Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus.

The relationship between late-onset gestational diabetes mellitus [GDM] and oxidative stress is not well known, and the importance of the oxidant/antioxidant equilibrium in the clinical evolution and its complications require elucidation. The aim of the study was to evaluate the relationships between maternal levels of markers of oxidative stress in women with late-onset GDM that, potentially, may have considerable clinical implications in the pathogenesis and/or the evolution of GDM. Pregnant women (n = 78; 53 with GDM, 25 controls), between the 24th and 29th week of gestation, were enrolled. Both groups were analysed for demographic data, perinatal and obstetrics outcomes together with the levels of the marker's oxidative stress and antioxidant status. Control versus patient results in the univariate analysis were the following: pre-gestational body mass index [BMI] 23.31 ± 4.2 vs. 27.13 ± 4.6 kg/m(2) (P = 0.001); weeks at delivery 39.2 ± 3.05 vs. 38.9 ± 1.8 (P = 0.09); Caesarean delivery 12.5 vs. 43% (P = 0.004); macrosomia 4 vs. 9.4% (P = 0.6); lipoperoxides [LPO] 2.06 ± 1.00 vs. 3.14 ± 1.55 µmol/mg (P = 0.001); catalase 3.23 ± 1.41 vs. 2.52 ± 1.3 nmol/min/ml (P = 0.03); superoxide dismutase [SOD] 0.11 ± 0.04 vs. 0.08 ± 0.01 U/ml (P = 0.0003); glutathione peroxidase [GPX] 0.03 ± 0.006 vs. 0.025 ± 0.006 nmol/min/ml (P = 0.01); glutathione reductase [GSH] 0.004 ± 0.002 vs. 0.004 ± 0.004 nmol/min/ml (P = 0.9)]; and glutathione transferase [GST] 0.0025 ± 0.0012 vs. 0.0027 ± 0.00017 nmol/min/ml (P = 0.7). Multivariate analysis showed catalase might have a protective effect against GDM development and LPO seems to be a risk factor for the disease. These data suggest an increase in oxidative stress and a decrease in antioxidative defence in women with late-onset GDM and, as such, may have considerable clinical implications in the pathogenesis and/or the course of the pregnancy in these patients.

Concomitant agranulocytosis and hepatotoxicity after treatment with carbimazole.

OBJECTIVE: To describe a case of agranulocytosis and severe hepatotoxicity associated with carbimazole treatment. CASE SUMMARY: A 37-year-old woman was diagnosed with severe hyperthyroidism resulting from Graves' disease. Treatment with carbimazole 30 mg/day was initiated. Within 15 days following the start of therapy, both minor (eg, pruritus, rash, urticaria, fever, arthralgias) and potentially life-threatening (eg, agranulocytosis, severe mixed hepatotoxicity with severe cholestatic jaundice) adverse effects developed. The patient's symptoms and laboratory abnormalities resolved following withdrawal of carbimazole. Treatment with other antithyroid drugs was not attempted, and (131)I ablation of the thyroid was successfully performed. Thyroid function was maintained with standard follow-up care. Agranulocytosis, identified following bone marrow biopsy, was treated with granulocyte colony-stimulating factor. DISCUSSION: Agranulocytosis and hepatotoxicity are rare adverse effects associated with carbimazole treatment and are usually dose- and age-related. The likelihood that carbimazole induced these undesirable events in our patient is rated as probable based on the Naranjo probability scale. We believe this case to be the first to describe minor and major adverse effects related to carbimazole therapy in a patient with Graves' disease. CONCLUSIONS: Major adverse effects associated with carbimazole are infrequent. However, clinicians need to be aware that the effects described here, including severe liver failure and bone marrow toxicity, may occur in patients receiving this drug.