1.
Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status.
Blehaut, H, Mircher, C, Ravel, A, Conte, M, de Portzamparc, V, Poret, G, de Kermadec, FH, Rethore, MO, Sturtz, FG
PloS one. 2010;(1):e8394
Abstract
BACKGROUND Seven genes involved in folate metabolism are located on chromosome 21. Previous studies have shown that folate deficiency may contribute to mental retardation in Down's syndrome (DS). METHODOLOGY We investigated the effect of oral folate supplementation (daily dose of 1.0+/-0.3 mg/kg) on cognitive functions in DS children, aged from 3 to 30 months. They received 1 mg/kg leucovorin or placebo daily, for 12 months, in a single-centre, randomised, double-blind study. Folinic acid (leucovorin, LV) was preferred to folic acid as its bioavailability is higher. The developmental age (DA) of the patients was assessed on the Brunet-Lezine scale, from baseline to the end of treatment. RESULTS The intent-to-treat analysis (113 patients) did not show a positive effect of leucovorin treatment. However, it identified important factors influencing treatment effect, such as age, sex, and concomitant treatments, including thyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period. This analysis of 87 patients (43 LV-treated vs. 44 patients on placebo) revealed a positive effect of leucovorin on developmental age (DA). DA was 53.1% the normal value with leucovorin and only 44.1% with placebo (p<0.05). This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment (59.5% vs. 41.8%, p<0.05). No adverse event related to leucovorin was observed. CONCLUSION These results suggest that leucovorin improves the psychomotor development of children with Down's syndrome, at least in some subgroups of the DS population, particularly those on thyroxin treatment. TRIAL REGISTRATION ClinicalTrials.gov, NCT00294593.
2.
Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area.
Ayturk, S, Gursoy, A, Kut, A, Anil, C, Nar, A, Tutuncu, NB
European journal of endocrinology. 2009;(4):599-605
Abstract
OBJECTIVE Metabolic syndrome (MetS) is a cluster of metabolic abnormalities with insulin resistance (IR) as a major component. It has been recently questioned whether MetS and its related components are associated with functional and morphological alterations of the thyroid gland. The aim of our study is to examine thyroid volume and nodule prevalence in a case-control study of patients with MetS in a mild-to-moderate iodine-deficient area. DESIGN Two hundred and seventy-eight patients with MetS were randomly matched for age, gender, and smoking habits with 261 subjects without MetS. Serum TSH, free tri-iodothyronine and thyroxine, and the level of IR, which was estimated by the homeostasis model assessment for IR, as well as other MetS parameters were evaluated. Thyroid ultrasonography was performed in all subjects. All subjects with thyroid nodules >1 cm were offered to undergo thyroid fine needle aspiration biopsy. RESULTS TSH was significantly positively correlated with the presence of MetS diagnosis. There was no association between free thyroid hormone levels and MetS and its related components. Mean thyroid volume was significantly higher in patients with MetS than in controls (17.5 + or - 5.5 vs 12.2 + or - 4.2 ml, P<0.0001). Also the percentage of patients with thyroid nodules was significantly higher in patients with MetS (50.4 vs 14.6%, P<0.0001). Subjects were also divided into two groups according to the presence of IR. The group of subjects with IR had increased thyroid volume and nodule formation. The odds ratio for the development of thyroid nodule in the presence of IR was 3.2. TSH as well as all MetS components were found to be independent predictors for thyroid volume increase. IR but not TSH was found to be correlated with thyroid nodule formation. Thyroid cancer was diagnosed in 3 out of 38 patients with MetS who agreed to have a biopsy (7.9%). None of the subjects in the control group was diagnosed to have thyroid cancer. CONCLUSIONS The results suggest that patients with MetS have significantly increased thyroid volume and nodule prevalence. Multivariate regression analysis model demonstrated that the presence of IR contributed substantially to this increased risk. Our data provide the first evidence that IR is an independent risk factor for nodule formation in an iodine-deficient environment.