The effects of hypothyroidism and replacement therapy on cholesteryl ester transfer.

Abstract

To characterize further the impact of thyroid dysfunction on the transport of cholesterol in plasma, we studied plasma lipids and cholesteryl ester transfer (CET) in 10 hypothyroid women before and 3 months after thyroid replacement therapy. CET, estimated as the net mass transfer of CE from HDL to the apolipoprotein B-containing lipoproteins (very low density and low density lipoproteins) was significantly decreased at 4 h (P < 0.05) and 6 h (P < 0.001) when the patients were hypothyroid (T4, 2.01 +/- 1.4; TSH, 55.5 +/- 39.9 microIU/mL) and increased to normal levels after hormone replacement and restoration of eumetabolism. Plasma lipid levels in the hypothyroid state closely resembled those in a female reference group, although total plasma cholesterol fell significantly [pretreatment, 218 +/- 36 vs. posttreatment, 192 +/- 49 (P < 0.025); control, 218 +/- 28 mg/dL (mean +/- SD)] after treatment. Concentrations of cholesteryl ester transfer protein (CETP) were unchanged (pretreatment, 2.35 +/- 0.83 vs. posttreatment, 2.30 +/- 1.19 mg/dL). The results of recombination studies using different lipoprotein fractions suggest that decreases in CET during hypothyroidism may be secondary to acceptor lipoprotein (low density and very low density lipoprotein) changes in the hypothyroid state and not to changes in the concentration of CETP itself.

Low cholesteryl ester transfer protein (CETP) concentration but normal CETP activity in serum from patients with short‐term hypothyroidism Lack of relationship to lipoprotein abnormalities

“…Furthermore, CETP mass levels were normalized in the present study after 2 months of L-T 4 administration. These observations are in contrast with the previous data of Ritter and colleagues (Ritter et al, 1996) who did not report any significant alteration of CETP mass levels, either when hypothyroid patients were compared to control subjects, or when hypothyroid patients were studied before and during L-T 4 treatment. The apparent discrepancy may be due, at least in part to differences in the number of study subjects [n = 10 (Ritter et al, 1996) vs. n = 66 patients in the present study].…”

“…(Chait et al, 1979;Thompson et al, 1981;Staels et al, 1990), and low activities of LCAT, HL and LPL (Lithell et al, 1981;Lam et al, 1986;Kussi et al, 1988;Packard et al, 1993;Pazos et al, 1995). Although a few recent studies suggest that alterations of CETP activity may also contribute to lipoprotein abnormalities of hypothyroidism (Dullaart et al, 1990;Ritter et al, 1996;Tan et al, 1998a;Asami et al, 2000), no definitive conclusions can be drawn, this being in particular due to the paucity of available information, as well as to the heterogeneity and small size of studied populations (Dullaart et al, 1990;Ritter et al, 1996;Tan et al, 1998a;Asami et al, 2000). The aim of the present study was to address in an extensive way the effects of hypothyroidism and of L-T 4 therapy on the concentration and activity of serum CETP, as well as on the lipoprotein structure and composition in a large population of hypothyroid patients that were compared to age-and sex-matched control subjects.…”

“…In addition, the expression of several plasma factors that are known to independently affect the plasma lipoprotein profile, was shown to be related to the thyroid state. Although lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin-cholesterol acyltransferase (LCAT) activities are significantly decreased in hypothyroid adults (Lithell et al ., 1981;Lam et al ., 1986;Kussi et al ., 1988;Packard et al ., 1993;Pazos et al ., 1995), the relative contribution of putative alterations of cholesteryl ester transfer protein (CETP) to individual lipoprotein abnormalities is uncertain (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a;Asami et al ., 2000). Indeed, only a few human studies of CETP activity have been conducted in small populations with thyroid disorders, leading to heterogeneous and fragmentary conclusions (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a;Asami et al ., 2000).…”

“…Although lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin-cholesterol acyltransferase (LCAT) activities are significantly decreased in hypothyroid adults (Lithell et al ., 1981;Lam et al ., 1986;Kussi et al ., 1988;Packard et al ., 1993;Pazos et al ., 1995), the relative contribution of putative alterations of cholesteryl ester transfer protein (CETP) to individual lipoprotein abnormalities is uncertain (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a;Asami et al ., 2000). Indeed, only a few human studies of CETP activity have been conducted in small populations with thyroid disorders, leading to heterogeneous and fragmentary conclusions (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a;Asami et al ., 2000). Although three earlier studies indicated decreased cholesteryl ester transfer rates in hypothyroidism (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a), no difference was reported between hypothyroid and euthyroid newborns (Asami et al ., 2000), and no definitive conclusion could be drawn in adults in terms of abnormally low CETP levels vs. impaired CETP-lipoprotein interactions (Dullaart et al ., 1990;Ritter et al ., 1996).…”

“…Indeed, only a few human studies of CETP activity have been conducted in small populations with thyroid disorders, leading to heterogeneous and fragmentary conclusions (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a;Asami et al ., 2000). Although three earlier studies indicated decreased cholesteryl ester transfer rates in hypothyroidism (Dullaart et al ., 1990;Ritter et al ., 1996;Tan et al ., 1998a), no difference was reported between hypothyroid and euthyroid newborns (Asami et al ., 2000), and no definitive conclusion could be drawn in adults in terms of abnormally low CETP levels vs. impaired CETP-lipoprotein interactions (Dullaart et al ., 1990;Ritter et al ., 1996). The latter point deserves further attention in consideration of the key role of CETP in the determination of the structure and the lipid composition of serum lipoproteins.…”