for thyroid papillary carcinoma.

The aim of this study was to evaluate serum calprotectin levels and oxidative stress status in patients with papillary thyroid carcinoma (PTC) and the changes in their levels after total thyroidectomy. The study involved 30 patients with PTC and 30 healthy controls. Blood samples were obtained from the PTC patients before and 1 month after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analysed for calprotectin, total antioxidant status (TAS), total oxidant status (TOS) and lipid hydroperokside (LOOH). The preoperative calprotectin, TOS, OSI and LOOH levels of the patients with PTC were significantly higher compared to those of the control group (p < 0.001, for each). The levels of calprotectin decreased significantly in patients with PTC after the operation (p < 0.001), while TAS, TOS and OSI levels remained unchanged (p = 0.313, p = 0.085 and p = 0.163, respectively). Preoperative serum calprotectin levels were positively correlated with TOS, OSI and LOOH levels and negatively correlated with TAS levels in patients with PTC. In conclusion, serum calprotectin levels is increased in patients with PTC, and calprotectin is positively correlated with TOS and LOOH. Serum calprotectin levels is significantly decreased after total thyroidectomy.

Relationship between the level of hippocampal leptin receptor gene expression and learning performance in diabetic rats.

Diabetes mellitus may be associated with impaired cognitive function. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. Leptin that is a peptide hormone, acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor mediated transmission. The aim of the present study is to investigate possible relationship between the hippocampal leptin receptor gene expression and learning performance in streptozotocin (STZ) induced diabetic rats. In this study was conducted on a total of 40 Winstar albino female rats, including a control group consisting of 20 rats and experimental group comprising of 20 rats in which diabetes was induced by means of STZ administration. Leptin receptor gene expression was detected in hippocampal samples by using real time-PCR. According to the evaluation, the learning performance of rats with induced diabetes was found to be same throughout the first 3 days after STZ in comparison to the control group rats. End of the 45 days the learning performance of the control group was found to be better than the diabetic group (p<0.05). Hipocampal leptin receptor expression was found lower in diabetic group than the control group (p<0.05). The results provide evidence that leptin receptor gene may related to learning performance in diabetic rats. Further, detailed studies are needed to address the exact role of leptin and related molecules in learning performance.

Hormonal synchronization of lipopolysaccharide-induced hypothermic response in rats.

BACKGROUND: Recent experimental evidence suggests that lipopolysaccharide (LPS)-induced hypothermia is an adaptive thermoregulatory strategy against immunological challenge in rats. We hypothesized that the hormones which are predominantly responsible for energy homeostasis may have efferent signaling roles for development of the hypothermia. AIM: The aim of the study was to evaluate the changes of hypothalamic-pituitary-thyroid (HPT) and hypothalamic- pituitary-adrenal (HPA) axis hormones, leptin and erythropoietin at various phases of LPS-induced hypothermia such as the initial phase, nadir and the end of the response in blood sampled rats. MATERIAL AND METHODS: Body temperature of adult male albino Wistar rats was recorded by biotelemetry. E. coli O111:B4 LPS (250 µg/kg, ip) was injected alone or with SC-560, a cyclooxygenase-1 selective inhibitor (1 mg/kg, sc). RESULTS: Serum FT4 levels elevated at the initial phase, but FT3 levels decreased at nadir and remained low at the end of the response. Meanwhile, no change was observed in TSH levels. Serum adrenocorticotropic hormone (ACTH) levels reduced at the initial phase and serum corticosterone levels decreased at nadir without any change in serum corticotropin-releasing hormone (CRH) levels throughout the hypothermia. Serum leptin levels increased only at the end of the response. No change was observed in the levels of serum erythropoietin. SC-560 treatment abolished both LPS-induced hypothermia and respective hormonal changes. CONCLUSION: Data suggest that HPT axis hormones may contribute to development of LPS-induced hypothermia in rats. Data also support the view that leptin may have a role for the recovery of hypothermic response.

Sunitinib-induced autoimmune thyroiditis in a patient with metastatic renal cell carcinoma: a case report.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor that was newly approved by the FDA for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. Although generally well tolerated, common side effects of sunitinib have been reported, with an important and well-recognized example being hypothyroidism. Although the exact mechanism of sunitinib-induced hypothyroidism is unclear, some authors have suggested sunitinib might induce hypothyroidism by the blockade of iodine uptake, destructive thyroiditis and inhibition of peroxidase activity. In these studies autoimmune-mediated hypothyroidism could not be demonstrated as an etiological factor. We herein report the case of a 71-year-old woman diagnosed as metastatic renal cell carcinoma with severe autoimmune hypothyroidism associated with sunitinib after 10 months of treatment. To the best of our knowledge, this is the first report that shows sunitinib may induce autoimmune thyroiditis. Further clinical and experimental studies with larger patient groups are required to verify the findings of the present study. Routine monitoring of thyroid autoantibodies including antithyroglobulin and antithyroid peroxidase antibodies and thyroid ultrasonography are recommended during the treatment of sunitinib-induced hypothyroidism.

