The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.

Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group.  During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.

Effects of vitamin D supplements on frequency of CD4+ T-cell subsets in women with Hashimoto's thyroiditis: a double-blind placebo-controlled study.

BACKGROUND: Vitamin D is a modulator of immune functions. Investigations on the mechanisms of vitamin D action and pathogenesis of Hashimoto's thyroiditis (HT) have revealed that vitamin D can reduce damages to thyroid cells caused by autoreactive immune cells. METHODS: Totally, 48 female patients with HT disease were introduced to the study by endocrinologists. Patients were divided into two major groups of 24 individuals and treated weekly with 50,000 IU of cholecalciferol (vitamin D group) or placebo (placebo group) using oral administration for 3 months. Eventually, 17 of the 24 patients in each group finished the study. Before and after supplementation, frequencies of Th1, Th17, Th2 and Tr1 cells and mean fluorescent intensity (MFI) of the associated cytokines, including IFN-γ, IL-17, IL-4 and IL-10, were assessed using flow cytometry. Furthermore, gene expression of IL-10 was assessed using real-time PCR. RESULTS: Results of this study showed that cholecalciferol supplementation caused a significant decrease in Th17/Tr1 ratio. The proportion and MFI of Th1, Th2, Tr1 and Th17 cells included no significant changes in vitamin D group, compared to those in placebo group. Expression rate and MFI of IL-10 increased in both groups. This increase was higher in vitamin D group than placebo group with no significance. CONCLUSIONS: In this novel preliminary clinical trial study, supplementation with cholecalciferol in HT patients for 3 months changed the balance of CD4+ T-cell subsets to improve the disease control. However, further studies are necessary to investigate effects of vitamin D on immune functions in HT patients.

HbA1c negatively correlates with LCAT activity in type 2 diabetes.

AIMS: Abnormal high-density lipoproteins (HDL) metabolism is a major cardiovascular risk factor in type 2 diabetes mellitus (DM2). Lecithin:cholesterol acyltransferase (LCAT) increases HDL size by transferring 2-acyl groups from lecithin or phosphatidylethanolamine to unesterified cholesterol. The purpose of this study was to determine the independent correlates of LCAT activity in DM2 patients. METHODS: A total of 45 (male: 20) consecutive adult DM2 patients aging 50.0+/-7.0 years (range: 40-64 years) with a median diabetes duration of 4 years (range: 2-18) were studied. Exclusion criteria were: smoking, positive history of cardiovascular, thyroid, renal or liver disease, pregnancy, treatment with metformin, insulin, lipid lowering drugs, angiotensin-converting enzyme inhibitors, aspirin or antioxidant supplements. Univariate and multivariate analyses were performed. RESULTS: From a comprehensive list of variables studied, only HbA1c (rho=-0.951) and oxidized LDL (rho=-0.779) had statistically significant correlation with LCAT activity (p<0.001). These two variables were themselves strongly correlated to each other (rho=0.809, p<0.001). To eliminate potential confounding effects, we performed multivariate analysis, where HbA1c emerged as a strong independent predictor of LCAT activity (adjusted OR=-0.928, p<0.001). CONCLUSIONS: Glycemia-induced glycation of HDL decreases LCAT activity. The fact that HbA1c is an accurate measure of glycation and can therefore reflect glycated HDL levels explains the association found in the present study. In conclusion, HbA1c provides an easy-to-assess, accurate measure of LCAT activity in DM2.

Outbreak of exogenous Cushing's syndrome due to unlicensed medications.

OBJECTIVE: Despite the widespread medical use of glucocorticoids, reports of factitious administration of these hormones have been uncommon. We herein report an outbreak of Cushing's syndrome in Tehran among the addicts using Tamgesic (a brand of Buprenorphine) to help them through the narcotic withdrawal stage, without knowledge of the glucocorticoid content of the black-market drug. DESIGN AND MEASUREMENTS: Case histories of 19 patients with a final diagnosis of iatrogenic Cushing's syndrome were reviewed. Liquid chromatography/mass spectrometry (LC-Mass) method was used to evaluate glucocorticoid existence in the brand. High performance liquid chromatography was used to determine plasma dexamethasone level. RESULTS: No buprenorphine was present in the vials. Each Tamgesic vial contained 0.4 mg of Dexamethasone disodium phosphate; Heroin was also found in them. The duration of injection abuse and the total dexamethasone intake was 4.5 (1-18) months and 2.6 (0.8-8) mg/day, respectively. Median plasma dexamethasone concentration was 5.8 nmol/l, with a range of 5-8.7. Physical findings of the cases were not different from those of the classic endogenous Cushing's syndrome but their serum cortisol and urinary free cortisol were suppressed. Severe life-threatening complications were demonstrated in five cases. CONCLUSION: Surreptitious use of steroids resulting in Cushing's syndrome may be more common in opium addicts; a high degree of suspicion is needed to uncover this disorder. Whenever facing a cushingoid appearance in addicts, the possibility of using black market drugs with corticosteroid contents should be kept in mind.