Serum concentrations of remnant-like particles in hypothyroid patients before and after thyroxine replacement
ABSTRACT Remnant-like particles (RLPs) reflect chylomicron remnants and very-low-density lipoprotein remnants, which are most likely to be atherogenic particles. To investigate the effect of thyroxine replacement on the metabolism of RLPs in hypothyroidism, we measured serum concentrations of RLPs during an oral fat-loading test in patients with hypothyroidism before and after thyroxine replacement.
Thirteen patients with hypothyroidism, having serum-free thyroxine (FT4) of 4.25 +/- 2.23 pmol/l (mean +/- SD) and TSH of 72.5 +/- 27.7 mU/l, participated in the study. Two-hundred grams of cream containing 32.9% of fat were given to each patient followed by blood draws every 2 h for 8 h. The patients became euthyroid after 3 months of T4 replacement, and the fat-loading tests were then repeated.
Fasting levels of serum total cholesterol and low-density lipoprotein cholesterol were remarkably decreased after T4 therapy (P < 0.0005). Serum high-density lipoprotein cholesterol and triglyceride were also decreased by T4 therapy, not so remarkably but significantly (P < 0.05). Activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) increased 52% and 85%, respectively, from the pretreatment values. Serum concentrations of remnant-like particle cholesterol (RLP-C) and remnant-like particle triglyceride (RLP-TG), measured by immunoseparation assays, significantly decreased from 0.14 +/- 0.03 to 0.09 +/- 0.03 mmol/l (P < 0.0005) and from 0.19 +/- 0.11-0.11 +/- 0.07 mmol/l (P < 0.01), respectively. In the fat-loading test, serum low-density lipoprotein cholesterol concentrations were not changed, while serum RLPs concentrations were increased and remained high throughout the test, with the peak value at 6 h in a hypothyroid condition. In an euthyroid condition after T4 therapy, the peak values of RLPs were obtained at 4 h, and the concentrations were decreased rapidly. As the result, areas under the curve of serum RLPs were decreased remarkably after T4 therapy.
Hypothyroidism seems to be associated with a decrease in metabolism of serum RLPs. Such altered metabolism of RLPs may be related to the decreased activities of LPL and HTGL and can be corrected by T4 replacement therapy.
- SourceAvailable from: Fabio Monzani
[Show abstract] [Hide abstract]
- "Other qualitative lipid alterations, such as abnormal catabolism of remnant lipoproteins, have been described in overt hypothyroidism . Serum concentrations of remnant-like particle cholesterol were corrected by T4 replacement therapy . The same authors, in a following clinical study, showed similar alterations also in sHT patients, reversed by LT4 replacement in most patients . "
ABSTRACT: Endothelial dysfunction represents an important pathway thereby cardiovascular risk factors promote the development and progression of atherosclerosis. Hypothyroidism is associated with an increased cardiovascular risk, and the assessment of endothelium function is recognised an effective tool for the detection of evidence of preclinical cardiovascular alterations. Both vascular smooth muscle cells and endothelium play pivotal roles in modulating vascular tone and both are potential targets of thyroid hormone action. The pathogenesis of the association between endothelial dysfunction and hypothyroidism is complex and still not well established. The presence of traditional and emerging risk factors may contribute to the development of endothelium impairment, generating a chronic state of injury that triggers abnormal endothelial response. Levothyroxine replacement therapy is currently used for restoring euthyroidism and improving cardiovascular risk of hypothyroid patients. The decision to treat patients with subclinical hypothyroidism should depend on the presence of risk factors, rather than on a TSH threshold. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events, especially in subclinically hypothyroid patients, remains to be elucidated. Large multicenter, placebo-controlled prospective trials are necessary to address the issue. The article also discusses recent patents in this field.Recent Patents on Endocrine Metabolic & Immune Drug Discovery 05/2008; 2(2):79-96. DOI:10.2174/187221408784534222
- [Show abstract] [Hide abstract]
ABSTRACT: Le gène de l'apolipoprotéine (apo) AV, est un nouveau gène candidat pour étudier les mécanismes des hyperchylomicronémies, largement méconnus. Nous avons identifié, dans une cohorte de 286 patients ayant présenté une hyperchylomicronémie, indemnes de mutation sur la lipoprotéine lipase (LPL) ou l'apoCII, 3 mutations de l'APOA5 : Q139X et Q97X, et L242P. Nous présentons, à travers 2 études, la description phénotypique et génotypique des cas index et de leurs familles ainsi que la caractérisation fonctionnelle des mutations. Les mutations Q97X et Q139X ont été clairement impliquées dans l'hyperchylomicronémie à l'état homo ou hétéroygote, et associée à un défaut de lipolyse intravasculaire. L'expression phénotypique des mutations chez les hétérozygotes était très variable, influencée par des co-facteurs génétiques, en particulier les haplotypes variants de l'APOA5, et plus faiblement par l'environnement métabolique. Par ailleurs, nous avons montré, dans une 3ème étude, l'association des haplotypes variants de l'APOA5 et la survenue d'une hypertriglycéridémie modérée ou sévère dans une cohorte de patients diabétiques de type 2. Nos travaux ont permis de confirmer pour la première fois chez l'homme le lien fonctionnel entre l'apoAV et la lipoprotéine lipase (LPL). Nous proposons un nouveau modèle d'interaction entre ces deux protéines : l'apoAV régulerait la lipolyse intravasculaire par la LPL en agissant sur son expression à la surface de l'endothélium vasculaire.
- [Show abstract] [Hide abstract]
ABSTRACT: Subclinical and overt hypothyroidism are relatively common disorders in the general population. Thyroid hormone is known to play a role in regulating the synthesis, metabolism, and mobilization of lipids. In patients with overt hypothyroidism there is an increase in serum total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B, lipoprotein(a) levels, and possibly triglyceride levels. The effects of subclinical hypothyroidism on serum lipid values are less clear. The preponderance of evidence suggests that total cholesterol, LDL cholesterol, and possibly triglycerides are increased in patients with subclinical hypothyroidism, whereas high-density lipoprotein (HDL) cholesterol and Lp(a) remain unchanged. Most lipid abnormalities in patients with overt hypothyroidism will resolve with thyroid hormone replacement therapy. However, clinical trials to date have not shown a beneficial effect of thyroid hormone treatment on serum lipid levels in patients with subclinical hypothyroidism. The lipid-altering effects of thyroid hormone make it an appealing target for drug development. The development of specifically targeted thyroid hormone analogues that could potentially treat hyperlipidemia without causing systemic thyrotoxicosis is currently ongoing.Current Cardiology Reports 12/2004; 6(6):451-6. DOI:10.1007/s11886-004-0054-3