Long-term thyroid replacement therapy and levels of lipoprotein(a) and other lipoproteins.

Abstract

There is a general interest to know whether lipoprotein(a) [Lp(a)] is under hormonal control. Hypothyroidism is a well known cause of secondary hyperlipidemia, which mainly affects low density lipoprotein (LDL) cholesterol levels, but the result on the effects of L-T4 replacement therapy on the Lp(a) concentration is controversial. We studied 12 severely hypothyroid, hypercholesterolemic patients under basal conditions and during L-T4 treatment. We found a rapid decrease in both LDL cholesterol (5.71 +/- 0.62 vs. 4.37 +/- 0.44 mmol/L basally and after 1 month of thyroid replacement, respectively) and apolipoprotein-B (Apo-B) levels (1.89 +/- 0.02 vs. 1.52 +/- 0.17 g/L, respectively); these changes persisted for up 1 yr of analytical euthyroidism and paralleled the improvement in the thyroid status of the patients. In contrast, the plasma Lp(a) concentration did not change at any time (496 +/- 123, 464 +/- 128, and 441 +/- 110 mg/L under basal conditions and after 1 and 14-15 months of thyroid replacement, respectively), and the small fluctuations observed in some patients did not correlate with those in LDL cholesterol or Apo-B, and were not associated with any particular Apo(a) phenotype. In relation to HDL fractions, high density lipoprotein3 (HDL3) remained stable, but HDL2 cholesterol and phospholipid levels decreased during treatment, changes that were the inverse of those in postheparin plasma hepatic lipase activity. Patients in the present study were normotriglyceridemic, except one who was hypertriglyceridemic at diagnosis, but even in this patient, triglyceride levels were unaffected by T4 substitution therapy, as was postheparin plasma lipoprotein lipase activity. The changes observed in LDL, HDL2, and hepatic lipase activity delineate the lipoprotein-related response to T4 replacement therapy, whereas potential individual fluctuations in Lp(a) levels are probably more dependent on other factors, such as the production rate, which are not affected by thyroid hormones.

Subclinical Hypothyroidism in a Biethnic, Urban Community

“…Not only does there seem to be an increase in serum total and LDL cholesterol and triglyceride concentrations, and a decrease in HDL cholesterol concentration, but an increase in lipoprotein (a), which is a strong, independent risk factor for coronary heart disease, has also been reported, 30 as seen in Group 3 in our study. Whereas LDL cholesterol decreases with thyroid replacement therapy, lipoprotein (a) concentrations apparently do not 30 . Of interest was the observation that the subjects with the highest TSH values (Group 3) had an increased prevalence of CHD, which might be explained, in part, by the higher mean serum LDL cholesterol concentrations.…”

“…Evidence is presented in our study that participants with elevated TSH values have affective (mood) and cognitive scores similar to individuals with normal TSH levels. Lipid levels, other than lipoprotein (a), were not different in the population under study, and the evidence that lipoprotein (a), a strong CHD risk factor, responds to thyroid replacement therapy is limited 30 …”

“…Because there is a strong association between the appearance of overt hypothyroidism and the development of hyperlipidemia and increased risk of ischemic heart disease, the effects of subclinical hypothyroidism and its treatment on circulating lipid concentrations have been examined 28 , 29 . Not only does there seem to be an increase in serum total and LDL cholesterol and triglyceride concentrations, and a decrease in HDL cholesterol concentration, but an increase in lipoprotein (a), which is a strong, independent risk factor for coronary heart disease, has also been reported, 30 as seen in Group 3 in our study. Whereas LDL cholesterol decreases with thyroid replacement therapy, lipoprotein (a) concentrations apparently do not 30 .…”

Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI

“…The lipid abnormalities may be, at least in part, mediated by the insulin resistance induced by GH excess [52]. TGs have been found to increase coagulation factor activity and to decrease fibrinolysis [53].…”

Effects of normalization of GH hypersecretion on lipoprotein(a) and other lipoprotein serum levels in acromegaly

“…Pharmacologically, lipoprotein(a) plasma levels can be decreased by administration of nicotinic acid or anabolic androgens ( Teruel et al ., 1997 ). Several hormones have been reported to affect lipoprotein(a) levels such as oestrogens ( Soma et al ., 1993 ; Sacks et al ., 1994 ) and GH ( Laron et al ., 1997 ; Olivecrona et al ., 1993 ; Olivecrona et al ., 1995 ), and there is some controversy regarding the effects on lipoprotein(a) concentrations of thyroid hormone replacement therapy in hypothyroid patients ( Dullaart et al ., 1995 ; Pazos et al ., 1995 ). During the past 10 years most researchers have shown an increase in lipoprotein(a) levels after GH treatment in normal adult subjects ( Olivecrona et al ., 1993 ), GH deficient (GHD) adults ( Eden et al ., 1993 ; Olivecrona et al ., 1995 ; Oscarsson et al ., 1996 ; Nolte et al ., 1997 ) and normal short children ( Hershkovitz et al ., 1996 ).…”