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Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies
Abstract
OBJECTIVE: The significance of mild hypercholesterolaemia in subclinical hypothyroidism and whether there is beneficial reduction after thyroxine replacement, remain controversial. We aimed to describe the association between hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect of thyroid substitution therapy by an analysis of previously published intervention studies. DATA SOURCES: Intervention studies cited in the Medline database from January 1976 until January 1995, with index terms cholesterol, hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION: We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre and post-substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS: (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypothyroidism, both subclinical and clinical. (2) Precision weighted pooled estimates of the effect of thyroid substitution therapy on the plasma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS: Subclinical hypothyroidism was two to three times more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevated in patients with subclinical dysfunction of the thyroid. Thyroid substitution therapy in patients with subclinical hypothyroidism, restoring the TSH levels to normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (Cl) 0.2-0.6 mmol/l) independently of the initial plasma level. The effect of thyroid substitution therapy on HDL-cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of total cholesterol. In these patients substitution therapy decreased total cholesterol by 1.2 mmol/l (95% Cl 0.9-1.5 mmol/l) when the plasma levels were elevated up to 8 mmol/l, and by 3.4 mmol/l (95% Cl 3.0-3.7) when plasma levels were higher than 8 mmol/l. The high density lipoprotein (HDL)-cholesterol level decreased and amounted to 0.16 mmol/l (95% Cl 0.07-0.24). CONCLUSIONS: Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.
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“Thus, an association, if present, is likely to be weak, with SCH contributing to a small increase in serum LDL-C, ranging between 3 and 15 mg/dl (0.1 to 0.4 mmol/l) (42).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [42]
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Items 101–181 of 181
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“Any beneficial effect of L-thyroxine (LT4) replacement on lipid profile in subjects with SH is also controversial (7,19,20).”
BackgroundResultInfluentialSubclinical thyroid disorders: The menace of the Trojan horse
Duntas, L. H. (2003) · Journal of Endocrinological Investigation · doi:10.1007/bf03345205 · Cited by 20
Screening for thyroid disorders in asymptomatic adults from Brazilian populations
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“To estimate efficacy in cholesterol reduction and prevention of ischaemic heart disease in patients with subclinical hypothyroidism they reviewed a meta analysis of observational studies and long-term follow-up of the Framingham cohort (Danese t al., 1996; Kannel, 1996; Tanis et al., 1996).”
MethodDyslipidemia in subclinical hypothyroidism
Caparevic, Z., Bojkovic, G., Stojanović, D., & Ilić, V. L. (2003) · Medicinski pregled · doi:10.2298/mpns0306276c · Cited by 18
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“A number of studies have noted a direct relationship between the degree of hypothyroidism and elevation of total and LDL cholesterol [64,65].”
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Song, Y., Lee, H. S., Park, G., Kang, S., & Lee, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.893461 · Cited by 11
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“Cholesterol concentrations were not reduced significantly by thyroid hormone therapy in 10 longitudinal studies (1, 9 ). When data were analysed according to the severity of SCH, some studies showed that cholesterol and LDL cholesterol concentrations are increased only in the severe form of SCH and in overt thyroid fa…”
ResultManagement of Dyslipidemia in Endocrine Diseases
Tannock, L. R. (2022) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2022.02.003 · Cited by 8
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“…cholesterol (HDL-C) (Erdem et al., 2008); (3) elevations in the levels of lowdensity lipoprotein cholesterol (LDL-C) and total cholesterol (TC) (Tanis et al., 1996; Danese et al., 2000; Luboshitzky et al., 2002; Jung et al., 2003; Monzani et al., 2004; Walsh et al., 2005; Erem, 2006; Duman et…”
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Schlienger, J.-L., Sapin, R., Vinzio, S., Luca, F., & Goichot, B. (2007) · Immuno-analyse & Biologie Spécialisée · doi:10.1016/j.immbio.2007.02.006 · Cited by 5
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“Two meta-analyses addressed the issue [158,160]; in the first one, considering intervention studies cited in the Medline database from January 1976 until January 1995, thyroid substitution treatment decreased TC by 0.”
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“Our findings and interpretations keep in track with the earlier as well as the recent observations that a mild thyroid failure does occur in SH state and that is sufficient to pose significant atherosclerotic and cardiovascular threat in these patients.[12,17] although, some degree of variable association of lipid pro…”
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“One meta-analysis of 13 studies from 1976 to 1995 found that after 6 months of LT4 replacement therapy, total cholesterol in SCH patients decreased by 15 mg/dL [21].”
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“However, the beneficial effect of L-thyroxine replacement on the lipid profiles of patients with sub-clinical hypothyroidism remains controversial (10-17, 27, 28).”
Effect of Levothyroxine Therapy on Hypothyroidism-induced Dyslipidemia
Chandra, S., Shekhar, A., Singh, H. K., Shaifali, I., & Mehra, D. (2017) · International Journal of Advanced and Integrated Medical Sciences · doi:10.5005/jp-journals-10050-10087 · Cited by 2
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Metadata
- Authors
- Tanis, B. C., Westendorp, R. G. J., & Smelt, A. H. M.
- Affiliations
- Leiden University Medical Center (NL)
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 1996-06
- Volume
- 44
- Issue
- 6
- Pages
- 643-649
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2078996989
- Cited by
- 177
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 5 · 2012: 2
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- subclinical hypothyroidism, hypercholesterolemia, thyroid hormone replacement, thyroxine, total cholesterol, HDL cholesterol, thyroid-stimulating hormone, overt hypothyroidism, serum lipids, meta-analysis of intervention studies, dose-response relationship, cardiovascular risk, dyslipidemia, thyroid function tests, lipoprotein cholesterol, triglycerides
- MeSH terms
- Adult, Female, Humans, Hypercholesterolemia, Hypothyroidism, Cholesterol, HDL, Thyrotropin, Thyroxine
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