Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Further studies on delineating thyroid-stimulating hormone (TSH) reference range.

The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.

Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers.

The purpose of this study was to evaluate the safety and pharmacokinetics of nemifitide, a synthetic antidepressant pentapeptide, following its subcutaneous (s.c.) administration by standard needle injection or by a needle-free (Biojecttrade mark) injection and to compare these two routes of administration for systemic exposure. This small-scale, randomized, single-dose, parallel design, open-label pilot study consisted of three treatment groups of four subjects each dosed as follows: group 1: 40 mg of nemifitide administered by standard needle/syringe and groups 2 and 3: 40 and 80 mg nemifitide, respectively, administered by using a needle-free (Bioject injection delivery system. Plasma concentrations of nemifitide were determined by LC/MS/MS in blood samples collected at 10 min and 0.5, 1, 2, 4, 6 and 24 h after dosing. PK parameters, including observed C(max), T(max) and AUC(0-24), were calculated and statistical analysis of the data was conducted. Safety assessments (dosing site evaluations) were done at 0.5, 1, 5 and 24 h after dosing. Vital signs and clinical laboratory tests were taken on day 1 prior to dosing and at 24 h post-dose. Adverse experiences in all subjects were observed only as drug-related local reactions at the injection sites. All were considered mild in severity and transient (resolved by 24 h after dosing). T(max) was observed at 10 min after dose and was the same in all subjects. In the three dosing groups, 1 (40 mg), 2 (40 mg) and 3 (80 mg), observed C(max) values were 226, 245 and 440 ng/ml, respectively, and AUC(0-24) values were 108, 106 and 205 ng.h/ml, respectively. Ratios of AUC(0-24) and observed C(max) for nemifitide in plasma between groups 1 and 2 were within the 80%-125% range, indicating that the two modes of drug administration resulted in similar systemic exposure to nemifitide. Pharmacokinetic parameters (AUC(0-24) and C(max)) indicate dose-proportionality between the doses of 40 and 80 mg.

[Case report of corpus callosum lipoma diagnosed with computer tomography]. / Slucaj lipoma corpus callosum-a dijagnostikovanog kompjuterizovanom tomografijom.

The case of corpus callosum lipoma that was accidentally discovered during the routine brain examination by computed tomography had been described. The CT features of corpus callosum lipoma were described as well as differential-diagnostic differences with epidermoid cyst agenesia of corpus callosum and cyst of the pellucid septum (cavum vergae).