Investigation of possible treatment-related changes in low density lipoprotein subfractions in hypothyroid patients receiving thyroxine replacement,by a newly developed 'short spin separation' ultracentrifugation technique

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Investigation of possible treatment-related changes in low density lipoprotein subfractions in hypothyroid patients receiving thyroxine replacement,by a newly developed 'short spin separation' ultracentrifugation technique

 

Author: Ma, Shuk-woon
Title: Investigation of possible treatment-related changes in low density lipoprotein subfractions in hypothyroid patients receiving thyroxine replacement,by a newly developed 'short spin separation' ultracentrifugation technique
Year: 1999
Subject: Low density lipoproteins
Hypothyroidism
Ultracentrifugation
Hong Kong Polytechnic University -- Dissertations
Department: Multi-disciplinary Studies
Dept. of Nursing and Health Sciences
Pages: xii, 129 leaves : ill. (some col.) ; 30 cm
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b1477325
URI: http://theses.lib.polyu.edu.hk/handle/200/3226
Abstract: Hypothyroidism is associated with hyperlipidaemia. It is a common consequence after radioactive iodine treatment for hyperthyroidism. Lipid changes in hypothyroidism involve elevation of total cholesterol and low density lipoprotein-cholesterol (LDL-C). This can constitute an increased risk of coronary heart disease (CHD). The distribution of low density lipoprotein (LDL) subfractions is also changed in hypothyroidism. The aims of the study are to establish a density gradient ultracentrifugation method for separation of LDL subfractions (LDL subfractionation) and to use the method to assess treatment-related changes in hypothyroid patients on thyroxine replacement. Preliminary results showed that substantial method development was needed, as no LDL subfractions were seen following the published protocol. A modified 'short spin separation' method (50 min, 285 000 g, 23 C) was developed, which minimised loss of density gradient and showed good recovery (mean = 99.98%, standard deviation (SD) = 4.18%, n = 60). This method was used to measure distribution of LDL subfractions in 30 subjects (13 males, 17 females) before and after 4 months of thyroxine replacement therapy. It was found that total cholesterol decreased significantly after treatment. The mean (SD) before and after treatment were 5.33 (0.84) mmol/L and 5.11 (0.73) mmol/L respectively (p < 0.05). The decrease in total cholesterol was owing to a decrease in the LDL-C fraction from 3.43 (0.88) mmol/L to 3.21 (0.83) mmol/L (p < 0.05). This decrease was quite small, averaging 0.22 mmol/L. However, from LDL subfractionation, it was found that the decrease in LDL-C was due to a significant decrease in the concentration of large, buoyant LDL-I from 1.48 (0.49) mmol/L to 1.31 (0.45) mmol/L (p < 0.005). Decreases in the concentration of intermediate, less dense LDL-II and small, dense LDL-III were smaller and did not reach statistical significance. Owing to the larger absolute decrease in amount of LDL-I, there was an apparent increase in the percentage of LDL-II and LDL-III. This caused a change in the LDL phenotype apparently, from A (a predominance of LDL-I) to I (a predominance of LDL-II) or B (a predominance of LDL-III) in some patients. It is suggested that the 'short spin separation' method developed in this study is an efficient and reliable method of LDL subfractionation. It is further suggested that the LDL phenotype A hypothyroid patients benefit more from thyroxine replacement therapy in terms of LDL subfractions: the concentration of all LDL subfractions were decreased. The changes found in LDL concentration and subfraction distribution indicate a decreased CHD risk. However, the larger decrease in LDL-I, which may have been related to improved clearance by LDL receptors, may lead to a misinterpretation of CHD risk based on the relative changes in LDL subfraction distribution. The LDL subfraction distribution is, therefore, best presented in terms of absolute rather than relative amounts. Further study is needed to completely validate the 'short spin separation' method and to examine the relationship between triglyceride and LDL subfraction distribution.

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