Clinical characteristics of patients with diabetic polyneuropathy: the role of clinical and electromyographic evaluation and the effect of the various types on the quality of life.

OBJECTIVE: This study was performed to identify the relationship between the quality of life and polyneuropathy which is one of the complications of diabetes. METHODS: Total 111 patients with diabetes mellitus were taken into the study as type 1 and type 2. Patients were accepted having polyneuropathy according to their electroneuromyography (ENMG) results. To evaluate the quality of life in the patients Short Form 36 (SF-36) and World Health Organization Quality of Life Questionnaire abbreviated version (WHOQOL-BREF) were used. RESULTS: Clinical polyneuropathy was found in 46% of the patients, while polineuropathy was found in 63% of the patients with evaluation ENMG. The patients with polyneuropathy had poor quality of life according to SF-36 and WHOQOL-BREF (p < 0.001). The mean quality of life scores of patients who had sensoriomotor and mix polyneuropathy, were lower than sensory type and axonal polyneuropathy. CONCLUSION: Diabetic polyneuropathy influences the quality of life in a negative way. The quality of life scores of patients who had polyneuropathy continuing with mixed pathogenesis and sensoriomotor type, become worse for this reason, even if the patients do not have any clinical polyneuropathy, this being evaluated with ENMG.

Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves' ophthalmopathy.

A prospective, randomised and single blind clinical trial was designed to compare intravenous methylprednisolone pulse (IVGC) with oral methylprednisolone (OGC) monotherapy in terms of effectiveness and tolerability in Graves' ophthalmopathy (GO). Fifty-two consecutive patients with untreated, moderately severe and active GO were randomly treated with either IVGC or OGC therapy for 12 weeks. IVGC therapy achieved a more rapid and significant improvement than OGC therapy according to clinical activity score (p < 0.01), proptosis (p < 0.038), lid width (p < 0.0001), extraocular muscle changes (p < 0.02), optic neuropathy. (p < 0.001), intraocular pressure (p < 0.04), visual acuity (p < 0.03), quality of life (p < 0.0001) and treatment response (p < 0.001). Diplopia was significantly improved in two groups but there was no difference between them (p < 0.6). Heavy smokers indicated alteration of ophthalmic signs with increased thyroid stimulating hormone (TSH)-receptor antibody during the therapy. In conclusion, IVGC therapy was more effective and better tolerated than OGC therapy in the management of GO.

Relationship between electroneurographic changes and serum ubiquitin levels in patients with type 2 diabetes.

OBJECTIVE: The aim of the present study was to investigate any relationship between serum ubiquitin levels and electroneurographic changes in peripheral nerves for patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study involved 34 patients (19 men, 15 women; mean age 46 +/- 13 years) with type 2 diabetes. Serum ubiquitin values were measured by sandwich enzyme-linked immunosorbent assay Measurement of nerve conduction velocity (NCV) was performed on three motor (median, tibial, and peroneal) and three sensory (median, ulnar, and sural) nerves. The value of motor compound muscle action potential (CMAP) was obtained from the sum of median, tibial, and peroneal motor nerve amplitudes, and sensory compound nerve action potential (CNAP) was computed as the sum of median and ulnar sensory nerve amplitudes. RESULTS: Patients with diabetes were divided into three groups: group 1 (n = 8) had normal electroneurography results, group 2 (n = 8) had slowed NCV, and group 3 (n = 18) had low values of motor CMAP and/or sensory CNAP as well as slowed NCV. Mean ubiquitin level in group 3 (20.4 +/- 2.9 ng/dl) was significantly higher than that in group 1 (11.2 +/- 1.1 ng/dl, t = 11.5, P < 0.0001) and group 2 (13.2 +/- 2.7 ng/dl, t = 5.9, P < 0.0001). Serum ubiquitin levels were inversely correlated with motor CMAP (r = -0.68) and sensory CNAP (r = -0.61) values. CONCLUSIONS: The results of this study indicate that there could be a relationship between the diminished amplitudes of axons of the peripheral nerve and the increase in serum ubiquitin levels in patients with type 2 diabetes. Further studies are required to confirm this relationship.