Thyroid function influences serum apolipoprotein B-48 levels in patients with thyroid disease.

AIM: Apolipoprotein B-48 (apoB-48) is a major apolipoprotein of intestine-derived chylomicrons (CM) and CM remnants (CMR). Clinically overt hypothyroidism (OH) has been associated with premature and accelerated coronary atherosclerosis. To clarify the clinical significance of apoB-48 measurement in patients with thyroid disease, we investigated the correlations between the serum apoB-48 level and thyroid hormones. METHODS: From outpatients of Osaka University Hospital, patients with OH, subjects with subclinical hypothyroidism (SH) and subjects with normal thyroid function were collected and analyzed by measuring serum TSH, FT4 and FT3 levels. Serum apoB-48 levels were measured by a chemiluminescence enzyme immunoassay and the correlations with thyroid hormone levels or lipid profiles were assessed. These levels were compared among subjects with OH, SH and healthy controls. RESULTS: Serum apoB-48 level was correlated with TSH, total cholesterol (TC) and triglycerides (TG), but negatively with FT4 and FT3 level. LDL-C and HDL-C levels were not correlated with serum apoB-48 levels. Serum apoB-48 in patients with OH (7.4 ± 5.9 µg/mL) was significantly higher than in those with hyperthyroidism (5.1 ± 3.5 µg/mL; p<0.01) and normal subjects (4.7 ± 3.7 µg/mL; p<0.01), but decreased after levo-thyroxine replacement. ApoB-48, TG and TSH were significantly higher in SH subjects than normal subjects, suggesting that serum apoB-48 level depends on the thyroid function status, similar to TC, LDL-C and TG. CONCLUSION: Increased serum apoB-48 concentrations and CMR may contribute to the increased risk of atherosclerosis and premature coronary artery disease in the hypothyroid state.

Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and its clinical applications for evaluation of impaired chylomicron remnant metabolism.

BACKGROUND: Apolipoprotein B-48 (apoB-48) is a constituent of chylomicron remnants synthesized in the small intestines. The serum concentration of apoB-48 at fasting has been reported to be a marker of postprandial hyperlipidemia, a presumed risk factor for atherosclerosis. METHODS: We evaluated the basal performance of a recently developed chemiluminescent enzyme immunoassay (CLEIA). We also examined the correlations between serum apoB-48 concentrations and other lipid concentrations or life style patterns, including smoking and drinking. We analyzed the data of 273 clinical samples by multiple regression analysis to examine the influence of other serum lipid values, age, sex, smoking, drinking status and BMI on serum apoB-48 values. RESULTS: Within-run and between-run precision was obtained with 1.7-2.7% and 1.2-7.3%, respectively. The correlativity of enzyme-linked immunosorbent assay was correlation coefficient r=0.953, and regression y=1.02×-1.59. Serum apoB-48 concentrations were higher in males than in females, and were correlated with the status of smoking as well as with remnant-like particle-cholesterol (RLP-C) concentrations. Patients with the metabolic syndrome showed higher values of serum apoB-48 compared with control subjects. CONCLUSION: Serum apoB-48 measurement by CLEIA was satisfactory for clinical use to assess abnormalities in the chylomicron remnant metabolism.

A solution for distinguishing Le(a-b-) sera in CA19-9 assays using SphereLight 180 and Architect i2000 assays.

BACKGROUND: Measurement of carbohydrate antigen (CA) 19-9 is not applicable in patients with Lewis (Le) blood type, Le(a-b-). It is important to distinguish cases with Le(a-b-) before CA19-9 measurement. Therefore, we prepared a cut-off solution that gives a clear index to distinguish Le(a-b-) sera. METHOD: The frequencies of Le blood types and the distribution of the CA19-9 values in each Le blood type were examined in 188 healthy subjects. The CA19-9 values for all Le(a-b-) sera and for a portion of Le(a-b+) sera exist below the limit of quantitation as measured by the SphereLight 180 kit. The cut-off solution, which gives a clear cut-off index (COI), was prepared to differentiate Le(a-b-) from Le(a-b+), and was evaluated using the SphereLight 180, Architect i2000, UniCel DxI 800, Elecsys 2010, and Lumipuls ƒ kits. RESULTS: The COI was calculated as the mean +3 SD of the CA19-9 values of a cut-off solution that is adjusted to the limit of detection. Both the sensitivities and specificities of the COIs were 100% using the SphereLight 180 kit and 100% and 91.7%, respectively, using the Architect i2000 kit, but these values were not satisfactory using the other CA19-9 assay kits. CONCLUSION: The COIs, determined by the cut-off solution, correctly identified all Le(a-b-) sera as Le(a-b-) and differentiated Le(a-b-) sera from other types of sera in CA19-9 assays using only the SphereLight 180 and Architect i2000 kits.

[Clinical significance of apolipoprotein B-48 (apoB-48) in patients with thyroid disease].

Apolipoprotein B-48 (apoB-48) is a constituent of chylomicrons and chylomicron remnants, and its serum concentration is thought to be one of the risk factors for atherosclerosis. Clinically overt hypothyroidism (OH) has been associated with accelerated and premature coronary atherosclerosis. In the current study, we measured the serum apoB-48 concentration in patients with hyperthyroidism and hypothyroidism. We also evaluated the correlations between serum apoB-48 and thyroid hormones, from which a clinical significance of apoB-48 measurement in thyroid disease was deduced. Serum apoB-48 concentration was measured by chemiluminescence enzyme immunoassay (CLEIA) and it correlated with thyroid stimulating hormone (TSH), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglycerides(TG), but negatively correlated with free thyroxine (FT4) and free triiodothyronine (FT3). In a cross-sectional study, serum apoB-48 concentrations were significantly higher in OH subjects (8.4 +/- 5.4 microg/ml) compared to those in 70 hyperthyroid subjects (5.0 +/- 3.9 microg/ml) and 50 normal subjects (6.3 +/- 4.9 microg/ml). After L-T4 replacement, serum apoB-48 concentrations were decreased in OH patients. However, these changes were smaller compared to those of TSH, FT4 and FT3. Serum apoB-48 levels and thyroid hormones and lipid profiles were measured in 31 SH patients and 34 normal subjects. Significant difference was noted in serum apoB-48, TG and TSH between patients with SH and normal. In conclusion, serum apoB-48 concentration depends on thyroid status like TC, LDL-C and TG. Thyroid hormone replacement therapy may reduce serum apoB-48 concentrations in patients with OH. Therefore, increased serum apoB-48 concentrations may contribute to the increased risk of atherosclerosis and premature coronary artery disease in the hypothyroid state.