Traditional Chinese medicine in thyroid-associated orbitopathy.

PURPOSE: Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies. METHODS: The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database. RESULTS: Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis. CONCLUSIONS: Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.

Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Metabolic and psychosocial effects of minimal invasive gastric banding for morbid obesity.

Obesity is considered a primary risk factor for cardiovascular disease and related mortality. The current study aimed to investigate the efficacy of minimal invasive gastric banding (GB) surgery for reducing caloric intake in morbid obesity, and to analyze the effects of weight loss on body composition and metabolic and psychosocial outcomes. Twenty-six adult severely obese patients (mean body mass index [BMI], 48.1 kg/m(2); range, 42 to 56) underwent adjustable silicone laparoscopic GB. Nine additional obese patients who declined surgery were treated with metformin (2 g daily) and served as a small additional group (BMI, 50.5 kg/m(2); range, 41 to 68). Presurgery and 17 +/- 2.2 months postoperatively, body composition (fat mass [FM], lean body mass [LBM], body water) and serum parameters (lipids, glucose, thyrotropin-stimulating hormone [TSH]) were determined. Quality of life (QoL) was evaluated by a standardized self-rating questionnaire (Short Form-36 [SF-36]), and supplemented by measures of physical complaints and psychological distress. After GB, weight loss was 21 +/- 14.9 kg (14%, P <.001). It was associated with a decrease in FM by 14 +/- 8.6 kg (18%, P <.001), LBM by 4 +/- 2.7 kg (5%, P <.001), body water by 4 +/- 3.4 L (7%, P <.01), systolic blood pressure by 16 +/- 26.3 mm Hg (10%, P <.05), total cholesterol by 0.69 +/- 1.29 mmol/L (12%, P <.05), and low-density lipoprotein cholesterol (LDL-C) by 0.38 +/- 0.39 mmol/L (10%, P <.05). Highly significant interactions between surgery and time were noted for weight (P <.005), BMI (P <.005), and FM (P <.007, analysis of variance [ANOVA]). Preoperatively, 14 of 26 patients (54%) had high fasting blood sugar levels (type 2 diabetics) and 11 (42%) had impaired glucose tolerance, whereas postoperatively, for baseline glucose levels a trend to decrease was noted. Neither malabsorption nor anemia was observed. QoL improved after GB; in particular, physical functioning and well being increased (P <.01), and somatic complaints (eg, dyspnea and heart complaints, pain in legs and arms) markedly decreased (P =.008). In the metformin group, neither relevant weight loss nor a significant decrease of biochemical values was observed. Minimal invasive GB is a successful therapeutic tool for reducing FM in morbidly obese patients. Weight loss resulted in improved metabolic parameters, suggesting a lowered atherogenic risk.